Bergenia ciliata: A comprehensive review of its traditional uses, phytochemistry, pharmacology and safety

Biomedicine & Pharmacotherapy 97 (2018) 708–721

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Biomedicine & Pharmacotherapy journal homepage: www.elsevier.com/locate/biopha

Review

Bergenia ciliata: A comprehensive review of its traditional uses, phytochemistry, pharmacology and safety ⁎

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MARK

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Mushtaq Ahmada,b, , Maryam Akram Butta, , Guolin Zhangb, Shazia Sultanaa,c, , Akash Tariqd,e, Muhammad Zafara a

Department of Plant Sciences, Quaid-i-Azam University Islamabad, Pakistan Center of Natural Products Research, Chengdu Institute of Biology, Chengdu 610041 China c Institute of New Energy and Low Carbon Technology, Sichuan University, Chengdu, China d Key Laboratory of Mountain Ecological Restoration and Bio Resource Utilization & Ecological Restoration Biodiversity Conservation Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, Sichuan, China e University of Chinese Academy of Sciences, Beijing 100039, China b

A R T I C L E I N F O

A B S T R A C T

Keywords: Berginia ciliata Medicinal uses Phytochemisry Pharamacology

Bergenia ciliata is a medicinal plant used for the treatment of kidney stones. The presented review is the first attempt to gather utmost information about the distribution, ethno-medicines, phytochemical analysis, pharmacology and toxicology of B. ciliata. This review was designed with the aim to compile fragmented information about B. ciliata in addition to explore its therapeutic potential and future research opportunities. A total of 185 research papers were reviewed using several data sources such as; Web of Science, Scopus, Google scholar, Science direct and PubMed. Results of this review revealed that B. ciliata is being used to cure 104 different types of ailments. Although among reported disorders B. ciliata showed high potential in the treatment of gastrointestinal disorders but it is well known for the treatment of kidney disorders particularly kidney stones. Literature review showed that traditional healers mostly utilize it in powder form. Moreover, B. ciliata was reported to possess high antifungal, antiviral, anti plasmodial and antibacterial activities. Pharmacological studies reported that it has good antioxidant, anti-inflammatory, anti-tussive, anti-ulcer and anti-neoplastic activities. Variety of secondary metabolites belonging to different classes of compounds such as phenols, alcohols, terpenoids and fatty acid were reportedly isolated from B. ciliata. In spite of having better efficiency of ethno medicines and good pharmacological potential, B. ciliata has also shown toxic effects on living system in several studies. We invite the attention of researchers to carry out detailed ethno-pharmacological and toxicological studies on this valuable plant species in order to provide reliable knowledge to the patients and discover more novel compounds for the development of new drugs with fewer side effects on the living system as compare to modern medicines.

1. Introduction B. ciliata belong (haw.) Sternb belongs to the family Saxifragaceae which consist of 30 genera and 580 species. B. ciliata commonly known as hairy Bergenia is a perennial herb found between the height of 800–3000 m throughout the temperate Himalayas [1,2] from Afghanistan to Southeast Tibet [1]. In Bhutan it is found in Deothang, Phuntsoling, Mongar and Ha districts. In India it is reported from Lushai hills, West Bengal, Arunachal Pradesh, Meghalaya, Himalayas (Kumaon), Kyongnosla, Karponanag, Gangtok in Sikkim, district Almora Uttarakhand [3–7]. In Nepal it occurs in Makanwanpur district [7] Karepalanchwok district [8] and Dolakha district [9]. In Pakistan it is

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distributed in northern parts mainly FATA region of Khyber Pukhtunkhwa province, Poonch valley, Swat, Abbottabad, Galliyat and Chitral [10–14]. It was long since this plant has been used as medicines for the treatment of different human ailments. In Himalaya region many rural communities use B. ciliata for the treatment of various diseases [15]. For century’s rhizome of B. ciliata has been used for curing pulmonary infections, leucorrhea, piles and for dissolving bladder and kidney stones [16]. In Ayurveda system of medicine it is commonly used as tonic, astringent, antiscorbutic, laxative, spleen enlargement, dysuria and ulcers [17]. Local people of West Bengal use rhizome juice as an anti-tussive for cough and cold [18]. As a medicinal plant B. cilata is

Corresponding authors at: Department of Plant Sciences, Quaid-i-Azam University Islamabad, Pakistan. E-mail addresses: mushtaqfl[email protected] (M. Ahmad), [email protected] (M.A. Butt).

http://dx.doi.org/10.1016/j.biopha.2017.10.141 Received 27 May 2017; Received in revised form 21 October 2017; Accepted 24 October 2017 0753-3322/ © 2017 Elsevier Masson SAS. All rights reserved.

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names are presented in Table 1.

being widely used against cough, cold, fever, pulmonary infections, heart diseases, ophthalmic, hemorrhoids and stomach disorders [15,19–21]. B. ciliata contains number of important phytochemicals such as bergenin, gallic acid, (+) – catechin, Paashanolactone, sitoindoside, quercitin, (+) afzelechin etc [22,23]. Presence of tannic acid, albumen, mucilage, glucose, wax, metarbin and mineral salts is also reported [24]. Biological analysis of B. ciliata revealed that this plant showed antioxidant, anti-inflammatory, antitussive, antiviral, antiulcer, hypoglycemic and toxicological activities. Rhizome of B. ciliata was found to show narrow spectrum of antibacterial activity, leaves and roots show antifungal activity [18,25]. Many researchers have studied this plant species in different aspects but there is no comprehensive review encountering detailed information about the therapeutic potential of B. ciliata. Present review is the first attempt to gather utmost fragmented literature about the ethnobotany, pharmacology and phytochemistry of B. ciliata. It would provide information about the effectiveness of this miracle herb against different kind of ailments and the responsible potent therapeutic compounds. Moreover, this review would disclose scientific gaps in current knowledge and help scientists around the globe for future studies regarding the discovery of new novel compounds and drugs from B. ciliata.

3.3. Ethno-medicinal uses of B. ciliata The use of plants as herbal medicine is as old as the origin of humans, however, now it has been identified an essential part of health care system worldwide [13]. Due to the lack of modern health care facilities and approachability, about 80% of world’s population is still dependent on wide range of herbal medicines for primary health care and use medicinal plants like B. ciliata [8]. Herbal medicines are used in a number of diseases and have no side effect and are more effective than allopathic medicines. Their mode of treatment is cheaper and easily available as compared to the modern synthetic drugs [14]. A tremendous revival in the interest and utilization of medicinal plant products has been witnessed in the past decade. Since long time B. ciliata is well known for its medicinal properties and extensively used for a wide range of medicine in traditional system in different regions especially of Asian countries like Pakistan, Nepal and India etc. A total of 104 ailments treated by B. ciliata are recorded in this review. These remedies were categorized into gastrointestinal, skin diseases, Renal/urinary disorders, muscular/skeletal disorders, respiratory diseases, eye diseases, oral infections, worm infections, and gynecological disorders, ENT, fever, cancer and others. Among these categories gastrointestinal accounted maximum percentage (23%), skin diseases (17%), urinary/ renal (14%), muscular/skeletal (10%), respiratory diseases (8%), fever (7%), eye diseases, oral infections, worm infections, gynecological (3%), ENT and cancer (1%) (Fig. 2). High value of carminative properties of B. ciliata rhizome is evident from highest percentage of gastrointestinal disorders. According to some studies [5], in the folk medicine of some areas of south East Asia the species is used for the treatment of stomach diseases. While in many studies [8,12,14,31,32] the use of rhizome to treat gastrointestinal disorders is mentioned while some authors reported the use of roots to cure gastrointestinal disorders [33–36]. [37,38] and mentioned the use of root for the treatment of diarrhea. Parts of B. ciliata used for treatment of different diseases were rhizome, roots, stem, leaves, latex, flower and as whole plant. However rhizome was most frequently used part (43%) followed by roots (27%), leaves (19%), whole plant (5%), stem, latex and flower (2%) (Fig. 3). It was found that most of the plant parts are taken individually to cure diseases. Frequent use of rhizome is may be due to the presence of many important phytochemicals. Phytochemical testing of B. ciliata rhizome showed the presence of high amount of tannins, phenolics and flavanoids [17]. In present study it was found that for the treatment of skin diseases most used parts were stem and leaves. According to some researchers [7,39,40] stem and leaves of B. ciliata are used for the treatment of cuts, wounds and boils. [41] also reported the use of leaves for the treatment of skin diseases. Kidney and urinary disorders was the third major category of diseases cured by B. ciliata. Some scientists [13,32,38,42] reported the use of roots and rhizome to cure kidney stones and urinary disorders. In literature [4], litholytic activity of B. ciliata rhizome is also reported in detail. Similarly the present review witnessed use of different parts of plant to cure muscular skeletal disorders (10%), respiratory problems (8%), eye diseases (3%), oral infection (3%), worm infection (3%), gynecological disorders (3%), ENT (1%), fever (7%) and many other diseases (8%). Blood cancer was also found to be cured from roots and leaves of B. ciliata [43]. Modes of utilization or preparations were decoction, juice, paste, powder, tea and extract. Most commonly used preparation were powder (29%) followed by decoction (20%), juice (21%), paste (21%), tea (6%) and extract (3%). Powder was found to be most common mode of utilization; this might be due to the hard nature of rhizome and roots. According to some workers [44], in traditional medicine system rhizome is used in powder form. All ethno-pharmacological uses of B. ciliata are mentioned in Table 2. Fig. 3 showed B. ciliata country wise research work on this plant along with their medicinal uses Fig. 4.

2. Methodology This review article has been designed by compiling and consulting published papers about the medicinal uses as well as scientific validation of B. ciliata. A total of 185 published papers were consulted using different data bases i.e. Web of Science, Scopus, Google scholar, Science direct and PubMed. In present review restriction of language was considered, only the published articles in English version were included for conducting a search targets on B. ciliata through different databases using a combination of key words including: B. ciliata ethno-pharmacology; phytochemistry; anti-microbial activities and anti-oxidant properties. In this paper the literature search was only targeted towards scientific publications which were included in above mentioned data bases which may available to scientific society for reference; though we may admit that there may be some other additional data in less available form like unpublished thesis and reports have not been included in this study. All the obtained data from previous published literature is summarized in 3 tables (traditional uses; phytochemistry and pharmacological activities) and 6 figures. Reported chemical constituents from this species were presented and IUPAC name; chemical and structural formulae draw and verified from Chemspider and Pubchem. 3. Comprehensive literature based information on Bergenia ciliata 3.1. Plant description B. ciliata is evergreen perennial herb up to 50 cm height with sub orbicular leaves which are rounded at the apex and base. Leaf margins are finely denticulate, fringed with soft hairs. Leaves are alternate, opposite and ex-stipulate. Flowers are showy pinkish white with obvate petals, lobes acute and denticular near apex, hermaphrodite, calyx 5 adnate to the ovary (more or less), corolla 4 or 5, perigynous and imbricate, stamens indefinite, ovary 4 or 5 and united, fruit capsular or sometimes baccate, seeds numerous, bloom in spring from February to April. Fruiting period is March-July [3,24,26,27]. The plant along with flowers and roots are shown in Fig. 1. 3.2. Vernacular names of B. ciliata B. ciliata has different synonyms and vernacular names vary from area to area. In India it is known as Sadpottar [28], Silpari in Nepal [29], in Swat (Pakistan) it is known as Ghat pana [30]. Some vernacular 709

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Fig. 1. Bergenia ciliata A. Floral branch with flowers & B. Roots.

3.4. Phytochemistry

Table 1 Vernacular/common names of B. ciliata across the world. Languages

Common/Vernacular names

Sanskrit Assamese Urdu English Bengali Garo Gujrati Hindi

Amabhedaka, Patharkuchi Zahkm -e -hayat Hairy bergenia, Stone breaker Patharkuchi, Himasagara, Patrankur Singkhantha Pashanbheda, Pakhanbheda Pakhanabheda, Silphara, Patharcua, Pakhanabhed, Silpbheda, Sadpottar, Dhoklumbo, patharchat, Pandamdawi, Laoo-patra Alepgaya, Pahanbhedi, Hittaga, Pasanaberu, Hittulaka La Khowang Pashanbhed, Batweyaa Kallurvanchi, Kallurvanni, Kallorvanchi Pashanbheda Pasanbhedi, Pashanabheda Kachalu, Pashanbhed Sirupilai Kondapindi Butpawh Kamargul, Ghat pana, Maknar path, Gatpanra, Qamar Panra, Barmia, Shapur, Batpia, But pewa, Budpiah Patharchur, Pakhanbhed Tatenpiu Besabur

Kannada Khasi Kashmiri Malayalam Marathi Oriya Punjabi Tamil Telugu: Pahari Pashto Kumaoni Meeteilon Chitrali

In the last two decades the demand for herbal medicines increased exceptionally so, to ensure the safety, quality and effectiveness of herbal drugs a need has been felt. Tool for quality assessment is phytochemical evaluation that includes chemo profiling, phytochemical screening and marker compound analysis [17]. Phytochemical screening of B. ciliata showed the presence of terpenoids, tannins, flavonoids, saponins, steroids [118]. Presence of alkaloids, tannins, flavonoids, coumarins and glycosides in B. ciliata rhizome [119]. In literature some workers [24] reviewed the presence of many secondary metabolites in B. ciliata and other Bergenia species. Fig. 5 shows the major classes of phytochemicals in B. ciliata. In present review total 58 compounds were found to be present in B. ciliata. [120] reported 48 volatile organic compounds in B. ciliata. These 48 compounds were divided into 11 categories which are phenol (19%), alcohol (19%), volatile organic compound (VOCs) (16%), terpenoids (14%), fatty acids (8%), sterol (5%), glycosides (5%), carboxylic acids (5%), flavonoids (3%), cinnamic acid (3%) and nitro compounds 3%. Some important classes and compounds are mentioned in Table 3. 3.4.1. Phenols Phenols are the most important constituents of B. ciliata. Different phenolic compounds like bergenin, tannic acid, gallic acid, catechin, [10]3-O-galloylcatechin and [10]-3-O-galloylepicatechin are present in B. ciliata [24,121,122]. Bergenin, catechin, (−)-3-O-galloylcatechin and [10]3-O-galloylepicatechin were isolated from rhizome of the plant [123]. Fig. 2. Major disease categories treated by B. ciliata.

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Tumor necrosis factor alpha. Bergenin stimulate anti-inflammatory messengers and protective prostaglandins secretions. Breaking down of fats is important role of bergenin that makes it a popular part of thermo genic fat burning dietary supplements. It is not directly involved in lipolysis but increase the activity of norepinephrine. Bergenin also show mild effect against an enzyme known as protein tyrosine phosphatase 1B which regulate insulin and leptin signaling negatively [127,128]. No adverse effects of bergenin have been reported even with very large dosages [5]. 3.4.3. Gallic acid Part of B. ciliata which possess gallic acid is seed. It is a type of phenolics also known as 3, 4, 5-trihydroxybenzoic acid [129]. Chemical formula of gallic acid is C6H2 [10]3COOH (Table 3). Due to the presence of gallic acid this plant shows antioxidant, antiviral and antifungal activities. To determine phenol content by Folin-Ciocalteau assay gallic acid is used as a standard. It is used to treat psoriasis in ointments. Gallic acid is inhibitor of weak carbonic anhydrase [130]. 3.4.4. Tannic acid Tannic acid is basically a form of tannin which is a polyphenol present in B. ciliata. IUPAC name of tannic acid is 2,3-dihydroxy-5({[(2R,3R,4S,5R,6R)-3,4,5,6-tetrakisphenyl 3,4,5-trihydroxybenzoate ({3,4-dihydroxy-5-[(3,4,5-trihydroxyphenyl)carbonyloxy]phenyl} carbonyloxy) oxan-2-yl] methoxy}carbonyl)phenyl 3,4,5-trihydroxybenzoate and its chemical formula is C76H52O46 (Table 3). Tannic acid is also known as tannimum, gallotannin, quercotannic acid, acidum, tannicum, digallic acid, oak bark tannin and quercitannic acid. Tannic acid show weak acidity due to the presence of many phenol groups in its structure. In the process of dyeing for cellulose fibers such as cotton, tannic acid is usually used combined with iron. To improve wash fastness properties of acid dyed polyamide tannic acid is used as an after treatment. It is also used as an agent to enhance chlorine fastness in textile auxiliary. Tannic acid possesses the property of inhibiting corrosion and to passivate ferrous metal objects. It is used in food applications also e.g. in juices and soft drinks it is used as aroma compound and as natural clarifying agent, taste enhancer and color stabilizer, it is important in beer clarification and wine industry. Tannic acid is important in the treatment of burns and injuries which decreases mortality rates significantly. In the late 19th and early 20th century it was used as treatment against many toxic substances (strychnine, ptomaine and mushroom poisonings). Tannic acid is used in the production of albumin tannate which is used in pharmaceutical industry as an antihistamins, anti-diarrhea and anti-tussives [131–133].

Fig. 3. Parts of B. ciliata used in ethno-medicines.

3.4.2. Bergenin Bergenin, also known as cuscutin which is the most abundant and important compound found in family Saxifragaceae. Chemical formula of bergenin is C14H16O9·H2O, IUPAC name is 4-methoxy-2[(1S,2R,3S,4S,5R)-3,4,5,6-tetrahydro- 3,4,5-trihydroxy-6-(hydroxyme thyl)- 2H-pyran-2-yl] −α-resorcylic acid (Table 3). 346.3 g per mole is the molecular weight of bergenin [5]. [124] reported that rhizome of B. ciliata contain 0.75% bergenin. Bergenin show some pharmacological effects as mentioned in Table 3 it shows anti-oxidant activity and protect against ascorbic acid. Plants containing bergenin are useful in arrhythmias. Various dosages of bergenin were effective for arrhythmias in several animal models [125]. Against E. coli and Pseudomonas aeruginosa bergenin showed germicide effect. Bergenin is also effective against different kinds of fungus as it blocks a crucial enzyme known as yeast alcohol dehydrogenase required for fermentation reactions [126,127]. Bergenin was found active against hepatitis C virus (HCV) and it also showed mild anti-HIV activity but not effective against HIV-I reverse transcriptase. It protects liver against damaging environmental poisons. By balancing cellular messenger secretion from immune system inhibitory cells bergenin effects anarchic or inflammation. It also blocks the secretion of inflammatory cytokines such as Interleukin-2, gemma interferon and

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Table 2 Ethno-medicinal uses of B. ciliata across the various parts of Himalaya. Ailment/Use

Part Used

Preparation

Locality

Local Name

Citation

Skin Disorders, Kidney Stone, Kidney Stone, Wounds Kidney Stone

Rhizome, Leaf

Paste, Juice

Lug Valley Of District Kullu, Himachal Pradesh N.W. Himalaya

Bhander

[45]

Rhizomes

Decoction

India

Paashaanbhed, Sadpottar

[4,28,46–52]

3.4.6. Sterol Important phytosterol β-sitosterol is present in B. ciliata roots and leaves [122]. Chemical formula of β-sitosterol is C29H50O and IUPAC name is 17-(5-Ethyl-6-methylheptan-2-yl)-10,13-dimethyl-,14,15,16,17dodecahydro-1H-cyclopenta[a]phenanthren-3-ol (Table 3). β-sitosterol is a waxy powder of white color having a characteristic smell. It is hydrophobic in nature [135,136]. β-sitosterol is important in reducing blood cholesterol level that is why it is used in the treatment of hypercholesterolemia. In the intestine it hinders cholesterol absorption. In herbal treatments β-sitosterol is used to treat benign prostatic hyperplasia [137,138]. During pregnancy β-sitosetrol use should be avoided because on newborn and unborn baby its effects are not enough known. Individuals with sitosterolemia should not take β-sitosterol because it is already present in high concentration with other such fats in the system so in this condition taking β-sitosterol will only decline the condition [139].

3.4.5. Catechin Catechin is present in B. ciliata rhizome [2,22]. IUPAC name of catechin is (2R, 3S)-2-(3, 4-dihydroxyphenyl)-3, 4-dihydro-2H-chromene-3, 5, 7-triol and its chemical formula is C15H14O6 (Table 3). Catechin is flavan-3-ol which is a kind of phenol present in plants as secondary metabolite and associated with [10]-epicatechin or (+)-catechin. Catechin is also recognized as Cyanidanol, Cianidol, Catechuic acid, Catechinic acid and D-Catechin. It is expected that encapsulation of catechin in cyclodextrins enhanced its taste to use it as an additive [134]. Catechin is histidine decarboxylase inhibitor which prevents the conversion of histidine to histamine that’s why it is useful over reduction of potentially damaging histamine related local immune responses. For the protection against cognitive decline due to HIV, catechin compounds are strong therapeutic candidates. Epicatechin and some catechin flavonoids may provide protection against neurotoxic oxidative stress. Epicatechins are able to traverse blood brain barrier more easily than resveratrol and neurotrophic factor pathways which are brain derived also activated by it. (+)-Catechin and [10]-epicatechin are monoamine oxidase inhibitors. Alzheimer’s and Parkinson’s disease can be treated with them.

3.4.7. Glycoside Glycoside present in B. ciliata is Arbutin. Its chemical formula is C12H16O7 and IUPAC name is (2R, 3S, 4S, 5R, 6S)-2-Hydroxymethyl-6(4-hydroxyphenoxy) oxane-3, 4, 5-triol. Arbutin also called as Arbutoside hydroquinone β-D-glucopyranoside is found in rhizome of B. ciliata [140]. Arbutin is used as a skin lightening agent because it reduces the formation of melanin. Arbutin is also present in B. crassifolia, B. ligulata, and wheat and pear skin. Arbitin found in bearberry is used traditionally for the treatment of urinary tract infections [141,142].

3.4.8. Flavonoid (+)Afzelechin is a flavonoid present in rhizome of B. ciliata [143]. Its chemical formula is C15H14O5 and IUPAC name is (2R, 3R)-2-(4hydroxyphenyl)-3, 4-dihydro-2H- chromene-3, 5, 7-triol. It is also found in B. ligulata rhizome. Afzelechin show α-glucosidase inhibitory activity [1,144]. Other flavonoids present in B. ciliata rhizome are quercetin 3o-β-D xylopyranoside and quercetin 3-o-α-L-arbinofuranoxide [145]. According to [146] quercetin show anti-oxidant, antiradical property and iron chelating effectiveness.

Fig. 4. Number of disease and country wise research work on B. ciliata.

Fig. 5. Major classes of phytochemicals reported in B. ciliata.

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Table 3 IUPAC names of phytochemicals along their activities. Phytochemicals

IUPAC Names

Chemical formula

Class of compound

Activity

Citation

Bergenin

C14H16O9·H2O

Phenol

[139,2,1]

C76H52O46

Phenol

Antioxidant activity and protects against ascorbic acid Pharmaceutical application

Gallic acid

4-methoxy-2-[(1S,2R,3S,4S,5R)-3,4,5,6-tetrahydro-3,4,5-trihydroxy-6(hydroxymethyl)- 2H-pyran-2-yl] −α-resorcylic acid 2,3-dihydroxy-5-({[(2R,3R,4S,5R,6R)-3,4,5,6-tetrakisphenyl 3,4,5trihydroxybenzoate({3,4-dihydroxy-5-[(3,4,5-trihydroxyphenyl) carbonyloxy]phenyl}carbonyloxy)oxan-2-yl] methoxy}carbonyl)phenyl 3,4,5-trihydroxybenzoate 3,4,5-Trihydroxybenzoic acid

C6H2(OH)3COOH

Phenol

Catechin

(2R,3S)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol

C15H14O6

Phenol

[139,2,151] [139,2]

(−)-3-Ogalloylcatechin. (−)-3-Ogalloylepicatechin

2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-1-benzopyran-3-yl 3,4,5-trihydroxybenzoate

C22H18O10

Phenol

Antifungal, Antiviral, Cytotoxicity, Antioxidant Histidine decarboxylase inhibitor –

2-(3,4-dihydroxyphenyl)-4-[2-(3,4-dihydroxyphenyl)-4-[2-(3,4dihydroxyphenyl)-3,5,7-trihydroxy-3,4-dihydro-,5,7-trihydroxy-3,4dihydro-2H-1-benzopyran-8-yl]- 5,7-dihydroxy-3(3,4,5trihydroxybenzoyloxy)-3,4-dihydro-2H-1-benzopyran-6-yl]-5,7dihydroxy-3,4-dihydro-2H-1-benzopyran-3-yl 3,4,5-trihydroxybenzoate 3,4,5-trihydroxybenzoic acid 17-(5-Ethyl-6-methylheptan-2-yl)-10,13-dimethyl,14,15,16,17-dodecahydro-1H-cyclopenta [a]phenanthren-3-ol (2R,3S,4S,5R,6S)-2-Hydroxymethyl-6- (4-

C59H46O26

Phenol

–

[1]

C8H8O5 C7H50O

phenolic acid Sterol

Inhibits Cholestrol inhibition

[2,1] [24,152]

C12H16O7

Glycoside

Prevents the formation of Melanin

[139,22]

C15H14O7

Glucoside

–

[2]

(2R,3R)-2-(4-hydroxyphenyl)-3,4-dihydro-2Hchromene-3,5,7-triol 1,7,7-Trimethylbicyclo[2.2.1]heptan-2-one

C15H14O5

Flavonoid

–

[24,152]

C10H16O

Terpenoid

[8]

glucoside 2-Pentanone 2,4-Dimethyl3pentanone Hexanal

4,11,11-trimethyl-8-methylene-bicyclo[7.2.0]undec-4-ene pentan-2-one

C15H24 C5H10O C7H14O

Terpenoid VOCs VOCs

Antinociceptive, Antispasmodic, Antimicrobial – – –

[139] [120] [8]

Hexanal

C6H12O

Antifungal activity

[8]

2-Methyl-1propanol Acetic acid

2-methylpropan-1-ol

C4H10O

–

[120]

Acetic acid

C2H4O2

Theraputic activity

[120]

Heptanol 2-Ethyl hexanol 3-Pentanol 2-Pentanol Octanol Pentanol Heptanal Limonene

Heptan-1-ol 2-Ethylhexan-1-ol

C7H16O C8H18O

Organic compound Organic compound Organic compound Alcohol Alcohol

– –

[126] [139]

3-Pentanol 2-Pentanol 1-Octanol Pentan-1-ol Heptanal 1-Methyl-4-(1-methylethenyl)-cyclohexene

C5H12O C5H12O C8H18O C5H11OH C7H14O C10H16

Alcohol Alcohol Alcohol Alcohol Aldehyde Terpene

[8] [120] [120] [120] [148] [136]

Linalool

3,7-dimethylocta-1,6-dien-3-ol

C10H18O

3-Methyl-4hexen-2one 2-Nitropropane

–

C7H12O

Terpene alcohol –

– – – Antibacterial and antifungal – Antiseptic and Chemotherapeutic agent Food additives and Shows bioactivity –

2-Nitropropane

C3H7NO2

Shows hepatotoxicity

[152]

Hexanol

1-Hexanol

C6H14O

Theraputic activity

[22]

2,4-Hexadienal β-

(2E,4E)-Hexa-2,4-dienal Caryophyllene

C6H8O 4,11,11trimethyl-8methylenebicyclo[7.2.0] undec-4-ene

Therapeutic activity Sesquiterpene

[13]

Myorelaxant and antispasmodic effects Fragrant causing agent Bioantimutagenic (continued

[120]

Tannic acid

Gallicin β-Sitosterol

Arbutin

Leucoanthocyanidin 4(2-galloyl) (+)-Afzelechin Camphor

Antimicrobial activity α-Terpineol Pentanoic acid 2,4-Nonadienal

hydroxyphenoxy)oxane-3,4,5-triol 2-phenyl-3,4-dihydro-2H-chromene-3,4-diol

Nitro compound Isomeric organic compound C15H24

[24,2,1]

[1]

[148] [14]

[77] 2-(4-methylcyclohex-3-en-1-yl)propan-2-ol

C10H18O

Pentanoic acid (2E,4E)-nona-2,4-dienal

C5H10O2 C9H14O

713

Carboxylic acid

[120] [120] on next page)

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Table 3 (continued) Phytochemicals

IUPAC Names

Chemical formula

Class of compound

Activity

Citation

Hexanoic acid Hexalactone Isobutyrophenone 5,6-Dihydro-2pyranone Decanoic acid

Hexanoic acid 6-methyloxan-2-one 1-phenylbutan-1-one

C6H12O2 C6H10O2 C10H12O

Carboxylic acid – –

Antifungal activity – –

[8] [153] [145]

5,6-Dihydro-2H-pyran-2-one

C5H6O2

–

–

[154]

Decanoic acid

C10H20O2

Fatty acid

[155]

Nonanoic acid methyl ester 2-Methyl butanoic acid Methyl nonanoate Methyl cinnamate β-phellandrene [E]-4-Hepten2-one Quercetin 3-oβ-D xylopyranoside Quercetin 3-oα-L arbinofuranoxide glycosides, saponins, carbohydrates, tannins, flavonoids and bergenin Polyphenols, Flavonoids

Nonanoic acid

C9H18O2

Fatty acid

Antimicrobial and Antifungal activity Herbicidal activity

3-Methylbutanoic acid

C5H10O2

Fatty acid

–

[5]

Methyl-nonanoat

C10H20O2

–

[153]

Methyl (E)-3-Phenylprop-2-enoate

C10H10O2

Cinnamic acid

Antimicrobial and Antifungal activity Antimicrobial activity

3-methylidene-6-propan-2-ylcyclohexene (4E)-hept-4-en-2-one

C10H16 C7H12O

Terpene Ketones

Used in fragrances Used in fragrances

[158] [8]

–

C20H18O11

Flavonoid

–

[22]

3-[(2S,3R,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-2(3,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one

C20H18O11

Flavonoid

–

[22]

Anti leishmanial activity

[153]

Anti-oxidative, detoxification, immune modulatory, antiinflammatory and anti-bacterial and anti-viral properties. Anti-microbial activity

[159]

[160]

antimicrobial and antioxidant activities phytotoxic activity

[161,162] [163]

Tannins, saponins, coumarins Phenolic and flavonoid tannins, terpenoids and cardiac glycoside Bergenin, Epicatechin, Catechin, and Gallicin Terpenoids, bergenine, phydroxybenzoyl bergenin, 11-Ogalloyl bergenin and methyl gallate Alkaloid, Saponin, Glycoside, Tannin and Phenol, Reducing Sugars, Flavonoid,

[156]

[157]

–

–

–

–

–

–

–

–

–

–

–

–

–

–

–

antiurolithiasis, antiinflammatory, antitussive activity, antioxidant

[164]

– –

– –

– –

– Antioxidant

[165] [166]

–

–

–

–

[167]

714

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M. Ahmad et al.

produce a severe diabetic model while comparatively mild diabetes was produced by 30 and 40 mg/kg in rats. The effects of different extracts of B. ciliata leaves on blood glucose showed that ethanolic extract lowered 70.13% the blood glucose level. Aqueous extract reduced 71.34% blood sugar level, Chloroform extract showed 42.23% reduction in blood glucose level while Ethyl acetate extract showed reduction in blood glucose level from 443.0 ± 22.3 mg/dl. Rats treated with Hexane and butanol extracts have not shown significant decrease in blood glucose level and any hypoglycemic activity [2]. Anti-diabetic activity of B. ciliata was also investigated using in vitro model that revealed the two active compounds (−)-3-O-galloylcatechin and (−)-3-O-galloylepicatechin, using ethyl acetate in soluble extract of the plant. These two compounds were responsible for the inhibition of rat intestinal maltase activity and porcine pancreatic, α-amylase activity in dose dependent manner [153]. The resulting compounds were also applied on in vivo models; α-amylase and α- glucosidase activities showed that there is a high potential to fight against type 2 diabetes [168,169]

Fig. 6. Number of studies on the phytochemical of B. ciliata in different countries.

3.4.9. Fatty acid Fatty acids present in B. ciliata are decanoic acid and nonanoic acid with chemical formula C10H20O2 and C9H18O2 respectively [8]. Decanoic acid shows antimicrobial and antifungal activity whereas nonanoic acid shows herbicidal activities.

3.5.2. Anticancer activity The drug involved in the chemotherapy which is used to treat tumors, malignancy and neo-plastic growth can be synthesized by the methanolic and aqueous extract of rhizome of B. ciliata. Both types of rhizome extracts have concentration-dependent cytotoxicity. According to a report by American national cancer institute, anticancer drugs can be produced if crude extract have IC50 value lower than a 30 μg/ml limit threshold value in addition both rhizome extract have IC50 value which falls in this threshold value [5,2].

3.4.10. Terpene Terpene present in B. ciliata rhizome are limonene with chemical formula C10H16 and lianalool C10H18O [8]. Their IUPAC names are 1Methyl-4-(1-methylethenyl)-cyclohexene and 3, 7-dimethylocta-1, 6dien-3-ol respectively (Table 3). Limonene is a chemotherapeutic agent and show antiseptic activity. Lianalool show bioactivities and used as food additive [147,148]. β-caryophyllene, a sesquiterpene was also found in B. ciliata rhizome [8]. Its chemical formula is C15H24 and IUPAC name is 4, 11, 11trimethyl-8-methylene-bicyclo [7.2.0] undec-4-ene (Table 3). It have woody and spicy smell so used as a fragrance chemical [149]. A terpenoid α-Terpineol is also present in B. ciliata oil [8] with chemical formula C10H18O and IUPAC name 2-(4-methylcyclohex-3-en-1-yl) propan-2-ol. α –Terpineol is a myrorelaxent and show antispasmodic effects [150,8].

3.5.3. Anti tussive activity The anti-tussive activity of B. ciliata had also been found in the methanolic extract of rhizome. It showed potential when it was induced by sulphur dioxide gas in mice in the form of cough model. The rate of antitussive activity depends on the dose. When comparison was made between extracts i.e methanolic, ethanolic and codeine phosphate, codeine phosphate extract was proved as standard anti-tussive agent. In the experiment of 90 min, the extract doses of 100, 200 and 300 mg/kg body wt. caused 28.7, 33.9 and 44.2% inhibition of cough reflex [24,1,2].

3.4.11. Other phytochemicals 2-Pentanone, 2,4-Dimethyl-3-pentanone, Hexanal, 2-Methyl-1-propanol, Acetic acid, Heptanol, 2-Ethyl hexanol, 3-Pentanol, 2-Pentanol, Octanol, Pentanol, Heptanal, 3-Methyl-4-hexen-2-one, 2-Nitropropane, Hexanol, 2.4-Hexadienal, 2,4-nonadienal, Pentanoic acid, Hexanoic acid, Hexalactone, Isobutyrophenone, 5,6-Dihydro-2-pyranone, Methyl nonanoate, Methyl cinnamate, β-phellandrene, [E]-4-Hepten-2-one are present in the oil extracted fom B. ciliata plant [8]. The studies on phytochemicals of B.ciliata in different countries are mentioned in (Fig. 6).

3.5.4. Antiulcer activity In some areas of South East Asia, for the treatment of stomach disorders B. ciliata is used in the folk medicines. The experiment for antiulcer activity of B. ciliata evaluated indomethacin and pylorus ligation-induced gastric ulcers in rats and gastro protective effects on HCl or ethanol. The doses of aqueous and methanolic extracts of rhizome of B. ciliata of 15, 30 and 60 mg/kg were given after ulcer genic treatment. After 3 h animals were killed and stomachs were reduced and the area for ulcer lesion was determined. The measurements included mucus and gastric acidity also. As compared to methanolic extract, the aqueous extract decreased ulcer lesion at the rate of p < 0.05 in all animals but as the dose quantity increased, the effect became reduced. The antiulcer activity can also be enhanced by cyto-protective effects when conferred with the enhancement of mucosal barrier with the lowering of pH and acidity [24,1,2].

3.5. Pharmacology 3.5.1. Anti diabetic activity In literature some researchers [153] first time reported the mode of action of B. ciliata as anti-diabetic and suggested that glucose lowering effect of this plant is because of inhibition of digestive enzymes, αglucosidase and α-mylase. Two active compounds, [10]-3-O-galloylepicatechin and [10]-3-O-galloylcatechin were isolated from 50% aqueous-methanol extract of B. ciliata rhizome. These compounds showed strong dose dependent enzyme inhibitory activity against rat intestinal α-glucosidase and porcine pancreatic α-amylase. Their results supported the use of B. ciliata in traditional medicines for treating diabetes [24]. Through determination of blood sugar level in rats, hypoglycemic activity of B. ciliata extracts was tested. The results showed that after the administration of streptozotocins (STZ) through intravenous rout, rats suffered severe hypoglycemic up to 6 h. By all doses for 30 mg–70 mg blood glucose level remained highly persistent after 24 h of STZ administration. It was concluded that 60–70 mg dose of STZ

3.5.5. Antineoplastic activity B. ciliata showed anti-neoplastic activities that had been used clinically. It showed anti-neoplastic activity when used as a precursor for preventive medicine [2,5]. The methanolic and aqueous extract of rhizome of B. ciliata were used in drug which was being used to check the growth of tumors and malignant. The values for both the extracts works well that is why this plant exhibit high potential against antineoplastic activities [1]. Another study also carried out on anti-neoplastic efficiency of methanolic and aqueous extracts of B. ciliata rhizome. The results revealed the high potency of this extract and consider 715

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viruses. Methnolic extract of B. ciliata inhibited the influenza virus A and HSV-1, which indicates that B. ciliata, could be one of the potent sources of antiviral drug. Methanolic and methanolic aqueous extract of B. ciliata exhibited strong anti-influenza viral activity. Methanolic extract of B. ciliata also inhibited the growth of Herpes simplex virus.

to be the potential source of anti-cancer drugs [170]. 3.5.6. Antibacterial activity Globally bacteria are the main cause of the prevalence of infectious diseases. This is a major public health problem [171,172]. Demand for natural antioxidants and antimicrobial drugs are rising gradually which has amplified thrust to search for different natural sources [173]. Recently some medicinally important plants extracts have been developed which are used as antimicrobials in food [174]. In current study different extracts of B. ciliata plant are reviewed which are used against human pathogenic bacteria. It has also [175] investigated the antibacterial activity of 3 medicinal plants including B. ciliata against human pathogenic. Root of the plant extract in cold water showed zone of inhibition 17 mm against Escherichia coli, 19 mm against Bacillus subtilis, 15 mm against Proteus vulgaris, 16 mm against Pseudomonas aerogenosa and Staphylococcus aureus. Against B. subtilis, B. ciliata the extract in cold water showed maximum antibacterial activity. In hot water root extract inhibition was 19 mm zone of inhibition against E. coli, 14 mm against B. subtilis, 16 mm against P. vulgaris and 13 mm against S. aureus. B. ciliata leaves extract showed 8–12 mm zone of inhibition against S. auereus and 10–20 mm zone of inhibition against B. megalerium [2,110]. Ethanolic extract of B. ciliata with 50 mg/ml concentration showed 22.8 ± 0.15 mm zone of inhibition against B. subtilis, 18.6 ± 0.15 mm against Klebsiella pneumonia, 24.0 ± 0.10 mm against S. aureus, 23.7 ± 0.25 mm against E. coli, 22.8 ± 0.15 mm against Salmonella typhi, 29.4 ± 0.47 mm against Shigella dysentriae, 23.4 ± 0.26 mm against Sacchromyces cerevisiae [14]. A study [18] reported that methnolic extract of B. ciliata rhizome showed maximum antibacterial activity against gram-positive S. aureus i.e zone of inhibition was 15 mm with 200 μg/disc, 16.5 mm with 400 μg/disc, 18 mm with 800 μg/disc, 20.5 mm with 1000 μg/disc and minimum activity against P. aeruginosa with different concentration i.e 3 mm with 200 μg/disc, 5 mm with 400 μg/disc, 6.5 mm with 800 μg/disc and 8 mm with 1000 μg/disc. It is suggested that antibacterial activity of B. ciliata leaves extract is much lower than its root extract [24,2]. This might be due to the presence of high concentration of active compounds in root and rhizome of B. ciliata as compared to leaves.

3.5.9. Anti-malarial activity The emergence of resistance against most of currently used drugs against malaria had provoked the disease load in endemic regions. Many plant species were being used for the cure of malaria in traditional health systems. For the treatment of fever, local communities of Himalayan Region conventionally use B. ciliata which was evaluated for its possible role as antimalarial drug. Ethanolic leaf extract of B. ciliata exhibit good in vitro anti-plasmodial activity with an IC50 < 10 μg/ml. This study confirmed the ethno-pharmacological use of plant for the treatment of fever. These results showed good antimalarial potential of ethanolic leaf extract [178]. 3.5.10. In vivo and in vitro study In vitro studies on anti lithiatic activity was also observed on the rhizome of B. ciliata through homogenous precipitation method which shows that this plants has less potential against this activity [179]. In vitro several anti-crystallization compounds were extracted from B. ciliata, which were used medicinally. Traditionally the species were used in vitro for the treatment of kidney stones. In vitro the rhizome of B. ciliata which inhibit calcium oxalate crystallization such as metallic ions and their complexes. Extract can inhibit the nucleation and aggregation of calcium crystallization in vitro [180]. B. ciliata also show in vitro and in vivo animals studies for the activity of calcium oxalate monohydrate growth inhibition, that declines calcium phosphate nucleation, diuretic, hypermagneseuric, calcium oxalate inhibition and antioxidant effect [154,181–183]. Leaves extract of B.ciliata shows in vivo anti-malarial activity applying different concentration of leaf extract in dose dependent manner [76]. Fig. 7 showed different pharmacological research on B. ciliata in different countries. 3.5.11. Toxicological investigation of B. ciliata B. ciliata showed acute systematic and intracutaneous toxicity when experimented in animals. It showed different symptoms related to toxicity as erythema and edema in case of intracutaneous toxicity and breathing problems with initiations of bloody diarrhea in case of acute systematic toxicity. The toxicological investigation showed that it also caused gastro-intestinal syndrome and toxicity in many diseases [184,185].

3.5.7. Antifungal activity Root and leaves extracts of B. ciliata were reported to have antifungal activity. The extracts used for antifungal investigation of B. ciliata were ethanol, hexane, ethyl acetate, chloroform, butanol and aqueous. These different root and leaves extracts were tested against Aspergillus niger, Alternaria solani, Penicillium funiculosium, Fusariam solani, Microsporum canis, Nigrospora oryza, Curvularia lunta, Pleuroetus oustreatus and Candida albicans. It was found that aqueous and ethanolic extract of leaves showed maximum activity against P. oustreatus and P. funiculosium i.e 22 mm and 20 mm zone of inhibition was observed (Table 4). All extracts of root showed no activity against N. oryza, C. lunta whereas all leaves extract showed no activity against A. niger and A. solani. Against M. canis aqueous root extract showed maximum response i.e 10 mm zone of inhibition and hexane and ethyl acetate showed minimum response i.e 6 mm zone of inhibition. Against P. oustreatus butanol showed 10 mm and hexane showed 6 mm zone of inhibition. Hexane extract of root showed 14 mm zone of inhibition and ethyl acetate extract showed 6 mm zone of inhibition against C. albicans [43,2].

4. Conclusions The present review reports detailed information about the medicinal uses, phytochemical, pharmaceutical and biological investigation of medicinal plant B. ciliate for the first time. It is found that this miracle herb had been traditionally used among the various communities across the Himalayan region of world for urinary, gastrointestinal, skin, respiratory, skeletal, gynecological, inflammatory, infectious diseases. In total of 104 different disease disorders were reported to be treated by this species while its highest potential was observed to cure gastrointestinal disorders primarily. In addition to this, the species is also well known to treat kidney stones and kidney disorders by the traditional healers. Almost all parts of the plant are used for curing different ailments; the most frequent part used is rhizome followed by root, leaf, flower, latex and whole plant. The preferred mode of utilization is in the form of powdered drug. Biological and pharmaceutical investigation showed that the species has potential antifungal, antiviral, antibacterial, antioxidant, antitussive, anti-inflammatory, anti-neoplastic and anti-ulcer activities. The major phytochemical compounds reported in this species are of wide range such as phenols, flavonoids, fatty acid and terpenoids. While some studies revealed the presence of certain

3.5.8. Antiviral activity In literature some workers [131] used 20 extracts of different plants to find antiviral activity against influenza virus. IC50 of these extracts ranged from < 6.25 to 97 mg/ml. Among them highest activity was shown by extract of A. filicinus. B.ciliata also showed high activity with IC50 values from 8 to 10 mg/ml and it was highly active against both 716

Anti-fungal activity

Rhizomes

Anti-Bacterial activity

717

Whole plant

Leaves

Aspergillus niger, Alternaria solani, Penicillium funiculosium, Fusarium solani, Microsporum canis, Nigrospora oryza, Curvularia lunta, Pleuroetus oustreatus, Candida albicans Penicillium funiculosium, Microsporum canis, Curvularia lunta Aspergillus niger

Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis

Rhizome

Root, leaves

B. subtilis, E. coli, P. vulgaris, P. aeruginosa, and S. aureus

Ethanolic, Ethyl acetate, Aqueous n-hexane, dichloromethane and methanol

Ethanol, Hexane, Ethylacetate, Chloroform, Butanol, Aqueous

Chloroform, Acetone, Methanol

Aqueous

aqueous, 50% ethanolic and methanolic extracts

Escherichia coli, Baccillus subtilis, and S. aureus

Leaves were affective against Microsporum canis 12 mm Afzelechin showed antifungal activity 7 ( ± 0.3) mm, while asarone, terpenin-4-o1, parascorbic acid, damascenone have moderate activity 5 ( ± 0.12)–2 ( ± 0.1) mm.

2 ml

roots and leaves extract were effective against Microsporum canis, Pleuroetus oustreatus and Candida albicans 5 mg/ml

5 mg/ml

Extracts dissolved in cold water showed maximum B. subtilis (19 mm), E. coli (17 mm), S. aureus (16 mm), P. aeruginosa (16 mm), and P. vulgaris (15 mm). Similarly, in hot water extracts, the results were as follows: E. coli (19 mm), P. aeruginosa (17 mm), P. vulgaris (16 mm), B. subtilis (14 mm), and S. aureus (13 mm) E. coli, showed 12 mm and 13 mm, P. aeruginosa showed 13 mm and 16 mm

At a dose level of 50 mg/ml, the antibacterial effect was most significant

Japan Bara Gali Hazara Division, NWFP, Pakistan

[177]

Pakistan

India

Hazara division

Kashmir valley in India

[153]

[157]

[160]

[175]

[176]

India.

[1]

Aqueous, 50% ethanolic and methanolic extracts

10, 25 or 50 mg/ml for each extract 10, 25 or 50 mg/ml for each extract

Thandyani, Abottabad, North West Frontier Province. Pakistan

[157]

Root Extract found Anti -bacterial activity against Pseudomonos aeruginosa (zone of inhibition 12mm–20 mm) and Escherichia coli (zone of inhibition 6mm–8 mm) leave extract found activity against Staphylococcus auereus (zone of inhibition range [8mm–12 mm), Bacillus subtilis, Bacillus megaterium and micrococus (zone of inhibition range 10mm–20 mm) At a dose level of 50 mg/ml, the antibacterial effect was most significant

ethanol, hexane, ethyl acetate, chloroform, butanol and aqueous

West Bengal, India

[18]

The antibacterial efficacy of the extract, concentration dependent against all tested strains, was potent at 1000 μg/disc, the maximum effect shown against S. aureus

200–1000 μg

Locality

Methanolic extract

Citations

Observations

Tested dose

Type of Extract Used

E. coli, B. subtilis, and S. aureus

Antibacterial activity by disc diffusion method using bot gram positive and gram negative Bacteria such as Bacillus pumilis, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Shigella dysenteriae, Vibrio cholerae Gram positive and gram negative bacteria viz. Bacillus subtilis, Bacillus megaterium and Pseudomonas aeruginosa

Model used and study design

Root

Rhizomes

leaves and roots

Parts/Used

Pharmacological Activity

Table 4 Summary of anti-fungal and anti-bacterial activities of B. ciliata.

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Fig. 7. The graph showed the pharmacological research work of different countries on B. ciliata.

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toxic constituents which need to be scientifically investigated further in order to the make the safer use of this herb across the globe for primary health care. Despite the presence of scientific evidence related to pharmaceutical and medicinal uses several gaps in present review paper occurs regarding the utilization of this plant species. First of all, experimental evidences of some traditional uses are reported by different researchers like anti-inflammatory, anti-diabetic, anti-tussive, antiulcer etc. But there is a dire need for experimental investigation in future for some provisions used for gynecological, skin, muscular/skeletal, ENT disorders and antidote activities. Furthermore some pharmaceutical activities are observed in vitro and in vivo. Deficiency in clinical trials of some activities has also been observed. Therefore for the future discovery of drugs it is necessary to conduct additional clinical studies on this plant. In future clinical trials should be conducted to test the efficiency of this plant against several ailments and proper utilization and improvement of a drug. The outcome of research in these areas will give convincing support for future clinical use of B. ciliata in modern medicine. Further phytochemical investigation may lead to the expansion of existing therapeutic potential of B. ciliate. Based on the present review, we further suggest that detailed ethno-pharmaceutical and toxicological research work should be carried out. These studies will provide valuable knowledge about different disorders and for the preparation of new drugs. Moreover, the plant has lesser side effects on living organisms as compared to modern medicines. Acknowledgement The authors are highly thankful for funding to PIFI-CAS, Chengdu Institute of Biology, China. References [1] K. Ruby, R. Chauhan, S. Sharma, J. Dwivedi, Polypharmacological activities of Bergenia species, Int. J. Pharm. Pharm. Sci. 1 (2012) 100–109. [2] P. Pokhrel, R.R. Parajuli, A.K. Tiwari, J. Banerjee, A short glimpse on promising pharmacological effects of Begenia ciliata, JOAPR 2 (1) (2014) 1–6. [3] A.J. Grierson, D.G. Long, Flora of Bhutan, including a record of plants from Sikkim, R. Bot. Gard. 1 (parts 1 and 2) (1983). [4] R. Hafidh, A. Abdulamir, F. Jahanshiri, F. Abas, F. Abu Bakar, Z. Sekawi, Asia is the mine of natural antiviral products for public health, Open Complement Med. J. 1 (2009) 58–68. [5] R. Chauhan, K. Ruby, J. Dwivedi, Bergenia ciliata mine of medicinal properties: a review, Int. J. Pharm. Sci. Rev. Res. 15 (2) (2012) 20–23. [6] A. Kumar, M. Mitra, B. Adhikari, G. Rawat, Depleting indigenous knowledge of medicinal plants in cold-arid region of Nanda Devi Biosphere Reserve, Western Himalaya, Med. Aromat. Plants 4 (195) (2015) 2167-0412.10001. [7] M. Hasan, P. Gatto, P. Jha, Traditional uses of wild medicinal plants and their management practices in Nepal—a study in Makawanpur district, Int. J. Med. Aromat. Plants 3 (2013) 102–112. [8] R. Gyawali, Phytochemical screening and anti-microbial properties of medicinal plants of Dhunkharka community, Kavrepalanchowk, Nepal, Int. J. Pharm. Biol. Arch. 2 (6) (2011). [9] P.M. Shrestha, S.S. Dhillion, Medicinal plant diversity and use in the highlands of

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