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Unveiling the Medicinal Potential of Berberis aristata: A Traditional Native Plant of Uttarakhand

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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.
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].
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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.
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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- 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-
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].
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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
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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.
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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
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Berberine is an alkaloid extracted from medicinal plants such as Coptis chinensis and Phellodendron chinense. It possesses anti-inflammatory, anti-tumour and anti-oxidation properties, and regulates Glc and lipid metabolism. This study explored the mechanisms of the protective effects of berberine on barrier function and inflammatory damage in porcine intestinal epithelial cells (IPEC-J2) induced by LPS. We first evaluated the effects of berberine and LPS on cell viability. IPEC-J2 cells were treated with 5 μg/ml LPS for 1 h to establish an inflammatory model, and 75, 150 and 250 μg/ml berberine were used in further experiments. The expression of IL-1β, IL-6 and TNF-α was measured by RT-PCR. The key proteins of the NF-κB/MAPK signalling pathway (IκBα, p-IκBα, p65, p-p65, c-Jun N-terminal kinase (JNK), p-JNK, p38, p-p38, ERK1/2 and p-ERK1/2) were detected by Western blot. Upon exposure to LPS, IL-1β, IL-6 and TNF-α mRNA levels and p-IκBα p-p65 protein levels were significantly enhanced. Pre-treatment with berberine reduced the expression of inflammatory factors and was positively correlated with its concentration, and dose dependently inhibited the expression of IκBα, p-IκBα, p-p65, p-p38 and JNK. These results demonstrated that pre-treating intestinal epithelial cells with berberine was useful in preventing and treating diarrhoea induced by Escherichia coli in weaned pigs.
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Background Numerous plants and plant isolates have been widely reported for the treatment of arthritis. Berberine, a cationic flavonoid, obtained from Berberis aristata DC. (Berberidaceae) has been well reported for the treatment of arthritis. The lipid-based vesicular system including invasomes overcome the stratum corneum barrier and can effectively deliver drugs beneath the skin. Methods The aim of the present study is to prepare berberine-loaded invasomes by the thin film hydration method. Prepared berberine-loaded invasomes were characterised for particle size and shape, zeta potential, entrapment efficiency, and skin permeation studies. These prepared berberine-loaded invasomes were further utilizesd for the preparation of gel containing carbomer for transdermal delivery. Prepared berberine-loaded invasomal gel was evaluated for homogeneity, viscosity, pH, speradability, extrudability, drug content, skin irritant and stability studies. Results The in vivo analgesic activity of prepared berberine-loaded invasomal gel using the tail-flick hotwater immersion method, revealed potential analgesic activity for a prolonged period of time. Furthermore, the anti-arthritic activity of berberine-loaded invasomal gel was evaluated in CFA-induced arthritis rat model by measuring paw diameter, which showed a considerable reduction after treatment, as compared to standard gel (omnilgel, 0.1%). Topical application of berberine-loaded invasomal gel improves haematological factors and normalizes proinflammatory biomarkers. The radiographical analysis of hind paw rats in CFA model showed bone resorption, definite joint gap reduction, and considerable connective tissue expansion after treatment with prepared berberine-loaded invasomal gel. Histopathological examination of ankle joints also confirms the deeper penetration ability of invasomes through berberine-loaded invasomal gel and produces profound effects. Conclusion The results revealed that the berberine-loaded invasomal gel has significant arthritic activity in the CFA rat model.
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Aim: To study the anti-viral activity of extracts of Berberis aristata and to scrutinize the novel lead compound present in it probably to combat Paramoxyviridae infection. Methodology: The phytochemicals present in the barks of Berberis aristata were extracted and screened by GC-MS analysis. Haemagglutination inhibition and cytotoxicity assay was performed to determine the anti-viral property, and the novel lead compound was selected using in-silico methods. Results: Haemagglutination assay provided anti-viral activity of the extract at 1/16 dilution in 4 HA viral concentration. At this concentration, the viability on Vero cell lines was precisely 92.8%. The GC-MS analysis enabled in identifying six molecules present in the extract. Among the six compounds present in the extract, five moieties exhibited drug likeliness property when passed through the Lipinski’s drug filter. QSAR predictions using T.E.S.T projected 3 compounds to be developmental non-toxicant with the predicted values of 0.12, 0.32 and 0.42 respectively. On performing docking studies with the predicted nontoxic moieties using iGEMDOCK, with the Sialic acid complexes host receptor, the highest binding energy was -213 kcal mol-1 for alpha-d-mannofuranoside, 1-o-decyl-, respectively. Interpretation: These findings enabled in understanding the anti-viral potency of bark extracts of B. aristata at 62.5mg ml-1 promoting high cellular viability of uninfected cells of host cell with low toxic effects. Probing molecularly, the in-silico analysis helped to predict alpha-d-mannofuranoside, 1-o-decyl as the possible lead molecule supporting its therapeutic efficacy as an anti-viral drug compound in future.
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Berberis aristata Dc. commonly known as Daruharidra is a popular drug which has been used globally in var�ious systems of Medicine viz. Ayurveda, Homeopathy, Allopathy, Unani. Ayurveda classics and Nighantus clearly mentioned Daruharidra in detail with specific synonyms and therapeutic indications. In Ayurveda it is mainly used Netra Roga,Pandu, Kamala, Kushtha, Mutrakruccha, Pratishyaya, Prameha. Clinical and exper�imental studies shows that it shows antioxidative, antiinflamatory,anticancer, hepatoprotective, immunomodu�latory properties. In this article we tried to compile all the information about Daruharidra mentioned in Ayur�vedic Samhitas, Nighantus and other text. Keywords – Daruharidra, Berberis Aristata, Ayurveda, Unani, Pandu, Prameha, Mutrakruccha, Netra rog, Antioxidative, Antiinflamatory, Hepatoprotective, Pharmacognocy.
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Background The plant Berberis aristata is traditionally used and scientifically validated for treating obesity and hyperlipidemia. It is also traditionally used to treat gynecological abnormalities. Therefore, the present study was designed to evaluate the therapeutic potential of Berberis aristata for obesity related reproductive changes and chemically characterize it. Methods High fat diet was given to 36 female rats for six weeks to induce obesity and infertility. These obese rats were treated with 10 mg/kg orlistat or the plant extract at 125-500 mg/kg for 45 days. Results The GC-MS analysis of the plant extract included fructose, thymic acid and other hydrocarbons. The plant extract revealed a remarkable free radical scavenging activity. The treated animals exhibited a decrease in total cholesterol and triglycerides (p<0.001), insulin and leptin levels (p<0.05), visceral fat and body weights while increasing the estradiol level at 500 mg/kg dose of the plant extract as compared with untreated animals as demonstrated from the histology of the ovary. Oxidative stress biomarkers such as superoxide dismutase, nitric oxide, malondialdehyde and reduced glutathione were significantly (p<0.01-0.001) ameliorated in treated rats. Conclutions B. aristata exhibited substantial potential against obesity induced reproductive damage in female rats by reducing oxidative stress and resistance to leptin and insulin.
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Introduction Vancomycin is used to treat bacterial infections but there is a risk of nephrotoxicity associated with it. Oxidative stress is the possible cause of this nephrotoxicity. Plant extracts have long been used in fighting oxidative stress and have proved quite useful. The present study investigated the treatment potential of Berberis aristata root extract against nephrotoxicity induced by vancomycin. Methods B. aristata was collected from Chikar Valley, Azad Kashmir, identified, and later analyzed by High-pressure liquid chromatography (HPLC). Vero cells were used to determine the effects of B. aristata extract. For the determination of apoptotic and anti-inflammatory effects cells were divided into three major groups; Control, Vancomycin, and Treated. The control groups were either left untreated or treated with 0.1% DMSO. Vancomycin group was treated with 0.6 mg/ml, 3 mg/ml, and 6 mg/ml of vancomycin, while treated groups were treated with (100 µg/ml, 200 µg/ml, 400 µg/ml) along with various vancomycin (0.6 mg/ml, 3 mg/ml, and 6 mg/ml) concentrations. The mRNA expression of antioxidant and proliferative markers (p53, p21, Cas 4, Cas 5, Cas 9, and Cyt-c) was assessed by qPCR. Results HPLC chromatogram indicated the presence of berberine component by comparing the peaks at retention time. The mRNA expression of all selected markers was found to be upregulated in the vancomycin group with a decrease of expression in treated groups, indicating the recovery from vancomycin-induced damage to kidney cells. Conclusion B. aristata extract can be used along with vancomycin treatment to minimize its toxicity.
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The objective of the present study was to evaluate the effect of Berberis aristata (BA) against oxazolone induced contact dermatitis in Balb/c mice and molecular docking with TLR-1 and TLR-2. Dermatitis was induced in Balb/c mice by sensitizing with topical application of 100 μl oxazolone (2%) and the effect of BA was screened in two doses (200 mg/kg and 400 mg/kg P.O.). The effect was evaluated by the change in ear thickness, anti-inflammatory cytokine (TNF-α, IL-6, and IL-1β) and oxidative stress on the sixth day in ear tissue homogenate. The ear skin of all group mice was subjected to histological analysis. This work was further evidenced by the docking of berberine with crystal structure of TLR1-TLR2 heterodimer caused by using the binding of tri-acylated lipopeptide (PDB ID: 2Z7X). In this study, we found that a significant reduction in ear thickness was found in BA (200 mg/kg and 400 mg/kg) as compared to 100 μl oxazolone(2%) treated mice. The reduction level of GSH and SOD found in 100 μl oxazolone (2%) sensitized mice. BA (200 mg/kg and 400 mg/kg) treated animals showed an increase in GSH and SOD levels. A significant reduction in inflammatory cytokines was observed in BA treated mice and indicates anti-inflammatory activity against oxazolone. Histopathological analysis showed minimal infiltration of lymphocytes and moderate harm to skin cells and layer in BA treated mice. Docking studies revealed promising binding interaction of berberine withTLR1-TLR2 heterodimer which can attribute to its anti dermatic effect. This present research shows that BA has a dose-dependent effect in contact dermatitis attenuated by oxazolone.