Saudi Pharmaceutical Journal 29 (2021) 879–907

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Saudi Pharmaceutical Journal

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Review

Herbal drugs and natural bioactive products as potential therapeutics:

A review on pro-cognitives and brain boosters perspectives
Swati Halder a,1, Uttpal Anand b,1, Samapika Nandy a, Patrik Oleksak c,⇑, Safaa Qusti d, Eida M. Alshammari e,
Gaber El-Saber Batiha f, Eapen P. Koshy b, Abhijit Dey a,⇑
a
Department of Life Sciences, Presidency University, 86/1 College Street, Kolkata 700073, West Bengal, India
b
Department of Molecular and Cellular Engineering, Jacob Institute of Biotechnology and Bioengineering, Sam Higginbottom University of Agriculture, Technology and Sciences,
Prayagraj 211007, Uttar Pradesh, India
c
Department of Chemistry, Faculty of Science, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic
d
Biochemistry Department, Faculty of Science, king Abdulaziz University, Jeddah, Saudi Arabia
e
Department of Chemistry, College of Sciences, University of Ha’il, Ha’il, Saudi Arabia
f
Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt

a r t i c l e i n f o a b s t r a c t

Article history: Memory, one of the most vital aspects of the human brain, is necessary for the effective survival of an
Received 17 January 2021 individual. ‘Memory’ can be defined in various ways but in an overall view, memory is the retention of
Accepted 4 July 2021 the information that the brain grasps. Different factors are responsible for the disbalance in the brain’s
Available online 15 July 2021
hippocampus region and the acetylcholine level, which masters the memory and cognitive functions.
Plants are a source of pharmacologically potent drug molecules of high efficacy. Recently herbal medicine
Keywords: has evolved rapidly, gaining great acceptance worldwide due to their natural origin and fewer side
Cognition
effects. In this review, the authors have discussed the mechanisms and pharmacological action of herbal
Memory impairment
Nootropics
bioactive compounds to boost memory. Moreover, this review presents an update of different herbs and
Memory enhancers natural products that could act as memory enhancers and how they can be potentially utilized in the near
Herbal medicines future for the treatment of severe brain disorders. In addition, the authors also discuss the differences in
Phytochemicals biological activity of the same herb and emphasize the requirement for a higher standardization in cul-
tivation methods and plant processing. The demand for further studies evaluating the interactions of her-
bal drugs is mentioned.
Ó 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 880
1.1. Memory: Brief background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 880
1.2. Storing of memory inside the brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 880
1.3. Memory impairment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 881
1.4. Memory enhancers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 881
1.5. Herbal remedies for impaired memory and cognition: Mechanisms and pharmacological actions . . . . . . . . . . . . . . . . . . . . . . . . . . . 881
1.6. History of memory enhancers in Ayurveda and TCM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 881

⇑ Corresponding author at: Department of Chemistry, Faculty of Science, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic.
E-mail addresses: [email protected] (P. Oleksak), [email protected] (A. Dey).
1
Both authors share equal contribution.
Peer review under responsibility of King Saud University.

Production and hosting by Elsevier

https://doi.org/10.1016/j.jsps.2021.07.003
1319-0164/Ó 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
S. Halder, U. Anand, S. Nandy et al. Saudi Pharmaceutical Journal 29 (2021) 879–907

2. List of herbs having memory and cognition-enhancing properties. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 881

2.1. Family Acoraceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 881
2.2. Family Apiaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 882
2.3. Family Aquifoliaceae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 883
2.4. Family Araliaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 883
2.5. Family Asteraceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 883
2.6. Family Caprifoliaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 883
2.7. Family Celastraceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 883
2.8. Family Combretaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 884
2.9. Family Convolvulaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 884
2.10. Family Cornaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 884
2.11. Family Fabaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 884
2.12. Family Ginkoaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 885
2.13. Family Hyperiaceae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 885
2.14. Family Iridaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 885
2.15. Fasmily Lamiaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 886
2.16. Family Magnoliaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 888
2.17. Family Malvaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 888
2.18. Family Menispermaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 888
2.19. Family Myristicaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 888
2.20. Family Orchidaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 888
2.21. Family Phyllanthaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 889
2.22. Family Plantaginaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 889
2.23. Family Rutaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 889
2.24. Family Solanaceae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 889
2.25. Family Theaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 890
2.26. Family Zingiberaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 890
3. Use of crude drugs from herbs in memory impairment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 891
4. Effective herbal formulations for memory enhancement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 891
5. Other advantageous compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 894
6. Quality and safety of herbal drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 898
7. Conclusions and future directions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901
Declaration of Competing Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901

1. Introduction i) Short-term memory (STM)–rapidly formed memory that is

retained for a short time (minutes to hours).
1.1. Memory: Brief background ii) Long-term memory (LTM)–a memory that is retained for
long periods, e.g.-from hours to days, weeks, months, even
The human brain is the most complex organ in the body. One of years. (Rho et al., 2005).
its most impressive aspects is the ability to retain information, iii) Sensory Memory or Iconic Memory-the potential to
what is called memory (Christophel et al., 2017; Postle, 2016). remember temporarily the huge amounts of information
Before this review work, we have to know the definition of what that people experience every day
memory is. ‘Memory’ perhaps can be defined in various ways. An
overall standard definition is: ‘‘Memory is the ability of an individ- The up mentioned ‘retention’ and ‘recollection’ deal with STM
ual to record sensory stimuli, events, pieces of information etc. and and LTM respectively (Rathee et al., 2008).
retain them over short or long periods and recall the same when-
ever needed at a later date” (Zlotnik and Vansintjan, 2019). In
short, memory is one of the most vital aspects for effective survival 1.2. Storing of memory inside the brain
of human beings (Shiksharthi et al., 2011). But when we discuss
memory, it is not only the retention of information, along with it When we are discussing memory, we have to know the mecha-
we also consider some associated terms like- cognition, intelli- nism by which various kinds of information are stored inside our
gence, attention, concentration, quality of life (QOL) etc. Intelli- brains. There is a region in our brain, named ‘Hippocampus’,
gence is according to Ayurveda the combination of three located in the medial temporal lobe of the brain. This hippocampus
capabilities of mind: is the center of all these memory and cognitive functions. At first,
our brain cells grasp whatever we see, hear or do; then the hip-
 Acquisition: Capacity to grasp any information and to analyze pocampus decides whether the information we grasped is impor-
it. tant to store or not; if hippocampus decides to store the
 Retention: Retain the information inside the brain. information, it retains inside our brains and we can memorize it,
 Recollection: Recall the information later (Rathee et al., 2008). otherwise, the information gets deleted from our brain automati-
cally (Shiksharthi et al., 2011; Kandel et al., 2014). This mechanism
Based on the different mechanisms and types, memory can be involves the interaction between various neurotransmitters in the
classified into 3 types (Camina and Güell, 2017): brain (Shiksharthi et al., 2011; Sheffler and Pillarisetty, 2019).
Acetylcholine (ACh) is the most important neurotransmitter

880
S. Halder, U. Anand, S. Nandy et al. Saudi Pharmaceutical Journal 29 (2021) 879–907

involved in memory and cognitive functions apart from several any other chemical compound (Anand et al., 2019). Our very own
neurodegenerative pathogenicities (Parle and Vasidevan, 2007; Indian Ayurveda possesses a treasury of such medicinal plants that
Akaike et al., 2018). One important enzyme involved in this mech- enhance memory, cognition and intelligence. These Ayurvedic
anism is Acetylcholinesterase (AChE). Estimation of this enzyme’s herbs are now popular all over the world (Anand et al., 2019).
activity is an important parameter to assess the central cholinergic Not only Indian Ayurveda, the Traditional Chinese Medicine
function. Acetylcholinesterase (AChE) modulates proper levels of (TCM), Japanese, Korean, African, American and European medici-
acetylcholine by breaking ACh into Choline (the building block of nes also come with a huge number of medicinal plants helping in
ACh). However, the excessive activity of AChE results in the defi- reversing memory impairment. The herbs acting upon brain cells
ciency of ACh, leading to memory impairment (Rathee et al., are termed ‘nootropic herbs/drugs’ and their isolated compounds
2008; Shiksharthi et al., 2011). are called as ‘smart drugs’ or ‘cognitive enhancers’ or ‘brain boos-
ter’ (Hildt, 2013; Frati et al., 2015). According to Ayurveda, herbs
1.3. Memory impairment that promote intelligence is known as ‘Medhya herbs/ Rasayana’
(Kulkarni et al., 2012; Reena et al., 2013) and includes 10 herbal
Poor memory, low retention power, difficulty to recall, lack of drugs namely Jatamansi, Ashwagandha, Vacha, Jyotishmati, Shankha-
concentration, weak analyzing ability-these are very much com- pushpi, Amalaki, Yashtimadhu, Kavach Beej, Bramhi, and Manduk-
mon problems of the modern world. Besides some of the condi- parni (Lele, 2010). All these medicinal herbs increase the
tions, such as stress, ageing and emotions may lead to memory neurotransmitter level (especially acetylcholine) in the brain by
impairment, amnesia, dementia etc., and sometimes to some seri- inhibiting excess AChE activity and also improve blood circulation
ous threats like Alzheimer’s disease (AD), Schizophrenia etc. (Gur inside the brain thus providing sufficient supply of O2 to the brain
and Gur, 2013; Hildebrandt, 2019). In AD, the function of the hip- cells (Colovic et al., 2013; Suliman et al., 2016). Some home reme-
pocampus is destroyed, so that the brain cannot manage to store dies against poor memory are found in commonly known food
different kinds of information, especially the new ones. Besides, plants, which we can have as oils and vegetables (Fernando et al.,
the neurons start to get degenerated. This disease affects mostly 2015; Hardman et al., 2016; Molz and Schröder, 2017). The World
the elderly population, ageing 65 years or more (Wortmann, Health Organization (WHO) states that at present date 80% of the
2015; Winblad et al., 2016; Alzheimer’s Association, 2016). Accord- world populations are using herbal remedies for the improvement
ing to cholinergic hypothesis, memory impairs due to deficiency in of health (Srivastava et al., 2019).
the cholinergic function inside the brain. Cognitive dysfunction is
correlated with this impaired cholinergic function (Dumas and
1.6. History of memory enhancers in Ayurveda and TCM
Newhouse, 2011; Bohnen et al., 2018).
Ayurveda, the science of life is a long traditional alternative
1.4. Memory enhancers
medicine system from the Indian subcontinent. This natural science
is based on the fundamental laws of nature with therapeutic
Functional foods, supplements and drugs that are able to
approach for treatment of innumerous human diseases. Aging rep-
improve memory, cognition intelligence and other mental func-
resents a systematic involution of the human body and the brain is
tions are known as memory and cognitive enhancers (Lynch
considered as the most vulnerable organ to this process. Therefore,
et al., 2014; Morè et al., 2020). There is another term that can be
to avoid this damage, the Rasayana therapy, a rejuvenation branch
used to describe memory and cognitive enhancers: ‘Nootropics’
of Ayurvedic medicine was established. Various natural drugs that
(Pieramico et al., 2014; Onaolapo et al., 2019).
act as brain tonic, promote health of the brain, lead to the allevia-
Nootropics. The word ‘nootropic’ (Greek: noos-mind, tropein-to
tion of behavioral disorders or improve memory impairment are
bend/turn or montor) was first coined in 1972 by Dr Corneliu E
utilized in Rasayana approach. Various memory enhancing and
Giurgea. Nootropics are referred to as ‘smart drugs’ that act upon
rejuvenating plants are used in Rasayana therapies, including:
our brain cells. A nootropic is extremely non-toxic neuroprotective
Acorus calamus, Bacopa monniera, Clitoria ternatea, Nardostachys
substance and can be used as memory and cognitive enhancer and
jatamansi, Terminalia chebula and many others (Singh 2013).
in AD treatment (Colucci et al., 2012; Chaudhari et al., 2017). The
Traditional Chinese medicine (TCM) is based on the balance
functions of nootropics are: (a) Improving Acetylcholine level in
between health and disease. According to theory of TCM, healthy
the brain, (b) Improving O2 supply to the brain, (c) Supplying neu-
body is the body in the balance, on the other hand disharmony is
rochemicals (e.g.-neurotransmitters, enzymes, hormones) to the
not the cause of disease. The disease is caused by life style, influ-
brain (Jeon, 2015; Suliman et al., 2016; Crespo-Bujosa and
ence of pathogens and various negative effects. However, the bal-
Rodríguez, 2019). To improve memory and mood several nootropic
ance can be restored by herbal treatment. For over thousands of
agents are generally used such as Aniracetam, Oxiracetam,
years, Chinese people have accumulated experiences in treatment,
Pramiracetam, Piracetam and Choline esterase inhibitors like Done-
diagnosis, and disease prevention to create a whole theoretical sys-
pezil, but the side effects of these agents (Talih and Ajaltouni, 2015;
tem of medicine therapy. Herbal medicines with memory enhanc-
Zaami et al., 2020) have made their applicability limited.
ing properties are also encompassed in the TCM. Between the
plants used in TCM for memory improvement belong: Huperzia ser-
1.5. Herbal remedies for impaired memory and cognition:
rata, Ginkgo biloba, Panax ginseng, Camellia sinensis and other (Yan
Mechanisms and pharmacological actions
et al., 2007). These and above-mentioned plants will be discussed
in following sections.
Herbal remedies are traditionally used all over the world to
enhance poor memory and related ailments (Giampieri et al.,
2014; Liao and Lin 2012; Banerjee et al., 2021; Gregory et al., 2. List of herbs having memory and cognition-enhancing
2021). Several medicinal plants and their extracts have shown noo- properties
tropic properties or memory-enhancing properties by suitable
character of their medicinal components (Aguiar and Borowski, 2.1. Family Acoraceae
2013; Onaolapo et al., 2019; Banerjee et al., 2021; Tandon et al.,
2021). The increasing demand for herbal remedies worldwide is Acorus calamus L. / Sweet flag is a medicinal valuable semi-
because herbal compounds have lesser or no side effects than aquatic herb that grows throughout India, Central Asia, Siberia,
881
S. Halder, U. Anand, S. Nandy et al. Saudi Pharmaceutical Journal 29 (2021) 879–907

Fig. 1. Hallmarks of nootropic herbs.

Eastern Europe, Southern Russia, and could be found in gardens 2.2. Family Apiaceae
too. This perennial plant is not frost-tender and grows to a height
of 1 m. It shows numerous therapeutic properties such as antipro- Centella asiatica (L.) Urban / Gotu kola (also known as Than-
liferative, antiulcerative, antibacterial, antioxidant, insecticidal, kuni) is native to the wetlands in Asia and is widely scattered
immunosuppressive, antifungal etc. (Pandit et al., 2011; Kumar across the subtropical regions tropical geographical regions of
et al., 2012; Parki et al., 2017). A plethora of bioactive chemical India, Indonesia, Madagascar, China, Sri Lanka, and Nepal. This
constituents like b-asarone (40) (AChE inhibitor) (Mukherjee evergreen perennial plant is self-fertile, frost-tender, and grows
et al., 2007a), phenylpropanoid, saponins, lectins, flavonoids, to height of 20 cm. It is commonly used as a green leafy vegetable
sesquiterpene, alkaloids, a-asarone (67), phenols, monoterpene, and as a medicinal herb in AM, Unani Medicine (UM), Traditional
and quinones, mucilages etc. are exhibited by this plant (Joshi, African Medicine (TAM) and TCM (Jahan et al., 2012). It contains
2016). The rhizome of this plant ‘Acori Calami Rhizoma’, is mainly a wide array of phytochemicals, which include flavonoids, tannins,
used to enhance/improve memory (May et al., 2016). Sweet flag is triterpenoids (Asiatic acid, asiaticoside, madecassic acid, and
a very essential brain tonic as it shows a very short time results. madecassoside), glycosides, essential oils, alkaloids, and volatile
Articles claiming this herb to cure AD are out (Nandakumar fatty acids (Das, 2011). It effective enhances the blood circulation
et al., 2013). Sweet flag strengthens the nervous system and in different body parts including the brain. Moreover, it helps to
increases the overall memory of the person. This is prescribed to protect the brain from damage and improves concentration. The
patients who have epilepsy, amnesia, hysteria, insomnia, neurosis, brain is more receptive to information and the memory is
remittent fevers, and melancholia (Huang et al., 2013; Sharma enhanced (Mannangatti and Naidu, 2016). The usage of this herb
et al., 2014). The sweet flag contains essential oil in which 67 is documented over the centuries in Indian medicine system for
and 40 are present as the main components, which harbour anti- the treatment and prevention of several diseases and health-
inflammatory properties to downregulate inflammatory cytokines related ailments including cancer, wound healing, dementia, dia-
(Shin et al., 2014; Lim et al., 2014). betes, skin problems, ulcers, for regenerating the brain and nerve

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cells, for combating ageing, asthma, (Singh et al., 2010; people. It contains saponins that enhance memory in the
Sabaragamuwa et al., 2018) (Fig. 1). The positive results of Centella scopolamine-induced learning impairment. It is proposed that
asiatica on the general ability, power of concentration and beha- the main active components in Ginseng roots, Ginsenosides (Rg1
viour of mentally retarded children has been found in pharmaco- (20), Rg2 (21), Rg3 (30), Rh2 (22) etc), induce in the central cholin-
logical and clinical trials. It is proposed that Centella asiatica and ergic nervous system the enhancement of choline uptake, which is
Bacopa monnieri have the similar medicinal value. A nervine tonic important for learning and memory. In rats, the cyproheptadine-
for treatment of various brain diseases or syrup to increase the induced recognition deficits were improved by a component of gin-
memory of children are prepared from the whole plant. C. asiatica seng saponin.
also inhibits scopolamine-induces memory impairment through
the inhibition of AChE enzyme activity (Orhan et al., 2013). An 2.5. Family Asteraceae
animal study on mice model has shown asiaticoside as a neuropro-
tective agent and this effect could be linked with asiaticoside’s anti- Eclipta alba (L.) Hassk. / Bhringaraj grows commonly in moist
inflammatory activity by inhibition of the overactivated p38 MAPK places and called as a weed by the farmers all over the world. This
pathway (Chen et al. 2014). In middle cerebral artery occlusion annual herb growing to a height of 30–40 cm, has cylindrical roots
(MCAO) rats, the ethanolic extract of C. asiatica has demonstrated and white flowers 6–8 mm in diameter. It is widely distributed in
to be enhanced neurobehavioral activity, educed infarction volume tropical areas worldwide e.g. in India, China, Bangladesh, Thailand,
along with preserved brain neuroanatomy, increased the status of and Brazil. Wedelolactone, luteolin, ursolic acid, apigenin, eclalbas-
antioxidants and decreased the levels of free radicals (Tabassum aponins, and oleanolic acid are some of the potential bioactive con-
et al., 2013). In vitro experiment of water extract of this herb pre- stituents of this plant. E. alba possesses multifunctional
served/protected human neuroblastoma MC65 cell line and SH- pharmacological properties and has proven beneficial effects in
SY5Y cells from b-amyloid toxicity (Soumyanath et al., 2012). the treatment of various disorders including cancer, gastrointesti-
Recently, in vitro examination of C. asiatica leaf extract significantly nal disorders, malaria, fever, snake bite, cuts and wounds, skin dis-
suppressed a-synuclein aggregation and prevented oligomer for- orders, arthritis, respiratory tract disorders (like asthma),
mation of aggregates that suggested the therapeutic potential of inflammation, graying of hair and hair loss, liver disorders (like
C. asiatica against Parkinson’s disease (PD) (Ruben et al., 2014). jaundice), microbial diseases, and spleen development (Jahan
et al., 2014). Bhringaraj is traditionally used for its memory
2.3. Family Aquifoliaceae enhancing quality, and thus it is not suprising that several studies
were conducted for this purpose. Dose of 100 and 200 mg/kg of the
Ilex paraguariensis (A.) St.-Hil. / Yerba mate is plant typically Bhringaraj leaves aqueous extract was administered to rats. Then
growing and processing in South America, especially in northern transfer latency (TL), which represents a measure of acquisition
Argentina, Paraguay, Uruguay and southern Brazil (Bracesco and retrirval learning was evaluated on an elevated plus-maze test.
et al., 2011). This evergreen tree/shrub growing up to height of The spatial habitual learning revealed a relevant advancement in
15 m has simple obovate-oblong leaves, 4-membered small retrieval memory of tested rodents (Banji et al., 2007; Bhaskar
green-white flowers and small red drupe fruits with diameter of and Chintamaneni, 2014). Notably, the antiepilepsy activity of E.
4–6 mm. It is traditionally used for a preparation of the beverage alba phytoconstituents (wedelolactone, b-amyrin, and luteolin)
called mate, which possesses high nutritional values. I. paraguar- have been widely reported by several groups of researchers
iensis extract contains polyphenols (chlorogenic acids), tannins, (Shaikh et al., 2012; Shaikh et al., 2013).
xanthines (caffeine, theophylline and theobromine), flavonoids
(quercetin (80), kaempferol), purine alkaloids (methyl xanthines), 2.6. Family Caprifoliaceae
saponins, and vitamins (A, C, B1, B12, E) (Bracesco et al., 2011).
It’s entry into the body exhibit neuroprotective, diuretic, antimuta- Nardostachys jatamansi (D.Don) DC. / Jatamansi is well-
genic, anti-inflammatory, antioxidant, antidiabetic, anti- reputed Medhya herb that has a place of respect in the Indian
hyperglycemic, antidepressant, anticonvulsant, hypocholestero- Ayurveda. This small perennial flowering herb grows to a height
laemic, antifungal, anti-obesity effects (Fernandes et al., 2017). of 10–50 cm and has bell-shaped pink flowers. It commonly grows
The memory-enhancing activity of mate tea leaves are reported in the Himalayas of Nepal, China and India. Ayurveda says the roots
on different models of memory and learning (Prediger et al., of Nardostachys jatamansi have anti-ischemic, antioxidant, anticon-
2008). The worthwhile effects of mate tea used for the enhance- vulsant and neuroprotective activities. The ethanolic extract of
ment of cognition, short- and long-term memory in animals were Jatamansi at a dose of 200 mg/kg b.w. significantly lead to the
reported. It also has properties to treat dementia. More recently, improvement in learning and memory power in young mice. More-
several groups of researchers have demonstrated that I. paraguar- over, the scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.
iensis derivatives are abundant with bioactive compounds which p.)-induced amnesia was considerably reversed. It also reversed
when enters CNS and produces significant therapeutic indices the natural ageing-induced amnesia in mice. From these results,
(Cittadini et al., 2019). Leaves aqueous extract of this medicinal it can be said that Jatamansi might prove to be a useful remedy
herb has been shown to potentially inhibit scopolamine-induced for the treatment of dementia in elderly persons.
memory loss in male Swiss mice (Santos et al., 2015).
2.7. Family Celastraceae
2.4. Family Araliaceae
Celastrus paniculatus Willd. / Jyotishmati (also known as Kan-
Panax ginseng C.A.Mey. / Ginseng grows only in the Northern gani and Malkangni) belongs to the genus of woody, climbing
Hemisphere, typically in cooler climates of North America and shrubs. The stems are up to 10 m long and twine into the surround-
eastern Asia (northeast China, eastern Siberia, Korea and Bhutan). ing vegetation. Pale brown bark is covered with small elongated
It is a perennial, hermaphrodite herb which grows to a height of lenticles. The leaves are simple, broad and oval with toothed mar-
80 cm, has green-white small (3 mm) flowers and oval-shaped gins. Jyotishmati, one of the most widely explored medicinal plant
red drupe fruits, 6–7 mm long. This herb has a significant applica- and well known Medhya Rasayana’ (nervine tonic) in Ayurvedic
tion in TCM for thousands of years. It is used mostly as a memory medicine (AM) (Malik et al., 2017). It is distributed in various
tonic and to improve memory and learning, especially in elderly geographical locations including Southeast Asian countries like
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Thailand, Sri Lanka, Nepal, Japan, Myanmar, China, India, Malaysia, et al., 2018; Anupama et al., 2019). In a preclinical study, the
Taiwan, Indonesia, Vietnam and Australia (Mishra 2011) at eleva- ethanolic extract of Convolvulus pluricaulis (in two doses- 100 mg
tions up to 10–18 m height. The seeds and seeds oil is the main and 200 mg per kg b.w.) reversed scopolamine-induced amnesia
part of this plant that contains a plethora of phytochemicals in rats (Nahata et al., 2008). Clinical studies of its polyherbal for-
including triterpenoid pristimerin, sesquiterpeniod polyalcohols mulation justified its potential for the ancient claim of brain tonic.
esters (celapnin, polyalcohol A–D, malkanguniol, malkangunin), The memory enhancing and learning behavior properties of
polyalcohol (paniculatusdiol, malangunin, malkanguniol and Shankphapushpi have become increasingly popular worldwide in
malkanginnol), alkaloids celastrine, paniculatin, calapagine, cela- recent years. Most recently, an aqueous extract of C. pluricaulis
panine, calapanigine, sesquiterpenes, sterols (b-amyrin and b- has demonstrated to the downregulated s protein level, enhances
sitosterol), saturated fatty acids (palmitic, stearic and lignoceric locomotor deficits and increases longevity in human
acid), unsaturated fatty acids (oleic, linoleic and linolenic), pheno- microtubule-associated protein tau (hMAPs) induced Drosophila
lic triterpenoids (paniculatadiol, celastrol), lipids etc. (Katekhaye AD model (Anupama et al., 2019).
et al., 2011). They have a bitter taste, an unpleasant odour and
are regularly used as neuroprotective properties, cognitive disor- 2.10. Family Cornaceae
ders, and to sharpen/enhancing the memory and boosting intelli-
gence (Bhanumathy et al., 2010; Arora and Pandey-Rai 2014). Cornus officinalis Siebold & Zucc. / Japanese cornel is a decid-
Whole plant extract of C. paniculatus has demonstrated anti- uous tree widely spread/occurs in China, Japan and Korea. The tree
epileptic function (Atigari et al., 2012). The seeds and the seed oil grows to a height of 10 m, has a brown-gray bark and ovate leaves
are commonly used as a brain tonic, in many central nervous sys- are 5–12 cm long. The flowers are bright yellow on bare stems in
tem (CNS) disorders and as neuro-protective agent (Bhagya et al., late winter or early spring. Fruits are red edible berries about
2016; Malik et al., 2017). The seed oil improved learning and mem- 1.5 cm long. This plant is usually used as a food or due to its medic-
ory whereas the levels of dopamine, noradrenaline and serotonin inal properties (Ma et al., 2014). A plethora of phytoconstituents is
were decreased in the brain of rats. The oil of this plant signifi- exhibited by C. officinalis including anthocyanins, flavonoids (quer-
cantly decreases AChE activity (Bhagya et al., 2016; Malik et al., cetin), and phenolic acids (trans-cinnamic acid, benzoic acid),
2017). In addition to neurological benefits, different plant parts triterpenoids, anthocyanin, carbohydrates (Rudrapaul et al.,
of C. paniculatus has potentially shown to exhibit potent activity 2015). Furthermore, this herb is known to harbour neuroprotec-
in wound healing, hypolipidemic, antioxidant, analgesic, anti- tive, antitumor, antidiabetic, immunomodulatory, cardioprotec-
inflammatory, stomach ulcers, dyspepsia (Palle et al., 2018). tive, anti-amnestic, antimicrobial, antioxidant, anti-inflammatory,
renal and hepatic protective, antiosteoporotic and insecticidal
2.8. Family Combretaceae property (Czerwińska and Melzig, 2018). Cornel iridoid glycoside
(CIG) is the main component in this herb, which has the ability
Terminalia chebula Retz. / Haritaki is a deciduous tree, which to promote neurogenesis and to improve neurological function
grows in Southeastern Asia (India, China, Sri Lanka, Malaysia and after ischemia in rats. Iridoids of C. officinalis also protect hip-
Vietnam). The tree grows to a height of 30 m, the leaves are oval pocampal cells that have suffered from glutamate (Jeong et al.,
with opposite or alternate arrangement. The yellow flowers occur 2012). Further assays in rats proved, that CIG treatment signifi-
in terminal spikes or short panicles and emit unpleasant odor. cantly improved the memory deficits seen in Fimbria-fornix trans-
The ovoid fruits are yellow to orange-brown. The ripe fruit of Ter- action (FFT). It also reduced the loss of neurone in the mouse
minalia chebula is valued due its beneficial health effects including hippocampus (Zhao et al., 2010). Many polyphenolic compounds
memory and intellect enhancement. Further, it is believed that obtained from C. officinalis fruits, e.g. tellimagrandin I, tellima-
consumption of the fruit is efficient to prolong life, to improve eye- grandin II and isoterchebin, are important regulators of certain
sight and can delay ageing. To achieve the desired effects, con- enzymes and downregulate total enzymes implicated in the devel-
sumption of one ripe fruit every morning is recommended. opment of AD neurodegeneration (Bhakta et al., 2017). The docu-
mented neuroprotective and anti-amnestic property of C.
2.9. Family Convolvulaceae officinalis is attributed because of antiozidant and radical scaveng-
ing effects (Cooper and Ma, 2017; Huang et al., 2018).
Convolvulus pluricaulis Choisy / Shankhpushpi (also known as
Bindweed) is a well-reputed Medhya herb commonly found in 2.11. Family Fabaceae
southern India and Burma. This perennial herb has 10–40 cm long
stems and small (5 mm) blue color flowers. In ancient times, it was Desmodium gangeticum (L.) DC. / Shalparni is widely used in
a prominent memory-improving drug, a psychostimulant and tran- Ayurvedic medicine. This small shrub grows to a height of 1.2 m.
quiliser in traditional Indian medicine (Shethiya and Mishra, 2010). The oblong leaves are simple with an alternative arrangement.
A brain tonic is prepared from the whole plant and is used for The purple-white flowers have a bilateral symmetry. D. gangeticum
memory and intellect improvements. Its consumption also claimed has traditionally been used as astringent, anthelmintic, diuretic,
to prevent memory loss. The plant contains diverse phytochemi- laxative, antipyretic, and in the treatment and prevention of neu-
cals including b-sitosterol, vitamin C or ascorbic acid (23), silane, rodegenerative diseases like dementia and mental disorders (Ma
decanoic acid, carbohydrates, vitamin E, valeric acid or pentanoic et al., 2011). Significant bioactive phytochemicals of this plant
acid, cinnamic acid, squalene, linoleic acid, phthalic acid, gums, include flavonoids, alkaloids, terpenoids, phenolic compounds,
proteins, mucilages, several alkaloids (tropane), flavonoids and steroids. Furthermore, D. gangeticum has been documented
(Kaempferol), and glycosides etc. as active chemicals that bring to display immunomodulatory, antidiabetic, antioxidant, antimi-
about its diverse beneficial pharmacological effects (Agarwa crobial, anti-writhing, anti-inflammatory, renal-protective, antiul-
et al., 2014). Several groups of researches have shown that bioac- cer, hepatoprotective, antileishmanial, wound healing, and
tive compounds of this herb displayed anti-ulcerogenic, neuropro- cardio-protective properties (Bhattacharjee et al., 2013). In laca
tective, antimicrobial (anti-bacterial, antiviral), antioxidant, mice, the alkaloid-rich fraction of D. gangeticum greatly reversed
antianxiety, nootropic, anxiolytic, antiobsessive, anticonvulsant, the scopolamine-induced amnesia at the dosage of 50 mg/kg
antithyroid, hepatoprotective, antidepressant, hypotensive, anxi- (Mahajan et al., 2015). Salparni in mice significantly improves
olytic, ameliorative property (Ravichandra et al., 2013; Rachitha learning and memory abilities and reverses the scopolamine or
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natural ageing induced amnesia. It also decreases acetyl- logical levels (Vellas et al., 2012; Jahanshahi et al., 2012; Zhang
cholinesterase activity in brain. Hence, D. gangeticum bears notable et al., 2013). The extract is widely used to treat AD and cerebrovas-
potential to its medicinal application for memory improving as cular disease (CD) (Zhang et al., 2017). Notably, during cerebral
well for the treatment of dementia and AD. ischemia (CI) bilobalide (BB) has proven to exhibit neuroprotective
Glycyrrhiza glabra L. / Licorice is a legume that is native to effects (Huang et al., 2012). Hence, From the molecular point of
Southern Russia and Asia, Mediterranean region and is broadly view, EGb761 display antioxidant activity and downregulating
planted throughout the Middle East and Europe. It is a perennial tau hyperphosphorylation in addition to the protection against
plant which grows to a height of 1.2 m. The herb has a compound Ab-induced neurotoxicity and hence it could be a potential medi-
leaves about 7–15 cm long, purple to pale-blue flowers long about cation for treating AD.
0.8–1.2 cm and produces oblong pods with several seeds. This herb
is known worldwide for its various curative properties. G. glabra 2.13. Family Hyperiaceae
contains diverse phytochemicals, which are of high medicinal
value including flavonoids (liquiritin, liquiritigenin, rhamnoliquir- Hypericum perforatum L. / St. John’s wort is native to subtrop-
ilin, isoliquiritin, etc.), triterpenes (glycyrrhizin or glycyrrhizic acid, ical and temperate geographical regions of Europe, western Asia,
glycyrrhetinic acid monoglucuronide), isoflavonoids (Dehydro- Middle-East India, northern Africa, Russia and China. This peren-
glyasperin C), saponin, tannins, glycosides etc. (Batiha et al., nial self-fertile flowering plant grows up to a height of 1 m. It
2020; Han et al., 2020). Various parts of this plant have been used has woody stems near the base, the leaves are oblong, narrow,
in the treatment of various health-related disorders such as roots and about 1–2 cm long. The five petal flowers are about 2.5 cm
in diabetes, flatulence and Graves’ disease, stem in tuberculosis, wide and colored bright yellow. H. perforatum is approved for ther-
and leaves in wounds. Furthermore, this perennial herb has been apeutic intervention (Božin et al., 2013) and contains diverse phy-
widely acknowledged to treat various pathological conditions tochemicals such as flavonoids derivatives (rutin, amentoflavone,
including epilepsy, stomach ulcers, jaundice, respiratory disorders, hyperoside, quercetin (80), biapigenin, isoquercitrin, kaempferol,
fever, hyperdipsia, hemorrhagic diseases, rheumatism, sexual etc.), phenolic compounds, acylated phloroglucinols (hyperforin
debility, paralysis, skin diseases etc. Licorice, a root extract of G. and derivatives), and naphthodiantrones (hypericin and deriva-
glabra is generally used as a brain tonic and a brain re-vitalizer. tives) (Russo et al., 2014; Oliveira et al., 2016). These phytochem-
This plant is termed in Ayurveda as ‘Medhya dravya’ and it was icals confer an array of pharmacological properties such as
commonly utilized to improve memory and intellect. The assays antiviral, neuroprotective, antifungal, anti-ischemic, wound-
on mice confirmed, that aqueous extract of liquorice at the dose healing, antibacterial, antioxidant, and antideprssant activity. In
of 150 mg/kg significantly boosts memory and learning skills. Fur- SH-SY5Y neuroblastoma cells, rutin prevents accumulation and
thermore, diazepam (1 mg/kg i.p.) and scopolamine (0.4 mg/kg i.p.) cytotoxicity of b-amyloids, mitigates mitochondrial damage, ROS,
induced amnesia was significantly reduced by liquorice extracts. oxidative stress, and reduces nitric oxide and proinflammatory
Liquiritigenin (LIQ), a bioactive compound of G. glabra root has cytokines production (Wang et al., 2012). It is an excellent tonic
shown to inhibit glutamate-induced hippocampal neuronal cell for brain damage and ameliorates spatial memory and learning
death by downregulating ROS production, Ca2+ influx and lipid per- behaviour against Ab25–35-induced toxicity (Liu et al., 2013). It
oxidation, protected mitochondria from stress and MAPKs phos- helps to regenerate the nervous system, specifically the myelin
phorylation (p38) thereby LIO is attributed as a strong sheath that surrounds nerves. Possibly, the usage of Hypericum
neuroprotective agent and could be a possibility to become a extract could be more beneficial for the treatment of depression
potent drug for AD and PD (Yang et al., 2013). associated with dementia than other antidepressants that may
cause sedation.
2.12. Family Ginkoaceae
2.14. Family Iridaceae
Ginkgo biloba L. / Ginkgo is a living fossil, native to China and
Japan. It is a large deciduous tree growing up to a height of 35 m. Crocus sativus L. / Saffron dried red–orange stigma (the only
The leaves are fan-shaped with two lobes, in antumn turn yellow usable part of this plant) is well-known as a fruit colouring, flavor-
and fall sometimes within a short period of time (1–15 days). Seeds ing agent, and exhibit beneficial biological/pharmacological effects.
are edible. EGb761, Ginkgo biloba leaves extract is famous globally It is a flowering perennial plant which forms small brown compact
for its beneficial pharmacological effect on neurotransmitter sys- corms that are flat on the base. The plant grows to a height of 10–
tems particularly in treating neurological disorders. EGb761 con- 25 cm. The purple flowers do not close during the night. The flow-
tain terpenoids (e.g., bilobalide, ginkgolides (28)) and ginkgolides ers consist of six petals, three stramens, and three stigmas. The
A (13), B (14) (Fig. 2), C, J, and M, flavonoids (e.g. kaempferol, quer- red–orange stigmas are 2.5–3 cm long and using as a noble spice.
cetin (80) and polymeric flavonoids) (Yuan et al., 2010). Among Saffron is the world’s most expensive regularly used dietary spice
these, ginkgolides, a bioactive constituent of EGb761 has proven (Moore et al., 2012). It is a native herb in Southwest Asia (Iran).
to interact with the cholinergic system and have neuroprotective The main bioactive chemical constituents are a-crocin (47)
and neural stem cells (NSCs) regenerative potential (Wang and (C44H64O24), crocetin (70) (C20H24O4), picrocrocin (C16H26O7),
Han, 2015; Ren et al., 2019). Ginkgo improves circulation of blood safranal (81) (C10H14O), water-soluble carotenoids (crocins), vita-
into the central nervous system and increases the distribution of mins (thiamine and riboflavin), carbohydrates, low concentration
nutrients and oxygen into the brain. It also eliminates free radicals of monoterpene aldehydes and its glucosides (81 and picrocrocin),
in the body thereby improves memory and alertness. The ginkgo lipids, polypeptides, proteins, flavonoids (quercetin (80), kaemp-
extract is prescribed for the treatment of amnesia and AD. Ginkgo ferol, isorhamnetin and anthocyanins e.g. petunidin, malvidin,
is used as one of the important compounds in several herbal nerve and delphinidin), starch, amino acids, gums, and minerals (Goupy
tonics. Recently, this plant has demonstrated a positive effect on et al., 2013; Zeka et al., 2015). For centuries, saffron has been
many neurological related health ailments including depression, extensively used as anxiolytic activity, antitussive, antibacterial,
psychosis, anxiety, and schizophrenia (Kumar et al., 2017). In clin- antiinflammatery, hypolipidemic, antifungal, anti-diabetic, anti-
ical practice, Ginkgo biloba extract (GBE) has proven to treat cogni- convulsant, antityrosinase, anti-neuropathic pain, anticancer, anti-
tive disorders, memory impairment, AD and coronary heart disease tussive, antioxidant, antiseptic, antidepressant, antinociceptive,
and showed therapeutic effects at the biochemical and pharmaco- anti-cancer, anti-tumor, liver and spleen enlargement prevention,
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Fig. 2. Chemical structure of selected pro-cognitives and memory enhancers.

lumbar pain remedy, chemoprotective, renal ischemia–reperfusion rats administered with aqueous extract of saffron demonstrated
prevention, anti-genotoxic, an aphrodisiac, antispasmodic, tension that saffron significantly upregulated brain-derived neurotrophic
relieving, expectorant, cardiovascular protective, antidote against factor (BDNF) (both transcriptomics and protein levels) and
poisoning, dysentery, cataract, measles, pre-eclampsia treatment, cyclic-AMP response element binding protein (CREB) (only protein
withdrawal syndrome inhibition, wound healing, and abscesses levels) in the hippocampus which manifestate that saffron could be
(Hosseinzadeh, 2014; Moshiri et al., 2015; Ghasemi et al., 2015). a potential lead molecule for AD treatment (Ghasemi et al., 2015).
In addition to its historical value as a food additive, several studies
recently indicated its potential use as neuroprotective (anti- 2.15. Fasmily Lamiaceae
Alzheimer, anti-Parkinson), learning and memory enhancer, anxi-
olytic and hypnotic, against cerebral ischemia, memory deficits Melissa officinalis L. / Lemon balm is a perennial lemon-
and brain damage, against morphine dependency mitigation scented herb, which grows naturally in south-central Europe and
(Hosseinzadeh et al., 2012; Tashakori-Sabzevar et al., 2013). More- the Mediterranean region. The herb is not frost tender and grows
over, enhancing disease in adjuvant-induced arthritis, minimizing to a height of 70 cm. During summer, the white flowers appear.
oxidative damage to the kidney (Zamani et al., 2015). These com- Although they are small and inconspicuous, honey bees love them.
pounds significantly reverse scopolamine-induced amnesia. A The tea prepared from this plant is used in TCM to calm nerves, for
study reveals that the treatment of mild-to-moderate AD with Saf- its spasmolytic effects (Kumar et al., 2013) and used in European
fron is safe and effective in adults ageing 55 years or more medicine to improve senses and memory. It also strengthens brain
(Akhondzadeh et al., 2010). Recently, a study on adult male Wistar cells and clears the head. Monoterpenes such as citral and citronel-
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Fig. 2 (continued)

lal are included in the essential oil of Melissa officinalis, which inhi- small purplish orr white flowers are placed on terminal spikes. It
bits the AChE in a dose-dependent manner. Randomized, placebo- is indigenous to the Indian Subcontinent and cultivated throughout
controlled, balanced-crossover and double blind studies confirmed the Southeast Asian tropics. Tulsi holds a place of respect since
influence of acute administered lemon balm on the modulation of ancient times in India. The whole plant extract reverses the amne-
mood and cognitive performance. It also shows a significant effect sia induced by scopolamine (0.4 mg/kg) and diazepam (1 mg/kg) in
on people having severe dementia. Different studies show that mice. It also reverses the memory deficits induced by ageing. The
Lemon balm has the potentials to manage the AD and to control extract from Ocimum tenuiflorum decreases transfer latency and
agitation in AD patients (Kumar et al., 2013). increases step-down latency in mice (in EPM test and PA para-
Ocimum tenuiflorum L. / Tulsi (also known as ‘holy basil’) is an digms as an exteroceptive behavioural model), in comparsion with
aromatic plant belonging to the family Lamiaceae. This well- control (treated with piracetam), scopolamine and age groups.
branched perennial herb grows up to a height of 1 m. The ovate, Salvia lavandulaefolia Vahl / Spanish sage is a perennial plant
long and slightly toothed leaves are green or purple color. The in family Lamiaceae. It is an evergreen shrub which grows to a

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height of 30 cm. The leaves are in opposite arrangement and con- small flowers are present at all times, however twice a year appear
tain essential oil with fragrance similar to rosemary. The small in abundance, their color can be white, yellow, reddish or pink.
flowers are purplish and very attractive to bees. This small woody Flowers are clustered, odourless or foul-smelling and placed
herb grows typically in rocky soil in the Mediterranean region directly on the trunk and limbs. The fruits are elongated pods in
(Spain and southern France). This herb become popular due its various color from yellow to deep purple. The ovoid pod is up to
worthwile effects on depression, cerebral ischemia, memory disor- 35 cm long, about 12 cm wide and contains 20–60 edible seeds,
ders and anticholinesterase activity. The essential oil of Salvia con- termed as beans. Cacao tree is native to Central and South America.
tains 1,8-cineole, linalool, carvacrol and luteolin. Based on clinical Theobroma cacao contains different types of chemical compounds
data, the essential oil and extracts from Salvia lavandulaefolia sug- e.g. alkaloids (theobromine, theophylline and caffeine), glycosides,
gested the potential for the therapy of AD and other memory- galactosides, tannins, polyphenols, triglycerides, coumarins, cate-
related disorders. chins, catechol, linoleic acids, rutin, vitexin etc. All these bring
Salvia officinalis L. / Common sage is evergreen, perennial herb about its significant effect on the enhancement of memory.
growing to a height of 60 cm. The oblong leaves are rugose, 6.5 cm
long, and are green-gray color. The flowers are placed in spike and 2.18. Family Menispermaceae
can be purple, pink, whire or red. The plant is native to the
Mediterranean area, however due its popularity it is now culti- Tinospora cordifolia (Willd.) Miers / Giloy is a deciduous
vated in different places worldwide. It is one of our best-known climbing shrub. The simple heart-shaped leaves are in alternative
herbs medicinally. It has a good reputation in British herbal ency- arrangement. The species is dioecious, female flowers usually
clopaedias memory enhancing agents. The oil of Sage contains occur solitary, while male flowers are clustered. Red or orange
caryophyllene, camphor and borneol (54) etc. The sage proved ovoid fruits are clustered. The plant is native to the tropical regions
the inhibition of acetylcholinesterase action. Furthur research (India, Sri Lanka and Myanmar). This multipurpose herb regener-
exhibit that this herb may be useful in the treatment of mild-to- ates brain cells and the whole body. Memory enhancing properties
moderate AD. of Tinospora cordifolia were observed on the memory and learning
Salvia rosmarinus Spenn. / Rosemary plant (synonym: Ros- skills in normal and memory deficits animals. It increases the syn-
marinus officinalis L.) in the family Lamiaceae, is an evergreen, thesis of Acetylcholine. The passive avoidance task and Hebb Wil-
perennial shrub growing to a height of 1.5 m. The plant is not frost liam maze proved its congnition enhancement property, when
tender, and has the linear leaves about 2–4 cm long, but only 2– applied on normal and cognition deficits animals.
5 cm wide. The leaves are green on the top and gray on the bottom.
The small flowers are purple, deep blue, pink or white color. Rose- 2.19. Family Myristicaceae
mary plant originated in the Mediterranean area. Since ancient
times, rosemary has been used for improvement and strengthening Myristica fragrans Houtt. / Nutmeg tree is an evergreen tree
of the memory. In ancient Greece, it was considered as a mind which usually grows up to a height of 20 m. The dark green leaves
stimulator. Even at the present date, students in Greece are burn- are in alternative arrangement, about 5–15 cm long and 2–7 cm
ing the plant when they are studying for exams. Indeed, it affects wide. The species is dioecious, the bell-shaped female and male
as a stimulator of the blood flow into the brain and enhancer of flowers are borne on different plants. The female flowers are in
mental alertness. small groups (1–3 flowers) and longer than the male flowers that
are aggregated in larger goups (1–10 flowers). The fruit, similar
2.16. Family Magnoliaceae in appearance to an apricot is a pendulous drupe with an edible
pulp. Inside the fruit is shiny purple-brown seed about 2 cm long,
Magnolia officinalis Rehder & Wilson / Magnolia tree grows covered with a red aril. Nugmet tree originated from Banda Islands,
naturally in China typically in mountains and valleys at altitudes Indonesia. The n-hexane extract of M. fragrans seeds in three doses
of 300–1500 m. It is a deciduous tree growing up to a height of (5, 10 and 20 mg/kg p.o.) was administrated to mice with scopo-
20 m. The tree has a brown and thick bark, ovate enormous green lamine (0.4 mg/kg i.p.) and diazepam (1 mg/kg i.p.) induced mem-
leaves about 20–40 cm long and 10–20 cm wide, and fragrant ory deficit. The passive-avoidance task and elevated plus-maze test
creamy-white to butter-yellow large flowers about 10–14 cm in were used to evaluate learning and memory parameters. A signif-
diameter. The bark of Magnolia officinalis (Magnoliaceae) is tradi- icant improvement in learning skills and memory power was rec-
tionally used in China as a medicine for the memory enhancement ognized after 3 successive days of M. fragrans extract
and for the treatment of neurosis, anxiety, stroke, dementia etc. administration at a dose of 5 mg/kg p.o. to young and aged mice.
Magnolia is able to inhibit scopolamine-induced memory impair- Scopolamine and diazepam-induced memory impairment in mice
ment through the inhibition of AChE. The active constituent of was also reversed with the extract.
Magnolia officinalis is 4-O-methylhonokiol, honokiol and magnolol
(61) (Lee et al., 2011). The polyphenolic compounds 61 and hono- 2.20. Family Orchidaceae
kiol are used in the treatment of fever, headache, neurosis, anxiety
and stroke (Woodbury et al., 2013) since ancient times. In vivo Gastrodia elata Blume is a perennial herb growing up to a
experiments showed that honokiol was found to promote the level height of 1 m. The unique botanical character of the herb is that
of acetylcholine in rat hippocampus. Both 61 and honokiol show the whole plant is chlorophyll-free. Except for florescence, the
AChE inhibitory property. The water maze and step-down avoid- main live-cycle stages of the plant running underground. The ver-
ance tests have shown that Magnolia officinalis increasing the tical, leafless stems are yellowish and fringy golden color inflores-
power of memory and learning skills. cence is about 13–30 cm long. The ovoid rhizome is about 8–12
long. Gastrodia elata is found in North Korea, Siberia, Nepal, Bhutan,
2.17. Family Malvaceae India, Japan (Hokkaido, Honshu, Shikoku, Kyushu), Taiwan as well
as mainland China. For centuries, the herb is used to treat various
Theobroma cacao L. / Cacao tree in the family Malvaceae, is a disorders including epilepsy, spasm, headache, amnesia, dizziness,
small evergreen tropical tree, growing to a height of about 8 m. stoke etc. (Chinese Pharmacopoeia Commission, 2015). Rhizoma
The large leaves about 40 cm long are simple, in alternative Gastrodiae (rhizome of G. elata) is the key part of this medicinal
arrangement and periodically and replaced by new leaves. The plant. Gastrodin (4-hydroxybenzyl alcohol-4-O-b-D-
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glucopyranoside) is considered as the most important bioactive ing power of the brain and the power to analyze grasped informa-
constituents of Rhizoma Gastrodiae which exhibit high pharmaco- tion are also increased by (Singh, 2013). Studies show that the
logical intervention. A plethora of research has been investigated major nootropic bioactive constituents in this herb are alkaloids
for gastrodin (C13H18O7), medicinal importance which has demon- (such as brahmine, nicotine (62), and herpestine), steroidal sapo-
strated remarkable beneficial bioactive activity including memory- nins (like; D-mannitol and hersaponin, bacopasides I-XII, bacopas-
improving, hypnotic, sedative, anti-epileptic, anti-vertigo, prevent- aponins, bacosides A (42) and B, acid A, and monnierin), (Aguiar
ing osteonecrosis, analgesic, antidepressant, anxiolytic, anti-aging, and Borowski, 2013; Le et al., 2015), which have beneficial influ-
lowering blood pressure etc. (Zhan et al., 2016). In the light of AD, ence on enhancement of memory and cognitive function. Bacopa
gastrodin extract or its bioactive constituents has demonstrated to monnieri exhibits neuroprotective, anti-oxidant, and hepatoprotec-
enhance learning and memory performance in an AD mouse model tive properties (Rastogi et al., 2012). These bioactive components
(Liu and Wang 2012; Hu et al., 2014). In vitro investigation of gas- have promising results in normal rats e.g. learning and memory
trodin has shown to suppress intracellular and extracellular Ab were facilitated whereas the amnesic effect induced by elec-
levels in a dose-dependent manner (Zhu et al., 2014) and further troshock, scopolamine and immobilization stress was inhibited.
investigation indicated that the cause of this reduction could be Furthermore, the activity of protein kinase C (PKC) in hippocamus
associated with the mitigation of b and c-secretase activities was enhanced by Brahmi, which contributes to its nootropic
(Zhou et al., 2016). action. Bacopa monnieri has also been documented to shown AChE
inhibitory activity in patients with AD (Goswami et al., 2011).
2.21. Family Phyllanthaceae There have also been preliminary clinical studies suggesting signif-
icant improvement of neurocognitive function in humans after
Phyllanthus emblica L. / Amla (synonym: Emblica officinalis treatment with Bacopa monnieri (Peth-Nui et al., 2012; Downey
Gaertn.) is a tropical deciduous tree that grows up to a height of et al., 2013; Neale et al., 2013). Brahmi contributes to soothing
18 m. It has green pinnately compound leaves with the greenish- and relaxing of the brain cells and restore them to a regular func-
yellow flowers. Edible globular fruits are greenish-yellow color. tioning state in adults. Hence, all these findings demand to take
The tree grows in tropical Southeastern Asia, Southern China, Pak- further research to know the real mechanism of action regulation
istan, and Bangladesh, particularly in central and southern India, these pathways/processes.
Ceylon, Malaya and the Mascarene Islands. P. emblica contains
diverse active constituents like different tannins, vitamin C, oils,
polyphenols (gallic acid (75), punigluconin, ellagic acid (73),
2.23. Family Rutaceae
chebulinic acid, leutolin, apeigenin, quercetin (80), etc.), phyllem-
blin, amino acids, 3,6-di-O-galloyl-D-glucose, 1-O-galloyl-b-D-
Murraya koenigii (L.) Sprengel / Curry tree in the family Ruta-
glucose, 3-ethylgallic acid (3-ethoxy-4,5-dihydroxybenzoic acid),
ceae is an evergreen tree which grows to a height of 6 m. The odd-
1,6-di-O-galloyl b-D-glucose, minerals, flavonoids (rutin and 80)
pinnate leaf usually consists of 11–21 green, ovate, leaflets about
etc (Variya et al., 2016, Yadav et al., 2017). Presence of vitamin-C,
2.5–5 cm long that are aromatic. The white, funnel-shaped flowers
in the amla possesses beneficial calming effects on the memory
are small, arranged in clusters and have a sweet fragrance. Fruits
improvement, cholesterol-lowering property and anti-
are bluish-black, oblong drupes with a sweet, edible pulp and a sin-
cholinesterase activity. Amla shows positive results on memory
gle, large, non-edible seed. Curry tree grows in tropical to sub-
enhancement in scopolamine (0.4 mg/kg, i.p.) and diazepam
tropical regions. This tree is native to Sri Lanka and India. Murraya
(1 mg/kg, i.p.) induced memory deficits. It also inhibits AChE activ-
koenigii leaves commonly known as ‘curry patta’, are used in Indian
ity (Reddy et al., 2010). A study in young and aged rats and mice
dishes as a very common food-additive. Reduction of brain choli-
model showed a dose-dependent improvement in memory scores
nesterase activity as well as cholesterol-lowering effects were
after administration of Anwalachurna (50, 100, and 200 mg/kg, p.
reported in diets added with curry leaves that may be attributed
o.) (Parle and Vasudevan, 2007). Numerous studies have shown
to the observed nootropic effect. Therefore, curry leaves can be
the neuropharmacological property of P. emblica in the treatment
investigated for use in the management of AD.
and prevention of dementia which is manifested by the multifunc-
tional characteristic including anti-oxidant property, cholesterol-
lowering property, anti-cholinesterase property, and potency to
improve and reverse memory deficits (Ashwlayan and Singh, 2.24. Family Solanaceae
2011; Perry and Howes, 2011; Golechha et al., 2012).
Withania somnifera (L.) Dunal / Ashwagandha is a perennial,
2.22. Family Plantaginaceae evergreen shrub in the family Solanaceae which grows up to a
height of 1 m. The species is hermaphrodite and frost tender. The
Bacopa monnieri (L.) Pennel / Brahmi (also known as water green leaves are elliptic about 10–12.5 cm long. The small, green
hyssop) is a perennial, non-aromatic herb which grows to a height flowers are bell-shaped. The fruit, enclosed in the calyx is a spher-
of 30 cm. The herb is frost tender, has oblong, succulent, thick ical, orange-red to red berry about 5–8 mm in diameter. It is usu-
leaves in alternative arrangement, that are edible. The small, white ally cultivated in the drier regions of India, but found also in Nepal.
flowers have 4–5 petals. Brahmi is native to India and Australia Withania somnifera belongs to one of the most researched Ayurve-
(Aguiar and Borowski, 2013) and also grows throughout the United dic herbs and its roots are one of the most remarkable ingredients
States and East Asia. Bacopa monnieri (BM) has a long history of use in AM, similar to the status of Ginseng in Chinese therapies. There-
in the AM tradition in the treatment of several ailments, including fore, it is not surprising that Withania somnifera is often termed as
epilepsy, learning enhancer, lack of concentration, mental illnesses, the ‘Indian Ginseng’. The root extract from Ashwagandha (50, 100
sedative, stroke, anxiety etc. (Srivastava et al., 2019). All of the and 200 mg/kg; p.o.) in mice led to improvement of retention of a
herbs investigated for their memory-enhancing properties Brahmi passive avoidance task in a step-down paradigm. Ashwagandha
is likely the most studied. The usage of Bacopa monnieri for mem- further reversed disruption of acquisition and retention induced
ory enhancement can be dated back to 800 BCE in India (Rathee by scopolamine (0.3 mg/kg). Moreover, the amnesia produced by
et al., 2008). In modern India, Brahmi is used as a tonic for acute treatment with electroconvulsive shock (ECS) was attenu-
school-going children to improve their mental capacity. The grasp- ated by Ashwagandha immediately after training (Dhulley, 2001).
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2.25. Family Theaceae interlocked, succulent leaf petioles. The simple leaves are long
and can be simple green color or variegated. The flower spikes arise
Camellia sinensis (L.) Kuntze / Green tea plant is an evergreen from the top of the pseudostem. The florets can be white, yellow,
shrub which grows up to a height of 4 m. The tree has a rough, gray orange or pink in color, and the bracts can be also in various colors.
bark and strong taproot. The dark green leaves are oval, in alterna- The rhizome has a strong orange-yellow color, pepper-like aroma
tive arrangement and about 5–10 cm long. The white flowers are and bitter taste. Turmeric is a traditional Chinese herbal plant
quite fragrant, solitary or arranged in small groups. The flower is and is native to tropical Tamilnadu in Southeast India. Turmeric,
about 4 cm in diameter with 5–9 petals. Green tea plant is native obtained from the rhizome of C. longa is known as the golden spice
to South, East and Southeast Asia. However, nowadays, it is culti- and is widely considered a medicine for the treatment of a plethora
vated across the subtropical and tropical regions of the world of diseases comprising inflammations, arthritic, diabetic wound
including Japan and Sri Lanka. Camellia sinensis plant produces healing, anorexia, microbial infections, muscular disorders, cancer,
three types of teas: non-fermented (white and green tea), partially hepatic disorders, diabetes, biliary disorders, sinusitis and cough
fermented (oolong and red tea) and completely fermented (black (Li et al., 2012; Kuete, 2017). The rhizomes are the reservoir of
tea) (Suzuki et al., 2016; Hayat et al., 2015) and interestingly its diverse compounds out of which curcuminoids (25) (curcumin,
bioactive constituents greatly depend on the degree and ease of 11), principal phenolic compound (Zhao et al., 2012) exhibit multi-
fermentation process. Tea is globally the second most consumed function that is potent in the management of various diseases.
beverage after the water and its pharmacological properties are Additionally, 11 also exhibited several pharmacological properties
extensively documented. It is having potent neuroprotective, free such as neuroprotective, hepatoprotective, cardiovascular protec-
radical scavenging, antioxidative, antioncogenic, hepatoprotective, tive, antidiabetic, anticoagulant, anti-inflammatory, antioxidant,
anti-diabetic, antiviral, and chemopreventive properties because of antifungal, antiviral, antibacterial, antineoplastic, antifertility and
its diverse chemical constituents including amino acids, aluminum, immunostimulant activities in animals (Singh and Sharma, 2011).
proteins, phenolic acids (chlorogenic acid, gallic acid (75) or trihy- The pivotal potential of 11 has been well established in treating
droxybenzoic acid, and caffeic acid), alkaloids (theophylline, caf- and preventing neurodegenerative disorders (Kim et al., 2012;
feine, and theobromine), caffeine, flavonoids (quercetin (80), Villaflores et al., 2012). In wistar rats, curcuma oil has been docu-
kaempferol, and myricetin) and polyphenols (catechins such as mented to minimize inflammation of the endothelial cells in post-
epigallocatechin-3-gallate (EGCG, 12), ( )-epicatechin gallate myocardial ischemia/ reperfusion (Manhas et al., 2014). Curcumin
(ECG), ( )-epicatechin (EC, 49), and (–)-epigallocatechin (EGC)), prevents the accumulation of Ab or facilitates its disaggregation at
carbohydrates, minerals, theanine, volatile organic compounds, low concentration levels (IC50 = 0.81–1 lM) (Fang et al., 2014).
trace elements, and fluoride (Mahmood et al., 2010; Legeay et al., Curcumin has also been shown to protect against Ab neurotoxicity
2015) that are beneficial in preventing a plethora of health related by downregulating Ab synthesis via inhibition of the presenilin 1
ailments including neurodegeneration, hypotension, vomiting, (PS1) expression and glycogen synthase kinase-3beta (GSK3b)
memory loss, skin cancer, lung cancer, and breast cancer, obesity, expression (Caesar et al., 2012; Zhang et al., 2011). In SH-SY5Y neu-
atherosclerosis, headaches, type 2 diabetes, stomach disorders, roblastoma cells treated with 6-hydroxydopamine, 11 has been
gastrointestinal cancer, ovarian cancer, PD, diarrhea, kidney stones indicated to arbitrate neuroprotective activity by attenuating
(Shivashankara et al., 2014; Yang et al., 2014; Yang and Wang, quinoprotein development, expression of p-p38 mitogen-
2016; Yokogoshi, 2017; Baliga et al., 2018). Since, green tree exhi- activated protein kinases (MAPKs), and activation of caspase-3
bits a plethora of bioactive molecules especially catechins, it is a (Meesarapee et al., 2014). Curcumin (11) substantially increased
well-known source of neuroprotection (Flores et al., 2014; cognitive function in a streptozotocin (STZ) model of sporadic AD
Schimidt et al., 2014; Fernando et al., 2017). It decreases the pro- by restoring downregulated IGF-1 levels (Agrawal et al., 2010). Fur-
duction of b-amyloid (Ab) monomers, the major cause of AD, which thermore, another research found that 11 enhanced the neurotox-
forms proteins that are able to create the amyloid plaques in the icity of 6-hydroxydopamine (6-OHDA) via its anti-inflammatory
brains of patients with AD (Polito et al., 2018). Several recent stud- action and by restoring the expression of SOD-1 (Tripanichkul
ies have found that teas (reg and green) as dietary supplements and Jaroensuppaperch, 2013). In mice, oral administrated aqueous
have significant potential to reduce/protect memory and learning extract of C. longa led to the inhibition of brain monoamine
deficits and hippocampus oxidative stress in an Alzheimer disease oxidase-A. 11, as the major bioactive compound from C. longa dis-
model and ischemia–reperfusion (IR) (Martins et al., 2017; plays the neuroprotective properties against ethanol-induced brain
Schimidt et al., 2017). The ability of green tea to stop the degener- injury. The 11 enhanced/increased locomotive function in a homo-
ation in neuronal cells results from the presence of EGCG in the cysteine rat model with PD (Mansouri et al., 2012). Concerning epi-
brain, meaning that it can impart its antioxidative effects on the lepsy, in the experimental seizure models, 11 has shown
free radicals causing the brain damage. A mouse study in China antiepileptic effects (Ahmad, 2013; Peng et al., 2012; Kiasalari
shows that EGCG from green tea supports the formation of brain et al., 2013) by its antioxidant activity (Choudhary et al., 2013;
cells, which areimportant to memory and spatial learning (Weath- Noor et al., 2012). Furthermore, 11 is effective in preventing brain
erby, 2012). Hence, bioactive teas might be a suitable potent ther- injury (cerebral stroke), in addition to antiepileptic effects
apeutic candidate against neurodegenerative disorder (Chen et al., (Lapchak, 2011; Liu et al., 2013; Yu et al., 2012; Zhao et al.,
2018) which demands an evaluation of these chemicals in a clinical 2010). 11 has boosted candesartan’s neuroprotective activity on
setting. Furthermore, in clinical studies and various animal models, brain ischemia via the repression of blood flow and oxidative stress
green tea intake has been shown to reduce cardiovascular disease (Awad, 2011). 11 pretreatment decreased infarction and brain
by reducing total and LDL cholesterol, blood pressure and CVD lesions, and increased neurological function in rats following Trau-
mortality (Onakpoya et al., 2014; Yarmolinsky et al., 2015; Zhang matic Brain Injury (TBI) (Samini et al., 2013). In rats experiencing
et al., 2015). TBI, curcumin derivatives administration enhanced locomotive
and cognitive functioning (Wu et al., 2011).
2.26. Family Zingiberaceae Zingiber officinale Roscoe / Ginger is a perennial, tropical, flow-
ering plant, which grows up to a height of 1.5 m. The leaves are
Curcuma longa L. / Turmeric is perennial, tropical, rhizoma- narrow and about 15–30 cm long. They are in alternative arrange-
tous, herbaceous plant, which grows up to a height of 1.5 m. The ment and arise from the pseudostem. Flowering heads are placed
leaves arise from the pseudostem, which is composed of long, on short stems and the herb produces pale yellow, cone-shaped
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flowers. The rhizomes are irregular in shape with variable color possible application of Ocimum tenuiflorum in the therapy of cogni-
from light bwown to dark yellow. Ginger was cultivated first in tive disorders (e.g. AD and demetia).
South Asia, but nowadays is also cultivated in the East Africa and Schisandra chinensis (Turcz.) Baill. (Schisandraceae): a decid-
the Caribbean region. Its rhizomes possess potent memory- uous climbing plant, which is native to Northern China and the Far
enhancing properties. It improves memory power and the whole- Eastern Russia. The water fraction of this plant at the dose of
body blood circulation including the supply of nutrients into the 25 mg/kg after one-week administration on rats resulted in the
brain. Ginger significantly improved learning and memory by prolongation of cycloheximide-induced step-through latency.
increasing whole-brain acetylcholinesterase inhibition activity in Interestingly, the water fraction of Schisandra chinensis seems to
case of scopolamine-induced memory impairment. It is also be the major active fraction of this plant (Kopustinskiene and
reported to inhibit b-amyloid peptide accumulation. Gingerin, gin- Bernatoniene, 2021; Szopa et al., 2017).
gerol (56), shogaol and zingerone are the major active compounds Scutellaria baicalensis Georgi (Lamiaceae): a flowering plant
in ginger. native to China, Korea and Siberia. The extracts of its roots are uti-
lized in the traditional Korean medicine and are beneficial in treat-
ment of the brain diseases. Further, it was reported that the orally
administered extracts of this plant improved the memory impair-
3. Use of crude drugs from herbs in memory impairment ment, which was induced by chronic lipopolysaccharide (LPS) infu-
sion or by chronic cerebral hypoperfusion (Hwang et al., 2011).
Artemisia asiatica Willd. (Asteraceae): a Korean tea plant.
Methanolic extract of this plant was administrated to the beta-
peptide infused rats. This b-peptide infusion caused toxicity in 4. Effective herbal formulations for memory enhancement
the PC12 cells in rats. Administration of Artemisia showed a signif-
icant result in reversing the toxicity in PC12 cells. A study demon- Abana is an Indian Ayurvedic polyherbal formulation, contains
strated that an alkaloid of Artemisia appeared to be an 16 well-known herbs as composition. It significantly reduces the
acetylcholinesterase (AChE) inhibitor with a blocker of b- activity of cholinesterase, which results to increase of acetylcholine
amyloid-induced neurotoxicity causing AD. level in the brain of aged and young mice. The ingredients of Abana
Celastrus paniculatus Willd. (Celastraceae): the aqueous frac- express the antioxidant property, which reduces oxidative stress of
tion of C. paniculatus seeds was administrated to rats with sodium the brain cells. Thus, Abana helps to reduce brain impairment and
nitrite induced amnesia. The results show an increase in the brain’s improves neuronal function. The influence of orally administered
acetylcholine (ACh) level by decreasing AChE activity, thus improv- Abana on cognitive functions was monitored on groups of aged
ing memory in amnesic models of mice (Bihaqi et al., 2011). and young mice. Testing of memory was evaluated by using exte-
Corydalis ternata (Nakai) Nakai (Papaveraceae): a total roceptive behavioral models (passive avoidance apparatus and ele-
methanolic extract of the tuber of Corydalis ternate exhibits consid- vated plus-maze test) as well as interoceptive behavioral models
erable inhibition of acetylcholinesterase (AChE). Protopine, an iso- (amnesia induced by diazepam, scopolamine and ageing). Abana
lated alkaloid from Corydalis showed a dose-dependent inhibitory improves the memory score in dose-dependent manner of both
effect on the acetylcholinesterase activity with IC50 = 50 lM. This aged and young mice. Even, Abana reverses the scopolamine-
inhibitory activity was specific reversible and competitive in the and diazepam-induced amnesia. Therefore, the polyherbal formu-
manner. lation Abana bears promising potential for the treatment of Alzhei-
Foeniculum vulgare Mill. (Apiaceae): a whole plant methanolic mer’s disease.
extract significantly increases latency in step-down avoidance test BR-16A (Mentat) is a herbal psychotropic preparation contain-
as well as the inhibition of acetylcholinesterase in mice. Therefore, ing various indigenous plant extracts which are well-reputed in the
Foeniculum vulgare can be utilized in the therapy of cognitive dis- AM. The compositional herbs are: Bacopa monnieri, Acorus calamus,
orders e.g. dementia and AD. Asparagus racemosus, Evolvulus alsinoides, Withania somnifera, Phyl-
Gastrodia elata Blume (Orchidaceae): the methanolic extract lanthus emblica and Triphala. Mentat on the elevated plus-maze
of the rhizomes of Gastrodia elata in the passive avoidance task test reduced transfer latency delay induced by scopolamine in
results in significant prolongation of the shortened step-through mice. Moreover, evaluation of passive avoidance paradigm
latency, induced by scopolamine. Similarly, the n-butanol and revealed that Mentat also reduces ECS-induced acute and chronic
ethyl acetate fractions prepared from crude methanolic extract of retrograde amnesia in rats. A combination of Mentat and a low
Gastrodia elata, administered at the dose of 50.0 mg/kg for one dose of aniracetam (a well-known nootropic) in the passive avoid-
week prolonged the scopolamine-induced step-through latency ance task brings much better results in the reduction of mistakes.
in rats. Moreover, the shortened step-through latency on the pas- Clinical studies on different age groups with Mentat show
sive avoidance task induced by scopolamine was prolonged by gas- improvement in memory quotient of tested subjects. In normal
trodin, as the product isolated from the n-butanol fraction and by adults Mentat attenuates fluctuations of attention and increases
p-hydroxybenzyl alcohol, obtained from the ethyl acetate fraction memory span. In children with minimal brain damage or beha-
of the methanolic extract. vioural problems improves the ability to learn.
Glycyrrhiza glabra L. (Fabaceae): the aqueous extract of Gly- Brain-o-brain is capsule with a unique mixture of herbs like
cyrrhiza glabra was administrated to one-month-old male albino Shankhpushpi, Brahmi and Sweet flag to improve learning ability,
Wistar rats with Diazepam-induced memory impairments. The memory power and naturally helps to avoid stress and depression.
experiment showed a significant increase in learning and memory These herbal brain enhancer pills are made especially for all age
in the rats and reversed the effect of Diazepam toxicity groups to prevent or decrease forgetting. Indeed, regularly taken
(Chakravarthi and Avadhani, 2013). Brain-o-brain is effective to increase gasping power and natural
Ocimum tenuiflorum L. (Lamiaceae): a whole plant aqueous ability of the brain. This fully natural remedy supports to overcome
extract of dried Ocimum tenuiflorum were evaluated on the passive nervous exhaustion and mental fatigue.
avoidance paradigm and elevated plus maze in mice. The step- Bramhi ghrita contains four Ayurvedic herbs including Brahmi
down latency increasing and the transfer latency decreasing were (Bacopa monnieri) and cowmilk’s ghee. The memory and learning
evident in comparison to control group (treated with piracetam), improvement effect of Brahmi ghrita applied in different doses
scopolamine group and age group of mice. The results suggested (30, 50 and 100 mg/kg, p.o.) was tested in rodents. The elevated
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Table 1
List of herbs having memory and cognition enhancing properties.

Sl. Botanical name Genus Common Parts used Active constituents Reference
No. Family name
1 Acorus calamus Acorus Sweet flag Rhizomes 1. a- and b-Asarone Shiksharthi et al., 2011
Aracaceae 2. Methyl isougenol
2 Allium sativum Allium Garlic Bulb (S)-allyl-L-cysteine Semwal et al., 2014
Amaryllidaceae
3 Amberboa ramosa Amberboa Sesquiterpene lactones: Ibrahim et al., 2013
Asteraceae  Amberin
 Amberbin A
 Amberbin B
 Amberbin C
4 Asparagus racemosus Asparagus Shatavari Roots Triterpene saponins: Shatavarin I-IV Shiksharthi et al., 2011
Asparagaceae
5 Bacopa monnieri Bacopa Brahmi Whole Bacosides A and B Shiksharthi et al., 2011
Plantaginaceae plant
6 Butea monosperma Butea Palash Leaves Malik et al., 2013
Fabaceae
7 Camellia sinensis Camellia Green tea Leaves 1. Flavanoids –Epigalactocatechin-3-gallate Shiksharthi et al., 2011;
Theaceae (EGCG) Compas, 2006
2. Isoflavone diadzein
8 Celastrus paniculatus Celastrus Jyotishmati Seeds Alkalloids: Celastrine, Paniculatin, Calapagone, Shiksharthi et al., 2011
Celastraceae Calapanigine etc
9 Centella asiatica Centella Thankuni Whole 1. Triterpenic pentacyclic saponins: Shiksharthi et al., 2011
Apiaceae plant Madicasoside
2. Asiaticoside
3. Brahmoside
10 Clitoria ternatea Clitoria Aparajita Roots 1. Histidine Shiksharthi et al., 2011
Fabaceae 2. Threonine
3. Tannin
11 Coeloglossum viride Coeloglossum Frog orchid Rhizomes Martha, 2010
Orchidaceae
12 Convolvulus pluricaulis Convolvulus Shankh Whole Flavanoids Shiksharthi et al., 2011
Convolvulaceae pushpin plant
13 Coriandrum sativum Coriandrum Corriander Leaves Parle and Vasudevan,
Apiaceae and Seeds 2009
14 Cornus officinalis Cornus Japanese Fruits Cornel iridoid glycosides (CIG): Zhao et al., 2010
Cornaceae cornel  Loganin,
 (7R)-O-methylmorroniside
 (7S)-O-methylmorroniside
15 Corydalis ternata Corydalis Nakai Tuber Alkaloids: Kim et al., 1999
Papaveraceae  Protopine
 Protoberberin
16 Crocus sativus Crocus Saffron Whole 1. Crocin Shiksharthi et al., 2011
Iridaceae plant 2. Crocetin
17 Curcuma longa Curcuma Turmeric Rhizomes 1. Curcuminoids: Curcumin, Bisdemethoxycur- Shiksharthi et al., 2011
Zingiberaceae cumin, Demethoxycurcumin
2. Calebin-A
18 Cyperus rotundus Cyperus Java grass Rhizomes (Sunil et al., 2011;
Cyperaceae Kumar et al., 2012)
19 Dendrobium moniliforme Dendrobium Sekkoku Whole
Orchidaceae plant
20 Eclipta alba Eclipta Bhringaraj Leaves 1) a-Amyrin Bhaskar and
Astearaceae 2) Seclabatin Chintamaneni, 2014
3) Urosilic acid
4) Oleanoic acid
5) Ecliptasaponin
21 Embelia ribes Embelia Black pepper Roots
Primulaceae
22 Euphrasia officinalis Euphrasia Powdered 1. Iridoid glycosides: Aucubin, Catalpol, Sticher and Salama,
Orobanchaceae herb Euphosid 1981
2. Tannins
3. Flavonoids
23 Foeniculum vulgare Foeniculum Fennel Whole Joshi and Parle, 2006
Apiaceae plant
24 Gastrodia elata Gastrodia Gastrodia Root 1. P-hydroxybenzyl alcohol (HBA) Shiksharthi et al., 2011
Orchidaceae tuber 2. Gastrodins
25 Ginkgo biloba Ginkgo Ginkgo Leaves 1. Flavanoids Shiksharthi et al., 2011
Ginkoaceae 2. Terpenoids
3. Kaempferol
4. Quercetin
5. Terepene lactones- Ginkolides
6. Bilobalide
26 Glycyrrhiza glabra Glycyrrhiza Licorice Roots Glycyrrhizine Shiksharthi et al., 2011
Fabaceae
27 Hibiscus asper Hibiscus Hibiscus Leaves Foyet et al., 2011
Malvaceae

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Table 1 (continued)

Sl. Botanical name Genus Common Parts used Active constituents Reference
No. Family name
28 Huperzia serrata Huperzia Club moss Moss Huperzine A and B Jesky et al., 2011
Lycopodiaceae
29 Hypericum perforatum Hypericum St. John’s wort Roots 1. Naphthodianthrone: Hypericin Shiksharthi et al., 2011
Hypericaceae 2. Prenylated phloroglucinol: Hyperforin
30 Ilex paraguariensis Ilex Mate tea Leaves 1. Flavanoids: Quercetin, Kaempferol Shiksharthi et al., 2011
Aquifoliaceae 2. Polyphenols: Chlorogenic acid, Xanthines
(Theophylline, Theobromine, caffine)
3. Vitamins: B1, B12
31 Illicium verum Illicium Star anise Sesquiterpenoids: Veranisatins A, B, and C
Schisandraceae
32 Magnolia officinalis Magnolia Houpu Bark 1. Magnolol Reddy et al., 2010
Magnoliaceae Magnolia 2. Honokiol
33 Marsilea minuta Marsilea Marsilea Leaves Marsiline Dwivedi et al., 2012
Marsileaceae
34 Melissa officinalis Melissa Lemon balm Leaves Rosmarinic acid Awad et al., 2009
Lamiaceae
35 Murraya koenigii Murraya Curry leaves Leaves Parle and Vasidevan,
Rutaceae 2009
36 Myristica fragrans Myristica Nutmeg Seeds Parle et al., 2004
Myristicaceae
37 Narcissus confuses Narcissus Daffodil Crude Galanthamine (Bastida and
Amaryllidaceae drug Viladomat, 2002)
38 Nardostachys jatamansi Nardostachys Jatamansi Whole 1. Jatamansone Shiksharthi et al., 2011
Caprifoliaceae plant 2. Nardostachone
39 Nicotiana tabacum Nicotiana Tobacco plant Leaves 1. Nicotine Dua et al., 2009
Solanaceae 2. Choline
40 Ocimum tenuiflorum Ocimum Holy basil Whole Joshi and Parle, 2006
Lamiaceae plant
41 Panax ginseng Panax Ginseng Roots 1. Ginsenosides: Rg1, Rg2, Rg3 Shiksharthi et al., 2011
Arialaceae 2. Saponins: Protopanaxdiol, Oleanoic acid,
Protopantriol
42 Phyllanthus emblica(synonym: Phyllanthus Amla Fruit 1. L-Ascorbic acid (vitamin C) Shiksharthi et al., 2011
Emblica officinalis) Phyllanthaceae 2. Phyllembin
3. Hypophyllanthin
4. Phyllanthin
43 Piper betle Piper Bittle leaf Leaves Arecoline Shiksharthi et al., 2011
Piperaceae
44 Piper nigrum Piper Black pepper Fruits Piperine Chonpathompikunlert
Piperaceae et al., 2010
45 Polygala tenuifolia Polygala Yuan zhi Roots Triterpenoid saponins Kumar et al., 2013
Polyagalaceae
46 Polygonatum multiflorum Polygonatum Solomon’s Emodin Lu et al., 2007
Asperagaceae seal
47 Prunus amygdalus Prunus Almond Nuts 1. Total flavonoid content Kumar and Seth
Rosaceae 2. Total phenolic content
48 Pueraria tuberose Pueraria Vidarikand Tubers Flavanoids Shiksharthi et al., 2011
Fabaceae
49 Punica granatum Punica Pomegaranate Seeds 1. Tannin Kumar et al., 2009
Lythraceae 2. Polyphenols: Gallocatechin, Catechin etc.
50 Rehmannia glutinosa Rehmannia Sheng di Roots 1. Iridoids Zhang et al., 2008
Orobanchaceae huang 2. Glycosides
3. Catalpol
51 Ricinus communis Ricinus Castor oil Beans Ricinine Dua et al., 2009
Euphorbiaceae plant
55 Salvia lavandulaefolia Salvia Spanish sage 1. Essential oils Reddy et al., 2010
Lamiaceae 2. 8-cineole
3. Linalool
4. a- and b-pinene
5. Carvacrol
6. Luteolin
53 Salvia officinalis Salvia Common sage Leaves 1. Monoferpenoid Shiksharthi et al., 2011
Lamiaceae 2. Camosic acid
3. Rosemarinic acid
54 Salvia rosmarinus(synonym: Salvia Rosemary Leaves 1. Carnosic acid (Kosaka and Yokoi,
Rosmarinus officinalis) Lamiaceae 2. Carnosol 2003)
55 Schisandra chinensis Schisandra Five flavor (Hsieh et al., 1999)
Schisandraceae berries
56 Scutellaria baicalensis Scutellaria Roots Flavanoid: Oroxylin A (Hwang et al., 2011)
Lamiaceae
57 Sphaeranthus indicus Sphaeranthus Flowers (Patel and Amin, 2012)
Asteraceae
58 Solanum indicum Solanum Brinjal Fruit Gunawardena J
Solanaceae
59 Solanum melongana Solanum Eggplant Fruit Gunawardena J
Solanaceae

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Table 1 (continued)

Sl. Botanical name Genus Common Parts used Active constituents Reference
No. Family name
60 Taverniera cunefolia Taverniera Jamdhade and
Fabaceae Surwase, 2013
61 Terminalia chebula Terminalia Haritaki Rhizomes Chebulic acid Shiksharthi et al., 2011
Combretaceae
62 Theobroma cacao Theobroma Cocoa Seeds 1. Catechin Adams et al., 2007
Malvaceae 2. Catechol
3. Polyphenols
4. Glycosides
5. Alkaloids
63 Tinospora cordifolia Tinospora Giloy Whole 1. Tinosporine Shiksharthi et al., 2011
Menispermaceae plant 2. Tinosporide
64 Uncaria tomentosa Uncaria Bulbs Alkaloids: Heitzman et al., 2005
Rubiaceae  uncarine E
 uncarine C
 mitraphylline
 rhynchophylline
 isorhynchophylline
65 Vitis vinifera Vitis Grapes Seeds Resveretrol Shiksharthi et al., 2011
Vitaceae
66 Withania somnifera Withania Ashwagandha Roots 1. Withanolides Shiksharthi et al., 2011
Solanaceae 2. Sitiindosites- VII, VIII, IX, X
3. Withaferin
67 Zingiber officinale Zingiber Ginger Rhizome 1. Gingerin Shiksharthi et al., 2011
Zingiberaceae 2. Gingerol
3. Shogaol
4. Zingerone

plus-maze test was used for evaluation of memory acquisition and Shimotsu-to literally mean ‘four substance decoction’. This
retention in rats. Morris water maze test was used to interpret spa- TCM formula consists of following four crude herbal extracts: Japa-
tial memory in mice. The elevated plus-maze transfer latency and nese angelica root, peony root, rehmannia root and cnidium rhi-
Morris water maze escape latency were significantly reduced after zome. Shimotsu-to have beneficial effects on spatial memory
administration of Bramhi ghrita (50 and 100 mg/kg, p.o.). improvement in rats. Moreover, the study in rat models suggests
Chyawanprash (Chy) is an Ayurvedic tonic, which contains importance of paeoniflorin (extracted form peony root) and
almost 50 herbs and herbal extracts. One of its basic ingredients tetramethylpyrazine (extracted from cnidium rhizome) as the
is Amla (Phyllanthus emblica) a rich natural source of vitamin C. enhancers of cognitive functions.
Consumption of Chy is popular in Indian households. Animal stud- Yukmijihwang-tang derivatives is a Chinese polyherbal for-
ies confirmed significant influence of Chy in the memory impair- mulation used as memory or cognition enhancer. It consists of
ment protection effect. Furthermore, administration of Chy (2% six diffrent herbal medicines. Chinese herbal textbook refers to
w/w) decreases thiobarbituric acid reactive substances (TBARS) YMJD as an anti-ageing prescription. Besides, it also helps to pre-
in the brain and increases the levels of glutathione. Results indicate vent memory and learning impairment in mice. Studies reported
a decrease in the free radical generation and an increase in the pro- that YMJD in stressed rats could increase neurogenesis in the den-
tection from free radical. Thus, Chy could be an efficient remedy for tate gyrus (hippocampus) along with improvement of cognitive
the therapy of AD. functions and memory retention.
Memorin is comprised of 21 kinds of herbal extracts. The
experimental studies of Memorin were made upon rats using pas-
sive avoidance learning paradigm in a shuttle box. Memorin at the 5. Other advantageous compounds
dose of 200 mg/kg b.w./day was administered for a fortnight to
animals. Administration of ECS produced significant retrograde Ascorbic acid (23) is found mainly in citrus fruits (e.g. lemon).
amnesia in rats. Memorin was found to attenuate the ECS- Studies in aged mice have shown that 23 increased step-down
induced amnesia. In clinical studies, when applied on human, latency and decreased transfer-latency, which indicated its ability
Memorin was found to reverse poor memory, age-related demen- to improve learning and memory. Moreover, memory impairment
tia and mental fatigue. induced by diazepam and scopolamine was significantly reduced
Optimized-Sopung Sunkiwon (OSS) is a polyherbal formula in young mice treated with 23.
comprising of six medicinal herbs from SopungSunkiwon. Sop- Bacosides (24) (bacoside A (42) and bacoside B) are derived
ungSunkiwon is a traditional medicine usually predescribed for from the well-reputed Bacopa monnieri. However, recent study
people suffering from neurodegenerative disorders. OSS signifi- identified bacoside A (42) as the mixture of four different saponins,
cantly improves the memory functions via inhibition of AChE termed as: bacoside A3 (3), bacopaside II (4), bacopasaponin C (6)
activity. Latency time in the passive avoidance test was signifi- and isomer of bacopasaponin C (5) (Fig. 2). Similarly, bacoside B
cantly longer for mice treated with OSS compared with control represents the mixture of saponins, which exact constitution is
group or group treated with scopolamine. Besides, mice treated not clearly identified to date. To the best of our knowledge, baco-
with OSS exhibited increase of synaptic proteins that facilitate side B consists of four following saponins: bacopaside N1 (7), baco-
acetylcholine release and synaptic growth (e.g. PSD-95 and synap- paside N2 (8), bacopaside IV (9) and bacopaside V (10) (Fig. 2)
tophysin). These results show that OSS may act upon memory (Deepak et al., 2013). In a clinical trial, 24 were administrated to
impairment and increase synaptophysin and PSD-95 in the brain elderly people (65 years or older) without a clinical sign of demen-
(Choi et al., 2011). tia in a double blind and placebo-controlled study (Table 4). The
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Table 2
Crude drugs to improve memory.

Sl Plant Genus Extracted Study model Biological effects Reference

no. Family in
1 Andrographis Andrographis Methanol Rats with streptozotocin and 1. Increased cognitive function in typeII dia- Radhika et al.,
paniculata Acanthaceae nicotinamide induced typeII diabetes betic rats 2012
2. Decreased latency period
2 Artemisia Artemisia Methanol In vitro: Abeta-induced toxicity in rat 1. Reduced Abeta induced toxicity, Heo et al., 2000
asiatica Asteraceae PC12 cells 2. appeared as an AChE inhibitor
3 Butea Butea Hydro Rats with scopolamine-induced amnesia 1. Decreased escape latency in MWM test Malik et al., 2012
frondosa Fabaceae alcohol 2. decreased AChE activity
4 Celastrus Celastrus Water Rats with sodium nitrite induced amnesia 1. Increase acetylcholine level inside the Bhanumathy
paniculatus Celastraceae brain by reducing AChE activity et al., 2010
2. Improves memory
5 Clitoria Clitoria Water Young and adult rats 1. Singificantly increased ACh content inrat Rai et al., 2002
ternatea Fabaceae hippocampus
6 Convolvulus Convolvulus Water Male Wistar rats with scopolamine 1. Decreased scopolamine induced increase Bihaqi et al., 2011
pluricaulis Convolvulaceae induced neorutoxicity in transfer latency in EPM test
2. In MWM test, increased spatial memory
3. AChE activity inhibited in cortex and
hippocampus
7 Cornus Cornus Methanol HT22 hippocampal cell with glutamate 1. Reversed glutamate toxicity in HT22 Jeong et al., 2011
officinalis Cornaceae toxicity hippocampal cells
8 Corydalis Corydalis Methanol Mice with scopolamine-induced memory 1. Protopine present in the extract chowed Kim et al., 1999
ternate Papaveraceae deficit AChE inhibitory activity
2. Reversed scopolamine-induced memory
impairment
9 Desmodium Desmodium Water Mice with scopolamine and ageing 1. Reversed both scopolamine and ageing Joshi and Parle,
gangeticum Fabaceae induced amnesia induced amnesia 2006
2. Decreased whole brain AChE activity
10 Eclipta alba Eclipta Distilled Mice 1. Decreased transfer latency in EPM test Banji et al., 2007
Asteraceae water
11 Foeniculum Foeniculum Methanol Mice 1. Increased step-down latency Joshi and Parle,
vulgare Apiaceae 2. inhibited AChE activity 2006
12 Gastrodia Gastrodia Methanol Rats 1. Increased shortened step through latency Wu et al., 1996
elata Orchidaceae induced by scopolamine
13 Glycyrrhiza Glycyrrhiza Water 1 month old male Wistar albino rats with 1. Enhanced learning and memory Chakravarthi and
glabra Fabaceae Diazepam induced amnesia 2. reversed the effect of diazepam Avadhani, 2013
14 Hibiscus asper Hibiscus Methanol Male Wistar rats with 6- 1. Showed antioxidant and free-radical scav- Foyet et al., 2011
Malvaceae hydroxydopamine-lesion enging activity
2. Improved spatial memory in Y-maze,
improved arm-maze task
15 Hypericum Hypericum Ethanol Albino rats with scopolamine and sodium 1. Decreased transfer latency in EPM Kumar et al., 2000
perforatum Hypericaceae nitrite induced amnesia 2. Reversed scopolamine and SA induced
memory impairment
16 Marsilea Marsilea Ethanol Rats with ECS treated and scopolamine 1. Revrsed amnesia Bhattamisra et al.,
minuta Mercileaceae induced amnesia 2. Inhibited AChE activity in the frontal cortex 2012
and hippocampus
17 Nardostachys Nardostachys Ethanol Young and aged mice with scopolamine 1. Reversed both scopolamine and diazepam Joshi and Parle,
jatamansi Caprifoliaceae and diazepam induced amnesia induced amnesia 2006
2. Reduced ageing related amnesia
18 Nepeta Nepeta Water Rats with ECS induced amnesia 1. Increased memory retention and retrieval Sarahroodi et al.,
menthoides Lamiaceae 2012
19 Ocimum Ocimum Water Rats with scopolamine and ageing 1. Decreased transfer latency in EPM model Joshi and Parle,
sanctum Lamiaceae induced amnesia 2. Increased step-down latency 2006
20 Schisandra Schisandra Water Rats 1. Increased shortened step through latency (Hsieh et al.,
chinensis Schisandraceae induced by scopolamine 1999)
21 Scutellaria Scutellaria 1. Rescued memory impairment caused by Hwang et al.,
baicalensis Lamiaceae chronic LPS infusion 2011
22 Sphaeranthus Sphaeranthus Petrolium Mice with scopolamine-induced memory 1. Reversed cognitive impairment by PA test, Patel and Amin,
indicus Asteraceae ether impairment 2. Reduced escape-latency in water maze 2012
task,
3. Has anti-cholinesterase activity may be
due to presence of sesquiterpene lactones

results showed significant enhancement in their auditory verbal increased PSD-95 and synaptophysin expression in the rat
learning and word recall. There are possibilities that the 24 can hippocampus.
help to manage AD too (Kumar et al., 2012). Epigallocatechin-3-gallate (EGCG, 12) is the major catechin
Curcuminoids (25) represent major chemical components pre- derivative found in green tea (Camellia sinensis). EGCG represents
sent in turmeric (Curcuma longa). Specifically, it is a mixture con- the most effective therapeutic component of green tea. EGCG pos-
sisting of: curcumin (11), demethoxycurcumin (71) and sesses antioxidant properties and reduces lipid peroxidation in bio-
bisdemethoxycurcumin (68) (Table 4). Effective on rats showing logical systems caused by free radicals (Kumar et al., 2012). A study
AD-like neuronal loss caused by a b-peptide infusion. 25 also in rats revealed the ability of EGCG to increase neurogenesis in hip-

895
 Table 3

S. Halder, U. Anand, S. Nandy et al.

Different herbal formulations for memory enhancement.

Sl no. Hebal formuation Components Study model Biological effects and targets Reference
1 Abana 1. Acorus calamus In vivo-young and aged mice  Abana elevates acetylcholine level in Parle and Vasudevan, 2007
2. Asparagus racemosus the brain through significant decrease
3. Celastrus paniculatus in cholinesterase activity
4. Centella asiatica  Improves memory of both young and
5. Crocus sativus aged mice
6. Cyperus rotundus  Has the potentiality to manage Alzhei-
7. Elettaria cardamomum mer’s disease
8. Foeniculum vulgare
9. Glycyrrhiza gabra
10. Nardostachys jatamansi
11. Ocimum sanctum
12. Phyllanthus emblica
13. Piper betel
14. Terminalia chebula
15. Withania somnifera
16. Zingiber officinale
2 Brahmi-ghrita 1. Acorus calamus In vivo-mice  May act as a memory enhancer Girish et al., 2004
2. Bacopa monnieri  May be useful for the treatment of
3. Evolvulus alsinoides impaired memory function
4. Saussurea lappa
5. Cow’s ghee
3 Brain-o-Brain 1. Acorus calamus In vivo-human (Chldren, adults and  Promotes brain function
2. Agati grandiflora elderly people)  Improves memory, learning ability,
3. Asparagus racemosus and concentration
4. Bacopa monnieri  Co-ordinates between mind and body
5. Bauhinia tomentosa  Reduces mental and physical stress
 Reduce nervous exhaustion and men-
896

6. Brunella vulgaris
7. Celastrus paniculatus tal fatigue
8. Clitoria ternatea  Reduce tension and anxiety
9. Convolvulus pluricaulis
10. Hibiscus rosa-sinensis
11. Lepidium sativum
12. Nardostachys jatamansi
13. Orchis mascula
14. Poley germander
15. Richolepsis claberrima
16. Rourea santiloides
17. Sphaeranthus indicus
18. Zizypus vulgaris
19. Gold
20. Silver

Saudi Pharmaceutical Journal 29 (2021) 879–907

4 YMJD 1. Rehmannia radix In vivo- stressed rats  YMJD increases neurogenesis in the Rho et al., 2005
2. Discoreae radix dentate gyrus of the hippocampus in
3. Alismatis radix stressed rats, while enhances memory
4. Corni fructus retention and cognitive activities
5. Mountain cortex radices  Reverses scopolamine-induced and p-
6. Holen chloroamphetamine-induced amnesia
in rats
 YMJD including Lycii fructus enhances
memory retention b protecting neu-
ronal cells from attack by reactive
oxygen
5 Chyawanprash 50 herbs employing Phyllanthus emblica In vivo-mice with memory deficit  Protects form memory impairment Parle and Bansal, 2011
 Decrease free radical generation and
increase scavenging of free radicals
 Table 3 (continued)

S. Halder, U. Anand, S. Nandy et al.

Sl no. Hebal formuation Components Study model Biological effects and targets Reference
 May be a useful remedy for manage-
ment of Alzheimer’s didease
6 Memofit 1. Achyranthus aspera In vivo- human  Enhances memory
2. Acorus calamus  Reduces stress and fatigue
3. Asparagus racemosus
4. Bacopa monnieri
5. Convolvulus pluricaulis
6. Embelia ribes
7. Terminalia chebula
8. Tinospora cordifolia
9. Withania somnifera
7 Memorin 1. Acorus calamus In vivo-rats with ECS-induced retrograde  Reversed ECS-induced retrograde Vinekar et al., 1998
2. Caryophyllus aromaticus amnesia amnesia successfully
3. Celastrus paniculatus
4. Centella asiatica
5. Convolvulus pluricaulis
6. Elettaria cardamomum
7. Embelia ribes
8. Foeniculum vulgare
9. Herpestis monniera
10. Mucuna prurita
11. Myristica fragrance
12. Nardostachys jatamansi
13. Oroxylum tuberosum
14. Prunus amygdalus
15. Pueraria tuberosa
16. Terminalia arjuna
897

17. T. belerica
18. T. chebula
19. Tinospora cordifolia
20. Withania somnifera
21. Zingiber officinale
22. Pearl paste
23. Salab mishri
8 Shimotsu-to 1. Japanese angelica root In vivo-rats  Improve spatial working memory Watanabe, 1997
2. Cnidium rhizomes  Paeoniflorin and Tetramethylpyrazine
3. Peony root (TMP) extracted from Peony root and
4. Rehmannia root Cnidium rhizome are the cognitive
enhancers
9 OSS In vivo- mice with scopalamine induced  Affect impairment and enhancement Choi JG et al, 2011
memory impairments of memory
 Increase synaptophysin and PSD-95

Saudi Pharmaceutical Journal 29 (2021) 879–907

facilitating acetylcholine release and
synaptic growth
10 Mentat 1. Acorus calamus In vivo- mice with ECS induced amnesia  Reduced scopolamine-induced trans- Kulkarni and Verma,1992
2. Asparagus racemosus and Clinical trial on human (adults and fer latency in mice
3. Centella asiatica children)  Attenuated acute and chronic retro-
4. Evolvulus alsinoides grade amnesia induced by ECS
5. Phyllanthus emblica  Improves memory quotient in differ-
6. Withania somnifera ent age group
7. Triphala  Increases memory span
 Enhances learning ability in children
11 PMCMT 1. Ginseng radix In vivo- rats with ischemia-induced  Significant improvement in escape Yun et al., 2007
2. Atractylodis Macrocephalae Rhizoma memory and cognitive impairment latency in MWM test
3. Poria  Protection against ischemia-induced
4. Glycyrrhizae radix neuronal and cognitive impairments

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 S. Halder, U. Anand, S. Nandy et al. Saudi Pharmaceutical Journal 29 (2021) 879–907

pocampus. Moreover, dietary EGCG study in mice proved enhance-

ment of spatial memory and object recognition (see Tables 1, 2, 3,
5, 6).

Adams et al., 2007

Ginkgolides (28), a kind of terpene lactones, are derived from
the living fossil tree Ginkgo biloba. Extract from Ginkgo biloba
enhances the rate of acetylcholine turnover. Further, the stimula-
Reference

tion of ligands binding to muscarinic receptors in the hippocampus

was observed after application of the extract. It improves dementia
and cognitive deficits. The extract also proves significant antioxi-
dant activity via reduction of free radicals in animals. In a study,
patients with dementia of AD type and multi-infract dementia
 Elevated catalase and glutathione per-
oxidase activities in H2O2 induced

were administrated with 28 supplement. The results showed

 Promote brain function and memory

improvement in their task-assessing speed for processing ability

(Kumar et al., 2012).
Ginsenosides are extracted from the plant Panax ginseng. There
Biological effects and targets

is about 30 major members of ginsenosides, including Rb1 (19) and

Rg1 (20) (Fig. 2), as the most active compounds. Other active ingre-
injury in PC12 cells
 Increase life span

dients are Rg2 (20), Rg3 (30) etc. Both major active ginsenosides 20
and 19 can increase the neuroplasticity in efficacy and structure. A
study in normal adult mice proved that small molecular drug 20 is
able to improve proliferation and differentiation of neural progen-
itor cells in hippocampus. Moreover, it also improved a global
ischemia model in gerbils. Further beneficial effects of 20 include
following results: enhancement of the deteriorated immune sys-
tem, improvement of motor and behavior response caused by
age-related alterations, promoting activity of the hippocampal
neuronal function in aged rats and partial protection against the
glutamate-induced excitotoxicity. The structure of 20 consists of
panaxatriol and two sugar moieties, while the structure of 19 is
composed of panaxatriol with four sugar moieties. Another study
revealed potential of ginsenoside Rh2 (22) to reverse suppresion
of long-term potentiation induced by scopolamine in the CA1 hip-
pocampal region (Kumar et al., 2012). Standardized ginseng extract
(G115) significantly improved retention, improves learning, greatly
increased the locomotor activity of mice.
Study model

Loganin (17) was used in oral treatment of mice in passive

avoidance test with Cornus officinalis fruits (100 mg/kg b.w.) as
one of its major constituent (1 and 2 mg/kg b.w.). Loganin
(Fig. 2) considerably reversed memory deficits induced by scopo-
lamine. Further, orally treated mice with 17 in the Morris water
maze test significantly improved memory deficits induced by
scopolamine, which showed the formation of long-term and/or
short-term spatial memory. Moreover, considerable inhibition of
AChE activity was observed after administration of 17 (2 mg/kg
Asparagus cochinchinensis
Dendrobium moniliforme
Angelicae Gigantis Radix

Acori graminei rhizome

b.w.) (Lee et al., 2009).

Alisma canaliculatum
Cinammomum cassia
Rehmannia glutinosa
Schizandra chinensis

Nobiletin (18) is derived from herb Aurantii nobilis, a compo-

Polyagala tenuifolia
Ligusticum rhizome

Dioscorea japonica
Morinda officinalis
Rehmanniae radix

Phlomis ambrosia
Cornus officinalis

nent of TCM. Nobiletin (Fig. 2) administered daily within four

Rubus coreanus
Thuja oreintalis

Acorus calamus
Polygalae radix

Torilis japonica

Cistanche salsa
Paeoniae radix

Panax ginseng

months avoided to the memory impairment in fear conditioning.

Immunohistochemical analysis in transgenic mice shows hip-
pocampal decrease of the Ab deposi (Yamakuni et al., 2010).
Components

Pseudocoptisine (34) is a hexacyclic quaternary alkaloid found

10.

10.
11.
12.
13.
14.
15.
16.
17.
5.
6.
7.
8.
9.

1.
2.
3.
4.
5.
6.
7.
8.
9.

in tubers of Corydalis turtschaninovii, which showed a dose-

dependent inhibitory activity of AChE with IC50 = 12.8 lM. The oral
administration of 34 at the dose of 2.0 mg/kg in mice reversed the
cognitive impairment in passive avoidance test and decreased the
escape latencies in training trials. According to these results, it is
Hebal formuation

assumed that 34 can be a useful remedy for treatment of cognitive

impairment (Huang et al., 2008).
PJBH
Table 3 (continued)

6. Quality and safety of herbal drugs

Phytochemical profile of plants is significantly affected by the

Sl no.

environment. In the same species, levels of bioactive constituents

12

can vary according to geographical location, weather condition, soil

composition and other aspects. Even on the same location, the
898
 Table 4

S. Halder, U. Anand, S. Nandy et al.

Different phytochemicals for memory improvement.

Sl Chemical compound Source plant In vivo study model Biological effect and target Reference
no.
1 L-Ascorbic acid (23) Citrus fruits Scopalamine and Diazepam-induced  Improve learning ability in aged mice (Parle and Dhingra,
young animals, Aged mice  Reduce transfer-latency and increase step-down latency 2003)
 Protect gainst scopolamine- and diazepam-induced memory
impairments
2 Bacosides (24) Bacopa monnieri Elderly people (65 years or older) without  Enhanced auditory verbal learning and word recall Kumar et al., 2012
clinical sign of dementia in double-blind,  Effective in patients with AD
placebo-controlled clinical trial
3 Curcuminoids (25) Curcuma longa Abeta-peptide infused rat models of AD  Positive effect on rats displayning AD-like meuronal loss Ahmed et al., 2010
 Increased PSD-95 expression in hippocampus
 Increased synaptophysin expression
4 Dehydroevodiamine (26) Evodia rutaecarpa Rats with Scopalamine-induced memory  Inhibited acetylcholinesterase activity Park et al., 1996
deficit  Reversed sopalamine-induced memory impairments
5 Dendrobium alkaloids (27) Dendrobium Rats with LPS-induced memory deficit  Improved neurobehavioral performance Li et al., 2010
moniliforme  Protection against LPS-induced memory impairments
6 Epigallocatechin-3-gallate (EGCG, 12) Camellia sinensis Mice  Boosts neurogenesis in brain areas important for memory (e.g., Weatherby, 2012
hippocampus)
7 Ginkgolides (28) Ginkgo biloba Patients with dementia of AD type and  Improved task assessing speed for processing ability Kumar et al., 2012
multi-infract dementia  Might improve cognitive process in older adults
8 Ginsenosides (29):Rg1 (20), Rg2 (21), Rg3 (30), Rb1 Panax ginseng Healthy and young volunteers  Improvement in speed of performing memory task and accuracy Kumar et al., 2012
(19), Rh2 (22), etc. of attentional task
9 Huperzine A (15) Huperzia serrata Individuals with AD  Improved cognition, mood and behaviour of patients with AD Kumar et al.,2012
10 Loganin (17) Cornus officinalis Scopalamine-induced amnesic mice  Significant mitigation in scopolamine-induced memory deficits Lee K.Y et al.,
in passive avoidance test
 Inhibition of acetylcholinesterase activity in mouse
hippocampus
899

11 Nobiletin (18) Aurantii nobilis Mice  Reduced memory impairment in fear conditioning Yamakuni et al., 2010
 Reduced Abeta deposit in mice hippocampus
12 Phosphatidyl choline (31)  Allium Human  Enhance healing of brain tissue and nerves Rathee et al., 2008
sativum  Increase level of acetylcholine in brain
 Soy bean  Useful for AD and bipolar depression
 Lettuce
 Whole grain
 Cauliflower
13 Piperine (32) Piper nigrum Adult male Wistar rats  Improve memory impairment Chonpathompikunlert
 Reduced neurodegeneration in hippocampus et al., 2010
 Showed neurotrophic effect in hippocampus
14 Polygala saponins XXXII (PGS32, 33) Polygala Mice with scopalalmine-induced cognitive  Reverse Abeta-induced memory impairment through its anti- Kumar et al., 2012
tenuifolia impairment oxidative property
 Reversed scopolamine effect by improving synaptic

Saudi Pharmaceutical Journal 29 (2021) 879–907

transmission
 Enhancement of brain derived neurotropic factor level
15 Pseudocoptisin (34) Corydalis tuber Mice with scopolamine-induced memory  Has anti-cholinesterase and anti-amnesic activity Hung et al., 2008
impairrment  Reversed cognitive impairments in PA test
 Reduced escape latencies
16 Oroxylin A (35) Scutellaria Rats with 2VO-induced memory  Reversed 2VO-induced memory impairments Kim et al., 2006
bicalensis impairments  Reduction in activated microgila
 Increased BDNF expression and CREB phosphorylation
17 Sauroine (36) Huperzia sqururus Male Wistar rats  Improved memory retention in step-down test Vallejo et al., 2009
 Increased hippocampal plasticity
18 Sesquiterpene lactone (37) Amberboa ramosa  Inhibits acetyl-cholinesterase and butyl-cholinestearse Ibrahim et al., 2013
enzymes
S. Halder, U. Anand, S. Nandy et al. Saudi Pharmaceutical Journal 29 (2021) 879–907

Table 5
Compound level in the natural sources.

No. Bioactive compound Content Source (part) Reference

1 (S)-Allyl-L-cysteine (38) 2.0–2.4 mg/100 g Allium sativum (bulb) Ryu and Kang, 2017
2 Arecoline (39) 1.5 ± 0.008% Areca catechu (raw nuts) Dutta et al., 2017
3 b-Asarone (40) 4.4% w/w Acorus calamus (rhizome) Hanson et al., 2005
4 L-Ascorbic acid (23) 34–38 mg/100 g Phyllantuhus emblica (fruit) Raghu et al., 2007
5 Bacopaside I (41) 0.29–1.36% Bacopa monnieri (whole plant) Christopher et al., 2017
6 Bacoside A (42) 1.44–5.40% Bacopa monnieri (whole plant) Christopher et al., 2017
7 Baicalin (43) 8.1–15.6% Scutellaria baicalensis (roots) Zheljazkov et al., 2007
Baicalein (44) 0.2–1.2%
8 Carnosic acid (45) 18.2–35.1 mg/g Salvia rosmarinus (leaves) Hidalgo et al., 1998
9 Chebulic acid (46) 7.99 g/kg Terminalia chebula (dry fruit) Pfundstein et al., 2010
10 a-Crocin (47) >10% Crocus sativus (dry saffron’s mass) Shahdadi et al., 2016
11 Curcumin (11) 3–5% Curcuma longa (rhizome) Guimarães et al., 2020
12 Emodin (48) 156.37 ± 0.179 lg/g Polygonum multiflorum (dried tuberous root) Yang et al., 2018
13 (-)-Epicatechin (EC, 49) 270–1235 mg/100 g Theobroma cacao (beans) Othman et al., 2010
14 Epigalactocatechin-3-gallate (EGCG, 12) 7380 mg/100 g Camellia sinensis (dried leaves) Sharifi-Rad et al., 2020
15 Essential oil 0.93% - Salvia officinalis (aerial parts) Damyanova et al., 2016
- a-Thujone (50) 26.68% (of essential oil)
- b-Thujone (51) 5.35% (of essential oil)
- a-Pinene (52) 3.58% (of essential oil)
- b-Pinene (53) 5.44% (of essential oil)
- Borneol (54) 3.69% (of essential oil)
16 Flavonoids (55) (total content) 14.30 mg/g Ginkgo biloba (fresh leaves) Shi et al., 2012
17 Gingerol (56) 75.25 ± 2.03 mg/100 g Zingiber officinale (fresh rhizome) Saensouk and Chumroenphat, 2018
18 Ginsenoside Rg1 (20) 3.3 mg/g Panax ginseng (roots) Lee et al., 2015
Ginsenoside Re (57) 2.0 mg/g
Ginsenoside Rb1 (19) 5.8 mg/g
Ginsenoside Rc (58) 1.7 mg/g
Ginsenoside Rb2 (59) 2.3 mg/g
Ginsenoside Rd (60) 0.4 mg/g
19 Huperzine A (15) 182.55 ± 0.18 lg/g Huperzia serrata (moss) Ma et al., 2005
20 Loganin (17) 10.4 lg/mg Cornus officinalis (dried fruit) Ahn et al., 2017
21 Magnolol (61) 2–10% Magnolia officinalis (bark) Patocka et al., 2006
22 Nicotine (62) 0.3–3.5% Nicotiana tabacum (dried leaves) Fatica et al., 2019
23 Piperine (32) 2–7.4% Piper nigrum (fruits) Gorgani et al., 2017
24 Resveratrol (63) 50–100 lg/g Vitis vinifera (grape skin) Singh et al., 2015
25 Ricinine (64) 0.13–0.26% Ricinus communis (fresh leaves) Burgess et al., 1988
26 Rosmarinic acid (65) 3.67–8.07% Melissa officinalis (leaves) Kittler et al., 2018
27 Tannic acid (66) 0.16–0.77 mg/g Clitoria ternatea (raw mature seeds) Al-Snafi, 2016
28 Tannic acid (66) 4.1 g/100 g Punica granatum (dry seeds) S. Mohammed, 2008

Table 6
Summarized biological assays of active compounds.

No. Compound Effective Biological activity Reference

concentration/dose
1 a-Asarone (67) IC50 = 46.38 ± 2.69 lM In vitro AChE inhibitory potential Mukherjee et al., 2007b
2 b-Asarone (40) IC50 = 3.33 ± 0.02 lM In vitro AChE inhibitory potential Mukherjee et al., 2007b
3 Bisdemethoxycurcumin (68) IC50 = 16.84 lM In vitro inhibition of AChE Ahmed and Gilani, 2009
4 (+)-Catechin (69) 1–10 lM Attenuation of hippocampal cell death Bastianetto et al., 2000
5 Crocetin (70) IC50 = 96.33 ± 0.11 lM Inhibition of AChE Geromichalos et al.,
2012
6 Curcumin (11) IC50 = 67.69 lM In vitro inhibition of AChE Ahmed and Gilani, 2009
7 Curcumin (11) IC50 = 0.81–1 lM Inhibition of Ab aggregation or its disaggregation Yang et al., 2005
promotion
8 Curcuminoids (25) IC50 = 19.67 lM In vitro inhibition of AChE Ahmed and Gilani, 2009
9 Demethoxycurcumin (71) IC50 = 33.14 lM In vitro inhibition of AChE Ahmed and Gilani, 2009
10 Dimethylcrocetin (72) IC50 = 107.1 ± 1.9 lM Inhibition of AChE Geromichalos et al.,
2012
11 Ellagic acid (73) IC50 = 45.63 lM Inhibition of AChE G and De, 2011
12 Epigalactocatechin-3-gallate (EGCG, Daily oral dose of 9 mg/kg Improvement of visual recognition memory de la Torre et al., 2016
12) of EGCG given for 12 months
13 Galanthamine (74) IC50 = 1.995 lM Inhibition of AChE (rat cortex) Tang and Han, 1999
14 Gallic acid (75) IC50 = 5.85 lM Inhibition of AChE G and De, 2011
15 Ginsenoside Rg5 (76) IC50 = 18.4 lM Inhibition of AChE Kim et al., 2013
16 Ginesnoside Rh3 (77) IC50 = 10.2 lM Inhibition of AChE Kim et al., 2013
17 Huperzine A (15) IC50 = 0.082 lM Inhibition of AChE (rat cortex) Tang and Han, 1999
18 Loganin (17) IC50 = 0.33 ± 0.05 lM Inhibition of AChE Bhakta et al., 2016
19 Physostigmine (78) IC50 = 1.42 lM Inhibition of AChE G and De, 2011
20 Protopine (79) IC50 = 50 lM Inhibition of AChE Kim et al., 1999
21 Quercetin (80) 5–25 lM Attenuation of hippocampal cell death Bastianetto et al., 2000
22 Resveratrol (63) 5–25 lM Attenuation of hippocampal cell death Bastianetto et al., 2000
23 Safranal (81) IC50 = 21.09 ± 0.17 lM Inhibition of AChE Geromichalos et al.,
2012

900
S. Halder, U. Anand, S. Nandy et al. Saudi Pharmaceutical Journal 29 (2021) 879–907

chemical composition in plants varies from year to year due to these herbs can be used for the treatment of some serious brain
local weather divergency (temperature, drought, flood, etc.). The disorders in humans (e.g. AD) in near future.
constituent levels in wild plants are in general more variable.
These negative effects in commercial plants can be reduced by Declaration of Competing Interest
standardization of cultivation techniques. Indeed, plants that orig-
inate from characterized and uniform genetic source and that The authors declare that they have no known competing finan-
grown under controlled conditions contain more stable levels of cial interests or personal relationships that could have appeared
bioactive compounds. to influence the work reported in this paper.
The concentration of nootropics depends on the mechanism of
plant processing. The whole plant, essential oil, roots, leaves, fruits, Acknowledgements
etc. contain various levels of desired compounds, therefore it is
important to use parts of plant with higher concentration of drugs. A.D. was supported by ‘‘Faculty Research and Professional
Diverse extraction methods produce mixture of substances in var- Development Fund” (FRPDF) from Govt. of West Bengal and Presi-
ious levels. Solvents, temperature, time of extraction, etc. signifi- dency University and DBT-BUILDER from Department of Biotech-
cantly affect composition of the final mixture. In addition, some nology, Govt. of India.
of the natural products containing bioactive compounds are pre-
pared without standardization, therefore the composition of the Funding
products may vary between producers and even batches. Detailed
standardization in plant processing is needed for a higher quality The author ’PO’ would also like to acknowledge the funding
of final products. received from UHK VT2019-2021.
An application of the same nootropic may result in various bio-
logical effects. The major advantage of herbal drugs is presence of
several active or supporting compounds compared to a single-
component drugs. This fact represents a unique challenge for the References
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