A REVIEW ON THERAPEUTIC POTENTIALS OF BERGENIA LIGULATA WALL

ABOUT AUTHORS:
Poonam Verma*, Bhuwan Chandra Joshi, Nitisha Negi
ISF College of Pharmacy,
Moga, Punjab
bhuwan.joshi000@gmail.com

ABSTRACT:
Bergenia ligulata Wall also known as Pashanbhedain Indian system of medicine. Etymologically, the name Pashanbheda means that which breaks or destroys stones. Bergenia ligulata Wall is perennial herb that grows wild in stones and rocks. This plant has been recognized for dissolving kidney stone along with various biological activities, proving its several traditional uses. Bergenia ligulata Wall is a herb mainly found in Himalayan valley. Since it imparts different properties i.e. diuretic, anti diabetic, astringent, cardio tonic, wound healer, expectorant, antipyretic, hepatoprotective, anti cancer, antiprotozoal, anti-inflammatory, kidney stone due to certain phytochemical constituents Bergenin, Tannic acid, Gallic acid, Stigmesterol, β-Sitosterol, catechin, (+)-Afzelechin, 1, 8-cineole, Isovalaric acid, (+)-(6S)-parasorbic acid, Arbutin, Phytol, Caryophyllene, Damascenone, β-eudesmol, 3-methyl-2-buten-1-ol, (Z)-asarone, Terpinen-4-ol, Paashaanolactone present in it. The aim of present article is to explore the medicinal importance of the plant Bergenia ligulata wall.

REFERENCE ID: PHARMATUTOR-ART-1900

INTRODUCTION
Bergenia ligulata Wall(Saxifragacea) is a perennial herb. It is main botanical source of Pashanbheda. It is also known as silabheda, Pashana, Zakhmehayat, Asmaribheda, Ashmabhid, Ashmabhed, Nagabhid, Upalbhedak, Parwatbhed. Pashanbheda is a drug mentioned in the Ayurvedic system of medicine for various ailments but mainly as a diuretic and kidney stone. In India Bergenia ligulata wall grows at high altitudes between 1800-5100 meters in Himalayas usually in rocky areas and cliffs. (1-5,12)

Bergenia ligulata wall whole plant is used for kidney and bladder stones, urinary problems. (8,9,27-32) It has been reported to exhibit various pharmacological activities and thus has several traditional uses. It is used as an antidiabetic, antipyretic.(33-35). Bergenia ligulata wallused as diuretic,(36-39) hepatoprotective, alcoholic extracts of Bergenia ligulata wall showed anticancer, antiprotozoal, diuretic, cardiovascular, antilithiatic(8,40,41) litholytic property, anti-inflammatory. (42,43) Animals study for the activity of calcium oxalate growth inhibition, calcium oxalate inhibition, diuretic, hypermagneseuric and antioxidant effect.(3,15,44)

Various medicinal books mentioned Bergenia ligulata wall as a drug treating different diseases described as below:

Ayurveda: Leaf juice in urinary troubles, cold, hemorrhagic disease, distension of stomach and epilepsy.
Sushruta Samhita: In stones and sugars.
Charak Samhita: Useful in urinary complaints and stones.
Unani: In dissolving stones.
Chakradatta: In urinary troubles and stones.
Rajnighantu: In urinary disease.
Bhavaprakash: Astringent, bitter and sweet, purifies the urinary bladder.
Bergenia ligulata wall root, rhizome, and whole plant is used for kidney and bladder stones, urinary problems.(8-11)

SCINTIFIC CLASSIFICATION
Kingdom- Plantae – Plants

Subkingdom- Tracheobionta – Vascular plants

Superdivision- Spermatophyta – Seed plants

Division- Magnoliophyta – Flowering plants

Class- Magnoliopsida – Dicotyledons

Subclass- Rosidae

Order– Rosales

Family - Saxifragaceae – Saxifrage family

Genus - Bergenia Moench – elephant-ear

Species- Bergenia ligulata (wall)

VERNACULAR NAMES
Assamese: Patharkuchi, Bengali: Patharkuchi,Himasagara, Patrankur, Gujrati: Pashanbheda, Pakhanbheda, Hindi:Pakhanabheda, Silphara, Patharcua, Pakhanabhed, Silpbheda,silparo, Dakachru, Kannada: Alepgaya, Pahanbhedi, Hittaga, Pasanaberu, Hittulaka, Kashmiri: Pashanbhed, Malayalam: Kallurvanchi, Kallurvanni, Kallorvanchi, Marathi: Pashanbheda, Mizoram: Khamdamdawi, Pandamdawi, Oriya: Pasanbhedi, Pashanabheda, Punjabi: Kachalu, Pashanbhed,

Sanskrit: Asmabhedaka, Silabheda, Pashnabheda, Tamil:Sirupilai, Telugu: Kondapindi

DISTRIBUTION
Bergenia ligulata wall is distributed in temperate Himalayas and central, East, Western and Asia Tropical i.e. Indian Subcontinent Bhutan; India – Assam, Nepal and Pakistan. It grow well in shady, moist areas of Himalayas (Kumaon to Bhutan), South Tibet, Meghalaya, West Bengal, Darjeeling, Arunachal Pradesh, Gangtok (domesticated) in Sikkim.(3,6,7)

Botanical Identification of Bergenia ligulata wall

A perennial herb, up to 35 cm tall. Root-stock very stout. Stems short, thick, fleshy, and procumbent. Leaves few, spreading, 4-11 x 3-10 cm, glabrous or hirsute, sub-orbicular to orbicular or broadly obovate, base cordate or sometimes rounded, apex rounded or sometimes abruptly acuminate; margin entire to occasionally denticulate at top, fringed with short stiff hairs, both surfaces hairy, becoming almost hairless in age. Petiole 1-2(-5) cm long, glabrous or hirsute, sheathing at the base. Inflorescence a one sided raceme or corymbose, often subtended by an ovate leafy bract; bract glabrous or sparsely ciliate; scape and

inflorescence greenish or pink tinged. Peduncle up to 10 cm long; flowers pink to purplish, pedicellate. Sepals 7 mm long, oblong. Petals 10 x 4 mm, unguiculate, limb orbicular. Filaments 1 cm long, pink to red. Carpels 2. Styles 7 mm long. Carpels and styles green or pinkish. Flowering tem flexible, leafless, 10-25 cm. long. Capsule 13 x 6 mm, including styles. Seeds elongated, 1 mm long, brown, minutely tuberculate.(12-13)

Rhizome, solid, barrel shaped, cylindrical, 1.5-3 cm long and 1-2 cm in diameter with small roots, ridges, furrows and root scars distinct, transversely cut surface shows outer ring of brown coloured cork, short middle cortex, vascular bundles and large central pith, odour, aromatic, taste, astringent.(13,14)

PHYTOCONSTITUENTS:
Bergenia ligulata wallrhizome has many bioactive chemical constituents such as Paashaanolactone, Arbutin, (+)-AfzelechinBergenin, Catechin and Minerals,Vitamins, Abumin , Glucose , Mucilage, Gallicin,Gallic acid, Starch .(15-19)Seeds of Bergenia ligulata wallcontain Coumarin, Tannic acid, Gallic acid, Minerals and Wax.(20) leaves contain two flavonols, quercetin and kaempferol along with three rhamnosides and afzelin and quercitrin.(12,21)Root of Bergenia ligulata wall showed the presence of alkaloids, glycosides, flavonoids, terpenoids, tannins, steroids, carbohydrates and saponins in investigation. β-Sitosterol, Stigmesterol, Tannic acid and Gallic acid were isolated.(22) Parasorbic acid, Isovalaric acid , 1,8- Cineole ,(Z)-Asarone , Terpinen-4-ol were the constituents.(23-26)

Figure-: Chemical constituents isolated from Bergenia ligulata wall.

PHARMACOLOGICAL REVIEW

Anti-inflammatory activity
Aqueous and 50% ethanolic extracts of the rhizomes of Bergenia ligulata wall are reported to attenuate the inflammatory response as determined by pharmacological and biochemical measurements. The treatment significantly decreased the inflammation. The study reports the anti inflammatory activity of the rhizomes of B. ligulata wall.(45-48,52) The methanolic extract of the rhizome of Bergenia ciliata (100, 200 or 300 mg kg⁻¹) exhibited significant anti-inflammatory activity when evaluated using two acute rat models (carrageenan- and serotonin (5-HT)-induced rat paw oedema) and a chronic rat model (cotton pouch-induced granuloma). At 300 mg kg⁻¹ the methanol extract had shown the most effective results.(77) Aqueous and 50% ethanolic extracts of the rhizomes of Bergenia ligulata wall(1 g/kg bw)are also reported to attenuate the inflammatory response as determined by pharmacological and biochemical measurements.(78)

Antidiabetic activity
80% Ethanolic extract of B. ligulata wall rhizome was fractionated to investigate for α-glucosidase or antidiabetic activity. Sample solution were evaluated at dose levels of 5.0, 0.5, 0.05 mg/ml to obtain dose response. The ethyl acetate extract exhibited an inhibitory effect of α-glucosidase activity. The α-glucosidase inhibitor was isolated by column chromatography with chloroform and methanol as eluents and identified as (+)-Afzelechin by EI-MS, IR, H1 and C13 NMR spectroscopy.This research suggests that the α-glucosidase inhibitor in B.ligulata wall was primarily (+)-Afzelechin.(49-52,76)

Diuretic activity
Ethanolic extracts of root of Bergenia ligulata wall were assessed for diuretic activity in albino rats that was compared with standard drugs. For evaluation of the diuretic activity. It was done by measuring the volume of urine collected at the end of 5 hrs and Na+,K+ and Cl- concentration in urine. The ethanolic extract of the roots of Bergenia ligulata was found to produce significant activity. (52-58)

Antilithic activity
Alcoholic extract had no effect in preventing stone formation in rats but it was significant help in dissolving preformed stones. Low doses of B.ligulata wall extract (0.5 mg/kg of alcoholic extract) promote diuresis in rats, but higher dose 100 mg/kg reduce the urine output and reduce the dieresis produced by urea .(49,59)

The crude aqueous-methanolic extract of Bergenia ligulata wall rhizome (BLR) was studied using in-vitro and in-vivo methods. The result was that BLR inhibited calcium oxalate (CaC2O4) crystal aggregation as well as crystal formation in the metastable solutions and exhibited antioxidant effect against 1,1-diphenyl-2- picrylhydrazyl free radical and lipid per- oxidation in the in vitro. BLR caused diuresis in rats accompanied by a saluretic effect. In an animal model of urolithiasis, developed in male wistar rats by adding 0.75% ethylene glycol (EG) in drinking water, BLR (5-10 mg/kg) prevented (CaC2O4) crystal deposition in the renal tubules. The lithogenic treatment caused polyuria, weight loss, impairment of renal function and oxidative stress, manifested as increased malondialdehyde and protein carbonyl contents, depleted reduced glutathione and decreased antioxidant enzyme activities of the kidneys, which were prevented by BLR. Unlike the untreated animals, EG intake did not cause excessive hyperoxalurea and hypocalciurea in BLR treated groups and there was a significant increase in the urinary Mg2+, instead of a slight decrease. These data indicate the antiurolithic activity in Bergenia ligulata wallmediated possibly through (CaC2O4) calcium oxalate crystal inhibition, diuretic, hypermagneseuric and antioxidant effects and this study rationalizes its medicinal use in urolithiasis.(52,60)

Antipyretic activity
Ethanolic (95%) extracted of roots, rhizomes and leaves and aqueous extract of whole plant of Bergenia ligulata Wall in yeast induced fever in albino rats of wistar strain were assessed for antipyretic activity. The yield of semisolid mass was obtained as ethanol extract of roots, ethanol extract of rhizomes, ethanol extract of leaves and aqueous extract of whole plant. Acute toxicity studies were carried out for all the extracts of Bergenia ligulata Wallon healthy swiss albino mice of body weight 25-35g by using Up and Down or Stair case method. The suspension of all the extracts of Bergenia ligulata Wall was prepared in 5% gum acacia and employed for assessment of antipyretic activity at the dose of (300 and 500mg/kg- body weight). The standard drug used was paracetamol (200mg/kg.p.o). Rectal temperature of experimental animals was recorded at a time interval of 1hr, 2hr, 3hr, 4hr and 5 hr after drug administration for evaluation of antipyretic activity. The ethanolic extract of roots and rhizomes of Bergenia ligulata Wall at a dose of 500mg/kg.p.o decreased the yeast induced fever in experimental animals.Bergenia ligulata wallwas found to produce significant antipyretic activity(61-63)

Hepatoprotective activity
Ethanolic extracts of root of Bergenia ligulata wall were assessed for hepatoprotective activity in albino rats that was compared with standard drugs. Acute toxicity studies were carried out for ethanolic extract of Bergenia ligulata root on healthy Swiss albino mice of body weight 25- 35g by using Up and Down or Stair case method. Evaluation of the hepatoprotective activity was done by measuring the levels of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transminase (SGOT) serum alkaline phosphatase and total bilirubin levels. The ethanolic extract of the roots of Bergenia ligulata wallwas found to produce significant activity.(34,64,65)

Antiviral activity
Methanol-water extract from rhizomes of Bergenia ligulata wall inhibited in vitro the replication of influenza virus in a dose dependent manner and did not show virucidal activity at effective concentration. Pretreatment of cells with B. ligulata wallextract was shown to be most effective to prevent cell destruction. The extract inhibited viral RNA synthesis and reduced viral peptide synthesis at10 microg/ml. The principal chemical compound was condensed tannins in the extract.Bergenia ligulata wallwas found to produce significant activity.(65,66)

Antibacterial activity
The antibacterial activity was tested using the disc diffusion method measured by 10, 25 and 50 mg/ml plant extract. The zone of inhibition was calculated by measuring the minimum dimension of the zone of no microbial growth around the well. Aqueous, 50% ethanolic and methanolic extracts of B. ligulata wall rhizomes were tested for their ability to inhibit the growth of E. coli, B. subtilis, and S. aureus at the dose levels of 10, 25 or 50 mg/ml for each extract. At a dose level of 50 mg/ml, the antibacterial effect was most significant. The antibacterial effect of the extracts at this level was comparable to ciprofloxacin (25 mg/ml). The results clearly suggest that B. ligulata wall possesses a strong antibacterial activity.(53,61,68)

Anti-bradykinin activity
Alcoholic extract of Bergenia ligulata wall rhizome displays marked anti bradykinin activity. Although it does not affect the action of 5-HT and acetylcholine on isolated guinea pig ileum. It has been shown to potentiate the action of adrenaline on guinea-pig trachea and ileum muscle. Its cardiotoxic, antidiuretic and CNS depressant action on experimental models have been reported with large doses. It is unlikely that these effects will be encountered with the doses in clinical use. In rats, the LD50of the aqueous extract was 650 mg/kg intraperitoneally. It is widely used in the treatment of dysuria and renal failure, cystitis and crystalluria. Its anti-inflammatory property finds a use in the treatment of abscesses and cutaneous infections. It is also used in the treatment of dysentery and diarrhea.(54)

Free radical scavenging activity
Free radical scavenging activity was measured by a decrease in the absorbance at 516 nm of methanolic solution of coloured DPPH brought about by the sample. A stock solution of DPPH (1.3 mg/ml methanol) was prepared such that 75 μl of it in 3 ml methanol gave an initial absorbance of 0.9. This stock solution was used to measure the antiradical activity. Decrease in the absorbance in the presence of methanolic extract of B. ligulata wall rhizome at different concentrations was noted after 15 min. EC50 was calculated from % inhibition.(69-71)

Insecticidal Effect
Chemical composition of the volatile oil from roots of Bergenia ligulata wall was analyzed by GC-MS. The volatile oil and the isolated compound were tested against Drosophila melanogaster. The results obtained showed that the volatile oil from roots could be considered as natural insecticidal effect.(72)

Anti-tussive activity
Methanol extract of the rhizome of Bergenialigulata wall has been evaluated for its potential in a cough model induced by sulphur dioxide gas in mice. The extract exhibited significant anti-tussive activity in a dose-dependent manner, as compared with control. The anti-tussive activity of the extract was comparable to that of codeine phosphate (10 mg/kg body wt.), a standard anti-tussive agent. The extract at doses of 100, 200 and 300 mg/kg body wt. (p.o.) showed significant inhibition of cough reflex by 28.7, 33.9 and 44.2%, respectively, within 90 min of the experiment.(73-75)

CONCLUSION
The present review depicts the various medicinal properties of Bergenia ligulata Wall which is very useful to researcher for further investigation. Even the anti-cancer property is being tested. The phytoconstituents responsible for the activities should be evaluated to identify the mechanistic study. In a nutshell, we can say that Bergenia ligulata wall is a reservoir plant for therapeutic applications.

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