Bergenia pacumbis (Buch.-Ham. ex D.Don) C.Y.Wu & J.T.Pan: A Comprehensive Review on Traditional Uses, Phytochemistry and Pharmacology

The influence of medicinal plants on humanity spans time immemorial. These plants are also used at present with local and tribal peoples for the cures of various illnesses. Nature has produced an immense number of medicinal plants, which directly or indirectly help to treat various ailments and have numerous applications in the fields of pharmaceuticals, agriculture, food flavors and preservatives, aromas, and cosmetics. Bergenia pacumbis (Buch.-Ham. ex D.Don) C.Y.Wu & J.T.Pan (synonym: Bergenia ligulate Engl.), is an important medicinal plant belonging to the Saxifragaceae family, and not to be confused with Bergenia ciliata (Haw.) Sternb., and is popularly known as Pashanbheda (meaning to dissolve the kidney stone). This plant is a rich source of secondary metabolites (SMs) such as coumarins, flavonoids, benzenoids, lactones, tannins, phenols, and sterols, which make this plant a highly valued medicinal herb with a broad spectrum of pharmacological activities such as anti-urolithic, antioxidant, anti-viral, free radical scavenging, antidiabetic, anti-hepatotoxic, diuretic, antipyretic, anti-oxaluria, anti-tumour, antibacterial, antifungal, anti-inflammatory, antimicrobial, and cardioprotective. This review summarizes traditional uses and offers up to date data for future research on B. pacumbis.

Bergenia pacumbis is recognised as an endangered or threatened and vulnerable medicinal plant species using the new IUCN (International Union for Conservation of Nature) criteria, so conservation of this plant is necessary. This article provides detailed procedures for the cultivation of B. pacumbis, which is very important and was lacking in previously published review papers [3,5,13,19,21,22]. Thus, the efficient strategies for usage, conservation, protection initiatives, and effective agro-techniques of the species are instantly required. Bergenia pacumbis is a rich source of a variety of naturally occurring bioactive secondary metabolites, but the extracts and naturally occurring bioactive secondary metabolites of this plant have not as yet been fully explored both in-vivo and in-vitro model studies [3,5,21]. Therefore, this plant has strong potential for further impact in the field of phytochemistry and pharmacology. Further, due to the lack of proper taxonomic profiling, people often misidentify B. pacumbis with other species of the same genus due to the misunderstanding in the morphology of the species. This article provides brief information about the morphology of the B. pacumbis and is helpful for the correct identification and authentication of this species. It is expected that this article will encourage the researcher worldwide to explore more and more about this medicinal plant. As this species is endangered, it is more important to study this plant thoroughly to know its full potency, and there is a need to find a better way to cultivate this plant. This review article summarizes the available literature on B. pacumbis regarding its botanical description, morphology, traditional uses, cultivation procedure, phytochemicals, pharmacological activities, and patents filed on this plant. It provides up to date data for future research in the potential manufacture of new drugs and further clinical studies. Bergenia pacumbis is one among the most vital species of the Bergenia genus, popularly known as the stone flower, the stone breaker, and pashanbheda [23]. It is a perennial herb rich in many phytochemical constituents, which mainly occur in temperate regions of the Himalayas from Kashmir to Bhutan in the Khasia Hills at 1800-5100 m [3,22,24], usually growing in rocky areas and cliffs. It acts as a prime storehouse of bioactive SMs like βsitosterol, tannic acid, stigmasterol, gallic acid, bergenin, (+)-afzelechin, (+)-afzelechin tetraacetate, (+)-5,7,4 trimethyl afzelechin, (+)-tetramethoxyafzelechin, and (+)-3-acetyl-5,7,4 trimethoxyafzelechi [3,4,21,22]. This plant is regarded as a highly valued medicinal herb in traditional Nepalese, Indian, and Chinese medicine systems. It is mainly used for the cure of pulmonary diseases, coughs, to increase immunity in humans, to stop bleeding, and to dissolve bladder or kidney stones [3,21,24]. Bergenia pacumbis also possesses wide clinical applications such as to treat psoriasis [3,5], airway mucus hypersecretion and asthma, kidney disorders [3,21,[25][26][27], the inhibition of blood cholesterol level absorption in the intestine [28], the inhibition of CaC 2 O 4 crystal formation, crystal aggregation, crystal deposition in renal tubules, the inhibition of calcium and phosphate accumulation, the inhibition of α-glucosidase [29,30], it suppresses arachidonic acid metabolism and production of cytokine in human monocytes [31], reduces the urine output and dieresis production of urea [32], and shows hypermagnesemia activity. Moreover, this plant has a wide spectrum of pharmacological effects such as anti-histamines, anti-tissusive, insecticidal, anti-convulsant in valerian, anti-oxidant [3,20,33,34], anti-viral against influenza virus [35,36], antidiabetic [37], hypoglycemic, diuretic, anti-oxaluria, and has cytotoxic activity [3,24,[37][38][39].
Although this plant is commonly grown and traditionally used by local people of the northern Himalayan region, Kashmir, Bhutan, and Khasia hills to cure various illnesses, its clinical applications have not been explored to their full potential. Furthermore, the plant is not used as a whole, instead its individual part demonstrates engaging pharmacological activities. The presence of many SMs implies a high chance to manufacture drugs, which can benefit humanity.

Methodology
Our information gathering started with the search of relevant literature on B. pacumbis, and all its synonyms were confirmed through the plant database (http://www.theplantlist. org/tpl1.1/record/kew-2674823, accessed on 20 April 2022,). This review article discusses medicinal uses, phytochemistry, pharmacological effects, and toxicity of B. pacumbis from various databases such as Google Scholar, Web of Science, Science Direct, Scopus, and PubMed. In total, 102 articles were reviewed. In this review, only the articles published in the English language were taken into consideration and search for the data gathered from various databases was carried out by using a set of keywords including B. pacumbis; phytochemistry; kidney stone healer; anti-influenza; and antioxidant properties. In this paper, the literature has only been taken from the published work though some additional data may be taken from unpublished work, Ph.D. theses, etc. Additionally, the reported phytochemicals in this species were verified using the IUPAC name from PubChem; structural and chemical formulae were drawn and confirmed from Chem Draw software in ACS format and Pubchem, respectively. Furthermore, for reference, we used the software Mendeley.

Botanical Description
The botanical classification and Indian vernacular names of B. pacumbis are given in Table 1 [3,19,21,40].

Morphology
Bergenia pacumbis ( Figure 1) is a rhizomatic perennial herb bearing leathery, rubbery, and fleshy leaves growing up to 30-35 cm tall, having a rhizomatous rootstock with intermittent auxiliary buds and a short stem [3,21,22,41]. The plant is very hardy and can survive throughout wintertime by turning red. It is an evergreen plant and has blooming flowers, which are bisexual with around 4-10 cm long cymose panicles in the period between April to June with characteristic white, pink, and purple. It has a surprising survival technique in which the rhizome arises out from the crevices of stones or rocks and hangs in the air on the slopes and can capture moisture from the air. Its leaves are glabrous, long, sparsely hairy in margins, widely obviate or elliptic, and finely or shallowly sinuate-dentate. The fruit is contained around a capsule-like structure containing numerous minute grey seeds in each capsule [3,22,[40][41][42].

Distribution
In India, the plant is found mainly in the northeast temperate Himalayas particularly in Jammu & Kashmir, Uttarakhand, Himachal Pradesh, and northeastern hilly states between the altitudes of 1200-3000 m, in rocky slopes of stone crevices present in cold or glacial mountains ( Figure 2). It is also reported at higher altitudes in the Himalayan area of adjoining countries of Indian such as Afghanistan, Pakistan, Nepal, China, and Tibet [3,21,40,42].

Cultivation and Soil Conditions
Bergenia pacumbis grows well in temperate and humid climatic environments, where the temperature usually remains less than 20 • C. The plant grows healthy in sandy soil, which is somewhat acidic, has higher porosity, and is richer in humic organic matters. Owing to its hardy nature, this species can also grow well in medium loamy to clay soils that is augmented with manure. It bears light shade and raises well beneath open sunny environments. Nevertheless, vegetative growth is better in the shade, which takes about one month to develop to supply planting material for raising cultivation. So, the B. pacumbis is not suitable for sunny areas but grows well in shady and moist areas [43].

Propagation by Rhizome
For faster regeneration of the species in the field during late summer or the onset of monsoons, the plant can be raised directly by planting 7.5-12.5 cm long rhizome segments with 2-3 nodes as propagation material. Raising crops by the aforementioned technique can lessen the crop cycle by one year in comparison to traditional method of propagation (by seeds). However, numerous rhizome segments have been required for planting to have faster regeneration. For this purpose, smaller rhizome segments (2 cm thick) can be imbedded in the soil at a spacing of 10 × 10 cm. The growing rate of the species is slow and it takes around 18 months to raise the species in the nursery for field imbedding [43,44].

Propagation by Seeds
The second method is using seeds that are tiny in size and show poor viability and propagation potential. The seeds are bedded at 4 • C for 15 days to enhance germination. The storing of seeds leads to a drop in viability of the seeds. Greenhouse conditions are needed for better results [43,44]. The seeds take around 60-90 days to germinate. After germination, the seedlings are ready to plant in fresh nursery beds once it reaches the two-three leaved stage. The seedlings are planted at a spacing of 10 × 10 cm. It takes a whole season to grow large enough for imbedding in the field [43,44].

Traditional Uses
Bergenia pacumbis is used to treat various ailments by the Indian people, referenced in ancient medicinal books of India. The literature revealed that the plant has been used to treat urinary diseases and many other ailments since ancient times ( Table 2).  [3,21,22,[45][46][47].

Indian Traditional Medicinal Systems and Related Books Traditional Uses
Ayurveda Ayureveda documented the use of leaf extract of B. pacumbis to treat various urinary disorders such as stone formation. It is also used to treat hemorrhagic disease, stomach related pain, and neurological disorders that cause seizures or unusual sensations and behaviour.

Sushruta Samhita
Sushruta Samhita highlighted the use of plant extract to dissolve kidney stones, inhibit stone formation, also help to treat sugar-related problems.
Charak Samhita and Chakradatta Charak Samhita and Chakradatta revealed the use of B. pacumbis mainly for treatment of urinary diseases.

Unani
Unani system of medicine documented the potential of B. pacumbis in stone dissolution.

Rajnighantu
Acoording to Rajnighantu B. pacumbis is mainly used for the treatment of various ailments associated with urinary bladder.

Bhavaprakash
Prevention of causing the contraction of skin cells and other body tissues, also helps to treat urinary related problems.
From the prehistoric time, B. pacumbis water-extract has been usually used to cure kidney-stone and urogenital disorders. In Nepal, the paste prepared from B. pacumbis rhizome is consumed as a remedy to treat various diseases including ulcers, diarrhoea, colds, dysuria, coughs, pulmonary infusions, spleen enlargements, and fevers. The rhizomes along with molasses are also consumed to remove intestinal worms. In India, the dried roots of the plant are used to treat wounds, boils, burns, and ophthalmia [3,21,[45][46][47]. Bergenia pacumbis possesses a vast range of disease curing properties but its full potential is still to be discovered. Literature has covered some traditional uses of this plant in its native habitats, and these are shown in Table 3. An extensive survey of the literature indicates that the plant is used not only to treat urinary diseases but also to treat many other ailments since ancient times and these are presented in Table 4. Though there are many traditional uses of B. pacumbis from the ancient days, researchers have currently manufactured some modern medicines using organic solvent extracts of various parts of this plant, which are described in Table 5.   [21].

Types of Diseases Method of Use
Dissolution of kidney and gall bladder stone Rhizome extract is dried and then swallowed [52] Wound healing Powder of dried leaves and rhizomes are applied to heal old wounds Cough and cold Leaves and rhizome are boiled with water and swallowed [53] Cuts and burns Crushed rhizome is mixed with curd and applied gently on burns [

Phytochemical Composition
The presence of a diverse range of phytochemicals ( Figure 3) imparts significant medicinal importance to B. pacumbis. Different phytochemicals are distributed all over the plant, as discussed in the following sub-sections. The qualitative analysis of various extracts obtained from different parts of B. pacumbis revealed the presence of tannins, flavonoids, quinines, phenols, carbohydrates, glycosides, cardio glycosides steroids, proteins, and saponins [3,21,42,59].

Quantitative Analysis Phytoconstituents Present in B. ligulata
The result of quantitative analysis of B. pacumbis revealed the presence of total phenol, flavonoid, and tannin in amounts of 139.8 ± 9.06 mg of gallic acid equivalent/g, 77 + 6.40 mg of quercetin equivalent/g and 70.4 + 6.40 mg of tannic acid equivalent/g of plant extract at 500 µg/mL concentration [59].

Anti-Inflammatory
Studies have exposed that aqueous and alcoholic extracts of fresh rhizomes of B. pacumbis show anti-inflammatory activity in biological systems at a dose level of 1 gm/kg. [64]. An amount of 0.1 mL of 1% carrageenan solution was injected into the left-hand paw of the rat and caused an increase in the volume of the rat's paw. This volume increment is measured every hour, and then the inhibition percentile is calculated. Results show that B. pacumbis has an excellent potential for anti-inflammatory activity [64,65]. Research has also revealed that B. pacumbis possesses some radical scavenging activity [66].

Antibacterial
The literature revealed that B. pacumbis extracts also possess antibacterial activity [3,21,64,67]. The plant extract was used in three concentrations (10, 25, 50 mg/mL), and the antibacterial activity was measured via the disc diffusion method. The various extracts of the plant (methanolic, ethanolic, and aqueous) was tested in a culture plate containing Escherichia coli, Bacillus subtilis, and Staphylococcus aureus at the dosages mentioned above and the extracts contain significant antibacterial activities. Reports show that at a concentration of 50 mg/mL, the antibacterial activity reached maximum levels, which were found to be equal to the antibacterial activity of ciprofloxacin (25 mg/mL) [64].

Anti-Viral
Anti-viral activities of B. pacumbis have been reported in a study on Nepalese medicinal plants [35,36]. The extracts (methanolic and hydromethanolic) were analyzed for influenza and herpes viruses, and the highest anti-influenza viral activity was observed at the dosage of 10 µg/mL [68]. The rhizome of B. pacumbis was used to prepare an extract containing methanol and water as a solvent, and this extract had good viral inhibitory properties against the influenza virus [21,68]. The extract inhibits the viral RNA synthesis, and the study shows that the peptide synthesis rate was decreased strongly at the concentration of 10 µg/mL. The study revealed that tannin is the main component present in the plant rhizome extract, increasing protein availability and acting as an antioxidant and as a metal ion chelator in the chosen biological systems [22].

Diuretic Activity
The ethanolic extracts of B. pacumbis roots were tested on albino rats to study their diuretic activity using the Lipschit method [13,69]. Diuretic activity was suspected by measuring the volume of urine collected at an interval of 5 h and also by measuring the Na + , K + , and Cl − ion concentrations in urine collected from the rats [70]. The ethanol extracts possess the highest diuretic activity. The same group of researchers also studied the effects of an ethanolic extract of B. pacumbis roots on artificial urine and human urine where CaC 2 O 4 crystals were introduced in the first one. In the case of human urine, the crystals were already present. On adding extract prepared from the roots of B. pacumbis, artificial urine showed the reduction of the crystal ring size, which confirms that the extract may be active in-vitro. Nevertheless, when the extract was applied to the human urine, it showed remarkably other characteristics than CaC 2 O 4 crystal inhibition such as antioxidant effects and hypermagneseuric effects. From these results, it was concluded that B. pacumbis possesses diuretic activity [64,69,70].
Further studies revealed that methanolic extracts of B. pacumbis and bergenin showed a noticeable dissolution of urinary calculi in the kidney. In-vitro antilithiatic/anti calcification potential of different extracts obtained from B. pacumbis and Dolichos biflorus L. were tested independently and in combination by the homogeneous precipitation method [33]. The results of tested extracts were compared against 'Cystone' (a Himalaya company formulation sold in India) aqueous extract. Bergenia pacumbis extract showed lesser activity while D. biflorus extract displayed almost equivalent activity as compared to 'Cystone'. Although, the combination of two extracts is less active in comparison to the individual extracts. The author concluded that active constituent/s may act by inhibiting calcium and phosphate accumulation and are non-protein and non-tannin in nature. Another study on rats revealed that, the low doses of B. pacumbis alcoholic extracts (0.5 mg/kg) promote diuresis, but higher doses (100 mg/kg) retard the diuresis produced by urea and urine output. It is also reported that, the aqueous extracts of B. pacumbis have better potential as compared to the aqueous extract of Tribulus terrestris L. for inhibiting the growth of calcium oxalate monohydrate crystals [32]. This study showed that there are secondary metabolites present in B. pacumbis known to play a significant role in the dissolution of calcium oxalate monohydrate crystals [33].

Antilithic
The antilithic property of an alcoholic extract of B. pacumbis showed no effect in rats in the inhibition of stone formation, but the low dosage of crude alcoholic extract (0.5 mg/kg of extract) endorses the diuresis, and higher dosage (100 mg/kg of extract) reduced the diuresis produced by urea [71,72]. The study also revealed that applying 0.75% ethylene glycol in water (5-10 mg/kg extract) of B. pacumbis rhizome in rats prevents the deposition of the crystal in the renal tubules of a rat. The application of B. pacumbis rhizome extract prevented the side effects after lithogenic treatment such as polyuria, decreased antioxidant, weight loss, renal dysfunction, etc. The study also showed that after extract application, there was a slight increase in the Mg 2+ ions in the urine, indicating the anti-urolithic activity of B. pacumbis [28,29,34,54,71].

Anti-Bradykinin Activity
Though the rhizome extract of B. pacumbis shows anti-bradykinin potential, it does not affect the activity of acetylcholine and 5-hydroxytryptamine (5-HT) on guinea-pig ileum. The rhizome extract increases the adrenaline level on the guinea pig trachea, and in addition, the smooth ileum muscle shows cardiotoxicity and central nervous system depressant activity. In rats, the lethal dosage of the aqueous extract of B. pacumbis rhizome was 650 mg/kg (i.p.). It is widely used to treat painful or difficult urination, renal failure, infection, or inflammation of the urinary bladder and crystalluria, which is caused due to the side effects of sulfonamides and penicillin, abscesses, cutaneous infection, dysentery, and diarrhoea [3,17,61].

Hepatoprotective
The hepatoprotective activity was investigated in albino rats (weight 25-35 gm) by using the ethanolic extract of B. pacumbis roots and compared with the standard drug "Liv-52" (manufactured by Himalaya Drug Company, Bangalore), by inducing hepatotoxicity using carbon tetrachloride (CCl 4 ). The investigation was performed using the Up and Down or Staircase method [70]. The ethanolic extract of B. pacumbis restored the integrity of hepatocytes indicated by improvement in physiological parameters, which was confirmed by measuring the levels of transaminase, serum alkaline phosphatase, oxaloacetate, serum glutamate, pyruvate transaminase, serum glutamate, and bilirubin levels and known to have a significant hepatoprotective potential [3,13].

Antipyretic
The literature revealed that B. pacumbis possess a substantial antipyretic potential. Singh and coworker examined the ethanol (95%) and aqueous extract obtained from the roots of B. pacumbis for their antipyretic potential. The extracts were mixed with 2% gum acacia and injected to Wistar rats (500 and 300 mg/kg body weight) infected with pyrexia [70]. Paracetamol (200 mg/kg, standard antipyretic) was used as a positive control. The rectal temperature of the infected rats was noted after an interval of 1 h. A noteworthy lowering in the rat's body temperature was noted with ethanol extract (500 mg/kg) ( Figure 5). The present study along with others reports validated that B. pacumbis owns substantial antipyretic activity [13,70,73].

α-Glucosidase Inhibition Activity
The ethanolic extract (80%) of B. pacumbis rhizome led to the investigation of αglucosidase activity at dose levels of 5.0, 0.5, and 0.05 mg/mL and the ethyl acetate extract was used to inhibit the effect of α-glucosidase activity. The trigger compound was identified as (+)-afzelechin (2 g), which was confirmed by EI-MS, IR, proton NMR, and 13 C NMR spectral analysis [29]. Further, the inhibitory activity of the compound at a concentration of 0.25 mM was studied at a 50% inhibition dose, i.e., 0.13 mm. ID 50 values of (+)-catechin and (-)-epicatechin were 12.8 mM and 0.18 mM, respectively. From these data, the α-glucosidase inhibitor in B. pacumbis is primarily due to the presence of (+)-afzelechin [20,29,37].

Antioxidant Activity
Bergenia pacumbis methanolic extract efficiently scavenge 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and exhibit good free radical scavenging potential with an IC 50 value of 50 µg/mL. The water and n-butanol fractions obtained from methanol extract were screened for their free radical scavenging potential (in-vitro) by DPPH and the nitric oxide assay. The n-butanol and water fractions showed the IC 50 value of 4.5 µg/mL and 30 µg/mL, respectively [48,74]. Bergenin isolated from B. pacumbis also showed significant antioxidant potential [59,75].

Analgesic
The analgesic potential of B. pacumbis rhizomes was assessed by employing hot plate and tail clip methods using hydroalcoholic extract (250 mg/kg), which was administered intra-gastrically in the mouse. However, the extract exhibited much less analgesic potential during the study [3,13,22].

Anti-Oxaluria
Anti-oxaluria activity on Indian adults was studied where tablets were prepared with Didymocarpus pedicellatus R.Br., B. pacumbis, Rubia cordifolia L., Cyperus scariosus R.Br., Achyranthes aspera L., Veronica cinerea Boiss. & Balansa, Hajrul yahood bhasma, and Shilajeet purified in the ratio 65:49:16:16:16:16:16:13 (in mg) and investigated on 32 healthy volunteers and 48 people suffering from stones. All patients were given two tablets (3 times/day) and advised to avoid oxalate-rich foods in their diet, and the treatment lasted for 8 weeks. A steady decrease in oxalate elimination was noted in persons infected with kidney stones, but the level of oxalate elimination was not as low as observed in usual adults. This study revealed that the present formulation might deliver a capable drug that regulate the activity of oxaluria [3,76].

Anti-Tumor
Bergenia pacumbis hydroalcoholic extract was injected intraperitoneally in rats to evaluate its anti-tumour potential. The extract exhibited activity against SARCOMA WM1256 IM cell culture at the dose of 20 mcg/mL, which pointed out that B. pacumbis hydroalcoholic extract exhibited cytotoxic activity [3].

Cardioprotective
The hypotensive activity of B. pacumbis hydroalcoholic extract was carried out in different animal models. A positive hypotensive activity was noted in dogs when injected with 50 mg/kg dose (i.v.) [3]. Further, the B. pacumbis extract also showed positive inotropic and chronotropic effects on a frog's heart [17]. While in the case of continuous rabbit's heart perfusions, the extracts exhibited adverse chronotropic and inotropic effects with a decrease in coronary flow. The alcoholic extract B. pacumbis elicited marked anti-bradykinin activity (in-vitro and in-vivo) but was unable to modify the response of acetylcholine and 5-HT on guinea-pig isolated ileum [3,77].

Insecticidal Activity
Kashima and coworkers evaluated the insecticidal potential of essential oil and parasorbic acid obtained from roots of B. pacumbis against adults of Drosophila melanogaster. The results revealed that both the essential oil and parasorbic acid were active against the insect, but parasorbic acid had more insecticidal potential as compared to the essential oil [20].

Patents
Mitra has filed a patent on a skincare product maintaining the skin around the eyes, prepared from the extracts of B. pacumbis, Emblica officinalis Gaertn., Cipadessa baccifera (Roxb. ex Roth) Miq., and cosmeceutically acceptable constituents [3,67]. Lee and Martin patented a skincare product to maintain skin and tanning [67,78]. Agarwal and Kumar also patented a better and improved process for isolating the main component, bergenin, from Bergenia species [3,79].

Safety and Toxicity Profile
Bergenia pacumbis is primarily used as one of the critical ingredients of various preparations for the treatment of kidney diseases, e.g., Nephrolex and Cystone (Himalaya Herbal Healthcare, Bangalore). The acetone extract obtained from B. pacumbis rhizomes is cardiotoxic in nature at higher dosages. It is also reported to have a depressant or sedative effect on the CNS (central nervous system) [3]. The CNS depressant, antidiuretic and cardiotoxic effect of B. pacumbis on experimental models have been noted only at higher dosages. The LD 50 of the aqueous extract in rats has been found to be 650 mg/kg when injected intraperitoneally [3,77].

Prospects and Medicinal Opportunities
Bergenia pacumbis is one of the essential folk medicinal herbs found in the Himalayan region. It is primarily used for coughs, to stop bleeding, and to increase immunity [3,21]. Among the numerous phytochemicals present in this plant, the polyphenols are mainly of interest, showing a wide range of medicinal properties.
Edible and Cosmetic: Bergenia pacumbis possesses many minerals and amino acids, which show antibiosis and dieresis properties and may be used as a disinfectant of urine. This study was performed both in-vivo and in-vitro on male Wistar rats to understand better the medicinal use of the various extracts of B. pacumbis [34].
For cosmetic aspects, the presence of arbutin in the plant can make a skin brightening agent because it causes inhibition of tyrosinase on the skin. Also, the presence of so many phenolic compounds implies a potential way to synthesize metallic nanoparticles, as literature has revealed that nanoparticle synthesis is possible from the extracts of other species of the Bergenia genus [81].
Gaurav and Gaurav raised various authentication, overexploitation, and standardization as drug pharmacology in their review article on B. pacumbis published in 2014 [3]. The present article addressed all these issues and will be very helpful for proper authentication, identification, cultivation, conservation, and utilization of B. pacumbis.

Conclusions
Much research has been performed on the B. pacumbis plant during the last few decades to investigate its phytochemical composition, biological potential, and traditional and modern uses. The present review reports recent information about medicinal uses, phytochemicals, biological investigations, and patents of B. pacumbis. Bergenia pacumbis is a highly valued medicinal plant and has been traditionally used among the various communities across India, Pakistan, Nepal, and Tibet, mainly in the Himalayan region to treat urinary disorders, respiratory problems, influenza, asthma, and inflammatory and infectious diseases. Further, rhizomes and leaves of the species are also used to treat kidney stones and various other disorders associated with the kidney. Almost all parts of B. pacumbis are used to treat various ailments, but the most used part is the rhizome. The preferred mode of utilization is powdered drug and aqueous extract of rhizome and leaves. Pharmacological investigations showed that it has potent anti-urolithic, antioxidant, anti-viral, free radical scavenging, antidiabetic, hepatoprotective, diuretic, antipyretic, anti-oxaluria, anti-tumour, antibacterial, anti-fungal, anti-inflammatory, antimicrobial, and cardioprotective potential.
It is quite evident from present review that the B. pacumbis is known to have a wide range of bioactive phytochemicals that possesses tremendous therapeutic values. The efficacy and safety of different parts of B. pacumbis have been well recognized and timetested during the prolonged historical traditional uses. However, still there are many pharmacological activities that are yet to be explored. In addition, there is a tremendous scope of research related to the investigations about the mechanisms of action of the various aforementioned pharmacological activities. Further, the toxicity and safety of B. pacumbis have not been explored much, so further work is also required in this particular domain.
The current review suggests a varied opportunity for several benefits of B. pacumbis in the field of pharmaceuticals, health foods, cosmetics, floriculture, and many other economic and industrial endeavors. The present study can be beneficial in proper authentication, identification, cultivation, conservation, and utilization of B. pacumbis and may contribute to the direction of further scientific research to explore more about its pharmacology, toxicology, cultivation techniques, conservation, and bioactive formulations. To conclude, B. pacumbis has a vast potential to act as a remedy to various health-related illnesses, and thus its conservation is requisite.