Available via license: CC BY 4.0
Content may be subject to copyright.
268
The Journal of Phytopharmacology 2024; 13(3):268-274
Online at: www.phytopharmajournal.com
Review Article
ISSN 2320-480X
JPHYTO 2024; 13(3): 268-274
May- June
Received: 19-05-2024
Accepted: 24-06-2024
©2024, All rights reserved
doi: 10.31254/phyto.2024.13312
Rashmi Goswami
Department of Veterinary Medicine,
C.V.A.Sc., G.B.P.U.A.&T., Pantnagar,
Uttarakhand, India
Damini Arya
Department of Veterinary Gynaecology
and Obstetrics, C.V.A.Sc.,
G.B.P.U.A.&T., Pantnagar,
Uttarakhand, India
Rukkiya Siddiqui
Division of Animal Nutrition, ICAR-
IVRI, Izatnagar, Bareilly, Uttar Pradesh,
India
Priya Chand
Department of Molecular Biology and
Genetic Engineering, C.B.S.H.,
G.B.P.U.A.&T., Pantnagar,
Uttarakhand, India
Correspondence:
Dr. Rukkiya Siddiqui
Division of Animal Nutrition, ICAR-
IVRI, Izatnagar, Bareilly, Uttar Pradesh,
India
Email: rukkiya1995@gmail.com
Unveiling the Medicinal Potential of Berberis aristata: A
Traditional Native Plant of Uttarakhand
Rashmi Goswami, Damini Arya, Rukkiya Siddiqui, Priya Chand
ABSTRACT
Since ancient times, indigenous medicinal system of India has included herbal plants as a traditional
source of medicine. India is known as a rich repository of medicinal plants, and one such plant is
Berberis aristata which belongs to the family Berberidaceae which grows mainly in the sub-Himalayan
region and the Nilgiri Hills of Southern India. Berberis aristata is used as traditional medicine in various
communities to treat eye disorders, piles, osteoporosis, joint pain, skin diseases, malaria, diarrhoea,
dysentery, fever, allergic conditions, ophthalmia, metabolic disorders and during menopause. The plant
contains various phytochemical constituents, mainly alkaloids like berberine, oxyberberine, berbamine,
aromoline, karachine, palmatine, oxyacanthine, and taxilamine. Berberine, the major alkaloid, is found in
roots, stem bark, rhizomes, and leaves, with the highest concentration in the roots. Various
pharmacological properties of Berberis aristata have been reported such as immunomodulatory, anti-
inflammatory, antioxidant, anti-viral, anti-cancer, anti-microbial, hepatoprotective, nephroprotective and
improved reproductive health. This review aims to highlight the phytochemistry and pharmacological
properties of Berberis aristata which will be helpful to give insights on medicinal utility of the plant.
Although more elaborated clinical trials and studies at molecular level will be required to fully
understand and validate these properties.
Keywords: Berberis aristata, Berberine, Berberidaceae, Herbal medicine, Pharmacology,
Phytochemistry.
INTRODUCTION
Long before the pre-historic period different plants have been used for their medicinal properties.
Evidence of using herbs or herbal plants as source of medicine exists in different cultures like by Indian
vaids, Unani hakims, European people, Mediterranean people etc. for over 4000 years. The various
reasons for shifting from the allopathic medicine towards plant material as source of medicine include
side effects of different synthetic drugs, development of drug resistance strains of different
microorganisms, extortionate cost of treatment, inadequate drug supply, rising population and many
more. Thus, since ancient times, the indigenous medicinal system of India has included herbal plants as a
traditional source of medicine as India is known as a rich repository of medicinal plants. One such plant
is Berberis aristata which belongs to the family Berberidaceae which was established in the early 1789
by A.L. Jussieu [1]. It is a hard, spinous and glabrous yellowish evergreen herb which is majorly found
growing in sub-Himalayan region and Nilgiri Hills of Southern India. It has a peak height of 3-5 metres
and is commonly named as Indian barberry, Chitra, Daru Haldi, Daruharidra and Tree turmeric. The bark
of the plant is fully carpeted with thorns and 5-8 leaf tufts with pinnate venation. The upper surface of
leaves is darkish green and lower surface of leaves are mild in colour. The stem and root parts of the
plant Berberis aristata is sold as Daruharidra in India [2]. Berberis aristata is used as a traditional
medicine in different communities. In Bhotiya communities of Himalayan parts of India the root
decoction of this plant is used to cure eye diseases [3]. Traditionally, the aqueous methanolic extract of
this plant have revealed potential to treat osteoporosis, joint pain and menopause [4]. In some rural parts
of India, polyherbal drugs containing Berberis aristata is used to cure piles [5]. In Malani tribal
communities of Himachal Pradesh, it is used in the treatment of disorders such as skin diseases, jaundice,
malaria and piles [6]. The plant extract has been reported to be used as anti-hepatopathic and anti-diabetic
in parts of Sikkim and Darjeeling, India [7]. The leaf and fruit juices are reported to possess anti-
diarrhoeal and anti-dysenteric properties and decoction of root and bark is used in the management of
jaundice and fever [8]. It is reported to be used to treat allergic conditions, ophthalmia, metabolic
disorders and as a laxative [9]. The plant is widely used in the treatment of urinary issues, skin disorders
and pores, syphilis, rheumatism, diarrhoea and it is widely used as a tonic, demulcent, diaphoretic and
diuretic [10].
The Journal of Phytopharmacology
269
The Himalayan region including Uttarakhand has a great variety of
Berberis species (about 29 species) followed by Jammu and Kashmir
(about 25 species), Himachal Pradesh (about 23 species), and Sikkim
(16 species) [11]. Thus, from the wide range of the pharmacological
research it is clear that the Indian barberry possess various properties
such as antioxidant, anti-inflammatory, anti-coagulant, anti-diabetic,
anti-microbial, anti-ulcer, anti-bacterial and anti-cancer [12]. This
review provides a comprehensive overview of the medicinal
significance of Berberis aristata as a valuable medicinal plant with a
rich heritage and significant potential for treating a variety of health
conditions, thereby supporting the growing interest in herbal therapy
as an alternative to conventional medicine.
Phytochemical analysis of the plant
Properties of the plant Berberis aristata also known as Daruharidra
are in close resemblance to those of Curcuma longa (Turmeric) also
known as Haridra, thus both the plants are together mentioned as
Haridra dvaya, meaning two Haridras viz. Haridra and Daruharidra.
Three major types of alkaloids are present in Berberis aristata which
includes bisbenzylisoquinoline, isoquinoline and protoberberine [13].
Berberis aristata is enriched with various phytochemical constituents
which mainly constitute of alkaloids. The various phytochemicals
present in plant of Berberis are berberine, oxyberberine, berbamine,
aromoline, karachine, palmatine, oxyacanthine, taxilamine,
protoberberine and bis isoquinoline [14]. Root of the plant contains
alkaloids such as berbamine, Berberine, oxycanthine, epiberberine,
palmatine, dehydrocaroline, jatrorhizine, karachine dihyrokarachine,
taximaline, oxyberberine, aromoline and columbamine [15]. Different
polyphenolic alkaloids are present in the flower of the plant like
meratin, rutin, quercetin and various acids like chlorogenic acid, E-
caffeic acid etc. [16]. The root bark of the plant contains karachine
which is a protoberberine alkaloid [17]. The major alkaloid present in
Berberis aristata is berberine which possess very important
pharmacological activities and may be present either in roots, stem
bark, rhizomes or leaves followed by palamatine. Berberine
(C20H18NO4) or benzyl tetrahydroxy quinoline is a pale-yellow
quaternary ammonium salt (5,6-dihydrodibenzo[a,g]quinolizinium
derivative) which is obtained from protoberberine group of
isoquinoline alkaloids extracted from Berberis and it is known to
possess different pharmacological activities such as
immunomodulatory, anti-inflammatory, anti-microbial,
hepatoprotective, analgesic, antipyretic and anti-depressant activity
[18]. The biosynthesis of Berberine is shown in Figure 1.
Figure 1: Berberine biosynthesis
HPTLC and spectrophotometric methods were used for detection and
quantification of berberine and it was found that root part of the plant
is more enriched with berberine as compared to the bark [19]. When the
micronutrients of the plant were studied, it was found that rhizome of
the plant is rich in different heavy metals and micronutrients such as
manganese, iron, zinc, chromium, lead, cadmium etc. [20]. HPLC
analysis of hydroalcoholic extract of Berberis aristata and total
berberine content was found to be 6.7% w/w of dry extract [21]. The
HPLC chromatogram indicated presence of berberine chloride as the
main component and the other components were karachine,
aromoline, oxyberberine, oxyacanthine and berbamine in the crude
ethanolic extract of the Berberis aristata roots [22]. When the LCMS
Fragmentation Profile of hydro-ethanolic extract of Berberis aristata
was performed, it showed presence of different alkaloids namely,
Berbamine, Berberine, Jatrorrhizine, Reticuline, Palmatine and
Piperazine [23]. GCMS analysis of aril aqueous extract of Berberis
aristata and two antioxidant compounds were extracted and recorded
viz. flavone (5,7-dihydroxy-3-phenylchromen-4-one) and phytol. In
detail the compounds found in the chromatogram included 2(5H)-
Furanone, Lilac aldehyde C, Davana ether, 2-Propenal, Lilac alcohol
B, Alpha-D-Glucopyranose, n-Hexadecanoic acid, Naphtho[2,1-
b]furan-2,8-dione, Phenol,3-pentadecyl-, 5-Hepten-3-one and 1-
Naphthalenemethanol [12]. The phytochemistry of Berberis aristata is
presented in Table 1.
Table 1: Phytochemistry of Berberis aristate
Phytoconstituents
Part of plant
Reference
(Protoberberine alkaloids): Berbamine, berberine, aromoline, karachine, palmatine,
oxyberberine, jatrorhizine, oxycanthine, epiberberine, and dehydrocaroline
Roots
[72]
Berberine phenoxide, Ketoberberine benzoate A, Ketoberberine benzoate B
Methanolic extract of Berberis aristata stem
bark
Pakistanine, 1-O-methyl pakistanine, pseudopalmatine chloride, pseudoberberine
chloride, isoquinoline and secobisbenzlisoquinoline
Berberis aristata
[73]
Bisbenzylisoquinoline alkaloid (Berbamine)
Berberis aristata roots
[74]
Oxyacanthine and Aromoline
Root and bark of Berberis aristata respectively
[75]
Phytosterol (sitosterolis) Stigmast-5-en-3-ol
Ethanolic extract of Berberis aristata
[76]
Flavonoids: E-caffeic acid, quercetin, meratin, chlorogenic acid and rutin
Flowers of Berberis aristata
[77]
Alkaloids, Steroids, Coumarins, Flavonoids, Terpenoids, Tanins, Glycosides, Saponins,
Acids
Berberis aristata
[78]
Different pharmacological activities of the plant
Berberis aristata is an important medicinal plant and is officially
recorded in Ayurvedic & Siddha Pharmacopoeia of India due to its
various pharmacological properties which are mentioned in the text
below and represented in Figure 2.
The Journal of Phytopharmacology
270
Figure 2: Pharmacological Properties of Berberis aristata
Immunomodulation properties
When the mitogen stimulated lymphocytes were treated with alcoholic
and aqueous extract of Berberis species it was found that the alcoholic
and aqueous extract of Berberis spp. suppress the proliferation of T-
cells and enhance the expansion of B-cells. It is also found that the
constituents present in Berberis spp. can also change the pattern of
cytokine production in lymphocytes for e.g., it can reduce the release
of IFN-γ which may contribute in suppression of T-cell expansion.
There was increase in the levels of IL-4, IL-10 and TGF-β [24]. The
immunomodulatory action of berberine is due to its interaction with
different immune cells like macrophages, T cells, B cells, mast cells,
dendritic cells, epithelial cells, keratinocytes etc. [25]. Also, evidences
are available that berberine can act as an epigenetic regulator by
influencing histone acetylation and methylation [26]. The constituents
of the Berberis spp. are able to promote STAT4 degradation which
leads to significant reduction in IFN-γ T cells [27]. In a study, it was
found that pre-treatment with berberine was able to inhibit the LPS
induced activation of NF-KB/MAPK signalling pathway and thus
inhibiting the production of inflammatory factors, hence, it could be
an effective product from natural plant source like Berberis aristata in
preventing inflammatory diseases caused by LPS [28]. In another
study, it was found that berberine showed anti-inflammatory activity
in primary splenocytes of mouse treated with or without LPS by
increasing the relative expression of IL-4/IL-2 which shifts the
Th1/Th2 balance toward Th2 polarization [29]. It is also hypothesized
that berberine can cause modulation of cytokine expression via
transcriptional and post-transcriptional regulation in Th1 and Th2
cells [30]. In DMBA induced mouse model of tumour, pure berberine
@ 30 mg/kg and Berberis aristata extract @ 400 mg/kg showed
cytoplasmic positivity for TNF-α in the ductal epithelial cells [31].
Anti-inflammatory properties
Inflammation if one of the major types of immune response that plays
a very important role in innate and acquired immune system for
protection from external harmful stimulus [32]. The aqueous extract of
roots of Berberis aristata, when tested in rats at the rate of 500-1000
mg/kg was found to possess anti-inflammatory activity [33]. When a
NOD mouse model was used to study the effect of Berberis spp. It
was found that there was a decrease in the expression ratio of Th1/
Th2 cytokines and reduction in the levels of proinflammatory
cytokines [34]. Berberine alkaloid which is abundant in Berberis
aristata is known to modulate and/or supress inflammation through
supressing the production of TNF-α, IL-6 and MCP-1, down-
regulating the expression of cyclooxygenase-2 (COX-2), reducing
generation of PGE2 and formation of exudates, and inhibiting the
expression of MMP-2 and MMP-9 through nuclear factor-kB (NF-kB)
and mitogen-activated protein kinase (MAPK) signalling cascades [35].
The spleen of an adjuvant-induced arthritis model of rats was taken
and naïve T-cells were isolated and when treated with berberine it
significantly reduced the differentiation and survival of Th17 cells, in
a concentration-dependent manner, through down-regulating surface
marker CD196 and transcription factor RORγt [36]. Berberine is also
able to decrease the phosphorylation of STAT3 and expression of
RORγt transcription factor during the differentiation of Th17 cells and
down-regulate phosphorylation of STAT4 and STAT1 and expression
of T-bet in differentiating Th1 cells [37]. When the splenic naïve T-
cells of the adjuvant-induced arthritis model of rats were treated with
berberine, a shift in differentiation of naïve CD4+ T cells into CD4+
Foxp3+ Treg cells was found, instead of Th17 cells, through
activating AhR/CYP1A1/Foxp3 axis and by this way berberine can
directly benefit the immune system by modulating naïve CD4+ T cells
differentiation [38]. In a mouse model of inflammatory bowel disease
berberine was able to reduce the production of TNF-α, IL-12, IL-6
and TGF-β in the maturated dendritic cells and thus decreasing the
population of Th1/Th17 cells in the mesenteric lymph nodes, and thus
helping in reducing the colon inflammation in colitis-induced mice
model [39].
Hydroalcoholic extract of Berberis aristata at the rate of 200 mg/kg
was found to show anti-inflammatory effect on carrageenan-induced
paw edema and cotton pellet-induced granuloma in rats. There was a
significant reduction in the level of serum inflammatory cytokines viz.
IL-6, IL-10, IL-1β and TNF-α as compared to the control group.
There was significant downregulation in the macrophage expression
of different pro-inflammatory cytokines, IL-6, IL-1β and upregulation
of anti-inflammatory cytokine IL-10. Protein expression of
proinflammatory receptor and TNF-R1 was also decreased along with
decreased expression of pro-inflammatory mediator COX-2 [40].
Berberine led to significant reduction of IL-1, IL-1β, IL-6, IL-12,
TNF-α and IFN-γ in 5% dextran sulfate sodium (DSS) induced
ulcerative colitis rat model. Berberine pre-treatment was able to
induce the mRNA expression of IL-4 and IL-10, decreased the
activity of iNOS (Inducible nitric oxide synthase), MPO
(myeloperoxidase)and MDA (malondialdehyde) and increased in the
level of SIgA [41]. Berberine obtained from Berberis aristata was used
as a prepared formulation of berberine-loaded invasomal gel by the
thin film hydration method which showed a significant analgesic and
anti-arthritic activity in rat model. There was reduction in paw
diameter, proinflammatory biomarkers such as IL-6, IL-10, and TNF-
α in serum were normalized at the end of day 35 which were found to
be increased in disease control group, and decrease in C-reactive
protein in the berberine treated group [42]. When aqueous extract of
bark of Berberis aristata at the dose rate of 400mg/kg was used in
oxazolone sensitized dermatic mice, there was suppression of ear
thickness, significant reduction in the level of TNF-α, IL-6, and IL-1β
and increase in the content of GSH and superoxide dismutase in ear
tissue homogenate [43].
Antioxidant properties
Oxidative stress is considered as the main source for the initiation and
development of different diseases like chronic disorders, heart
diseases, neurodegenerative diseases, cancer, autoimmune disorders,
cataract etc. [44]. The polyherbal ethanolic extract of Berberis aristata,
Nigella sativa and Anethum sowa at the rate of 250 µg/ml have shown
antioxidant effects in H2O2 assay, FRAP assay and ABTS assay with
maximum inhibition rate of 82.56%, 83.77% and 87.5% respectively
[45]. The aril aqueous extract of Berberis aristata showed DPPH
radical scavenging activity of 99.29%, superoxide (O2˙-) radical
scavenging activity of 99.94%, total antioxidant activity of 99.83%
and Ferric (Fe3+) reducing power activity of 99.81% [12]. Methanolic
extract of Berberis aristata showed a significant DPPH radical
scavenging activity, H2O2 radical scavenging activity and reduce the
ferric ions in a concentration dependent manner [46]. In LPS-stimulated
murine macrophages it was found that berberine is able to inhibit NO
production and iNOS expression in a dose-dependent manner [47].
Polyherbal preparation containing Berberis aristata and the hydro-
alcoholic extract of Berberis aristata showed a significant percent
scavenging of DPPH, ABTS, superoxide radical and nitric oxide (NO)
[48].
The Journal of Phytopharmacology
271
Berberis spp. inhibit the production of TBARS, lowered NO levels
and inhibited the oxidation of DPPH along with increase in
glutathione peroxidase and superoxide dismutase activities [49]. When
diabetic rats were administered the root extract of Berberis aristata
the activity of superoxide dismutase and catalase increased by 90.32%
and 41.04%, respectively along with improvement in the levels of
glutathione peroxidase, glutathione reductase, improved level of
reduced glutathione. There was decrease in the levels of
TBARS/MDA and protein carbonyl content by 48.53% and 30.13%,
respectively [50]. When the heat stressed quails were treated with the
root extract of Berberis spp. there was a decrease in the level of MDA
by 25.5% and increase in the activity of superoxide dismutase,
catalase and glutathione peroxidase by 23·5%, 35·4% and 55·7 %,
respectively. The expression of hepatic NF-kB and HSP70 decreased
whereas hepatic Nrf2 and HO-1 increased [51]. Hydroalcoholic extract
of Berberis aristata at a dose rate of 100 and 200 mg/kg was able to
successfully manage adjuvant induced arthritis model and was able to
normalize the levels of endogenous antioxidants viz. glutathione,
catalase and superoxide dismutase and decreased the level of
prooxidants viz. TBARS and NO [21].
Anti-viral properties
In a Haemagglutination Inhibition test, it was found that Berberis
aristata extract (upto a dilution of 62.5µg/ml) is able to combat
Paramoxyviridae infection by interacting with the receptors present in
the erythrocytes of Gallus gallus domesticus (host) in the microtiter
plate. Vero cell lines which were having antiviral activity for 4HA
viral concentration were used to perform the cytotoxicity assay and it
was found that at a concentration of 62.5µg/ml of Berberis aristata
extract the cell viability percentage was 92.8% and the higher cell
viability percentage means less threat of toxicity [52].
Anti-cancer activity
Berberine which is the main phytochemical present in Berberis spp.
has a proven anti-cancerous activity. Berberine was able to induce
apoptosis in prostate cancer cell lines LNCaP (p53 expressing) and
PC-3 (p53 lacking) by arresting cell cycle at G0/G1 phase and
decreasing the levels of G0/G1 regulatory proteins in p53-dependent
cell growth [53]. Berberine has a cytotoxic effect on murine melanoma
cell line/ B16 and human tumour cell line/ U937 [54]. Berberine has
also shown a selective cytotoxic effect on mitochondria in the
melanoma cell line/ K1735-M2 [55]. Methanolic extract of the stem of
the Berberis aristata is efficient in the treatment of human breast
cancer cell line (MCF-7). It was able to inhibit the proliferation of the
cancer cells, inhibition of DNA synthesis and prevention of metastasis
due to activation of apoptosis pathways [56]. The methanolic extract of
Berberis aristata at the rate of 400 mg/kg is able to show a significant
antitumor activity and it provides additional benefits such as
increasing the haemoglobin and RBC count towards normal.
Berberine is able to inhibit the tumour cell target along with good
proapoptotic and cell cycle arrest properties. In DMBA induced
mouse model of tumour, berberine at the rate of 30 mg/kg and
Berberis aristata extract at the rate of 400 mg/kg shows significant
improvement in tumour pathology [31]. Berberine when used @ 0.5,
2.5 and 5 mg/kg body weight was effective for significantly reducing
the incidence of tumor in carcinogenesis induced (by using 20-
methylcholanthren or N-nitrosodiethylamine) mouse model. Berberine
extract at a concentration of 200 μg/ml showed cytotoxicity activity as
high as 32.81% against HeLa cell lines and the IC50 of the tested
sample of the Berberine extract against HeLa cell line was 118.97
μg/ml [12]. Berberine which is a major alkaloid present in the Berberis
aristata plant has a planar quaternary and highly aromatic structure
and has the ability to intercalate with the DNA and inhibition of
protein biosynthesis, which may be responsible for the observed
cytotoxic effect [57]. In a study, it was found that the polyherbal
formulation containing Berberis aristata plant as a component have a
high anticancer activity when assessed by using MTT assay against
MCF 7 cells in a concentration dependent manner and the IC50 value
of the herbal extract was found to be 181.97 µg [45]. Thus, the plant
extract containing Berberis aristata have a potent anticancer activity.
Anti-microbial activity
The aril aqueous extract of Berberis aristata plant at a concentration
of 500 µg when tested for the in vitro antibacterial action against
some gram-positive microbes like Bacillus subtilis, Micrococcus
luteus, Staphylococcus aureus and some gram-negative microbes like
Escherichia coli, Shigella flexneri expressed a zone of inhibition of 10
mm, 12 mm, 27 mm, 24 mm and 22 mm respectively which was
found significantly effective as that of standard drug [12]. The aqueous
extract of root and bark of Berberis aristata plant exhibit a broad
spectrum of anti-bacterial potential and zone of inhibition ranging
from 12-25 mm. The most susceptible organism was Klebsiella
pneumoniae followed by Staphylococcus aureus, MRSA, Salmonella
typhimurium 2 and Staphylococcus epidermidis. Enterococcus
faecalis was found to be the least sensitive organism, whereas
Klebsiella pneumoniae 2, Shigella fexneri and Salmonella
typhimurium 1 were found completely resistant to the extract of the
plant. A cytotoxic effect was found against the L20B, RD and Hep2
cell lines with IC50 ranging from 245 to 473 µg/mL [58]. Berberine
isolated from methanolic extract of stem of Berberis aristata was
found to be potentially active against drug resistant Helicobacter
pylori infection which was isolated from gastroesophageal reflux
disease patients with no previous antimicrobial therapy and this
extract was found to be effective at a concentration of 0.000075
μg/ml. Thus, anti-Helicobacter pylori activity of the berberine
alkaloid may be beneficial for the treatment of ulcer mediated by
Helicobacter pylori [59].
Anti-plasmodial activity of the aqueous extract of roots of Berberis
aristata was checked against Plasmodium berghei NK-65 (lethal
rodent malarial parasite) infected BALB/c mice and it was found
effective at higher doses and the IC50 value for in vitro anti-
plasmodial activity was found to be 40 µg/mL. In in vivo studies
chemosuppression was found to be variable in a dose dependent
manner with higher efficacy at lower doses and a dose rate of 350
mg/kg/day was found to have a 67.1% suppressive activity and 53.9%
preventive activity and the mean survival period was improved to 12.8
days in treated mice versus 7.5 days in untreated mice [60]. Berberis
aristata showed a 91.3% anti-adhesion activity, 96.06% anti-Quorum
sensing and 51.3% anti-Biofilm formation
against Carbapenem Resistant Escherichia coli and thus attenuating
its virulence [61]. The extract of Berberis aristata significantly
inhibited H2O2 induced haemolysis. Significant annihilation of
bacterial infectivity was seen by inhibition of binding of
Carbapenem Resistant Escherichia coli to RBC membrane receptors
thus inhibiting hemagglutination at a concentration of 25 mg/mL. It
also showed bactericidal activity by damaging the bacterial cell
membrane as seen in flow cytometry analysis [23]. A polyherbal
preparation containing Berberis aristata when given at a dose rate of
800mg/kg/day was used to treat induced amoebic liver abscess in
golden hamsters with a cure rate of 73% [62].
Anti-hyperglycaemic effect
In alloxan induced diabetic rats the ethanolic root extract of Berberis
aristata plant was able to significantly lower the body weight and
significant reduction of fasting blood glucose level [50]. In alloxan
induced diabetic rats the ethanolic root extract of Berberis aristata
was found to possess significant anti-diabetic effect at the rate of 50
mg/kg and 100 mg/kg body weight with 63.01% and 66.27%
reduction in blood glucose level respectively when compared to
diabetic control. It was also found that in plant extract treated group
the level of total cholesterol and triglycerides were in control at a
significant level as compared to the diabetic control. The serum level
of alanine aminotransferase and aspartate aminotransferase were
found to be significantly reduced in the plant extract treated group. It
was also found that the levels of marker of diabetic nephropathy viz.
blood urea nitrogen and serum creatinine were in control after
The Journal of Phytopharmacology
272
administration of the extract [63]. The significant antidiabetic effect of
the plant extract may be due to dipeptidyl peptidase-IV (DPP-IV)
inhibition [64]. In a study conducted, methanolic extract of Berberis
aristata was found to have DPP-IV inhibition activity with an IC50
value of 14.46 µg/ml as compared to the standard Diprotin A which
showed an IC50 value of 1.543 µg/ml [65]. The aqueous extract of
Berberis aristata showed hypoglycemic activity in different in vitro
assays as it showed increased glucose adsorption and inhibitory
effects on movement of glucose into external solution in amylolysis
kinetic experimental model and increased glucose uptake by the yeast
cells [66].
Reproductive Potential
When Berberis aristata extract was given at the rate of 500 mg/kg for
a period of 45 days in high fat diet induced obesity related
reproductive changes in female wistar rats, there was a significant
decrease in total cholesterol, triglycerides, insulin, leptin, visceral fat
and body weight and a significant increase in the levels of estradiol
when compared to the untreated rats. There was significant
improvement in the levels of oxidative stress biomarkers like
malondialdehyde levels, reduced glutathione levels, NO and
superoxide dismutase levels after treatment with the plant extract [67].
Hepatoprotective activity
The ethanolic extract of stem bark of Berberis aristata when given at
the rate of 100 mg/kg bwt and 300 mg/kg body weight in high dose
carbon tetrachloride (CCl4) induced hepatotoxicity model in albino
wistar rats was able to reduce the levels of different liver specific
parameters such as direct bilirubin, total bilirubin, alanine
transaminase, aspartate transaminase and alkaline phosphatase which
were raised above the normal range in the positive control liver
damaged group [68]. When berberine chloride was given in
intraperitoneal CCl4 induced hepatic damage model in rats, it showed
preventive as well as curative hepatoprotective effects as there was a
significant reduction in the level of alanine transaminase, aspartate
transaminase and alkaline phosphatase in dose dependent manner [69].
In Rifampicin-Isoniazid (50mg/kg body weight each) induced
hepatotoxicity model in rats, the Berberis aristata plant given at the
rate of 50mg/kg body weight showed curative effects. In plant treated
group there was significant increase in the values of total protein and
reduction in elevated liver specific enzymes viz. aspartate
aminotransferase and alanine aminotransferase, alkaline phosphatase
[70].
Nephroprotective
The decoction of root bark of Berberis aristata is found to be effective
against cisplatin induced urinary trouble or nephrotoxicity as it was
able to reverse the side effects of cisplatin due to its antioxidative
properties [71]. Ethanolic root extract of Berberis aristata was able to
down regulate the mRNA expression of antioxidant and proliferative
markers i.e., p53, p21, Cas 4, Cas 5, Cas 9, and Cyt-c in vancomycin
induced nephrotoxicity model in vero cells which were upregulated in
the vancomycin group without any treatment [22].
CONCLUSION
From the above review it can be concluded that Berberis aristata is a
valuable medicinal plant with a rich heritage and significant potential
for treating various health conditions on the basis of indigenous
traditional knowledge as well as scientific studies. The various
phytoconstituents present in the plant make it a good source of
antioxidants. Its diverse pharmacological properties and studies shows
that it has good immunomodulatory, anti-inflammatory, antioxidant,
anti-viral, anti-cancer, anti-microbial, anti-hyperglycaemic,
hepatoprotective and nephroprotective activity. These properties make
it a suitable plant for herbal therapy as an alternative to conventional
medicine. Further research and clinical studies are essential to fully
explore and validate the therapeutic potential of this traditional plant.
Conflict of interest
The authors declared no conflict of interest.
Financial Support
None declared.
REFERENCES
1. Srivastava S, Srivastava M, Misra A, Pandey G, Rawat A. A
review on biological and chemical diversity in Berberis
(Berberidaceae). EXCLI journal. 2015;14:247-267.
2. Murad HM, Abdulameer SA, Aljuboory DS, Neamah DA,
Maktouf AH. Defensive effects of breberine against
cypermethrin induced male reproductive system toxicity in
rabbits. Systematic Reviews in Pharmacy. 2020;11(9):841-
846.
3. Phondani PC, Maikhuri RK, Rawat LS, Farooquee NA,
Kala CP, Vishvakarma SR, et al. Ethnobotanical uses of
plants among the Bhotiya tribal communities of Niti Valley
in Central Himalaya, India. Ethnobotany Research and
Applications. 2010;8:233-244.
4. Yogesh HS, Chandrashekhar VM, Katti HR, Ganapaty S,
Raghavendra HL, Gowda GK, et al. Anti-osteoporotic
activity of aqueous-methanol extract of Berberis aristata in
ovariectomized rats. Journal of ethnopharmacology.
2011;134(2):334-338.
5. Saraf G, Mitra A, Kumar D, Mukherjee S, Basu A. Role of
nonconventional remedies in rural India. International
Journal of Pharmacy and Life Sciences. 2010;1(3):141-159.
6. Sharma PK, Chauhan NS, Lal B. Studies on plant associated
indigenous knowledge among the Malanis of Kullu district,
Himachal Pradesh. Indian Journal of Traditonal
Knowledege. 2005;4(4):403-408.
7. Chhetri DR, Parajuli P, Subba GC. Antidiabetic plants used
by Sikkim and Darjeeling Himalayan tribes, India. Journal
of Ethnopharmacology. 2005;99(2):199-202.
8. Kunwar RM, Adhikari N. Ethnomedicine of Dolpa district,
Nepal: the plants, their vernacular names and uses. Lyonia.
2005;8(1):43-49.
9. Joshi AR, Joshi K. Ethnomedicinal plants used against skin
diseases in some villages of Kali Gandaki, Bagmati and
Tadi Likhu watersheds of Nepal. Ethnobotanical leaflets.
2007;(1):27.
10. Chander V, Aswal JS, Dobhal R, Uniyal DP. A review on
Pharmacological potential of Berberine; an active
component of Himalayan Berberis aristata. Journal of
Phytopharmacology. 2017;6(1):53-58.
11. Sharma S, Gupta S, Dhar MK, Kaul S. Diversity and
bioactive potential of culturable fungal endophytes of
medicinal shrub Berberis aristata DC.: a first report.
Mycobiology. 2018;46(4):370-381.
12. Sharmila KJ, Monisha SM, Beevi AA, Deebarathi V.
Antibacterial, antioxidant, anticancer effects and GCMS
analysis of Berberis aristata. Biomedicine. 2020;40(3):286-
293.
13. Imenshahidi M, Hosseinzadeh H. Berberine and barberry
(Berberis vulgaris): a clinical review. Phytotherapy
Research. 2019;33(3):504-523.
14. Ambastha SP. The Wealth of India. Publication and
Information Directorate, New Delhi, CSIR 1988;2:118.
15. Saied S, Batool S, Naz S. Phytochemical studies of Berberis
aristata. Journal of Basic and Applied Sciences. 2007:1-3.
16. Sivakumar R, Kamachandran Nair AG. Polyphenolic
constituents of the flowers of Berberis aristata. Journal of
the Indian Chemical Society. 1991;68(9):531-532.
17. Blasko G, Murugesan N, Freyer AJ, Shamma M, Ansari
AA. Karachine: an unusual protoberberine alkaloid. Journal
of the American Chemical Society. 1982;104(7):2039-2041.
The Journal of Phytopharmacology
273
18. Shahid M, Rahim T, Shahzad A, Latif TA, Fatma T, Rashid
M, et al. Ethnobotanical studies on Berberis aristata DC.
root extracts. African Journal of Biotechnology.
2009;8(4):556-563.
19. Andola HC, Rawal RS, Rawat MS, Bhatt ID, Purohit W.
Analysis of berberine content using HPTLC fingerprinting
of root and bark of three Himalayan Berberis species. Asian
Journal of Biotechnology. 2010;2:239-245.
20. Meena AK, Bansal P, Kumar S, Rao MM, Garg VK.
Estimation of heavy metals in commonly used medicinal
plants: a market basket survey. Environmental monitoring
and assessment. 2010;170(1):657-660.
21. Kumar R, Nair V, Gupta YK, Singh S, Arunraja S. Berberis
aristata ameliorates adjuvant-induced arthritis by inhibition
of NF-κB and activating nuclear factor-E2-related factor
2/hem oxygenase (HO)-1 signaling pathway.
Immunological investigations. 2016b;45(6):473-489.
22. Malkani N, Sohail MI, Ijaz F, Naeem A, Mumtaz S, Saeed
Z. Berberis aristata reduces vancomycin-induced
nephrotoxicity by down-regulation of cell proliferation
markers. Journal of Herbal Medicine. 2022;31:100540.
23. Thakur P, Chawla R, Narula A, Goel R, Arora R, Sharma
RK. Anti-hemolytic, hemagglutination inhibition and
bacterial membrane disruptive properties of selected herbal
extracts attenuate virulence of Carbapenem Resistant
Escherichia coli. Microbial pathogenesis. 2016a;95:133-
141.
24. Fateh S, Dibazar SP, Daneshmandi S. Barberry's (Berberis
integerrima) ingredients suppress T-cell response and shift
immune responses toward Th2: an in vitro study. Future
Science OA. 2015; 1(4):FSO49.
25. Ehteshamfar SM, Akhbari M, Afshari JT, Seyedi M, Nikfar
B, Shapouri‐Moghaddam A, Ghanbarzadeh E, Momtazi‐
Borojeni AA. Anti‐inflammatory and immune‐modulatory
impacts of berberine on activation of autoreactive T cells in
autoimmune inflammation. Journal of cellular and
molecular medicine. 2020;24(23):13573-13588.
26. Wang Z, Liu Y, Xue Y, Hu H, Ye J, Li X, et al. Berberine
acts as a putative epigenetic modulator by affecting the
histone code. Toxicology In Vitro. 2016;36:10-17.
27. Ren Y, Lu L, Guo TB, Qiu J, Yang Y, Liu A, et al. Novel
immunomodulatory properties of berbamine through
selective down-regulation of STAT4 and action of IFN-γ in
experimental autoimmune encephalomyelitis. The Journal
of Immunology. 2008;181(2):1491-1498.
28. Zhu Z, Xueying L, Chunlin L, Wen X, Rongrong Z, Jing H,
et al. Effect of berberine on LPS-induced expression of NF-
κB/MAPK signalling pathway and related inflammatory
cytokines in porcine intestinal epithelial cells. Innate
immunity. 2020;26(7):627-634.
29. Lin WC, Lin JY. Berberine down-regulates the Th1/Th2
cytokine gene expression ratio in mouse primary
splenocytes in the absence or presence of
lipopolysaccharide in a preventive manner. International
Immunopharmacology. 2011;11(12):1984-1990.
30. Cheadle C, Fan J, Cho-Chung YS, Werner T, Ray J, Do L,
Gorosspe M, Becker KG. Control of gene expression during
T cell activation: alternate regulation of mRNA
transcription and mRNA stability. BMC genomics.
2005;6:1-6.
31. Mazhar M, Agrawal SS. Standardization of Berberis aristata
DC and Nigella sativa L. using HPTLC and GCMS and
their anti-neoplasia activity in 7, 12-dimethylbenz [a]
anthracene-induced mouse models. Frontiers in
Pharmacology. 2021;12:642067.
32. Grivennikov SI, Greten FR, Karin M. Immunity,
inflammation, and cancer. Cell. 2010;140(6):883-899.
33. Chaudhari VM, Kokate KK. A comprehensive review of
daruharidra. International Journal of Research in Ayurveda
and Medical Sciences. 2018;1:153-159.
34. Chueh WH, Lin JY. Protective effect of isoquinoline
alkaloid berberine on spontaneous inflammation in the
spleen, liver and kidney of non-obese diabetic mice through
downregulating gene expression ratios of pro-/anti-
inflammatory and Th1/Th2 cytokines. Food Chemistry.
2012 15;131(4):1263-1271.
35. Kuo CL, Chi CW, Liu TY. The anti-inflammatory potential
of berberine in vitro and in vivo. Cancer letters.
2004;203(2):127-137.
36. Tong B, Yuan X, Dou Y, Wu X, Chou G, Wang Z, et al.
Norisoboldine, an isoquinoline alkaloid, acts as an aryl
hydrocarbon receptor ligand to induce intestinal Treg cells
and thereby attenuate arthritis. The International Journal of
Biochemistry & Cell Biology. 2016;75:63-73.
37. Liu X, Zhang X, Ye L, Yuan H. Protective mechanisms of
berberine against experimental autoimmune myocarditis in a
rat model. Biomedicine & Pharmacotherapy. 2016;79:222-
230.
38. Dinesh P, Rasool M. Berberine mitigates IL-21/IL-21R
mediated autophagic influx in fibroblast-like synoviocytes
and regulates Th17/Treg imbalance in rheumatoid arthritis.
Apoptosis. 2019;24(7):644-661.
39. Kawano M, Takagi R, Kaneko A, Matsushita S. Berberine
is a dopamine D1-and D2-like receptor antagonist and
ameliorates experimentally induced colitis by suppressing
innate and adaptive immune responses. Journal of
Neuroimmunology. 2015;15:289:43-55.
40. Kumar R, Gupta YK, Singh S. Anti-inflammatory and anti-
granuloma activity of Berberis aristata DC. in experimental
models of inflammation. Indian journal of pharmacology.
2016a Mar 1;48(2):155-61.
41. Zhu L, Gu P, Shen H. Protective effects of berberine
hydrochloride on DSS-induced ulcerative colitis in rats.
International Immunopharmacology. 2019;68:242-251.
42. Jain S, Tripathi S, Tripathi PK. Antiarthritic potential of
berberine loaded invasomal gel. Phytomedicine Plus. 2022;
2(4):100373.
43. Shinde SD, Cheke RS, Tathe PR, Jain PG, Narkhede RR.
The Berberis aristata ameliorates oxazolone induced contact
dermatitis: In-vivo and in silico evidences. Advances in
Traditional Medicine. 2021;21:685-692.
44. Costa RM, Magalhães AS, Pereira JA, Andrade PB,
Valentão P, Carvalho M, et al. Evaluation of free radical-
scavenging and antihemolytic activities of quince (Cydonia
oblonga) leaf: a comparative study with green tea (Camellia
sinensis). Food and Chemical toxicology. 2009;47(4):860-
865.
45. Suchitra MR, Sulthana RM, Sivakumar R, Parthasarathy. In
Vitro Antioxidant And Anticancer Activity Of Nigella
Sativa, Anethum Sowa And Berberis Aristata Herbal
Formulation Using MCF-7 Cell Line. Journal of
Pharmaceutical Negative Results. 2022;13(2):40-45.
46. Bhatt LR, Wagle B, Adhikari M, Bhusal S, Giri A, Bhattarai
S. Antioxidant activity, total phenolic and flavonoid content
of Berberis aristata DC. and Berberis thomsoniana CK
Schneid. from Sagarmatha National Park, Nepal.
Pharmacognosy Journal. 2018;10(6).167-171.
47. Lee DU, Kang YJ, Park MK, Lee YS, Seo HG, Kim TS,
Kim CH, Chang KC. Effects of 13-alkyl-substituted
berberine alkaloids on the expression of COX-II, TNF-α,
iNOS, and IL-12 production in LPS-stimulated
macrophages. Life sciences. 2003;73(11):1401-1412.
48. Joshi P, Yadaw GS, Joshi S, Semwal RB, Semwal DK.
Antioxidant and anti-inflammatory activities of selected
medicinal herbs and their polyherbal formulation. South
African journal of botany. 2020;130:440-447.
49. El-Wahab AE, Ghareeb DA, Sarhan EE, Abu-Serie MM, El
Demellawy MA. In vitro biological assessment of Berberis
vulgaris and its active constituent, berberine: antioxidants,
anti-acetylcholinesterase, anti-diabetic and anticancer
The Journal of Phytopharmacology
274
effects. BMC complementary and alternative medicine.
2013;13:1-2.
50. Singh J, Kakkar P. Antihyperglycemic and antioxidant
effect of Berberis aristata root extract and its role in
regulating carbohydrate metabolism in diabetic rats. Journal
of ethnopharmacology. 2009;123(1):22-26.
51. Sahin K, Orhan C, Tuzcu M, Borawska MH, Jabłonski J,
Guler O, et al. Berberis vulgaris root extract alleviates the
adverse effects of heat stress via modulating hepatic nuclear
transcription factors in quails. British Journal of Nutrition.
2013;110(4):609-616.
52. Shreenivasan YS, Keerthana S, Praveena A, Dhasarathan P.
Revealing Berberis aristata potential as an anti-viral agent to
combat Paramyxoviridae infection. Journal of
Environmental Biology. 2022;43(4):520-526.
53. Choi MS, Oh JH, Kim SM, Jung HY, Yoo HS, Lee YM,
Moon DC, Han SB, Hong JT. Berberine inhibits p53-
dependent cell growth through induction of apoptosis of
prostate cancer cells. International Journal of oncology.
2009;34(5):1221-1230.
54. Seo YS, Yim MJ, Kim BH, Kang KR, Lee SY, Oh JS, et al.
Berberine-induced anticancer activities in FaDu head and
neck squamous cell carcinoma cells. Oncology Reports.
2015;34(6):3025-3034.
55. Rad SZK, Rameshrad M, Hosseinzadeh H. Toxicology
effects of Berberis vulgaris (barberry) and its active
constituent, Berberine: a review. Iranian Journal of Basic
Medical Sciences. 2017;20(5):516-529.
56. Vijayakumar S, Bhuvaneshwari V, Sumathi A. Antioxidant
and anticancer potential of methanolic leaf extract of
Moringa concanensis Nimmo against human breast cancer
cell line MCF-7. International Journal of Pharmacognosy
and Phytochemical Research. 2017;9(6):750-754.
57. Merschjohann K, Sporer F, Steverding D, Wink M. In vitro
effect of alkaloids on bloodstream forms of Trypanosoma
brucei and T. congolense. Planta Medica. 2001;67(7):623-
627.
58. Sood H, Kumar Y, Gupta VK, Arora DS. Scientific
validation of the antimicrobial and antiproliferative potential
of Berberis aristata DC root bark, its phytoconstituents and
their biosafety. AMB Express. 2019;9:1-6.
59. Das S, Das MK, Das R, Gehlot V, Mahant S, Mazumder
PM, Das S, Falls N, Kumar V. Isolation, characterization of
Berberine from Berberis aristata DC for eradication of
resistant Helicobacter pylori. Biocatalysis and agricultural
biotechnology. 2020; 1;26:101622.
60. Chandel S, Bagai U, Semwal RB, Semwal DK.
Antiplasmodial activity of aqueous extract of Berberis
aristata roots against Plasmodium berghei-infected BALB/c
mice. Pharmaceutical biology. 2015;53(12):1735-1740.
61. Thakur P, Chawla R, Tanwar A, Chakotiya AS, Narula A,
Goel R, et al. Attenuation of adhesion, quorum sensing and
biofilm mediated virulence of carbapenem resistant
Escherichia coli by selected natural plant products.
Microbial pathogenesis. 2016b;92:76-85.
62. Sohni YR, Bhatt RM. Activity of a crude extract
formulation in experimental hepatic amoebiasis and in
immunomodulation studies. Journal of ethnopharmacology.
1996;54(2-3):119-124.
63. Mittal M, Juyal V, Singh A. Phytochemical, antidiabetic,
and cytoprotective properties of Berberis aristata DC. root
extracts. Pharmaceutical Crops. 2012;3(1):64-68.
64. Thirumurgan K, Chakrabarti R, Singh B, Prakrith N,
Varghese N, Shihabudeen MS. Dipeptidyl peptidase-IV
inhibitory activity of Berberis aristata. Journal of natural
products. 2011;4:158-163.
65. Chakrabarti RC, Singh Bhavtaran SB, Prakrith Narendra
PN, Nimisha Varghese NV, Lalthanzama Vanchhawng LV,
Shihabudeen HM, Kavitha Thirumurgan KT. Dipeptidyl
peptidase-IV inhibitory activity of Berberis aristata. Journal
of Natural Products. 2011;4:158-163.
66. Bhutkar MA, Bhinge SD, Randive DS, Wadkar GH.
Hypoglycemic effects of Berberis aristata and Tamarindus
indica extracts in vitro. Bulletin of Faculty of Pharmacy,
Cairo University. 2017;1;55(1):91-104.
67. Mushtaq F, Akhtar MF, Saleem A, Sharif A, Akhtar B,
Askary AE, et al. Berberis aristata DC Extract Counteracts
the High Fat Diet-Induced Reproductive Toxicity in Female
Wistar Rats via Modulating Oxidative Stress and Resistance
to Leptin and Insulin. Endocrine, Metabolic & Immune
Disorders-Drug Targets (Formerly Current Drug Targets-
Immune, Endocrine & Metabolic Disorders).
2022;22(14):1390-1402.
68. Rathi B, Sahu J, Koul S, Khosa R, Raghav P.
Hepatoprotective activity of ethanolic extract of stem bark
of Berberis aristata against carbon tetrachloride (CCl4).
International Journal of Pharmaceutical Sciences.
2015;1(2):43-45.
69. Dehar N, Walia R, Verma RB, Pandey P. Evaluation of
Hepatoprotective Activity of Berberis Aristata Root Extract
against Chemical-induced Acute Hepatotoxicity in Rats.
Current Overview on Pharmaceutical Science. 2023;2:126-
136.
70. Thalla S. Hepatoprotective Activity Of A Combination Of
Hydroalcoholic Extracts Of Berberis Aristata And
Cichorium Intybus. Linn On Rifampicin-Isoniazid Induced
Hepatic Damage In Rats. Journal of Pharmaceutical
Negative Results. 2022;13(9):4038-4044.
71. Sreedevi A, Bharathi K, Prasad KV. Effect of decoction of
root bark of Berberis Aristata against cisplatin induced
nephrotoxicity in rats. International Journal of Pharmacy
and Pharmaceutical Sciences. 2010;2(3):51-56.
72. Ahamad J, Naquvi K, Ali M, Mir S. ChemInform Abstract:
new isoquinoline alkaloids from the stem bark of B.
Aristata. Indian Journal of Chemistry. 2015;46(17):1237-
1241.
73. Pfoze NL, Myrboh B, Kumar Y, Rohman MR. Isolation of
protoberberine alkaloids from stem bark of Mahonia
manipurensis Takeda using RP-HPLC. Journal of Medicinal
Plants Studies. 2014;2(2):48-57.
74. Zhu H, Ruan S, Jia F, Chu J, Zhu Y, Huang Y, et al. In vitro
and in vivo superior radiosensitizing effect of berbamine for
head and neck squamous cell carcinoma. OncoTargets and
therapy. 2018;14:8117-8125.
75. Khan I, Najeebullah S, Ali M, Shinwari ZK.
Phytopharmacological and ethnomedicinal uses of the
Genus Berberis (Berberidaceae): A review. Tropical Journal
of Pharmaceutical Research. 2016;15(9):2047-2057.
76. Katiyar, D., Singh, V., Gilani, S., Goel, R., Vats, A., Bajaj,
U. Isolation and characterization of stigmast-5-en-3-ol from
heartwood of B. Aristata. International Journal of Drug
Development and Research. 2013;6:92-98.
77. Bhardwaj D, Kaushik N. Phytochemical and
pharmacological studies in genus Berberis. Phytochemistry
reviews. 2012;11:523-542.
78. Thusa R, Mulmi S. Analysis of phytoconstituents and
biological activities of different parts of Mahonia nepalensis
and Berberis aristata. Nepal Journal of Biotechnology.
2017;5(1):5-13.
HOW TO CITE THIS ARTICLE
Goswami R, Arya D, Siddiqui R, Chand P. Unveiling the Medicinal
Potential of Berberis aristata: A Traditional Native Plant of Uttarakhand.
J Phytopharmacol 2024; 13(3):268-274. doi: 10.31254/phyto.2024.13312
Creative Commons (CC) License-
This article is an open access article distributed under the terms and conditions of the
Creative Commons Attribution (CC BY 4.0) license. This license permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited. (http://creativecommons.org/licenses/by/4.0/).