Alternative Medicines for Diabetes Management Advances in
Pharmacognosy and Medicinal Chemistry 1st Edition
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Library of Congress Cataloging‑in‑Publication Data
Names: Rambaran, Varma H., author. | Singh, Nalini K., author.
Title: Alternative medicines for diabetes management : advances in
pharmacognosy and medicinal chemistry / Varma H. Rambaran, Nalini K.
Singh, University of Trinidad and Tobago, Tamana Campus, Trinidad and
Tobago.
Description: First edition. | Boca Raton, FL : CRC Press, 2023. | Includes
bibliographical references and index.
Identifers: LCCN 2022017667 (print) | LCCN 2022017668 (ebook) | ISBN
9781032344898 (hbk) | ISBN 9781032344973 (pbk) | ISBN 9781003322429
(ebk)
Subjects: LCSH: Diabetes--Alternative treatment. | Diabetes--Ayurvedic
treatment. | Materia medica, Vegetable--Therapeutic use. | Medicinal
plants--Therapeutic use. | Pharmacognosy.
Classifcation: LCC RC661.A47 R36 2023 (print) | LCC RC661.A47 (ebook) |
DDC 616.4/62--dc23/eng/20220716
LC record available at https://lccn.loc.gov/2022017667
LC ebook record available at https://lccn.loc.gov/2022017668
ISBN: 9781032344898 (hbk)
ISBN: 9781032344973 (pbk)
ISBN: 9781003322429 (ebk)
DOI: 10.1201/9781003322429
Typeset in Times
by Deanta Global Publishing Services, Chennai, India
For my mentors:
Dr Richard A. Fairman and Professor Alvin A. Holder
Thank you for your continued guidance and support
Varma
Contents
Preface.......................................................................................................................xi
Acknowledgements ................................................................................................ xiii
Authors..................................................................................................................... xv
Chapter 1 Etiology ................................................................................................1
1.1 Diabetes Mellitus (DM) ............................................................ 1
1.1.1 Type-1 Diabetes............................................................1
1.1.2 Type-2 Diabetes............................................................2
1.1.3 Hyperglycaemia in Pregnancy ..................................... 3
1.1.4 Other Types of Diabetes...............................................3
1.2 Insulin Transduction Pathway ................................................... 4
1.3 Our Goal....................................................................................5
Chapter 2 Allopathic Medicines ...........................................................................7
2.1 Introduction ............................................................................... 7
2.1.1 Overview and Signifcance...........................................7
2.1.2 History..........................................................................8
2.1.3 Downfalls .....................................................................8
2.2 Biguanides ................................................................................. 9
2.3 Sulfonylureas ........................................................................... 11
2.4 Meglitinides............................................................................. 14
2.5 Alpha-Glucosidase Inhibitors.................................................. 15
2.6 DPP-4 Inhibitors...................................................................... 18
2.7 Thiazolidinedione....................................................................20
2.8 SGLT-2 Inhibitors.................................................................... 22
Chapter 3 Ayurvedic Medicines: (Ethnopharmacological Treatments) ............. 39
3.1 Introduction ............................................................................. 39
3.1.1 Overview and Signifcance......................................... 39
3.1.2 History........................................................................40
3.1.2.1 Traditional Indian Medicine .......................40
3.1.2.2 Traditional Chinese Medicine .................... 41
3.1.2.3 Traditional Arabic and Islamic Medicine ..... 42
3.1.3 Downfalls ................................................................... 42
3.2 Abelmoschus esculentus Linn. (AE)........................................ 43
3.3 Ageratum conyzoides Linn. (AgC) .......................................... 45
3.4 Allium cepa Linn. (AC)............................................................ 47
3.5 Allium sativum Linn. (AS) ....................................................... 48
vii
viii Contents
3.6 Aloe barbadensis Mill. (ABM) ................................................ 50
3.7 Annona muricata Linn. (AM).................................................. 52
3.8 Apium graveolens Linn. (AG).................................................. 54
3.9 Azadirachta indica Linn. (AI) ................................................. 56
3.10 Bidens pilosa Linn. (BiP) ........................................................ 58
3.11 Bixa orellana Linn. (BO).........................................................60
3.12 Brassica juncea Linn. (BJ)...................................................... 61
3.13 Bryophyllum pinnatum Linn. (BP).......................................... 63
3.14 Capparis spinosa Linn. (CaS).................................................64
3.15 Carica papaya Linn. (CaP).....................................................66
3.16 Catharanthus roseus Linn. (CR) ............................................. 68
3.17 Cecropia obtusifolia Linn. (CeO) and Cecropia
peltata Linn. (CeP) .................................................................. 70
3.18 Centella asiatica Linn. (CeA).................................................. 72
3.19 Chromolaena odorata Linn. (CO) .......................................... 74
3.20 Citrus aurantiifolia Linn. (CiA) .............................................. 75
3.21 Citrus limon Linn. (Cil)........................................................... 77
3.22 Citrus paradisi Linn. (CiP) ..................................................... 78
3.23 Citrus sinensis Linn. (CiS) ...................................................... 81
3.24 Coriandrum sativum Linn. (CoS)............................................ 82
3.25 Crescentia cujete Linn. (CrC) .................................................84
3.26 Cucumis sativus Linn. (CS)..................................................... 86
3.27 Cucurbita fcifolia Linn. (CF) and Cucurbita
pepo Linn. (CP) ....................................................................... 88
3.28 Curcuma longa Linn. (CL) ...................................................... 89
3.29 Cymbopogon citratus Linn. (CC)............................................ 91
3.30 Euphorbia hirta Linn. (EH) .................................................... 93
3.31 Hibiscus rosa-sinensis Linn. (HRS) ........................................94
3.32 Justicia secunda Vahl (JS) ......................................................96
3.33 Lantana camara Linn. (LC)....................................................97
3.34 Leonotis nepetifolia Linn. (LN)............................................... 98
3.35 Mangifera indica Linn. (MI) ................................................. 100
3.36 Mentha................................................................................... 102
3.37 Mimosa pudica Linn. (MP) ................................................... 104
3.38 Momordica charantia Linn. (MC) ........................................ 105
3.39 Morinda citrifolia Linn. (MoC)............................................. 108
3.40 Moringa oleifera Linn. (MO) ................................................ 109
3.41 Murraya koenigii Linn. (MK)................................................ 111
3.42 Neurolaena lobata Linn. (NL)............................................... 114
3.43 Ocimum gratissimum Linn. (OG) and Ocimum
tenuiforum Linn. (OT) .......................................................... 117
3.44 Panax ginseng Linn. (PG) and Panax
quinquefolius Linn. (PQ)....................................................... 120
3.45 Parthenium hysterophorus Linn. (PaH) ............................... 122
3.46 Peperomia pellucida Linn. (PP)............................................ 123
Contents ix
3.47 Phyllanthus amarus Linn. (PA)............................................. 124
3.48 Scoparia dulcis Linn. (SD).................................................... 126
3.49 Senna italica Linn. (SI) ......................................................... 128
3.50 Stachytarpheta jamaicensis Linn. (SJ) ................................. 129
3.51 Syzygium cumini Linn. (SC) .................................................. 131
3.52 Tamarindus indica Linn. (TI)................................................ 134
3.53 Tournefortia hirsutissima Linn. (TH) ................................... 135
3.54 Urena lobata Linn. (UL) ....................................................... 136
3.55 Zingiber offcinale Linn. (ZO)............................................... 137
Chapter 4 Metallopharmaceuticals ................................................................... 153
4.1 Introduction ........................................................................... 153
4.1.1 Overview and Signifcance....................................... 153
4.1.2 The Challenge .......................................................... 154
4.1.3 The Future for Insulin-Enhancing Drugs? ............... 155
4.2 Vanadium............................................................................... 155
4.3 Chromium.............................................................................. 159
4.4 Zinc........................................................................................ 161
4.5 Cobalt..................................................................................... 164
4.6 Tungsten................................................................................. 166
4.7 Molybdenum.......................................................................... 169
Conclusion ............................................................................................................ 171
Bibliography ......................................................................................................... 173
Abbreviations .......................................................................................................207
Glossary ................................................................................................................ 211
Index...................................................................................................................... 215
Preface
Apart from diet and exercise, the strategic use of different classes of prescribed and
non-prescribed xenobiotic compounds for the restoration of euglycaemic levels in
the body is well known. The ongoing rivalry between the recommended usage of
allopathic medicines versus herbal remedies has encouraged many researchers to
focus their studies on thoroughly isolating and characterizing extracts from different
parts of plants, and then evaluating their relative activities via in vitro, in vivo, and, in
some cases, clinical studies. To further support this drive, the respective rich histories
of many countries with regard to both colonization and immigration have enabled a
wider selection of botanical sources to become more accessible to their inhabitants,
and it is observed that these plants are already integrated into their regular diets and
lifestyles.
Stepping aside from the aforementioned controversy between fact and folklore,
the emergence of a revolutionary class of therapeutics that belongs to a family of com-
pounds known as coordination complexes has also been reported. Fondly dubbed by
their developers as insulin mimetics or insulin enhancers, these metallo-drugs have
struggled for acceptance by the medical fraternity due to the divisive claims behind
them. However, perseverance driven by passion in this area has continued to yield
promising data, and this has stoked hope for their further development.
xi
Acknowledgements
The authors wish to thank the University of Trinidad and Tobago for all the assis-
tance given throughout the development of this book.
We also wish to thank our families and friends for their undying encouragement
and support throughout our endeavours.
Finally, we would like to give special thanks to Mrs Ashmini Motilal, Miss Pritivi
Narine, Miss Kajol Jagessar, Mr Dheeresh Ramcharan, and Mr Narendra Maharaj
for their invaluable contributions to the completion of this book.
xiii
Authors
Dr Varma H. Rambaran is currently employed as an
Associate Professor at the University of Trinidad and Tobago
(UTT), Offce of the Vice President of Research and Student
Affairs (VP-RASA). He graduated from the University of the
West Indies in 1999, with a Bachelor of Science in Chemistry,
and in 2005, obtained a Doctor of Philosophy degree in
Inorganic Chemistry. During his years as a post-graduate stu-
dent, he developed a keen interest in the behaviour of coor-
dination complexes in biological systems. However, it was
during his post-doctoral fellowship at the University of Southern Mississippi that
the ameliorative effects of vanadium-based complexes in diabetes therapy caught his
attention. Through the support of the International Centre for Genetic Engineering
and Biotechnology (ICGEB), he was able to successfully explore and develop his
idea of using a family of novel vanadyl complexes (PDOV and PYTOV) as insulin-
enhancing agents. The fndings from his studies were awarded a patent by the US
Patent and Trademark Offce in March 2021.
While working on his project, Dr Rambaran noticed a partiality to certain medi-
cines that were being prescribed to diabetic patients. The seemingly undying contro-
versy over the superiority of allopathic medicines, versus their ethno-pharmaceutical
counterparts has resulted in the polarization of many groups, due to their lack of
awareness and understanding of the different forms of therapies. To further com-
plicate matters, the majority of reference books on the market commonly lack the
supporting scientifc data of compound identity, mechanism of action, and safety
in use. Unfortunately, this has led to a bias against the use of herbal medicines by
insinuating that the claims being made are more witchcraft than science.
Inspired by this, Dr Rambaran saw a need to furnish a comprehensive book of
this nature, which would impartially and holistically educate its readers on the oral
therapeutic options that are available to them.
Nalini Kathleen Singh is currently employed at UTT as
a Research Assistant, under the Offce of VP-RASA. Ms
Singh’s research interests fall under the umbrella of non-
communicable diseases (NCDs), focusing mainly on the
epidemiology and etiology of hypothyroidism. Her extended
interest in natural medicines used in NCD-therapies has war-
ranted her invaluable contributions in this book.
Ms. Singh holds a Bachelor of Science in Chemical and
Process Engineering, which she obtained from the University
of the West Indies (UWI, St Augustine Campus) in 2013. She
also completed an Occupational Safety and Health Administration (OSHA) general
xv
xvi Authors
industry training course at the School of Business and Computer Science (SBSC) in
2014, and participates in short courses on a regular basis to improve her professional
skills. Since 2016, she has been an active member of the Association of Professional
Engineers of Trinidad and Tobago (APETT) in both the electrical and chemical divi-
sions, with her current grade being Associate Member. Ms Singh has also received
awards in leadership and good citizenship owing to her involvement in volunteer
programmes since 2002. Due to her positive attitude, her desire to learn, and her pas-
sion for scientifc research, Ms Nalini Singh continues to take steps to continuously
improve, both professionally and personally.
1 Etiology
1.1 DIABETES MELLITUS (DM)
Diabetes mellitus is ranked as one of the top four non-communicable diseases in the
world. According to its most recent release, the International Diabetes Federation
(IDF) has estimated a world population of 537 million people (aged 20–79 years)
who are living with the disease, which, if left unaddressed, will rise to a staggering
784 million by 2045! Within the North American and Caribbean region alone there
are 51 million adults, representing a regional prevalence of 9.5% (Figure 1.1); this
prevalence had an associated health expenditure of approximately US$415 billion
and accounted for 42.9% of total global diabetes-related health expenditure in 2021
(IDF Diabetes Atlas 2021: 10th Edition 2021).
DM’s diagnosis as a metabolic disease arises from either the pancreas’s inabil-
ity to produce suffcient quantities of insulin or the desensitization of the human
insulin receptor glycoprotein (INS-R) (due to the overproduction of the hormone).
Its etiology encompasses a range of factors that include genetics, viral infections,
autoimmunity, and obesity (Ramasamy and Schmidt 2014). Stemming from these
are its clinical manifestations, which include hyperglycaemia, glycosuria, insulin
resistance, fat and carbohydrate metabolism abnormalities, and chronic complica-
tions resulting from macro- and micro-vascular pathology. DM can be categorized
under two major classes: type-1 and type-2. However, the diagnosis of a patient with
DM and the classifcation under which type they suffer from, can vary according to
the individual. As such, it has been observed in recent times that endocrinologists
have further expanded the subclasses according to their contrasting occurrences and
symptoms. An example of this is a patient who was initially diagnosed with gesta-
tional diabetes (GDM) and continued to be hyperglycaemic even after delivery and,
as a consequence, was later diagnosed with type-2 diabetes mellitus (T2DM) (IDF
Diabetes Atlas 2021: 10th Edition 2021). To best understand this and other occur-
rences, a brief discussion of the various classifcations of the disease follows.
1.1.1 TYPE-1 DIABETES
Type-1 diabetes mellitus (T1DM) or “immune-mediated diabetes” was previously
classifed as “insulin-dependent diabetes” or “juvenile-onset diabetes.” It occurs as
a result of the cellular-mediated autoimmune destruction of the pancreatic β-cells,
which may be either genetically or environmentally infuenced. However, there has
been some suspicion of its occurrence due to toxic and some dietary factors (Sesti
2006, Nelson and Cox 2008). The rate of destruction of the β-cells has been observed
to vary from slow (occurring mainly in adults) to rapid (being highly peculiar to
infants and children). The condition can develop at any age, although it occurs most
frequently in children and young adults.
DOI: 10.1201/9781003322429-1 1
