Bergenia

Other Names

AshmabhedAshmabhidAsmaribhedabadanBergenia bifloraBergenia ciliataBergenia cordifoliaBergenia ligulataBergenia mediaBergenia pacumbisBergenia purpurascensBergenia stracheyiBergenia thysanodeselephant earselephant's earselephant-eared saxifragefringed bergeniaGeryonia crassifoliahairy leaf bergeniaheart-leaved bergeniaheartleaf bergeniaKorean elephant-earlarge rockfoilleather bergenialeather cabbageMegasea ciliataMegasea crassifoliaMegasea mediaMongolian teaNagabhidPaashaanbhedParwatbhedPashanaPashanabhedaPashanbhedaPiarophyla cordifoliapicnic platespig squeakpigsqueakPrashanbhedarockfoilSaxifraga ciliataSaxifraga cordifoliaSaxifraga crassifoliaSaxifraga delavayiSaxifraga ligulataSaxifraga pacumbisSaxifraga purpurascensSaxifraga thysanodesShilabhedShiyancaiSiberian teastone breakerstone flowerUpalbhedakwinter-blooming bergeniaXuetoukaihuaYanbaicaiYanqi

Synopsis

Bergenia: A Comprehensive Reference

1. Identity and Botanical Classification

The genus Bergenia harbors 32 species of flowering plants, including highly valued ornamental, rhizomatous, and temperate medicinal herbs, with Central Asia as its native place. The plant family Saxifragaceae encompasses 48 genera and 775 species, which are mostly distributed in South East Asia. The name "Bergenia" was coined by Conrad Moench in 1794, in memory of Karl August von Bergen, a German botanist and physician.

Bergenia species are evergreen, perennial, drought-resistant, herbaceous plants that bear pink flowers produced in a cyme. Due to their leaf shape and leathery texture, Bergenia species have earned common nicknames such as "pigsqueak," "elephant-ear," "heartleaf," "leather cabbage," or "picnic plates."

They are clump-forming, rhizomatous, evergreen perennials with a spirally arranged rosette of leaves 6–35 cm long and 4–15 cm broad, and pink flowers produced in a cyme. The leaves are large, leathery, ovate or cordate, and often have wavy or saw-toothed edges. For most of the year, the leaves have a glossy green colour, but in cooler climates, they turn red or bronze in the fall. The flowers grow on a stem similar in colour to a rhubarb stalk, and most varieties have cone-shaped flowers in varying shades of pink.

Pharmacologically Relevant Species

The genus Bergenia encompasses 32 known species, of which nine are of pharmacological relevance. The most widely studied species include:

Bergenia ligulata (Wall.) Engl. — The primary species used in Ayurvedic medicine, known as "Pashanabheda" or "Paashanbheda." This herb ranges from the Himalayas to the foothills, including the north-eastern states of India, and has traditionally been used as a remedy against various diseases, most prominently kidney stones.
Bergenia crassifolia (L.) Fritsch — Common names include heart-leaved bergenia, leather bergenia, winter-blooming bergenia, elephant's ears, Korean elephant-ear, badan, pigsqueak, Siberian tea, and Mongolian tea. This species alone possesses 104 identified bioactive compounds.
Bergenia ciliata (Haw.) Sternb. — Considered a highly valued medicinal herb popularly known as "Pashaanbheda" (meaning "to dissolve stone") in the Indian system of medicine and belonging to the family Saxifragaceae.
Bergenia purpurascens (Hook.f. & Thomson) Engl. — An important alpine endemic species of the Himalaya-Hengduan Mountains, used as a source of medicine and as an ornamental plant.
Bergenia stracheyi (Hook.f. & Thomson) Engl. — A species recognized for its therapeutic value in Indian ethnomedicine.

Geographic Distribution

In China, seven species are reported from three provinces and two autonomous regions: Shanxi, Sichuan, and Sanxi, and Tibet and Xinjiang, respectively. Among the seven species, four (B. yunnanensis, B. scopulosa, B. emeiensis, and B. tianquanensis) are endemic to China. Bergenia purpurascens is endemic to the Himalaya-Hengduan Mountains and inhabits the highest altitude and greatest altitude range within the genus, ranging from 2700 to 4800 m above sea level.

In the Indian subcontinent, B. ligulata is distributed along the high-altitude Himalayan regions ranging from Kashmir to Bhutan, including West Bengal and the northeastern states. Bergenia ciliata grows at altitudes ranging from 1200 to 2600 meters and belongs to the Saxifragaceae family.

Common Preparations and Dosage Forms

Bergenia is used in multiple forms across traditional and scientific contexts:

Rhizome extracts (aqueous, methanolic, ethanolic, or hydroalcoholic) — the most common preparation in both traditional use and research studies.
Leaf infusions and decoctions — used particularly in Russian and Siberian folk medicine.
Rhizome paste — applied topically for wound healing and skin conditions.
Dried rhizome powder — consumed orally, often mixed with honey.
Tea — Bergenia crassifolia is used as a tea substitute in its native Siberia, Altay, and Mongolia.
Standardized botanical extracts — such as IIIM-160, a B. ciliata-based extract used in preclinical pharmaceutical research.
Gastroretentive sustained-release capsule formulations — developed to achieve sustained release of bergenin over 24 hours, resulting in improved plasma exposure in research models.

2. Traditional and Historical Use

Ayurvedic and Unani Systems (South Asia)

In the Indian system of traditional medicine (Ayurveda), "Pashanabheda" (stone breaker) is an elite drug formulation obtained from the rhizomes of B. ligulata. The plant has been used as a folk medicine since ancient times for dissolving kidney stones and is referred to as "Paashanbheda" (Sanskrit: Paashan meaning "rock/stone" and bheda meaning "piercing") in the Indian traditional system of medicine — Ayurveda.

The drug is listed in ancient Indian chronicles of medicine including "Charak Samhita," "Sushruta Samhita," and "Ashtang-Hridaya."

In Unani and Ayurvedic systems of medicine, Bergenia spp. rhizomes and roots have been used for curing kidney and bladder diseases, dysuria, heart diseases, lung and liver diseases, spleen enlargement, tumors, ulcers, piles, dysentery, menorrhagia, hydrophobia, biliousness, eyesores, cough, and fever.

Burns or wounds may be treated with rhizome paste for three to four days. The paste can be applied on dislocated bones after setting, or consumed to treat diarrhea, or along with honey in fevers.

Himalayan communities consume the roots and rhizomes of the plant to treat wounds, septic conditions, cough and cold, cardiac diseases, asthma, inflammation, gastrointestinal disorders, and different kinds of urinary problems.

Russian and Siberian Folk Medicine

Infusions of the rhizomes have been used in Russian traditional medicine for the treatment of cold, gastritis, enterocolitis, headache, diarrhoea, and fever. The rhizomes are also known for the treatment of oral diseases: periodontal disease, stomatitis, gingivitis, and bleeding gums.

An infusion is recommended in gynaecology for the treatment of excessive menstruation, bleeding after abortions, and cervical erosion.

Aqueous extracts of rhizome and leaves are used in Russian folk medicine for colitis and enterocolitis of a non-infectious nature, tuberculosis, acute and chronic pneumonia, pulmonary haemorrhage, influenza and some other infections, laryngitis, headaches, fevers, articular rheumatism, and gastrointestinal diseases. For medicinal purposes, rhizomes are collected by hand, cleaned, and washed in cold running water.

In the official medicine of Russia, rhizomes only are claimed as haemostatic, astringent, anti-inflammatory, and antimicrobial agents.

Traditional Chinese Medicine

The thick leaf is used in Traditional Chinese Medicine to supplement vacuity and stanch bleeding; to relieve cough and settle asthma; and to treat dizziness, blood ejection, and hemoptysis.

In recent years, direct and indirect evidence has been found of the efficacy of the traditional Chinese medicine Bergenia purpurascens in treating arthritis and osteoarthritis.

Tibetan Medicine

The roots and rhizomes of B. crassifolia are claimed as antimicrobial, anti-inflammatory, haemostatic, and astringent in the official medicine of Mongolia. Tibetans apply fresh leaf-paste on their skin to protect it.

South and Southeast Asia

In some areas of South East Asia, B. ciliata has been used in the treatment of stomach disorders as a folkloric medicine. Bergenia ligulata is used as a cure for dysuria and strangury and for stones in the kidney and ureter.

3. Key Chemical Constituents and Active Compounds

Overview of Phytochemical Diversity

To date, 152 chemical constituents have been identified and characterized from the genus Bergenia, belonging to the chemical classes of polyphenols, phenolic-glycosides, lactones, quinones, sterols, tannins, terpenes, and others. The review of the extant literature reveals the presence of 152 chemical compounds (volatile: 47 and non-volatile: 105).

Phytochemical investigation of nine Bergenia species (B. ciliata, B. crassifolia, B. emeiensis, B. ligulata, B. scopulosa, B. stracheyi, B. hissarica, B. purpurascens, and B. tianquanesis) led to the characterization of several chemical constituents.

Major Identified Bioactive Compounds

The major bioactive compounds identified across the genus are: bergenin, (+)-catechin, gallic acid, β-sitosterol, catechin-7-O-β-d-glucoside, (+)-afzelechin, arbutin, 4-O-galloylbergenin, 11-O-galloylbergenin, caffeoylquinic acid, pashaanolactone, 3,11-di-O-galloylbergenin, bergapten, kaempferol-3-O-rutinoside, quercetin-3-O-rutinoside, and (+)-catechin-3-O-gallate.

Green leaves of B. crassifolia consist of 55% ellagitannins, 29% gallic acid derivatives, and 11% flavonoids, with the remaining comprising gallic acid, arbutin, bergenin, and caffeoyl quinic acid. In fermented leaves, 31% of gallic acid is found, followed by 28% ellagitannins, 18% gallic acid derivatives, and 18% flavonoids, with the remaining comprising caffeoyl quinic acid, bergenin, and arbutin.

Hydrolysable tannins (+)-catechin 3-O-gallate and (+)-catechin 3,5-di-O-gallate as well as polymeric proanthocyanidin have been isolated from rhizomes.

Bergenin: The Principal Active Compound

Bergenin is a glycosidic derivative of trihydroxybenzoic acid that was discovered in 1880 by Garreau and Machelart from the rhizomes of the medicinal plant Bergenia crassifolia (currently: Saxifraga crassifolia—Saxifragaceae), though it was later isolated from several other plant sources. Bergenin is distributed in many plant species (at least 112 species belonging to 34 families).

Bergenin is a compound that consists of trihydroxybenzoic acid and is a derivative of 4-O-methyl gallic acid. This compound is a hydrolysable phenolic glycoside that is synthesized as colorless crystals. It has limited solubility in water and readily degrades in alkaline solutions, and its stability relies on the circumstances in which it is stored.

Bergenin has been found to be a major component of B. ciliata-based botanical extracts, measured at 9.1% w/w in standardized preparations.

Up to 9.77% of bergenin has been estimated to be deposited in the rhizome of B. purpurascens.

Arbutin

Arbutin is the major compound in green leaves of B. crassifolia, whereas gallic acid is the primary bioactive compound in the black (fermented) leaf variety. Arbutin (hydroquinone-β-D-glucopyranoside) is a hydroxyphenolic glycoside also present in significant quantities across other Bergenia species and is associated with antimicrobial properties.

Other Notable Constituents

Phytochemicals in Bergenia include a wide range of constituents such as flavonoids, terpenoids, sterols, saponins, glucosides, phenols, tannins, coumarins, fatty acids, carboxylic acids, and various other compounds.

From the roots of B. crassifolia, two new compounds — (2R,3S)-3-O-p-hydroxybenzoyl-5-O-galloylcatechin and 6-O-(3′′-O-methylgalloyl) arbutin — have been isolated together with 20 known flavonoids, including catechins, kaempferols, arbutin derivatives, and bergenin derivatives.

4. Established Mechanisms of Action

Anti-Inflammatory Pathways

Research has demonstrated that bergenin plays an anti-inflammatory role via the modulation of MAPK and NF-κB signaling pathways in experimental models of inflammation.

Bergenin is a C-glycoside derivative of 4-O-methyl gallic acid. Studies showed that pre-treatment with bergenin (25 mg/kg) significantly reduced edema induced by carrageenan, compound 48/80, histamine, and prostaglandin E2 (PGE2) (p < 0.05) in Swiss mice.

The anti-inflammatory mechanism of action of bergenin may be associated with the alteration of branched-chain amino acid (BCAA) metabolism, glycine, serine, and threonine metabolism, and glycolysis. Studies have proven that these metabolic changes influence the inflammatory response.

Antioxidant Mechanisms

The antioxidant mechanism of action of Bergenia bark extract against membrane peroxidation is multifactorial and multisystem, involving catalase inhibition, enhancing the SOD capacity of the liver and red blood cells, and sparing tissue depletion and use of vitamins C (ascorbic acid) and E (α-tocopherol).

Bergenin reduced both nitric oxide (NO) production in vitro and malondialdehyde (MDA)/nitrite amounts in vivo. These antioxidant properties can be attributed to the modulation of gene expression by the downregulation of inducible nitric oxide synthase (iNOS) and upregulation of glutathione peroxidase and Nrf2 in the nervous system.

Immunomodulatory Mechanisms

Bergenin has been shown to induce Th1 immune responses and potently inhibit bacillary growth in a murine model of Mycobacterium tuberculosis infection by activating the MAP kinase and ERK pathways.

Bergenin can induce the transmembrane glycoprotein CD64, which has an important role in the humoral immune response, using an Fc receptor that binds to monomeric antibodies such as IgG.

Anticancer Signaling Pathways

Bergenin efficiently inhibited the proliferation of human cancer cells by stimulating the production of intracellular reactive oxygen species (ROS), causing DNA damage and leading to cell cycle arrest in the G1/G2 phases by blocking cell signaling pathways.

Bergenin targets several deregulated components of cell signaling pathways associated with the progression of human cancers, including ERK1/2, JAK/STAT, STAT3/Akt, and NF-κB signaling.

Urolithiatic Mechanisms

Bergenia ligulata rhizome extract (BLR) has been shown to inhibit calcium oxalate (CaC₂O₄) crystal aggregation as well as crystal formation in metastable solutions, and exhibited antioxidant effects in vitro. BLR also caused diuresis in rats accompanied by a saluretic effect.

Antiurolithic activity in Bergenia ligulata is mediated possibly through CaC₂O₄ crystal inhibition, diuretic effects, hypermagneseuric effects, and antioxidant effects.

Nociceptive (Pain) Mechanisms

The antinociceptive activity of bergenin is linked to the analgesic activity; it blocks sensory neurons and gives the sensation of pain relief in vivo.

Osteogenic Mechanisms

Bergenin treatment significantly elevated collagen synthesis, alkaline phosphatase activity, osteocalcin synthesis, and mineralization in osteoblast cells (p < 0.05). Additionally, bergenin increased the ratio of osteoprotegerin to receptor activator of nuclear factor kappa-B ligand (RANKL), and cyclophilin B release.

5. Scientific Evidence by Area of Use

5.1 Urolithiasis (Kidney Stones)

This is the area with the most substantial and convergent preclinical evidence for Bergenia.

In vitro evidence: The aqueous extract of Bergenia ligulata rhizome inhibited homogenous precipitation of CaC₂O₄ crystals, and in vitro growth of CaC₂O₄ and calcium hydrogen phosphate dihydrate crystals.

Animal study evidence: In an animal model of urolithiasis developed in male Wistar rats by adding 0.75% ethylene glycol 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 — all of which were prevented by BLR. EG intake did not cause excessive hyperoxaluria and hypocalciuria in BLR-treated groups, and there was a significant increase in urinary Mg²⁺.

The alcoholic extract of B. ligulata has been found effective in dissolving calculi developed in the bladder of rats by foreign body insertion, and in reducing idiopathic hyperoxaluria in stone formers.

Histological study revealed a lower number of calcium oxalate deposits with minimum damage in the kidneys of mother extract- and DCM fraction-treated rats, providing a scientific basis for its traditional claims.

Evidence strength: Primarily preclinical (in vitro and animal). No large-scale randomized clinical trials in humans have been reported. One older human study noted reduction of idiopathic hyperoxaluria with alcoholic extract, but this has not been replicated under modern clinical trial standards. The mechanistic and animal evidence is convergent and consistent, rationalizing traditional use.

5.2 Anti-Inflammatory and Antiarthritic Activity

The botanical extract IIIM-160 displayed inhibition of lipopolysaccharide-induced production of proinflammatory cytokines in THP-1 cells, with selectivity toward interleukin-6 (IL-6), and had an excellent safety window. It showed anti-inflammatory, anti-arthritic, and antinociceptive activity in animal models, and was not toxic at oral doses up to 2 g/kg in Swiss-albino mice.

Bergenin demonstrated antiarthritic activity through inhibition of the inflammatory cytokines (IFN-γ, TNF-α, and IL-2) in BALB/c mice.

Direct and indirect evidence has been found of the efficacy of the traditional Chinese medicine Bergenia purpurascens in treating arthritis and osteoarthritis. Several major components, such as bergenin and 11-O-galloylbergenin, have demonstrated good anti-inflammatory activity.

Evidence strength: Predominantly in vitro and animal model evidence. The preclinical characterization of IIIM-160 is notable for its rigor, but clinical human trials are absent. Evidence is preliminary.

5.3 Hepatoprotective (Liver-Protective) Activity

In a study, the ethanolic root extract of B. ligulata was evaluated for its hepatoprotective activity in CCl₄-treated albino rats. The estimation of hepatoprotective activity was confirmed by measuring the decline in elevated levels of serum marker enzymes such as SGPT, SGOT, ALP, and total bilirubin.

B. ligulata leaf extract at a dose of 500 mg/kg fully restored the carbon tetrachloride (potent hepatotoxicant)-induced variations in carbon tetrachloride-intoxicated rats. Moreover, histopathological examination of the liver tissue further confirmed the hepatoprotective effect.

B. crassifolia dry extract has also been reported to exhibit hepatoprotective property in rats intoxicated with 4-pentenoic acid, confirming its hepatoprotective potential.

The hepatoprotective and neuroprotective activities of bergenin were reported to be mediated through its free radical scavenging property in both in vitro and in vivo models.

Evidence strength: Animal model evidence only (rat CCl₄ and 4-pentenoic acid models). No published human clinical trials on liver protection have been verified. Evidence is preliminary.

5.4 Antidiabetic Activity

Research demonstrated that bergenin protected beta cells from cytokine-induced apoptosis and restored insulin secretory function by virtue of its anti-inflammatory, antioxidant, and anti-apoptotic properties. Bergenin restored mitochondrial membrane potential (EC₅₀ = 2.27 ± 0.83 μM), decreased ROS production (IC₅₀ = 14.63 ± 3.18 μM), and improved mitochondrial dehydrogenase activity (EC₅₀ = 1.39 ± 0.62 μM).

Bergenia ciliata is commonly used in traditional remedies due to numerous health benefits. Studies aimed to determine its phytochemicals as well as total phenolic content and enzyme inhibitory activity against α-glucosidase and α-amylase. The aqueous extract of B. ciliata showed an IC₅₀ of 16.99 ± 2.56 μg/mL against α-glucosidase inhibition.

Bergenin impeded the generation of TGF-β1 and extracellular matrix components, decreased the levels of intracellular superoxide anion and hydrogen peroxide, and increased the activity of antioxidant enzymes in glomerular mesangial cells treated with high glucose.

Evidence strength: In vitro (cell line and enzyme inhibition assays) and animal studies only. No human clinical trials confirmed. The pancreatic beta-cell protection data (in INS-1E cells) is scientifically notable but remains preclinical.

5.5 Diabetic Neuropathy

This work characterized the therapeutic effect of bergenin in a mouse (C57/BL6) model of streptozotocin-induced painful diabetic neuropathy. Nociceptive thresholds were assessed by the von Frey test. Cytokines, antioxidant genes, and oxidative stress markers were measured in nervous tissues by ELISA, RT-qPCR, and biochemical analyses. Single (3.125–25 mg/kg) or multiple (25 mg/kg; twice a day for 14 days) treatments with bergenin reduced the behavioral signs of diabetic neuropathy in mice.

Evidence strength: Animal model only (mouse STZ-induced neuropathy). No human trials. Preliminary.

5.6 Antimicrobial Activity

Phytochemical studies proved that Bergenia contains many bioactive compounds which mainly show a wide spectrum of pharmacological activities such as antiviral, antifungal, antibacterial, antidiabetic, anti-inflammatory, hepatoprotective, and antioxidant activity.

Evidence strength: Primarily in vitro cell-line and microbiological assays. Mechanism plausible but no clinical evidence in humans. Preliminary.

5.7 Anticancer Activity

Bergenin demonstrates antiviral, antifungal, antitussive, antiplasmodial, anti-inflammatory, antihepatotoxic, antiarrhythmic, antitumor, antiulcerogenic, antidiabetic, and wound healing activities. Bergenin efficiently inhibited the proliferation of human cancer cells by stimulating the production of intracellular reactive oxygen species (ROS), causing DNA damage and leading to cell cycle arrest in the G1/G2 phases by blocking cell signaling pathways.

Bergenin has been reported to modulate oncogene and tumor suppressor gene expression to inhibit carcinogenesis.

Evidence strength: To date, about 8 in vitro studies on antiviral activity have been performed, though no study has evaluated in vivo conditions. Anticancer evidence is exclusively in vitro and animal-based. No clinical trials have been reported. Evidence is very preliminary.

5.8 Osteogenic / Bone Health Activity

Bergenin treatment significantly elevated collagen synthesis, alkaline phosphatase activity, osteocalcin synthesis, and mineralization in osteoblast cells (p < 0.05). Additionally, bergenin increased the ratio of osteoprotegerin to receptor activator of nuclear factor kappa-B ligand (RANKL), and cyclophilin B release.

Evidence strength: In vitro cell study only. No animal or human trials confirmed. Evidence is very preliminary.

5.9 Gastrointestinal (Antiulcer) Activity

An experiment was performed to assess the gastro-protective activity of B. ciliata extracts on stomach ulcer-induced rats. Different doses (15, 30, and 60 mg/kg) of the aqueous and methanolic rhizome extracts were administered 1 hour after the ulcerogenic treatment. Among the two treatments, the aqueous extract reduced stomach-ulcer lesions to a better degree.

Evidence strength: Animal study only. No human clinical trials. Preliminary.

6. Body Systems Associated with Bergenia

Bergenia species possess several biological activities including diuretic, antidiabetic, antitussive, insecticidal, anti-inflammatory, antipyretic, anti-bradykinin, antiviral, antibacterial, antimalarial, hepatoprotective, antiulcer, anticancer, antioxidant, antiobesity, and adaptogenic actions.

Urinary / Renal System: Anti-urolithiatic (kidney stone inhibition), diuretic, and renoprotective actions, most notably demonstrated in B. ligulata.
Musculoskeletal System: Anti-arthritic and anti-inflammatory properties, demonstrated in animal models of arthritis and osteoarthritis, including for B. purpurascens and B. ciliata.
Hepatic (Liver) System: Hepatoprotective activity against chemical toxicants demonstrated in rat studies using B. ligulata and B. crassifolia.
Metabolic / Endocrine System: Antidiabetic activity through alpha-glucosidase inhibition, beta-cell protection, and anti-hyperuricemic mechanisms.
Neurological System: Neuroprotective and antinociceptive properties, including evidence in models of diabetic neuropathy.
Gastrointestinal System: Antiulcer, gastroprotective, antidiarrheal, and antidysenteric uses documented in both traditional medicine and animal models.
Immune System: Immunomodulatory activity documented, including modulation of NF-κB, MAPK, TLR4, and ERK signaling.
Respiratory System: Antitussive, anti-bronchitis, and antiasthmatic properties noted in traditional use and animal models.
Skin and Wound Healing: Rhizome paste application for wound healing documented in multiple traditional systems; antimicrobial properties support this use.
Reproductive System: Used in Russian traditional medicine for excessive menstruation, bleeding after abortion, and cervical conditions.
Skeletal System: Preliminary in vitro evidence for osteoblast differentiation enhancement and bone mineral deposition.

7. Dosage Forms and Doses Reported in Studies

The following doses are reported only as stated in identified peer-reviewed sources and relate to experimental or preclinical contexts unless otherwise stated.

Antiurolithiatic (animal study): BLR (crude aqueous-methanolic extract of B. ligulata rhizome) at doses of 5–10 mg/kg prevented CaC₂O₄ crystal deposition in renal tubules in a male Wistar rat model.
Gastroprotective (animal study): Different doses (15, 30, and 60 mg/kg) of the aqueous and methanolic rhizome extracts of B. ciliata were administered to rats 1 hour after ulcerogenic treatment.
Hepatoprotective (animal study): B. ligulata leaf extract at a dose of 500 mg/kg was used to evaluate hepatoprotective activity in CCl₄-intoxicated rats.
Diabetic neuropathy (animal study): Single doses of 3.125–25 mg/kg or multiple doses of 25 mg/kg (twice a day for 14 days) of bergenin were administered to mice in a streptozotocin-induced neuropathy model.
Anti-inflammatory / bergenin (animal study): Pre-treatment with bergenin at 25 mg/kg significantly reduced edema in Swiss mice models.
Immunomodulatory / antioxidant (animal study): Bergenin at doses of 10 and 20 mg/kg reversed immunosuppression-induced reductions in SOD, CAT, and GSH-Px activity in BALB/c mice.
Preclinical acute oral toxicity threshold: A B. ciliata-based extract (IIIM-160) was not toxic at oral doses up to 2 g/kg in Swiss-albino mice.
Bergenin oral bioavailability study (animal): The bioavailability of bergenin was determined by administering this bioactive compound at doses of 50 mg/kg (oral) and 5 mg/kg (intravenous) in rats.

No validated human clinical dosing regimens for Bergenia preparations or isolated bergenin have been established in the available peer-reviewed literature.

8. Pharmacokinetics of Bergenin

Bergenin (BER), a key constituent of Bergenia crassifolia, has gained extensive attention owing to its array of pharmacological actions. Despite ever-intensifying support for its therapeutic features, the poor solubility, lower oral bioavailability, shorter half-life, and more intestinal pH degradation (pH 6.8 or above) of BER have puzzled researchers.

Following a single oral gavage administration of bergenin to male Sprague-Dawley rats (50 mg/kg), median time to reach maximum plasma concentration was found to be 0.25 hours, with peak plasma concentration (Cmax) of 170 ng/mL. Plasma exposure (AUClast) was found to be 269 h·ng/mL. The terminal plasma half-life was found to be 1.74 hours, and the absolute oral bioavailability of bergenin was determined to be 3%.

Bergenin gets degraded at intestinal pH (pH 6.8 and above), and its degradation half-life at pH 7 and pH 8 is 14.4 and 2.9 hours, respectively. In pharmacokinetic studies in rats, the plasma half-life of bergenin is low (t½ = 1–3 h).

After oral administration in humans, bergenin was absorbed quickly but incompletely, with a short half-life and low bioavailability.

Following oral administration of bergenin at a dose of 12 mg/kg, the whole amount is excreted in the bile within 24 hours. The majority of bergenin, approximately 97.67%, is eliminated during the first 12 hours.

Despite the extensive utilization of bergenin, its limited oral bioavailability remains a barrier to its continued employment. Bergenin, classified as a class IV chemical, exhibits insufficient solubility and permeability to achieve total absorption.

Research on a gastroretentive sustained-release (GRSR) formulation indicated a 4-fold increase in AUClast of bergenin compared to plain extract. Tmax, t½, and Tlast values were all increased in the GRSR formulation compared to plain extract, because of the sustained release of bergenin.

9. Safety Considerations and Toxicology

Recent studies have proven that bergenin possesses good pharmacological properties with low side effects and little toxicity.

IIIM-160 (B. ciliata-based extract) showed anti-inflammatory, anti-arthritic, and antinociceptive activity in animal models, and was not toxic at oral doses up to 2 g/kg in Swiss-albino mice. This represents the most comprehensive acute oral toxicity finding documented in the peer-reviewed literature for a standardized Bergenia extract.

Despite having good pharmacological activity, some toxic effects of B. ciliata preparations on living systems have been observed in several studies. However, specific characterization of these toxicological findings remains an area requiring further research.

Heavy metal and contaminant safety: In preclinical safety characterization of IIIM-160, the extract was analyzed for heavy metal content, aflatoxins, pesticides, and microbial load as part of its standardization.

Degradation at intestinal pH: The poor solubility, lower oral bioavailability, shorter half-life, and more intestinal pH degradation (pH 6.8 or above) of bergenin are recognized pharmacological challenges. This degradation at intestinal pH is a pertinent pharmacological consideration that affects the reproducibility of dosing effects.

Interaction with cytokine pathways: Because bergenin modulates NF-κB, MAPK, and interleukin pathways, theoretical interactions with immunosuppressive or immunomodulating therapies exist, although these have not been characterized in human drug-interaction studies in the reviewed literature.

No human drug interaction data: To date, no formal human pharmacokinetic drug-interaction studies for Bergenia preparations or bergenin have been identified in the peer-reviewed sources reviewed here.

Tannin content considerations: Tannins are found in considerable amounts in Bergenia species. Tannin content in the leaves is approximately 2-fold higher than in the rhizomes. High tannin intake at pharmacological doses over extended periods is associated with potential gastrointestinal effects in general phytomedicine research, though this has not been specifically characterized for Bergenia preparations.

10. Current Research Status and Evidence Gaps

The overwhelming majority of Bergenia research resides at the in vitro and animal model stages. Since bergenin's first report, it has aroused interest because of several pharmacological activities, mainly antioxidant and anti-inflammatory. In addition, bergenin has shown potential antimalarial, antileishmanial, trypanocidal, antiviral, antibacterial, antifungal, antinociceptive, antiarthritic, antiulcerogenic, antidiabetic/antiobesity, antiarrhythmic, anticancer, hepatoprotective, neuroprotective, and cardioprotective activities.

Meticulous pharmacological and phytochemical studies on Bergenia species and its conservation could yield more reliable compounds and products of pharmacological significance for better healthcare.

Key evidence gaps include: the absence of randomized controlled trials in humans for any indication; the lack of validated human dosing ranges; limited pharmacokinetic data in humans beyond the finding that absorption is rapid but incomplete with low overall bioavailability; and the absence of long-term safety data in human populations. The development of bioavailability-enhanced formulations (such as gastroretentive sustained-release capsules and cyclodextrin complexes) is an active area of pharmaceutical research seeking to address bergenin's pharmacokinetic limitations.

References

Health Conditions

Health conditions that Bergenia may help support.

TriglyceridesTraditional
Bergenia (Bergenia crassifolia/ligulata), known as 'pashanbheda' in Ayurveda and 'saxifrage' in European herbalism, has some preclinical and traditional evidence for lipid-lowering including TG modulation, primarily via bergenin and gallic acid content. Human clinical evidence for TG lowering specifically is limited.

Body Systems

Body systems that Bergenia may help support.

No body systems available.