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Table of Contents
REVIEW ARTICLE
Year : 2022  |  Volume : 1  |  Issue : 2  |  Page : 67-75

A review on anticancer potential of Berberis aristata and berberine with focus on quantitative methods


Department of Pharmaceutical Quality Assurance, PES Modern College of Pharmacy for Ladies, Pune, Maharashtra, India

Date of Submission04-Feb-2022
Date of Decision05-Feb-2022
Date of Acceptance06-Feb-2022
Date of Web Publication15-Jun-2022

Correspondence Address:
Ms. Manasi Rokade
PES Modern College of Pharmacy for Ladies, Moshi, Pune - 412 105, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpdtsm.jpdtsm_9_22

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  Abstract 


Berberis aristata (BA) is a traditional herbal ayurvedic medicine widely used from ancient time and has various therapeutic effect. In this review, we had tried to emphasize on its pharmacognistic as well phytochemical parameters. We had aiming to focus on estimation of berberin in extract using different analytical techniques such as high-performance liquid chromatography, high-performance thin-layer chromatography from various parts of BA plant. It contains different isoquinoline alkaloids, namely berberine, palmitine, berbamine which are contributing in the pharmacological action of BA. As it has various pharmacological actions such as anti-bacterial, anti-diarrheal, anti-inflammatory, anti-pyretic, and anti-hemorrhagic. Along with that, it is also a potential anticancer agent as its methanolic extract showed potent activity against different cell lines such as breast cancer, colon cancer, cervical cancer cell lines. In this review, we had emphasized on phamacognosy, phytochemistry, and analysis for berberine content of BA along with its anticancer potential. A brief spotlight had also given on anticancer prospective of berberine.

Keywords: Berberine, Berberis aristata, cancer, cell lines, high-performance liquid chromatography, high-performance thin-layer chromatography


How to cite this article:
Rokade M, Vichare V, Neve T, Parande B, Dhole S. A review on anticancer potential of Berberis aristata and berberine with focus on quantitative methods. J Prev Diagn Treat Strategies Med 2022;1:67-75

How to cite this URL:
Rokade M, Vichare V, Neve T, Parande B, Dhole S. A review on anticancer potential of Berberis aristata and berberine with focus on quantitative methods. J Prev Diagn Treat Strategies Med [serial online] 2022 [cited 2022 Sep 24];1:67-75. Available from: http://www.jpdtsm.com/text.asp?2022/1/2/67/347549




  Introduction Top


Berberis aristata (BA) usually known as “Indian Barberry,” Daruhaldi, or tree turmeric is shrub that belongs to the family Berberidaceae with genus Berberis.[1] It is found in temperate and sub-tropical regions of Asia, Europe, and America. It is native to the Himalayas region of India and widely distributed in Sri Lanka, Bhutan, and hilly areas of Nepal. It is 1.8–3.6 m at elevation of 1000–3000 m in height.[2] It is extensively used in ayurvedic medicines from ancient times. Conventionally, it is used as anti-microbial, anti-bacterial, anti-pyretic, anti-hemorrhagic, anti-inflammatory, immunostimulant.[3] Available ayurvedic marketed formulations of BA are tablets, capsules, syrups which are useful in the treatment of malaria, bleeding, fever, jaundice, diabetes, skin and eye infection, hepatitis, diarrhea.[4]


  Literature search strategy Top


The main focus of this article is to provide pharmacognosy and anticancer potential of BA. Evidences obtained from experimental, preclinical, and clinical studies are evaluated and presented in subject area.

The data mentioned below are taken from different sources such as Scopus, Web of science, Google scholar, Elsevier, ScienceDirect, PubMed using different terms, keywords, and title words during the search. The terms used in these searches were as follows: berberine, BA, analytical methods of BA, anticancer potential of berberine, anticancer activity of BA, cancer cell lines against berberine. In this, only English articles were measured. The irrelevant information was omitted and the key features of appropriate search studies were considered. The conclusions are summarized in this review.

Taxonomical classification[5],[6]

[Table 1] shows Taxonomical Classification of Berberis aristata.
Table 1: Taxonomical classification

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Pharmacognostic description

Macroscopy

Flower

Flowers are yellowish, complete, stalked, cyclic, perigynous, actinomorphic with racemose of 11–16 flowers per raceme and average diameter of fully opened flower is 12.5 mm. The calyx is polysepalous with 3 small and 3 large seplas with 4 –5 mm long. Corolla is yellow, polypetalous with 6 petals. Androecium 5 –6 mm long with 6 stamen and gynoecium 4–5 mm broad with broad stigma and short style.[4],[5]

Fruits

Fruits are edible, acidic, sour, and elliptical to oviodal covered with plum with bright red in color having length 7 mm and diameter 4 mm,[4],[5] shown in [Figure 1]a.[8]
Figure 1: Macroscopy of Berberis aristata. (a) Leaves and fruit of Berberis aristata. (b) stem of Berberis aristata. (c) Roots of Berberis aristata

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Leaves

Leaves are present as cluster of 5–8 simple spiny, lanceolate, toothed, sessile, leathery, acuminate, with reticulate pinnate venation, 4–5 cm long, 1–2 cm in breadth. Leaves are light green on ventral surface and deep green on dorsal surface,[7] shown in [Figure 1]a.

Stem

Stems are cylindrical, cut tortuous pieces of varying length and thickness, bark about 0.4–0.8 cm thick, pale yellowish gray, soft, surface rough, brittle, yellow wood portion with more or hard radiate with xylem fibers. Small pith with branched stem, thin bark, short fractured surface[8],[9] is shown in [Figure 1]b.

Roots

Roots are thick, woody, cylindrical, knotty, strongly branched, cut into varying length up to 45 mm in diameter, scaly and longitudinally wrinkled, yellowish brown in color,[10] shown in [Figure 1]c.

Seeds

Seeds are yellow to pink 2–5 in number with weight 25 mg.[12]

Microscopy

Stem

Cork containing rectangular to squarish yellow colored thin wall radially arranged cells, irregular shaped sieve elements, tangentially arranged thick-walled phloem fibers containing calcium oxalate crystal, scattered stone cells, secondary phloem consist of sieve elements and phloem fibers, transverse by multi seriate phloem rays, sieve elements in tangentially arranged bands with compressed cells altering with short, lignified phloem fibers with thick walls. Secondary xylem is broad with xylem vessels, tracheid, and xylem fibers with transversed multi seriate xylem rays.[9],[10] Showed in [Figure 2].
Figure 2: Microscopy of Berberis aristata stem

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Root

The outer most cork composed of rectangular cork cells followed by cork cambium. The cortical region contains rectangular parenchymatous cells filled with tannins, some regions contain yellow-colored alkaloidal content.[11] Just below cortex 3–4 celled thick secondary phloem consist of sieve tube, companion cells, and phloem fibers. The secondary xylem is wide celled with vessels, fibers, tracheids, and parenchyma. The medullary rays are thin, radiating, parenchymatous with pitted alkaloidal content.[12]

Phytochemistry

Most of the parts of BA plant contain different chemical constituents majorly alkaloids like protoberberine and bisisoquinoline.[13],[14] Berberine is considered as major alkaloid found in the plant having yield of 2.23% followed by palamatine.[15] Root bark of plant contains alkaloids such as berberine, epiberberine, palmatine,[16] tetrahydropalmitine, karachine, dihydrokarachine, dehydrocaroline, jatrorhizine, and columbamine.[17] The other extracted alkaloids are oxyberberine, berbamine, aromoline, oxycanthine, and berberine chloride.[18] Alkaloids such as pakistanine, 1-O methyl pakistanine, pseudopalmatine chloride, and pseudoberberine chloride were also isolated from bark of BA.[19],[20] Berberine content varies with altitude in roots and stem of plants and also influenced by potassium and moisture content of soil. It was seen that plant growing in lower altitude has more berberine content.[21] The flowers of plant contain polyphenolic flavonoids named quercetin, meratin, rutin,[22] other acids such as E-caffeic acid and chlorogenic acid.[23] The rhizome part of plant contains heavy metals such as lead, zinc, cadmium, chromium, and manganese.[24] The major alkaloids present in plant are shown in [Figure 3].[25]
Figure 3: Major alkaloids Present in Berberis aristata. (a) Berberine. (b) Berbamine. (c) Aromoline. (d) Oxyberberine

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As the BA is certainly available and used in traditional medicine and also exists as pharmaceutical/ayurvedic formulations, its analysis and quantification of phytoconstituents are essential. Researchers used different analytical methods for estimation of phytoconstituents in different parts of plants. This helped to develop quality standards and analyze the pharmacokinetic properties of its phytoconstituents to achieve desirable doses for its pharmacological actions. It is necessary to focus on qualitative and quantitative analytical studies for determining phytoconstituents in real samples, as they play a significant role in designing and developing pharmaceutical/ayurvedic formulations. A detailed list of various analytical methods reported for estimation of berberine from BA is given in [Table 2].
Table 2: Analytical methods used for estimation of berberine from Berberis aristata

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From the above table, it has been observed that there are various methods reported for analysis of phytoconstituents available in BA extract. It is also reported that soxhlet apparatus was used for the extraction using methanol as solvent. For high-performance liquid chromatography (HPLC) determination, most of researchers used C-18 column and acetonitrile with water as a mobile phase. For HPTLC precoated silica gel, 60 F254 plates were used by researchers using n-propanol, formic acid, water as part mobile phase with varying proportions

Anticancer potential of berberis aristata

Berberine is one of the potent agent used for anticancer therapy which is obtained from various plants such as Berberis vulgaris (barberry), BA (tree turmeric), Mahonia aquifolium (Oregon grape), Hydrastis canadensis (goldenseal), goldthread, Oregon grape, phellodendron, Tinosporia cardiofolia (Gulvel).[42] BA has been reported to have anticancer activity against different types of cancers such as breast cancer, colon cancer, cervical cancer, kidney cancer, liver cancer, lung cancer. A detailed data of anticancer activities of BA against various cancers are presented in [Table 3].
Table 3: Berberis aristata against cancer cell lines

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Serasanambati et al. and team carried out the anticancer activity of methanolic extract of BA against Michiagan Cancer Foundation-7 (MCF-7) human breast cancer cell lines. They have found that antiprolifarative effects of methanolic extracts carried out using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay exhibited a suppressive effect on cell proliferation in dose-dependent manner. It was significantly (P ≤ 0.001) decreased by viabilities of tested groups. Soft agar colony formation assay was used for the determining the in vitro anti-neoplastic activity from which 500 μg caused significant inhibition (80%, P ≤ 0.001) of colony formation. The live/dead assay used for determining the potentiating effect shows significant (P ≤ 0.001) increase of apoptotic cells on dose-dependent manner. Cell migration was carried out using in vitro scratch assay which shows significant inhibition of cell migration up to 50% when treated with 250 μg of methanolic extract for 48 h.[43] S. Kumari studied the cell viability and antiproliferative effect of alkaloids isolated from roots of BA on breast cancer and normal epithelial breast cell lines by treating the cell lines with BA1 (9.8 μg/ml), BA2 (10 μg/ml), and BA3 (10.2 μg/ml). These compounds exhibited decrease in cell viability on MCF-7 cell line and negligible effect on MCF-10A with similar conditions compared to untreated control. Antiproliferative activity using Brdu proliferation assay of compounds was determined as 51%–55% on MCF-7 cell lines and with negligible effect on MCF-10A. The cell cycle analysis of BA extracts using cell cycle phase distribution analysis G1 phase arrest on MCF-7 cell line, indicating that these compounds possess anticancer activity against breast cancer cell lines by inhibiting cell cycle progression.[44] Basanta Lamichhane et al. and team studied the anticancer activity of BA stem extract using MTT Assay against NIH/3T3, MDA-MB-231, and U-87 MG cell lines which shows significant cytotoxicity against MDA-MB-231 and U-87 MG cell lines in comparison to NIH/3T3 cell lines. At exact concentration of 40 μg the cell viability of MDA-MB-231 and U-87 MG cell lines is half of NIH/3T3.[45] Mazumdar et al. studied the cytotoxic activity of Methanolic extract of BA and Hemidesmus indicus against MCF-7 breast cancer cell line by determining the inhibition percentage with respect to cytotoxicity was found as 89% at 1000 μg/ml with IC50 value of 50 ± 0.03 g/ml, which shows dose-dependent cytotoxicity.[46] Das et al. studied the cytotoxic activity against colon cancer cell lines using MTT assay. It showed increased in dose causes incuses increment in cell killing. The IC50 value of methanolic extract was found as 1.9648 μg/ml. It was observed that methanolic extract induces a concentration-dependent inhibition of HT29 Cells. It shows due to presence of alkaloids in extract shows potent anticancer activity.[47] Sharmila et al. carried out MTT assay against HeLa cell lines to determine the anticancer effects of bark of Berberis extract, which shows concentration-dependent increment of cytotoxicity along with cell disintegration after 48 h of treatment against cell lines at higher concentrations. The IC50 value was found to be 118.97 μg/ml.[48] K. S. R. Pai et al. evaluate the antineoplastic activity of extracts of BA in ehrlich ascites carcinoma bearing mice using cisplatin as positive control. It was found that ethanolic extract increases the weight due to tumor cell proliferation and also survival time when compared to control group. The cytotoxicity was carried out using BSL test, the cisplatin and extracts reversed the tumor-induced alteration in total WBCs, RBCs, total leukocyte count, and hemoglobin content. It also shows that the ethanolic extract is more efficient for anticancer activity due to the presence of alkaloids, flavonoids present in it.[49] K. V. Anis et al. studied the effect of alkaloid extracted from BA which found to significantly inhibit the carcinogenesis induced by 20-methylcholanthrene or N-nitrosodiethylamine in dose-dependent manner in small animals after oral administration.[50]

Analysis of isolated berberine

The presence of different alkaloids in BA is responsible for the pharmacological activity. Researchers also found that these alkaloids showed potent anticancer activity. Berberine is one of the alkaloids present in BA that exhibit anticancer potential against different cancer cell lines. Berberine sulfate and hydrochloride consider as a promising agent in treating cancer.[49],[51] [Table 4] shows the recent studies of berberine against different cancer cell lines.[75]
Table 4: Recent studies of berberine against different cancer cell lines

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From above table, it has been observed that, berberine showed good cytotoxic activity against triple negative breast cancer cell lines, from which MDA-MB-468 is the most sensitive with IC50 = 0.48 μM. Treatment of berberine with colorectal cancer cell lines showed suppression in cell viability by increasing their apoptosis level. Berberine inhibits the DNA synthesis and proliferation of pancreatic ductal adrenocarcinoma cells and also retards the development of their cell cycle. Berberine against gastric cancer cell lines shows dose-dependent impairment of cell viability. It suppress cancer cell growth and migration in a dose-dependent manner. In case of liver cancer cell line, berberine shows selective inhibitory effect on the proliferation of hepatocellular cancer cell in dose-dependent manner. Berberine shows decrease in tumor growth in glioblastoma polymorphic cells. Induction of cellular morphological alteration and decrease in number of viable cell caused by berberine against skin cancer cell lines. Berberine shows dose-dependent suppression of cellular testosterone synthesis and also proliferation of human prostate carcinoma epithelial cell lines.


  Conclusion Top


Cancer or other disorders such as cardiovascular or metabolic, which causes chronic illness to require long-term treatment. Chemical therapy used for such a long duration may cause serious side effects. BA is a safe and effective natural product that is used in various pathological conditions. Thus, it is a potential choice for long-term treatment and management of various diseases. BA due to the presence of various alkaloids not only inhibits the proliferation, invasion, and metastasis of cancer but also enhances the effects of chemoradiotherapeutic treatment. Therefore, it can be considered as a drug of choice. In this article, we had tried to explain the pharmacognosy, phytochemistry, its estimation using analytical techniques, and also the anticancer potential which are already reported by the researchers. However, very few researchers have studied its activity against different cancer cell line. It has potent activity against breast cancer, colon cancer, and cervical cancer cell lines and also in various types of other cancers. However, still, there are numerous other cancer cell lines which have not been tested against BA. Considering the literature BA can be studied for remaining cancer cell lines and may exhibit good anticancer potential against them. Berbeine available from different plant sources was also reported to have anti-cancer activity against various cancer cell lines. Therefore, it can be judged that most of the plants containing berberine in sufficient amount may exhibit good anticancer potential.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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