001

Journal of Applied Pharmaceutical Science Vol. 13(10), pp 083-091, October, 2023

Available online at http://www.japsonline.com
DOI: 10.7324/JAPS.2023.135164
ISSN 2231-3354

Phytochemistry and pharmacology of Curculigo orchioides Gaertn:

A review

Pallishree Bhukta1 , Santosh Kumar Ranajit1 , Pratap Kumar Sahu2* , Deepankar Rath1
1
Department of Pharmacology, School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Jatni, India.
2
Department of Pharmacology, School of Pharmaceutical Sciences, Siksha O’ Anusandhan University, Bhubaneswar, India.

ARTICLE HISTORY ABSTRACT

Received on: 30/05/2023 Curculigo orchioides Gaertn. is a rare rasayana herb (family Amaryllidaceae) popularly known as “Kali Musli”.
Accepted on: 21/08/2023 Traditionally used in Ayurvedic medicine as an aphrodisiac and adaptogen, the plant is native to India. There is
Available Online: 04/10/2023 evidence that the plant contains mucilage, phenolic glycosides, saponins, and aliphatic compounds. This folk medicine
can treat a wide range of ailments, including impotency, aphrodisiacs, tonics, jaundice, and skin conditions. There are
also many scientists who have investigated its antioxidant, anticancer, and hepatoprotective properties. Curculigo was
Key words:
isolated for its chlorophenolic glucosides, curculigine, phenolic glycosides, orcinosides, and polysaccharides. As an
Curculigo orchioides,
herbal medicine, Curculigo’s quality can be controlled through new analyzing methods. Furthermore, Curculigo has
phytochemicals,
been investigated for its pharmacological activity against diabetes, bacteria, inflammation, osteoporosis, oxidative
pharmacological activity, Kali
stress, cancer, and neurodegeneration. Scientific methods were gradually developed for the application of herbal
Musli, curculigoside.
medicine. A more comprehensive pharmacological study of the genus Curculigo is needed to determine its medicinal
value. An updated and comprehensive review of the medicinal plant C. orchioides Gaertn is presented here describing
traditional uses, phytochemistry, pharmacology, and toxicology, and understanding its future research and development
prospects.

INTRODUCTION as Golden Eye Grass, Talamuli, Kalimusli, Nilappani, and

The traditional Indian medical system is called Nilapanaiin English, Sanskrit, Hindi, Malayalam, and in Tamil,
Ayurveda. There is a long history of disease management in respectively (Joy et al., 2004).
Ayurvedic practice dating back about 3000 years (Hankey, Originally native to India, C. orchioides occur
2001). The Ayurvedic healing process relies heavily on plant- everywhere, especially in rocky areas, especially at sea level
based preparations (Sastri, 2002). In Ayurvedic medicine, and up to 2,300 m above the sea level (Mehta and Nama, 2014).
approximately 90% of the preparations are derived from plants Tonic medicine has been used for centuries with the rhizome
(Kumar et al., 2017). There are many Asia’s subtropical regions, of C. orchioides by the Chinese since the Tang Dynasty for the
including China and India, where Curculigo orchioides grows as maintenance of health, energy, and nourishment of renal and
a perennial herb of the Amaryllidaceae family (Bafna and Mishra, hepatic systems. The root of C. orchioides was commonly used in
2005; Jiao et al., 2009; Wang et al., 2012). Curculigo orchioides the treatment of impotence, limb limping, lumbar and knee joint
Gaertn, of the Amaryllidaceae family has different names such arthritis, and diarrheal water (Chauhan et al., 2010). Jaundice,
asthma, urinary and skin diseases, and bladder and kidney
infections were treated with C. orchioides in the Ayurvedic System
of Medicines (Khare, 2007).
*Corresponding Author
Pratap Kumar Sahu, Department of Pharmacology, School of Pharmaceutical A variety of secondary metabolites are found in
Sciences, Siksha O’ Anusandhan University, Bhubaneswar, India. the genus Curculigo plants. Ten species: their chemistry and
E-mail: pratapsahu @ soa.ac.in pharmacology have been studied to date. These species include

© 2023 Pallishree Bhukta et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License
(https://creativecommons.org/licenses/by/4.0/).
084 Bhukta et al. / Journal of Applied Pharmaceutical Science 13 (10); 2023: 083-091

Curculigo capitulata, Curculigo sinensis, Curculigo crassifolia, 3, a homogeneous heteropolysaccharide compound (Wang
C. orchioides, Curculigo breviscapa, Curculigo gracilis, et al., 2019) were found in the rhizomes of C. orchioides. In a
Curculigo recurvata, Curculigo glabrescens, Curculigo pilosa, preparative reversed-phase liquid chromatography, levoglucosan
and Curculigo latifolia. The main compounds found in Curculigo was obtained (Niu et al., 2020). The primary metabolites
species include phenols, phenolic glucosides, terpenoids, and of Curculigo plants are phenolic compounds. Two phenolic
norlignans (Nie et al., 2013). Curculigo plants are increasingly glucosides named curculigoside H and orcinoside I, along with
studied phytochemically due to their traditional uses. This genus 10 known phenolic glucosides such as curculigoside A, B, C, and
of plants contains more than 110 compounds, among which are as G, orcinol glucoside (OG) B, benzyl-O-β-D-glucopyranoside,
follows: phenolic glycosides and phenols (Chang and Lee, 1998; 3-hydroxy-5-methylphenol-1-O-[β-glucopyranosyl-(1-6)-β-D-
Xu and Xu, 1992; Zuo et al., 2010), lignan glycosides and lignans glucopyranoside], glucosyringic acid, 3-hydrox-5-methyl-phenol-
(Li, 1559; Li et al., 2005a, 2005b; Wang et al., 2008; Zhu et al., 1-O-[β-apiosyl-(1-6)-β-glucopyranoside], and OG were isolated
2010), triterpenoid glycosides and triterpenes (Xu et al., 1992; from C. orchioides rhizomes (Wang et al., 2013, 2014) (Fig. 1).
Yokosuka et al., 2010; Zuo et al., 2012), eudesmanes, flavones Four other known phenolic compounds, including orcinoside
(Tiwari and Mishra, 1976), alkaloids (Li et al., 2005a, 2005b), I and J, have been proclaimed to be new heterocyclic phenolic
and other constituents. In China, C. orchioides is considered as a derivatives, including 3-(4-hydroxy-3-methoxyphenyl) propane-
supplemental health product in the form of tea bags and alcoholic 1,2-diol, 3-(4-hydroxy-3,5-dimeth-oxyphenyl) propane-1,2-diol,
beverage (Liu et al., 2022). Curculigo orchioides is reported to piperoside, 4-ally-2, and 6-dimeoxy phenol glucoside (Chen et al.,
have the effects of dissipating carbuncle, strengthening muscles 2017).
and bones, dispelling cold and dampness, tonifying kidney yang, Curculigo rhizomes powdered and dried were used to isolate
benefiting essence and blood, immunoregulation, hepatoprotective 3,5-Dihydroxy-4-methoxybenzoic acid and p-Hydroxycinnamic
and neuroprotective activities (Fang et al., 2020). These plants are acid (Niu et al., 2020). Curculigo orchioides contains natural and
most likely characterized by norlignans, phenol glycosides, and rare chlorinated compounds called cuculligines. It was discovered
triterpenoids as their major constituents. Bio-active compounds that the rhizome of C. orchioides contains three chlorophenolic
and extracts of Curculigo plants exhibited a variety of activities glucosides, B, C, and curculigine D (Cao et al., 2009; Xu et al.,
including antidiabetic, immunostimulatory, anti-oxidant, radical 1987; Xu and Xu, 1992). The C. orchioides rhizomes were collected
scavenging, mast cell stabilization, sweet-tasting and taste- for the purpose of obtaining 11 chlorophenolic glucosides, including
modifying, estrogenic and sexual behaviour-modifying, anti- curculigine E–G, I, and K–O (Wang et al., 2013, 2014, 2018). The
inflammatory, antihistaminic, antidepressant, antitumor, anti- C. orchioides rhizomes contain two new chlorophenolic glucosides
asthmatic, anti-osteoporotic, neuroprotective, nephroprotective, named ascurculigine P and Q (Deng et al., 2021). Terpenoids
antiarthritic, vasoconstrictor, anti-microbial, hepatoprotective, are second metabolites produced by Curculigo species. There is
antistress activity, and adaptive activity (Table 1) (Wang et al., evidence that C. orchioides produces cycloartane-type triterpenoid
2021). By using C. orchioides embryos for the green fabrication ketone in its rhizomes (Jiao et al., 2013) (3S,5R,6S,7E,9R)-
of gold nanoparticles, an environmentally friendly method for megatigma-7-ene-3,5,6,9-tetrol, actinidioionoside, (6S,9R)-
maintaining medicinal plants and preventing them from being roseoside, (−)- angelicoidenol-2-O-β-D-glucopyranoside,
overutilized was conducted (Thamilchelvan et al., 2023). (−)-angelicoidenol-2-O-β-apiofuranosyl-(1→6)-β-D-gluco-
pyranosidetetillapyrone[(7R,9S,10R)-3-methyl-5-(4-hydroxyl-5-
PHYTOCHEMISTRY
hydroxylmethyltetrahydrofuryl)]-6-hydroxypyran-2-one are six
Curculigo plants have yielded about 111 secondary terpenoids content of C. orchioides (Zhang et al., 2019a, 2019b).
metabolites, 3 proteins, and 2 polysaccharides so far. A number Rhizomes of C. orchioides contain eight cyclodipeptides, such as
of compounds are isolated from extracts of Curculigo species cyclo-(L-Ala-L-Tyr), cyclo- (Gly-D-Val), cyclo-(LeuAla), cyclo-
which includes phenolic glycosides, phenols, lignan glycosides, (Val-Ala), cyclo-(L-Ser-L-Phe), cyclo-(LeuThr), cyclo-(S-Pro-R-
lignans, triterpenoid glycosides, triterpenes, polysaccharides Leu), and cyclo- (Leu-Ser), which are previously known (Chen
such as COPb-1 and COPf-1, flavones, aliphatic compounds, et al., 2017). The aqueous leaf extract of the plant was observed
alkaloids, eudesmanes, and bioactive proteins such as neoculin, to contain different alkaloids and phenolic compound from the
curculin, and β-amylase (Goyal and Kabra, 2020; Nie et al., post preliminary phytochemical analysis using Fourier-transform
2013). Phytochemicals such as alkaloids, phenols, flavonoids, infrared spectrophotometer (Umar et al., 2021). The presence of
and tannins were present in the extracts of methanol, ethanol, alkaloids, phenols, and saponins could be a plausible explanation
and chloroform but were found to be absent in the ethyl acetate for the observed toxic effects of C. orchioides’ AL extract in
extract of C. orchioides (Saxena, 2022). Curculigo orchioides organismal-level toxicity in Drosophila (Kushalan et al., 2022a,
rhizome methanolic extracts were found to contain alkaloids, 2022b).
carbohydrates, steroids, saponins, phenols, tannins, and flavonoids
(Agrahari et al., 2010; Asif, 2012). Curculigo orchioides rhizome PHARMACOLOGICAL ACTIVITY
extracts contain an alkaloid lycorine, sterols including sitosterol,
sapogenin, and flavone glycoside 5,7- dimethoxy glucopyranoside. Immunomodulatory activity
Flavonoids include 5,7-dimethoxy glucopyranoside, and fatty Adaptation to hypoxia and high temperatures is
acids such as linolenic, palmitic, behenic, arachidic, and oleic improved by C. orchioides ethanol extract. Extracts from C.
acids (Mehta et al., 1980). O-acetyl-glucomannan COP90-1, orchioides have been found to be sedative, anticonvulsant, and
a compound soluble in water (Wang et al., 2017) and COP70- androgen-like. In mice, immunological activity increased as well
 Bhukta et al. / Journal of Applied Pharmaceutical Science 13 (10); 2023: 083-091 085

Table 1. Effect of C. orchioides in many metabolic ailments.

Species Plant part Extract Experimental model Dose Effects References

Hydroalcoholic STZ-nicotinamide induced diabetic

C. orchioides Rhizome 600 mg/kg Anti-diabetic activity Zhang et al., 2017
extract nephropathy

STZ-nicotinamide induced diabetic

C. orchioides Rhizome Ethanol extract 600 mg/kg Anti-diabetic activity Zhang et al., 2017
nephropathy
Karigidi and Olaiya,
C. latifolia Rhizome Aqueous extract HFD + STZ-induced diabetic rats 5 g/day Anti-diabetic activity
2020
10 and 100
C. orchioides Rhizome Ethanol extract 3T3-L1 Anti-diabetic activity Gulati et al., 2015
g/ml
C. orchioides Rhizome Methanol extract HFD + STZ-induced diabetic rats 600 mg/kg Antihypertensive activity Joshi et al., 2012
Hexane 10, 20–80
C. orchioides Rhizome Hela cells Anticancer activity Xia et al., 2016
/chloroform extract mg/ml

Ethyl acetate Selvaraj and Agastian,

C. orchioides Rhizome MCRF-7 cells 80 μg/ml Anticancer activity
extract 2017
C. orchioides Whole plant Aqueous HFD + STZ-induced diabetic rats 40 mg/kg Anticancer activity Xia et al., 2016
0.5, 1.0, and
C. orchioides Rhizome Ethanol extract HFD + STZ-induced diabetic rats Anticancer activity Cao et al., 2008
2.0 g/kg
25, 50–200 Bagna and Mishra,
C. orchioides Rhizome Ethanolic extract Radical scavenger for DPPH Antioxidant activity
μg/ml 2005
25, 50–125 Bagna and Mishra,
C. orchioides Rhizome Ethanolic extract Visitation by peroxidation of lipids Antioxidant activity
μg/ml 2005
Decoctions and
43.57 ± 4.21
C. orchioides Rhizome hydro-alcoholic Scavenging DPPH radical Antioxidant activity Tacchini et al., 2015
mg/ml
extracts
Cyclophosphamide-induced Murali and Kuttan,
C. orchioides Rhizome Ethanol extract 25 mg/kg Antioxidant activity
oxidative stress 2015
C. pilosa Rhizome Aqueous extract Rat penile homogenate 0.95 mg/ml Antioxidant activity Adefegha et al., 2018
An assay to measure ferric reducing 0.16–500.70 Surveswaran et al.,
C. orchioides Rhizome Methanolic extracts Antioxidant activity
antioxidant power mmol/l 2007
C. orchioides Rhizome Ethanol extract S. pyogenes 49 µg/ml Antibacterial activity Marasini et al., 2015
Microorganisms that cause human
C. orchioides Rhizome Rhizome oil pathogens and phytopathogens 2 mgl/ml Antibacterial activity Jaiswa et al., 1984

Fibroblasts from the foreskin of

C. orchioides Rhizome Curculigoside humans 30 mg/ml Antibacterial activity Li et al., 2011

Nagesh and
C. orchioides Rhizome Chloroform extract S. typhimurium, P. aeruginosa 2 mg/ml Antibacterial activity
Shanthamma, 2009
Ethanol crude
extract Streptococcus faecalis, P. aeruginosa,
C. pilosa Rhizome 100 mg/ml Antibacterial activity Nwokonkwo, 2014
and the neutral E. coli, S. aureus
metabolite
Mast cells isolated from mouse
C. orchioides Rhizome Ethanol extract 400 mg/kg Antiasthmatic activity Venkatesh et al., 2009
peritoneum
Induction of catalepsy in Swiss mice 250, 375 mg/
C. orchioides Rhizome Ethanol extract Antiasthmatic activity Pandit et al., 2008
by haloperidol kg
Anaphylaxis due to passive paws in
C. orchioides Rhizome Ethanol extract 350 mg/kg Antiasthmatic activity Pandit et al., 2008
Wistar rats
1.5, 3, 6 mg/
C. orchioides Rhizome OG Depressive rats induced by CUMS Neuroprotective effect Pandit et al., 2008
kg
Exposure to N-methyl-d-aspartate
1, 10, and
C. orchioides Rhizome Curculigoside (NMDA) leads to the loss of neurons Neuroprotective effect Ge et al., 2014
100 μmol/ml
in cortex
086 Bhukta et al. / Journal of Applied Pharmaceutical Science 13 (10); 2023: 083-091

Species Plant part Extract Experimental model Dose Effects References

10, 20, 40
C. orchioides Rhizome Curculigoside Mice Neuroprotective effect Tian et al., 2012
mg/kg
C. orchioides Rhizome Curculigoside Neuronal cell stimulation by NMDA 1 and 10 µM Neuroprotective effect Ge et al., 2014
25–100 µg/
C. orchioides Rhizome Curculigoside osteoblasts Anti-osteoporosis Wang et al., 2016
ml
Zhu et al., 2015a,
C. orchioides Rhizome Curculigoside Iron-overload mice model 100 mg/kg Anti-osteoporosis
2015b
A rat model of liver injury induced Zhang et al., 2019a,
C. orchioides Rhizome Methanolic extract 70 mg/kg Hepatoprotective activity
by carbon tetrachloride (CCl4) 2019b
300, 600 and Sexual behaviour and Venukumar and
C. orchioides Rhizome Ethanolic extract Ovariectomized young albino rats
1,200 mg/kg estrogenic activity Latha, 2002
Sexual behaviour and Vijayanarayana et al.,
C. orchioides Rhizome Ethanolic extract Druckery rats 100 mg/kg
estrogenic activity 2007
Immunostimulatory
C. orchioides Rhizome Methanol extract BALB/c mice 25 mg/kg Chauhan et al., 2007
effect
Immunostimulatory
C. orchioides Rhizome Methanol extract BALB/c mice 100 μg/ml Lakshmi et al., 2003
effect
100, 200,
Cyclophosphamide-induced Immunostimulatory Bafna and Mishra,
C. orchioides Rhizome Methanol extract 400 and 800
immunosuppressed mice effect 2006
mg/kg

depending upon the dose (Bafna and Mishra, 2006). One of

the contents of C. orchioides rhizomes, Curculigo saponin,
acycloartane-type triterpene saponin, enhanced the number
of lymphocytes of the spleen remarkably in mice without
affecting antibody production (Lacaille-Dubois and Wagner,
1996). Polysaccharides resulted in increased spleen and thymus
indexes in normal mice, along with increased hemolytic index
and thicker plantar tissue in serum; Mice immune function is
enhanced by polysaccharides, according to these results (Ji,
2011).

Antioxidant activity
DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) and
nitric oxide radicals are scavenged effectively by methanol
extracts of C. orchioides rhizomes, but lipid peroxidation is
moderately effective (Bafna and Mishra, 2005). In addition to
DPPH testing, ferric reducing ability of plasma testing as well as
2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) testing has
Figure 1. Chief active constituents of C. orchioides. also been performed on C. orchioides to confirm its antioxidant
activity (Surveswaran et al., 2007). DPPH, reducing power, and
phosphomolybdenum assays were used to assess C. orchioides’
(Chen et al., 1989). Curculigo orchioides phenolic glucosides antioxidant potential ethanolic extract of C. orchioides root
increased haemagglutination titer and delayed type hypersensitivity demonstrated significant anti-free radical activity, reducing power,
(DTH) response (Lakshmi et al., 2003). Although polysaccharides and antioxidant properties compared with a reference standard,
stimulate splenocyte proliferation, they do not affect thymocyte gallic acid (Table 1) (Ratnam et al., 2013). Methanolic extract
proliferation. Using ConA-induced splenocyte proliferation as of elevated rhizomes treated hepatotoxic rats showed increased
a model, polysaccharides demonstrated an inhibitory effect on levels of antioxidant enzymes such as glutathione transferase
thymocyte and spleenocyte proliferation in vitro. Mice with (Venukumar and Latha, 2002). Methanolic root extract showed
immunosuppression had larger thymuses and spleens as a result of DPPH radical scavenging activity (Kushalan et al., 2022a, 2022b).
these effects (Zhou et al., 1996). A major component of C. orchioides’ antioxidant activity is
It has been suggested that the methanolic extract of phenolic compounds (Wu et al., 2005).
C. orchioides (MECO) Gaertn’s could be used to prevent the
cytotoxic effects of drugs. When the extract was administered to Anti-inflammatory activity
normal mice or cyclophosphamide-induced immunosuppressed Curculigoside A which is the vital component of C.
mice, humoral antibodies, DTH, and leukocytes increased orchioides, reduced paw swelling and arthritis index in mice
 Bhukta et al. / Journal of Applied Pharmaceutical Science 13 (10); 2023: 083-091 087

significantly and decreased serum IL-1β, TNF-α, IL-6, and PGE2 anti-osteoporotic properties (Zhu et al., 2021). COP50-4, a crude
levels, decreased malondialdehyde (MDA) and increased serum polysaccharide (CO50) from C. orchioides shows great potential
superoxide dismutase activity very effectively downregulated NF- for the treatment of osteoporosis (Yu et al., 2022).
κB/NLRP3 pathways in Freund’s complete adjuvant-induced rats
with adjuvant arthritis (Ding et al., 2016). Type II collagen-induced Antidepressant activity
arthritis rat showed arthritis scores and paw swelling inhibition, The immobility time of the forced swimming test, osmotic
serum pro-inflammatory factor levels of IL-10, TNF-α, IL-17A, fragility test, and tail suspension test was significantly reduced by
IL-6, IL-12, and IL-1β reduced, the expression of JAK3, STAT3, curculigoside treatment. In the hippocampus of chronic mild stress
and JAK1 down-regulated and NF-κB p65 and IκBup-regulated rats, serotonin, dopamine, and norepinephrine levels significantly
because of the active compound curculigoside A (Tan et al., 2019). increased along with brain-derived neurotrophic factor (BDNF)
Carrageen-induced paw oedema in rats was significantly reduced by protein expression following the treatment. There is evidence that
C. orchioides rhizome gel formulation (Dode et al., 2009). curculigoside can treat depression in this way (Wang et al., 2016).
Mice peritoneal mast cells were significantly inhibited
from degranulating by an extract of C. orchioides rhizome in Neuroprotective activity
ethanol and mice exposed to 48/80-induced systemic anaphylaxis. Acetylcholinesterase was effectively inhibited by the
Anti-inflammatory properties of C. orchioides are attributed to extracts of C. orchioides rhizomes, suggesting their potential use
their inhibitory effects on mast cell degranulation and mast cell- in the treatment of Alzheimer’s disease (Pratap and Shantaram,
derived immediate-type allergic reactions (Venkatesh et al., 2009). 2019). Curculigoside remarkably reduced NMDA-induced loss
of neuron cells, apoptosis, necrosis, excitotoxicity, and reactive
Estrogenic activity oxygen species (ROS) production in cultured cortical neurons.
Total glucosides from C. orchioides were found to The inhibitory properties of curculigoside in cultured cortical
increase the thymus, uterus, and spleen indices, testosterone neurons may cause the production of intracellular ROS to be
levels, and estrogen levels, and decrease luteinizing hormone reduced and apoptosis may be inhibited. When neurons are
levels in perimenopause model mice (Cao et al., 2016; Miao et al., exposed to NMDA-induced neuronal excitoxicity, curculigoside
2017). Curculigo orchioides also alleviate streptozotocin-induced prevents them from dying and reduces their apoptosis and
hyperglycaemia in male rats, improving sexual dysfunction as well. necrosis (Tian et al., 2012).
The effects of the treatment were observed in male sexual behaviour, Spectrophotometry and autobiography were used to
penile erection index, seminal fructose content, and sperm counting evaluate the anti-acetylcholinesterase activity of C. orchioides
the test samples (Thakur et al., 2012). It increases steroid synthesis extracts in vitro. The anti-acetylcholinesterase role of rhizome
and restores sexual function by enhancing the spermatogenesis extract methanol in the treatment of Alzheimer’s disease appears
process. It could also facilitate hormone absorption into the gonads to be explained by its inhibition of the acetylcholinesterase enzyme
if C. orchioides was administered (Chauhan et al., 2007). (Pratap, 2020). Using curculigoside A, rats with Alzheimer’s can
be effectively treated because it inhibits apoptosis in hippocampal
Anti-osteoporosis activity neurons and reduces cellular damage (Li et al., 2019). In vitro,
The rhizomes of C. orchioides are asserted to strengthen curculigoside A modulated VCAM-1/Egr-3/CREB/VEGF
bones and tendons (Cao et al., 2008). The proliferation of bone signalling in cerebroendothelial cells, providing stroke and brain
marrow stromal cells was enhanced by 100 mM curculigoside, injury therapies by neurovascular repair (Zhu et al., 2015).
osteogenic genes were enhanced, and osteoprotegerin secretion was It was demonstrated that OG decreased over activity of
increased (Shen et al., 2013). A study indicates that cuculigoside A the hypothalamic-pituitary–adrenal axis and reduced depressive
chemical compound inhibits the inflammatory cytokines TNF-a, IL- behavior in chronic unpredictable mild stress rats by up-regulating
1a, IL-6, and COX-2 production by rat calvarial osteoblasts induced BDNF expression and phosphorylating ERK1/2 (Ge et al., 2014).
with dexamethasone and regulates osteoblast COX-2 expression, Mice showed reduced anxiety-like behaviors after administration of
proliferation, and differentiation (Zhu et al., 2015a, 2015b). OG, but no sedation was seen (Wang et al., 2016).
The chlorophenolic glucosides (Curculigine M,
Curculigine N, and Curculigine O) isolated from the dried rhizomes Hepatoprotective activity
of C. orchioides Gaertn showed moderate effect on osteoblast Aspartate aminotransferase, alkaline phosphatase,
proliferation against MC3T3-E1 cell line by using MTT assays gamma-glutamyl transpeptidase, and gamma-glutamyl
(Wang et al., 2018). A novel homogeneous heteropolysaccharide, transpeptidases were reduced in rats exposed to carbon
COP70-3, was isolated and purified from the crude polysaccharide tetrachloride. Food consumption and weight gain were increased
(CO70) isolated from the rhizomes of C. orchioides (0.94 and by MECO rhizomes. In addition to lowering liver and serum
1.87 nM) significantly improved the osteogenic mineralization protein levels, serum lipids, cholesterol, and phospholipids were
rate and has favorable anti-osteoporosis activity in vitro (Wang normalized. These studies showed that C. orchioides rhizome has
et al., 2018). Curculigoside was able to alleviate bone loss induced hepatoprotective properties (Venukumar and Latha, 2002).
by oxidative stress resulting from iron overload, suggesting its
potential use for the treatment of primary osteoporosis and bone Nephroprotective activity
loss in iron-overload–related diseases (Zhang et al., 2019a, 2019b). Treatment of cyclophosphamide-induced hepatotoxicity
The major bioactive component of found in the plant’s rhizomes, and intestinal toxicities with C. orchioides does not compromise
curculigoside, a phenolic glycoside, exhibits neuroprotective and cyclophosphamide’s chemotherapeutic efficacy. When
088 Bhukta et al. / Journal of Applied Pharmaceutical Science 13 (10); 2023: 083-091

administered along with cyclophosphamide, the whole plant be attributed to the alkaloids and phenols present in it (Aloysius
extract of C. orchioides significantly decreased serum creatinine et al., 2020). A new chlorophenolic glucosides curculigines P,
levels and blood urea nitrogen levels. Induced urotoxicity isolated from the dried rhizomes of C. orchioides showed the most
and nephrotoxicity by cyclophosphamide are alleviated by C. potent inhibitory effect on 5α-reductase activity by a HaCaT-based
orchioides (Murali and Kuttan, 2016) bioassay and, hence, may be useful in benign prostatic hyperplasia
(Deng et al., 2021).
Antidiabetic activity Ethyl acetate fractions of C. orchioides Gaertn down
Alloxan-induced diabetic rats and glucose-loaded regulated the levels of antiapoptotic Bcl-2 expression and
diabetic rats were shown to be antihyperglycemic with upregulated the expression of apoptotic proteins caspase-3 and
aqueous and ethanol extracts (Chauhan et al., 2007). Using caspase-8 through an intrinsic ROS-mediated mitochondrial
streptozotocin–nicotinamide-induced diabetic nephropathy rats, dysfunction pathway (Hejazi et al., 2018). The plant extract when
extracts of C. Orchiodies using ethanol and hydroalcoholreduced administered in combination with cyclophosphamide enhanced
hyperglycemia-induced lipid changes, oxidative stress, and renal the anticancer properties of cyclophosphamide and ameliorated its
dysfunction (urea, creatinine, and andalbumin) (Singla and Singh, toxic side effects (Murali and Kuttan, 2015). Silver nanoparticles
2020). Curculigo orchioides was shown to inhibit adipogenesis using C. orchioides rhizome extracts showed efficacy against
and enhance glucose uptake in 3T3-L1 adipocytes in an ethanolic human breast cancer cell line (MDA-MB-231) after 48 hours of
extract in a cell-based assay (Gulati et al., 2015). incubation (Kayalvizhi et al., 2016). Polysaccharides from C.
orchioides showed a significant anti-tumor effect on cervical
Anti-microbial activity cancer in vivo and in vitro by enhancement of immune function
As well as being antimicrobial against Bacillus anthracis and induction of apoptosis (Xia et al., 2016).
and Bacillus subtilis, oil of C. orchioides rhizomes inhibited Fusarium
solani, Salmonella newport, Staphylococcus aureus, Salmonella Anti-gout activity
pullorum, and Aspergillus flavus, Fusarium moniliforme, and Two heterocyclic phenolic derivatives, orcinosides I and
Cladosporium species (Jaiswa et al., 1984). The C. orchioides extract J, displayed xanthine oxidase inhibitory activities with IC50 values
prepared by steam distillation process showed antibacterial activity 0.25 and 0.62 mM, respectively. Hence, they may have anti-gout
significantly against several Gram-positive bacteria (Staphylococcus effect (Chen et al., 2017).
epidermidis and S. aureus) and Gram-negative bacteria (Salmonella
typhimurium, Pseudomonas aeruginosa, and Escherichia coli). Anti-hypertensive activity
Antiseptic properties make the extract ideal for preventing bacterial MECO root possesses antihypertensive activity by
infections (Nagesh and Shanthamma, 2009). inhibiting angiotensin-converting enzyme in deoxycorticosterone
With a minimum inhibitory concentration value of 49 acetate salt-induced hypertensive rats (Joshi et al., 2012).
g/ml, C. orchioides alcohol extract inhibited methicillin-resistant
P. aeruginosa, whereas Gram-negative bacteria were not affected Anti-malarial activity
(Marasini et al., 2015). Curculigo orchioides leaf extracts contain Silver nanoparticles using C. orchioides rhizome extracts
phytochemical-loaded silver nanoparticles which are effective showed the highest mortality rate against the malarial vectors such
against S. aureus and P. aeruginosa, but less effective against as Anopheles subpictus and Culex quinquefasciatus (Kayalvizhi
Klebsiella pneumonia and E. coli (Perumal et al., 2017). et al., 2016).
Anti-asthmatic activity CONCLUSION
Goat tracheal chains and guinea pig ileum are relaxed This review aims to summarize the existing
by C. orchioides ethanol extract. Curculigo orchioides ethanol phytochemistry and pharmacological activities of plant C.
extract significantly reduced bronchoconstriction and passive paw orchioides which is a perennial herb, belonging to the family
anaphylaxis in guinea pigs, rats, and mice with haloperidol-induced Amaryllidaceae. The content gives a brief proof of the traditional
catalepsy, suggesting an antiasthmatic effect (Pandit et al., 2008). uses of this plant. The plant is reported to show immuno-modulatory,
anti-oxidant, hepatoprotective, neuroprotective nephrpprotective,
Anti-stress activity anti-inflammatory, anti-gout, anti-arthritis, anti-cancer, anti-
In forced swimming and tail suspension tests, Curculigo microbial, anti-bacterial, anti-malarial, anti-diabetic, anti-stress,
orichioides ethanol extract at 200 mg/kg reduced immobility and antihypertensive activities. These effects may be attributed
times. It increased mobility in actophotometer-based tests. to the anti-oxidant principles present in them. Many authors and
Ethanolic extract of C. orchioides’ rhizomes increased resistance researchers reported the phytochemical, pharmacological, and
to heat [50 and 70 infrared (IR) units] in IR testing and rotarod toxicological results which may provide suitable data for further
testing. It provides strong evidence that ethanolic extracts have scientific research.
antistress activity (Chauhan et al., 2021).
AUTHORS’ CONTRIBUTIONS
Anti-cancer activity All authors made substantial contributions to the
Aqueous fresh root extract and methanolic dried root conception and design, acquisition of data, or analysis and
extract showed significant cytotoxicity activity on the human lung interpretation of data; took part in drafting the article or revising
adenocarcinoma NCI-H-522 cancer cell line. The cytotoxicity may it critically for important intellectual content; agreed to submit
 Bhukta et al. / Journal of Applied Pharmaceutical Science 13 (10); 2023: 083-091 089

to the current journal and agree to be accountable for all aspects Chen X, Zuo A, Deng Z, Huang X, Zhang X, Geng C, Li T, Chen
of the work. All the authors are eligible to be an author as per J. New phenolic glycosides from Curculigo orchioides and their xanthine
the international committee of medical journal editors (ICMJE) oxidase inhibitory activities. Fitoterapia, 2017; 122:144–9.
Deng XL, Zheng RR, Han ZZ, Gu LH, Wang ZT. New
requirements/guidelines.
chlorophenolic glycoside from Curculigo orchioides and their activities on
5α-reductase. J Asian Nat Prod Res, 2021; 23(4):333–40.
FINANCIAL SUPPORT
Ding H, Gao G, Zhang L, Shen G, Sun W, Gu Z, Fan W. The
There is no funding to report. protective effects of curculigoside A on adjuvant-induced arthritis by inhibiting
NF-κB/NLRP3 activation in rats. Int Immunopharmacol, 2016; 30:43–9.
CONFLICTS OF INTEREST Dode PA, Wani NS, Deshmukh TA, Patil VR. Anti-inflammatory
The authors declare no conflicts of interest. activity of hydrogel formulations of Curculigo orchioides Gaertn. rhizomes.
Pharmacology, 2009; 2:1367–81.
ETHICAL APPROVALS Fang Z, Meng Y, Qian W, Si-Cheng W, Wei W, Chang-xiao
L, Bin L, Cai-yun P. Research progress on chemical constituents and
This study does not involve experiments on animals or
pharmacological activities of Curculigo orchioides. Chin Tradit Herbal
human subjects. Drugs, 2020; 51:2238–47.
Ge JF, Gao WC, Cheng WM, Lu WL, Tang J, Peng L, Li N,
DATA AVAILABILITY Chen FH. Orcinol glucoside produces antidepressant effects by blocking
All data generated and analyzed are included in this the behavioural and neuronal deficits caused by chronic stress. Eur
article. Neuropsychopharmacol, 2014; 24:172–80.
Goyal P, Kabra A. A review on phytochemical and
PUBLISHER’S NOTE pharmacological profile on Curculigo orchioides. Plant Cell Biotech Mol
Bio, 2020; 21:243–52.
This journal remains neutral with regard to jurisdictional
Gulati V, Gulati P, Harding IH, Palombo EA. Exploring the
claims in published institutional affiliation. anti-diabetic potential of Australian Aboriginal and Indian Ayurvedic plant
extracts using cell-based assays. BMC Complement Altern Med, 2015; 15:8.
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