Bergenia crassifolia (L.) Fritsch--Pharmacology and phytochemistry.
ABSTRACTPurpose: Bergenia crassifolia (L) Fritsch, a species in the Bergenia genus belongs to the family Saxifragaceae, is valuated for its medicinal application. The review focuses on the medicinal uses, phytochemistry, and the biological activities of B. crassifolia to explore its benefits and potential uses.
Methods: In this review, we summarized data, published in Russia and in other countries related to B. crassifolia.
Results: Rhizomes and leaves of this plant are in use as traditional remedies for the treatment of different disorders in the folk medicine systems of Russia and Asia. The plant is a potential source of tannins, benzanoids, flavonoids, polysaccharides and other active compounds. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb and individual compounds, which include adaptogenic, antiinflammatory, antihypertensive, antimicrobial, antioxidant, antiobesity, antitussive, cerebro-protective, hepatoprotective, immunomodulating, and diuretic.
Conclusion: The review highlights the potential of B. crassifolia for further development of herbal medicines on its base.
Keywords:
Bergenia crassifolia
Pharmacological effects
Active compounds
Contents
Introduction
Botany and ethnopharmacology
Botany
Ethnopharmacology
Phytochemistry
Phenolic compounds
Flavonoids
Volatile compounds
Others
Pharmacological effects
Adaptogenic
Anticancer
Antidiabetic
Antihypertensive
Anti-inflammatory and immunomodulating
Antimicrobial
Antiobesity
Antioxidant
Antitussive
Antiviral
Cerebro-protective
Diuretic
Gastroprotective
Hepatoprotective
Skin whitening
Toxicity
Conclusion
Conflict of interest
Acknowledgment
References
Introduction
For more than 100 years Bergenia crassifolia has been used as a medicinal and ornamental plant. Due to its rich and varied chemical composition (arbutin, tannins and bergenin) the species continues to be the object of pharmacological studies (Utkin. 1931; Gammerman et al., 1984; Sokolov, 2000; Hendrychova and Tumova, 2012).
In this review we summarized data, published in Russia and in other countries related to B. crassifolia which have log history of applications in the Russian Federation and the review highlights the potential for further developing of herbal medicines on its base.
Botany and ethnopharmacology
Botany
B. crassifolia (L.) Fritsch, a species in the Bergenia genus belongs to the family Saxifragaceae, the order Rosales, is commonly known as badan (Rus = [TEXT NOT REPRODUCIBLE IN ASCII]), Siberian tea, Mongolian tea, leather bergenia, or elephant's ears. The name of genus Bergenia commemorates Karl August of Bergen (1704-1759), a German physician and botanist (Anisko, 2008). The detailed systematic of the genus Bergenia was compiled by Borisova (1956). She described 11 species, their various names, morphology, distribution, and economic uses. After Borisova, B. crassifolia (L.) Fritsch have next synonyms: B. sibirica Hort, B. crassifolia var. cordifolia (Haw.) Boriss. = B. cordifolia (Haw.) A.BC, B. crassifolia var. baicalensis Boriss. But Yeo (1966) offered a revision of the genus Bergenia and gave the key to the determination of only 6 Bergenia species and 8 hybrids. He described next botanical markers of B. crassifolia: leaves ovate, cuneate or rounded at base, often reddish or purplish; inflorescence compact, subsecund, its branches not becoming conspicuously spreading; flowers more or less nodding, campanulate; petals elliptic to broad-ovate, tapering into the claw. While B. cordifolia have orbicular leaves, rounded or cordate at base, often bullate, usually green; inflorescence spherical at first, usually becoming umbraculiform with spreading branches; flowers mostly spreading or erect, broadly campanulate; petals broadly ovate to orbicular, abruptly contracted into the claw (Yeo, 1966). B. crassifolia is only plant of Bergenia genus included in Pharmacopoeia USSR (The State Pharmacopoeia of the USSR, 11th edition, 1990; Shikov et al., 2014).
B. crassifolia (L.) Fritsch, syn. Saxifraga crassifolia L, is an evergreen perennial plant with rhizomes up to 1 meter long and up to 3.5 cm in diameter, 10-50 cm long leather-like large spoon-shaped leaves and pink flowers. Evergreen glossy leaves turn red or bronze after first frost. The globose, dense, compound cyme inflorescence is growing on a stem up to 50 cm. The cone-shaped flowers are purplish pink. The flowering season is from May to July (Gammerman et al., 1984; Turova and Sapozhnikova, 1989).
The plant is widely distributed in Siberia (Altai, Sayan, Baikal region and Transbaikalia), Maritime Territory and grows in the mountain forest belt at an altitude of 300-2600 m above sea level on stony, rocky soils. It forms dense thickets sometimes hundreds of hectares (Plant Resources of the USSR, 1987). It is distributed in Mongolia in Khuvsgul, Khentii, Khangai, and Mongolian Altai (Medicinal plants in Mongolia, 2013). As an ornamental plant it became widespread in North-West and central Russia.
Ethnopharmacology
Infusions of Bergenia rhizomes have been used in Russian traditional medicine for the treatment of cold, gastritis, enterocolitis, head-ache, diarrhea and fever (Gammerman et al., 1984). Rhizomes are known for the treatment of oral diseases: periodontal disease, stomatitis, gingivitis and bleeding gums (Vereschagin et al. 1959). In Russian ethnomedicine the leaves are widely used as a beverage. Buryats and Mongols are known to have used B. crassifolia leaves to make tea. As B. crassifolia educes during some years, a single plant usually contains green (young), brown (after one winter), and black (after two winters) leaves. In Altai old blackened wintered leaves, known as chagirsky tea, are preferred for this purpose as the green leaves contain higher amounts of tannins (Vereschagin et al. 1959).
Tibetans apply topically the mashed fresh leaf pastes of bergenia on the skin to prevent sunburn and skin damage from UV radiation (Zhao et al., 2006). The thick leaf of bergenia (HOU YE YAN BAI CAI ([TEXT NOT REPRODUCIBLE IN ASCII]) is used in Traditional Chinese Medicine (TCM) to supplement vacuity and stanch bleeding, relieve cough and settle asthma as well as against dizziness, blood ejection, and hemoptysis (Zhou et al., 2011).
Mongols have been used extract and decoction of Zuzaannavchit (Badgar) badaan for the treatment of typhoid and lung fever, stomach and intestine disorders, diarrhea, and in case of lung inflammation. Roots and rhizomes are used in officinal medicine of Mongolia (Medicinal plants in Mongolia, 2013).
Phytochemistry
Now, more than 100 chemical components have been isolated and identified from B. crassifolia, including tannins, benzanoids (hydroquinone), flavonoids, polysaccharides, terpenes, aldehydes, etc. (Table 1). The chemical structures of main compounds are presented in Fig. 1.
Phenolic compounds
The leaves of the Bergenia are an especially important source of arbutin also knows as arbutoside hydroquinone ([beta]-D-glucopyranoside. Arbutin was first isolated from the fresh B. crassifolia leaves by Tschitschibabin et al. (1930). The content of this compound in old leaves may reach up to 22% (Shnyakina et al., 1981). Three O-galloyl esters of arbutin were identified in leaves of B. crassifolia: 2-O-caffeoylarbutin, 6-O-galloylarbutin, p-galloyloxyphenyl [beta]-D-glucoside (Britton and Haslam, 1965). Hydroquinone (benzene-1,4-diol) was found in leaves of B. crassifolia as product of oxidative decarboxylation of p-hydroxybenzoic acid (Zenk, 1964). Arbutin, hydroquinone, bergenin, gallic, protocatechuic, and ellagic acids were proposed as key compounds for fingerprinting of extracts from leaves (Shikov et al., 2007, 2010, 2012). The concentration of key phenolic compounds is varied according to leaves type. Arbutin was the major in green leaves whereas gallic acid is the primary bioactive compound in the black (Shikov et al., 2007).
Other important group of chemical compounds found in the Bergenia in considerable amounts is tannins, of which the species is also considered one of the main sources. Tannin content in leaves approximately 2-fold higher than in the rhizomes (Fedoseeva, 2005). Green leaves consisted of 55% ellagitannins, 29% gallic acid derivatives and 11% flavonoids, with the remaining gallic acid, arbutin, bergenin and caffeoyl quinic acid. In fermented leaves, 31% of gallic acid was found followed with 28% ellagitannins, 18% gallic acid derivatives and 18% flavonoids, with the remaining caffeoyl quinic acid, bergenin and arbutin (Salminen et al., 2014). Hydrolysable tannins (+)-catechin 3-O-gallate and (+)-catechin 3,5-di-O-gallate as well as polymeric proanthocyanidin were isolated from rhizomes (Haslam, 1969; Ivanov et al., 2011).
Ellagitannins: tellimagrandin 1 and pedunculagin, gallic acid derivatives: monogalloyl quinic acid, 1-0-galloylglucose, 1,2,6-tri-O-galloylglucose, and 1,2,3,4,6-penta-O-galloylglucose were identified in green and fermented leaves (Salminen et al., 2014). 1,2,4,6-tetra-O-galloy-[beta]-D-glucopyranose was isolated from rhizomes of bergenia (Haddock et al., 1982). Pyrogallol was identified in green leaves (Chernetsova et al., 2012).
Number of phenolic acids: acetylsalicylic, fumaric, furancarboxylic, malic, and quinic acids were suggested in green leaves by ID CUBE DART HRMS (Chernetsova et al., 2012).
Flavonoids
Bergenin (C-glycoside of 4-O-methyl gallic acid) was first isolated from the roots of B. crassifolia by Tschitschibabin et al. (1929). Bergenin derivatives, 3,11-di-O-galloylbergenin, 4,11-di-O-galloylbergenin and 11-O-(p-hydroxybezoyl)bergenin were isolated from the roots of B. crassifolia (Janar et al., 2012). B. crassifolia accumulates 3-O-monoglycosides and 3-O-diglycosides of kaempferol and quercetin (Bohm et al., 1986). Bergapten, norathyriol, norbergenin, and trihydroxycoumarin were found in green leaves by ID CUBE DART HRMS (Chernetsova et al., 2012).
Volatile compounds
The dried green leaves contained 0.05% essential oil. In result of GC-MS analysis, 3-methyl-2-buten-l-ol (26.56%), hexadecanoic acid (16.06%), dodecanoic acid (9.99%), linalool (5.63%) and octadecadienoic acid (4.10%) were the most abundant volatiles detected in the distillate (Zhao et al., 2006). In another study green and fermented leaves of B. crassifolia were distilled (Chernetsova et al., 2014). The contents of clear and yellowish volatiles were 0.012% (w/w) for green leaves, and 0.010% (w/w) for the fermented leaves. The volatile oil of green leaves consisted mainly of hexadecanoic acid followed by phytol, tetradecanoic acid, and [alpha]-bisabololoxide B. The main constituents identified in the oil of fermented leaves, were [alpha]-bisabololoxide B followed by hexadecanoic acid, phytol, and tetradecanoic acid. Fermentation resulted in increase of [alpha]-bisabololoxide B (2.9-folds), [alpha]-terpineol (2.5-folds), geraniol (2.4-folds), linalool (1.8-folds), and nerolidol (1.7-folds) comparing to green leaves.
Others
The pectic polysaccharide named bergenan BC was extracted from green leaves. Bergenan was shown to consist of galacturonic acid (82%) residues mainly, together with minor residues of arabinose (3.3%), galactose (2.0%), glucose (1.4%), and rhamnose (1.1%) (Popov et al., 2005; Golovchenko et al., 2007). Leaves of B. crassifolia have been shown to accumulate lipophilic substances such as chlorophyll, carotenoids and vitamins A and E (Fedoseeva and Maloletkina, 1999). Glucoside rhododendrin (betuliside) was isolated from leaves of B. crassifolia by Thieme et al. (1969).
Pharmacological effects
In officinal medicine of Russia rhizomes only are claimed as haemostatic, astringent, anti-inflammatory and antimicrobial agents. Infusions are recommended in gynecology for excessive menstruation, bleeding after abortions, and cervical erosion treatment (Turova and Sapozhnikova, 1989; Shikov et al., 2014). It is recommended to strengthen capillary walls, to have local vasodilatation activity, to decrease arterial blood pressure and to increase hearth rate (Sokolov, 2000). However a lot of publication confirmed efficacy of leaves. We have collected data about effects of rhizomes and leaves in scientific literature and discuss there.
Adaptogenic
B. crassifolia is appearing to meet the criteria of being adaptogens (Suslov et al., 2002; Panossian, 2003). Historically, the term adaptogen (phytoadaptogen) derived from an extensive survey and screening of active substances of botanical origin during 1960-1980 in USSR. Adaptogen must; produce a nonspecific response, i.e. increase the power of resistance against multiple (physical, chemical or biological) stressors; have a normalizing effect, irrespective of the nature of the pathology and be non toxic; be innocuous and not influence normal body functions more than required (Brekhman and Dardymov, 1969; Panossian et al., 1999).
Adaptogenic effects of black and fermented B. crassifolia leaves were studied in mice forced swimming test. The swimming time of mice treated with infusion of fermented leaves (9ml/kg, intragastrically) was increased in 2.2-folds comparing to control. It was accompanied with increasing glucose utilization and decreasing lactate level by 92% compared with the control group. There was a positive correlation between forced swimming capacity and the content of arbutin and protocatechuic acid. Glucose and lactate utilization had a positive correlation with the content of gallic and ellagic acids and hydroquinone. Additionally it was mentioned that infusions of B. crassifolia leaves increase fat utilization during swimming resulted in decrease of body weight of mice (Shikov et al., 2010).
The running time in treadmill of rats treated with of bergenia black leaves extract (300 mg/kg, 10 days) was increased in 30% comparing to control group and was similar to that of rats treated with 5 ml/kg of Eleutherococcus senticosus extract (Tsyrenzhapova et al., 1996). Endurance capacity of rats subjected to chronic exposure to cold (-15[degrees]C, 3h, during 21 days) was markedly improved after supplementation with extract of bergenia black leaves. The swimming time of rats treated with extract (100 mg/kg, per oral) was significantly increased after 21 days of treatment, while in rats treated with the same dose of liposomes loaded with extract it was increased after 7 days of experiment (Bolshunova et al., 2010). Stress protective effect of extract was evaluated in rats in the model of immobilization stress. Significant reversal in stress-induced inhibition in adrenal weight, thymus involution and bleeding from gastric red spots was observed after administration of bergenia black leaves extract (300 mg/kg, intragastrically, 1 h before stress) (Tsyrenzhapova et al., 1996). Activation of mitochondrial ATP-dependent potassium channel ([mitoK.sub.ATP]) and increase in ATP-dependent [K.sup.+] transport in mitochondria are an essential stage, which initiates the adaptive response of organism under extreme conditions (e.g. hypoxia). Antihypoxic activity of lyophilized and standardized water-soluble extract of Bergenia was studied ex vivo. Activation of [mitoK.sub.ATP] channel in mitochondria isolated from rat heart by 200-250% was most pronounced after treatment with extract at 0.5-1.0 mg/1 (Mironova et al., 2008).
Anticancer
Ethanol extract (40%) of Bergenia rhizomes displayed the cytotoxicity against human lymphoblastoid Raji cells, near to completely suppressing the growth of cells at the concentrations of 200 [micro]g/ml, while alcoholic extract from green leaves was less effective with 82% inhibition at the same concentration (Spiridonov et al., 2005). Pedunculagin showed the dose-dependent cytotoxicity against human chronic myelogenous leukemia (K-562), human promyelocytic leukemia (HL-60), mouse lymphoid neoplasm (P388), mouse lymphocytic leukemia (LI 210) and mouse sarcoma 180 (SI80) cell lines with [ED.sub.50] = 5.30,0.92,2.78,9.35, and 1.38 [micro]g/ml, respectively. The survival of mice intoxicated with SI 80 was increased after treatment with pedunculagin (50, 100 [micro]g/kg, intraperitoneally, 20 days) (Chang et al., 1995).
Antidiabetic
Bergenin (10 mg/kg per oral) was found to reduce significantly blood glucose level in normal rats which were subjected to oral glucose tolerance test, while it showed a significant reduction in fasting blood glucose level in streptozotocin (STZ)-nicotinamide induced diabetic rats at same dose level on 14th day of treatment. Bergenin reversed plasma lipid profile to normal values except triglycerides. Histopathological studies demonstrated the regenerative effect of bergenin on pancreatic [beta] cells (Kumar et al., 2012).
Antihypertensive
Hypotensive effect of extract of B. crassifolia leaves (50 mg/kg, per oral, 14 days) has been studied in SHR rats. Decrease of systolic blood pressure by 20-25 mmHg was observed after 3-6 h after each daily administration, while decrease of diastolic blood pressure by 20-25 mmHg was observed after 1 h each day. Cumulative effect was registered after 7 days of treatment (Makarova and Makarov, 2010). The ethanol (70%) extract of B. crassifolia rhizomes was found to inhibit angiotensin I-converting enzyme (ACE I) with [IC.sub.50] = 0.128 mg/ml in vitro (Ivanov et al., 2012).
Anti-inflammatory and immunomodulating
The effect of dry extract of Bergenia leaves (min 18% arbutin) on the specific immune response parameters was studied in DBA/2 mice. The extract (50 mg/kg, intragastric, 5 days) produced normalizing effect on the content of antibody-forming cells in the spleen of experimental mice under the conditions of humoral response stimulation by antigen and in immunodepression models. The extract decreases expression of inflammatory processes under delayed hypersensitivity reaction conditions, by preventing the accumulation of T-lymphocytes and reducing the ability of cells to produce anti-inflammatory cytokines (Churin et al., 2005). Arbutin (100-500 [micro]M) suppressed lipopolysaccharide (LPS)-induced production of NO and expression of iNOS and COX-2 in a dose-dependent manner without causing cellular toxicity in murine BV2 microglial cells model. Arbutin also significantly reduced generation of proinflammatory cytokines, including IL-1[beta] and TNF-[alpha], and other inflammation-related genes such as MCP-1 and interleukin IL-6 (Lee and Kim, 2012). The anti-arthritic activity of bergenin in the model of adjuvant-induced arthritis of balb/c mice was increase in a dose dependent manner up to dose 40 mg/kg but a decrease was registered at 80 mg/kg. Oral administration of bergenin inhibits the production of proinflammatory Th 1 cytokines (IL-2, IFN-[gamma] and TNF-[alpha]) (Nazir et al., 2007). Bergenin was found to be selective inhibitor of cyclooxygenase COX-2 in vitro with [IC.sub.50] = 1.2 [micro]mol/1, while was not active against COX-1 and phospholipase A2 (Nunomura et al., 2009). Treatment of mice with 50 and 100 mg/kg of bergenin inhibited both the early and late phases in a formalin test, inhibited mechanical hyperalgesia, edema, and paw production of hyperalgesic cytokines (TNF-[alpha] and IL-1 [beta]) induced by complete Freund's adjuvant (De Oliveira et al., 2011). The delayed type hypersensitivity (DTH) reaction on footpad swelling was significantly increased in mice treated with the pectic polysaccharide bergenan BC (2 mg/ml, 3 weeks). Bergenan BC (100 [micro]g/ml) was found to enhance the uptake capacity of human neutrophils and was shown to stimulate the generation of oxygen radicals by mouse peritoneal macrophages (Popov et al., 2005). Galacturonans prepared from the bergenan by acidic hydrolysis were shown to reduce the neutrophil adhesion stimulated by phorbol 12-myristate 13-acetate and dithiothreitol by 36-45% and 33-42%, respectively, at a concentration of 50 [micro]g/ml (Popov et al., 2007).
Antimicrobial
The antimicrobial activity of B. crassifolia leaves extract has been demonstrated against Pseudomonas aeruginosa n Proteus spp. with bactericidal concentration 25 [micro]g/ml and against Staphylococcus spp., Micrococcus spp., Enterococcus spp. with bactericidal concentration 3.125 [micro]g/ml (Fedoseyeva et al. 2000). Crude ethanol (80%) extracts of Bergenia leaves showed potent antibacterial activity against P. aeruginosa with MIC of 15.63 mg/ml, Bacillus cereus, Escherichia coli, and Staphylococcus aureus with MIC of 62.50 mg/ml. While crude ethanolic (80%) extracts of rhizome was more active against B. cereus, Candida albicans, and E. coli with MIC of 15.63 mg/ml, and S. aureus with MIC of 62.50 mg/ml (Kokoska et al., 2002).
Antiobesity
Ethanol (70%) crude extract of B. crassifolia rhizomes strongly inhibited human pancreatic lipase activity with [IC.sub.50] = 3.4 [micro]g/ml in vitro (Ivanov et al., 2011). Extracts of black and fermented leaves of B. crassifolia are reported as appetite and energy intake suppressants in rats with high-calorie diet-induced obesity. The daily dietary intake of rats treated with Bergenia aqueous extracts (50 mg/kg, 7 days, per oral) was reduced to 40% compared with the control group. A significant improvement in glucose tolerance was noted after 7 days of treatment. Reduction in the serum triglyceride level (45%) compared with the control group was observed in rats treated with an extract of black leaves (Shikov et al., 2012). Galloylbergenin derivatives 3,11-Di-O-galloylbergenin and 4,11-di-O-galloylbergenin exhibited moderate anti-lipid accumulation activities with IC50 values of 38.4 [micro]M and 60.5 [micro]M, respectively in vitro (Janar et al., 2012).
Antioxidant
The crude aqueous ethanol (70%) extract of B. crassifolia scavenged 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) with [SC.sub.50] = 3.7 pg/ml in vitro (Ivanov et al., 2011). The radical-scavenging activities of the extracts of green and black leaves of B. crassifolia were investigated by monitoring of oxygen uptake rate in a universal gasometric system with 2,2'-azobisisobutyronitrile (AIBN)-initiated oxidation of isopropylbenzene. Most pronounced effect was observed for crude ethanol (70%) extract of green leaves (Shilova et al., 2006). The separation of major phenolic compounds of B. crassifolia and the quantification of antiradical activity in situ with DPPH was done with the use of the postchromatographic derivatization of TLC plates. The increasing order of activity was gallic acid > arbutin > ellagic acid > hydroquinone > ascorbic acid with estimated [ID.sub.50] values of 0.488, 0.879, 0.937, 1.227 and 3.080 nmol, respectively (Pozharitskaya et al., 2007). (+)-Catechin 3,5-di-O-gallate and (+)-catechin 3-O-gallate possessed strong antioxidant properties in DPPH assay with [SC.sub.50] = 1.04 and 1.33. [micro]g/ml, respectively (Ivanov et al., 2011)
Antitussive
Arbutin (50 and 100 mg/kg, per oral and intraperitoneally) at booth doses and administration routes elicited a statistically significant decrease in the number, intensity, and frequency of coughs of cats. But no dose depended effect was observed (Strapkova et al., 1991). Mice with ammonia-induced cough were treated with arbutin (50-200 mg/kg, per oral and intraperitoneally). The antitussive effect was dose-dependent and at the dose of 200 mg/kg was as potent as that of codeine phosphate (30 mg/kg), but arbutin had no analgesic or anesthetic effects (Li et al., 1982).
Antiviral
Antiviral activity of different extracts and fractions from B. crassifolia leaves has been studied against herpes simplex virus HSV strain L2. The data revealed that aqueous extract enriched with lectins inhibit the virus-induced cytopathic effect for 95% at the concentrations of 1.5-15 [micro]g/ml (Litvinenko et al., 2002). The inhibitory activities of galloyl glucosides against hepatitis C virus (HCV) NS3 serine protease were evaluated in vitro. The [IC.sub.50] values of penta- to tri-galloyl-[beta]-D-glucose, were 0.68-1.01 [micro]M with inhibition of 98.7-94.7% at 100 [micro]g/ml (Zuo et al., 2005). Tellimagrandin I was found as the HCV invasion inhibitor using the model virus, expressing the HCV envelope proteins E1 and E2. The inhibition was dose depended and reached 93.8% at 10 [micro]M (Tamura et al., 2010).
Cerebro-protective
Rats after 14 days of experimental hypoxia were treated with B. crassifolia green leaves extract (300 mg/kg, itragastrically, 5 days). The extract of Bergenia prevented the death of experimental animals which occurred in 33-45% cases on day 21 after hypoxic exposure in control. Cerebroprotective effect was associated with normalization of succinate-dependent energy production and rapid metabolic cluster reactions (Khazanov and Smirnova, 2000).
Diuretic
Arbutin and hydroquinone were intragastrically administered to rats at the doses of 5 mg/kg first 7 days and 15 mg/kg next 7 days. Administration of arbutin at booth doses resulted in increase of urine volume accompanied with creatinine and potassium excretion from the first day of experiment while hydroquinone increase of urine volume without effect on creatinine and potassium excretion during experiment (Voloboy et al., 2012).
Castroprotective
Pre-administration of arbutin (30, 60 mg/kg, per oral, 14 days) to Sprague Dawley rats with ethanol or aspirin induced ulcer protected the gastric mucosa as seen by reduction in ulcer area and mucosal content, reduced or absence of edema, inflammation and leucocytes infiltration on both models (Taha et al., 2012). Oral administration of bergenin showed significant protection against pylorus-ligated and aspirin-induced gastric ulcers in rats and cold restraint stress-induced gastric ulcers in rats and guinea pigs. The study on prostaglandins release by human colonic mucosal incubates, indicated a concentration-dependent (1-10 [micro]g/ml) stimulatory effect of bergenin. (Goel et al., 1997).
Hepatoprotective
The hepatoprotective effects of dry extract of bergenia (50 mg/kg, intragastric, 14 days) were shown in rats intoxicated with 4-pentenioc acid (Shutov, 2007). Arbutin (100-150 [micro]M) has protective effects against tert-butyl hydroperoxid induced toxicity in HepG2 cells (Seyfizadeh et al., 2012). The hepatoprotective effects of bergenin were evaluated against D-galactosamine (GalN)-induced liver damage in rats. Pretreatment with bergenin (50-200 mg/kg, per oral, 7 days) reduced the increased enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase, [gamma]-glutamyltransferase and the elevated level of malondialdehyde induced by GalN. Bergenin restored the decreased hepatic contents of glutathione as well as the decreased activities of glutathione S-transferase and glutathione reductase by GalN toward normalization (Lim et al., 2001).
Skin whitening
One of the major phenolic of Bergenia--arbutin inhibits tyrosinase and has been employed as a cosmetic skin-whitening agent in humans. Arbutin inhibits melanin production in B16 melanoma cells induced with [alpha]-melanocyte-stimulating hormone ([alpha]-MSH) and decreases tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation effects of [alpha]-MSH were abrogated by the addition of arbutin to brownish guinea pig and human skin tissues (Lim et al., 2009).
Toxicity
Aqueous infusions (1:10) of B. crassifolia both black and fermented leaves were safe in mice after 7 days of continuous per-oral administration at the dose of 9 ml/kg (Shikov et al., 2010). No signs of toxicity were observed in the rats after oral administration of dry extracts of black and green leaves (50 mg/kg, 7 days) (Shikov et al., 2012). The acute toxicity studies of arbutin (1000 and 2000 mg/kg) in Sprague Dawley rats show no abnormal signs, behavioral changes, body weight changes or macroscopic findings during 14 days of observation (Taha et al., 2012). No toxic effects of arbutin (8000 mg/kg, intraperitoneally, 2 weeks) were observed in mice. It had no effect on tracheal smooth muscle contraction, respiratory activity, spontaneous behavior, blood pressure, heart rate or electrical activity (Li et al., 1982). Hydroquinone, at the doses of 0.05% and 0.2%, in the daily diet by itself did not cause any toxicity as determined by the body and liver weights and microscopic evaluation of rats and even diminished 2-acetylaminofluorene-induced cancer initiating effects in the rat liver (Williams et al., 2007). Humans are able to tolerate hydroquinone up to 450 mg daily or 6.5 mg/kg for up to 5 months (Carlson and Brewer 1953; Williams et al., 2007). Intraperitoneal injection of bergenin (50 and 100 mg/kg, 7 days) in mice did not induce any variations in the general appearance or toxic signs. It was safe from the viewpoint of gastric inflammatory events and ulcer induction, did not induce any systemic toxicity or motor performance alteration, produced consistent antinociceptive effects in different models of inflammatory pain (De Oliveira et al., 2011). Bergenin (2000 mg/kg, per oral) was found to be safe in mice (Nazir et al., 2007). The bergenan BC was found to be nontoxic and failed to influence the body weight or the length and weight of intestine (Popov et al., 2005). The LD50 for sulfated pectin derivatives of B. crassifolia after single intraperitoneal injection was more than 1000 mg/kg (Vityazev et al., 2012).
According to state standards of ex USSR and Russian Federation (Shikov et al., 2011), the effectiveness and safety of B. crassifolia have been studied in considerable details. However, our literature analysis is limited by the fact that a lot of unpublished documents are deposited in the state regulatory archive and not available to the public. In the available literature no clinical data for B. crassifolia were found. In officinal medicine rhizomes of B. crassifolia are recommended for internal administration at the dose of 1-2 tablespoons of the decoction (1:20), 3 times per day as astringent, haemostatic, and anti-inflammatory (Sokolov, 2000).
Conclusion
In this paper, we reviewed the advances in phytochemistry, pharmacological activities and toxicology of B. crassifolia, and the increasing data supports the utilization and the exploitation for new drug. It is interesting that black leaves and rhizomes have been used in the traditional medicines of different countries, but rhizomes only are referred to in the State Pharmacopoeia USSR 11 ed. (The State Pharmacopoeia of the USSR, 11th edition, 1990). The safety and efficacy of B. crassifolia both leaves and rhizomes are confirmed during a long period of traditional application. However publications about chemistry, pharmacological effects and safety are fragmentary. This plant should be an interesting subject for further investigations especial in aspect of adaptogenic properties. It is important to reproduce and confirm the non-clinical studies and perform clinical trials according to modern regulation.
Conflict of interest
The authors declare that they have no conflict of interests.
https://dx.doi.Org/ 10.1016/j.phymed.2014.06.009
Acknowledgment
This work was supported by the project SPECICROP, ENPI CBC2007-2013.
References
Anisko, T., 2008. When Perennials Bloom: An Almanac for Planning and Planting. Timber Press, Portland, pp. 121-123.
Bohm, B.A., Donevan, LS., Bhat, U.G., 1986. Flavonoids of some species of Bergenia francoa, Pamassia and Lepuropetalon. Biochem. Syst. Ecol. 14,75-77.
Bolshunova, E.A., lamazhapova, G.P., Zhamsaranova, S.D., 2010. Research of liposomal form of Bergenia crassifolia (L) Fritsch influence on formation of adaptation potential of the body. Bull. East Siberian State Univ. Technol. 4, 83-88.
Borisova, A.G., 1956. Badan (Bergenia Moench) ego sistematica i chozjajstwennoe znaczenije, vol. 4. Trudy Botanicheskogo Instituta im. A Komarowa Akademii Nauk SSSR, seria 5, pp. 297-339 (in Russian).
Brekhman, I.I., Dardymov, I.V., 1969. New substances of plant origin which increase nonspecific resistance. Annu. Rev. Pharmacol. 9, 419-430.
Britton, G., Haslam, E., 1965. Gallotannins. Part XII. Phenolic constituents of Arctostaphylos uva-ursi L Spreng. J. Chem. Soc. 1342, 7312-7319.
Carlson, A.J., Brewer, N.R., 1953. Toxicity studies on hydroquinone. Proc. Soc. Exp. Bio! (N. Y.) 84, 684-688.
Chang, J.H., Cho, J.H., Kim, H.H., Lee, K.P., Lee, M.W., Han, S.S., Lee, D.I., 1995. Antitumor activity of pedunculagin, one of the ellagitannin. Arch. Pharm. Res. 18(6), 396-401.
Chernetsova, E.S., Crawford, EA, Shikov, A.N., Pozharitskaya, O.N., Makarov, V.G., Morlock, G.E., 2012. ID-CUBE direct analysis in real time high-resolution mass spectrometry and its capabilities in the identification of phenolic components from the green leaves of Bergenia crassifolia L Rapid Commun. Mass Spectr. 26 (11), 1329-1337.
Chernetsova, E.S., Shikov, A.N., Crawford, E.A., Grashorn, S., Laakso, L, Pozharitskaya, O.N., Makarov, V.G., Hiltunen, R., Galambosi, B., Morlock, G.E., 2014. Characterization of volatile and semi-volatile compounds in green and fermented leaves of Bergenia crassifolia L by gas chromatography-mass spectrometry and IDCUBE direct analysis in real time-highresolution mass spectrometry. Eur. J. Mass Spear. 20(2), 199-205.
Churin, A.A., Masnaya, N.V., Sherstoboev E.Y., Suslov, N.I., 2005. Effect of Bergenia crassifolia extraa on specific immune response parameters under extremal conditions. Eksperimental'naya i Klinicheskaya Farmakologiya 68 (5), 51-54.
De Oliveira, C.M., Nonato, F.R., De Lima, F.O., Couto, R.D., David, J.P., David, J.M., Soares, M.B.P., Villarreal, C.F., 2011. Antinociceptive properties of bergenin. J. Nat. Prod. 74 (10), 2062-2068.
Fedoseeva, L.M., 2005. Investigation of tannin substances in underground and aerial parts of Bergenia crassifolia (L) Fitsch. from Altai. Khimija Rastitel'nogo Syr'ja 3, 45-50.
Fedoseeva, L.M., Maloletkina, T.S., 1999. Investigation and rating of lipophilic substances in green, red and black leaves of Bergenia crassifolia of Altai area. Khimija Rastitel'nogo Syr'ja 2,113-117.
Fedoseyeva, L.M., Kerasheva, S.I., Karabasova, E.V., 2000. Antimicrobial activity of dry extract from leaves of Bergenia crassifolia (L.) Fritsch. with respect to pathogens of some uppurative inflammatory diseases. Rastitel'nye Resursy 36,153-157.
Gammerman, A.F., Kadaev, G.N., Yacenko-Khmelevsky, A.A., 1984. Medicinal Plants (Herbs-healers). High School, Moscow (in Russian).
Goel, R.K., Maiti, R.N., Manickam, M., Ray, A.B., 1997. Antiulcer activity of naturally occurring pyrano-coumarin and isocoumarins and their effect on prostanoid synthesis using human colonic mucosa. Indian J. Exp. Biol. 35,1080-1083.
Golovchenko, V.V., Bushneva, O.A., Ovodova, R.G., Shashkov, A.S., Chizhov, A.O., Ovodov, Yu. S., 2007. Structural study of bergenan, a pectin from Bergenia crassifolia. Russ.J. Bioorg. Chem. 33 (1), 47-56.
Haddock, E.A., Gupta, R.K., Al-Shafi, S.M.K., Haslam, E., Magnolato, D., 1982. The metabolism of gallic acid and hexahydroxydiphenic acid in plants. Part 1. Introduction. Naturally occurring galloyl esters. J. Chem. Soc. Perkin Trans. 1, 2515-2524.
Haslam, E., 1969. (+)-Catechin-3-gallate and a polymeric proanthocyanidin from Bergenia species. J. Chem. Soc. C: Org. 14,1824-1828.
Hendrychova, H., Tumova, L, 2012. Bergenia genus--content matters and biological activity. Ceska a Slovenska farmacie 61 (5), 203-209.
Ivanov, S.A., Garbuz, S.A., Malfanov, I.L., Ptitsyn, L.R., 2012. Screening of Russian medicinal and edible plant extracts for angiotensin I-converting enzyme (ACE 1) inhibitory activity. Khimija Rastitel'nogo Syr'ja 2,165-172.
Ivanov, S.A., Nomura, K., Malfanov, I.L, Sklyar, I.V., Ptitsyn, L.R., 2011. Isolation of a novel catechin from Bergenia rhizomes that has pronounced lipase-inhibiting and antioxidative properties. Fitoterapia 82,212-218.
Janar, J., Fang, L, Wong, C.P., Kaneda, T., Flirasawa, Y., Shahmanovna, B.G., Abduahitovich, A.Z., Morita, H., 2012. A new galloylbergenin from Bergenia crassifolia with anti-lipid droplet accumulation activity. Heterocycles 86 (2), 1591-1595.
Khazanov, V.A., Smirnova, N.B., 2000. Kinetic characteristics of the energy production system in rat brain under conditions of posthypoxic encephalopathy and its correction with Bergeniae crassifoliae extracts. Bui. Exp. Biol. Med. 1, 63-65.
Kokoska, L, Polesny, Z., Rada, V., Nepovim, A., Vanek, T., 2002. Screening of some Siberian medicinal plants for antimicrobial activity. J. Ethnopharmacol. 82, 51-53.
Kumar, R., Patel, D.K., Prasad, S.K., Laloo, D., Krishnamurthy, S., Hemalatha, S., 2012. Type 2 antidiabetic activity of bergenin from the roots of Caesalpinia digyna Rottler. Fitoterapia 83 (2), 395-401.
Lee, H.-J., Kim, K.-W., 2012. Anti-inflammatory effects of arbutin in lipopolysaccharide-stimulated BV2 microglial cells, Inflamm. Res. 61 (8), 817-825.
Li, S., Liu, G., Zhang, Y., Xu, J., 1982. Experimental study on antitussive effect or arbutin. Yaoxue Tongbao 17(12), 720-722.
Lim, H.K., Kim, H.S., Choi, H.S., Choi, J., Kim, S.H., Chang, M.J., 2001. Effects of bergenin, the major constituent of Mallotus japonicus against o-galactosamine-induced hepatotoxicity in rats. Pharmacology 63,71-75.
Lim, Y.J., Lee, E.H., Kang, T.H., Ha, S.K., Oh, M.S., Kim, S.M., Yoon, T.J., Kang, C, Park, J.H., Kim, S.Y., 2009. Inhibitory effects of arbutin on melanin biosynthesis of alpha-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues. Arch. Pharm. Res. 32, 367-373.
Litvinenko, V.I., Martynov, A.V., Popova, N.V., Kozukh, LA., 2002. Some technological and biopharmaceutical features of Bergenia crassifolia lectins extraction. Pharmacom 3, 123-127.
Makarova. M.N., Makarov, V.G., 2010. Molecular Biology of Flavonoids (Chemistry, Biochemistry, Pharmacology): Manual for Doctors. Lema Publishing, St-Petersburg, pp. 272-290.
2013. Medicinal Plants in Mongolia. WHO Regional Office for the Western Pacific, pp. 235.
Mironova, G.D.,Shigaeva, M.I., Belosludtseva, N.V., Gritsenko, E.N., Belosludtsev, K.N., Germanova. E.L., Lukyanova, L.D., 2008. Effect of several flavonoid-containing plant preparations on activity of mitochondrial ATP-dependent potassium channel. Bull. Exp. Biol. Med. 146 (2), 229-233.
Nazir, N., Koul, S., Qurishi, M.A., Taneja, S.C., Ahmad, S.F., Bani, S., Qazi, G.N., 2007. Immunomodulatory effect of bergenin and norbergenin against adjuvant induced arthritis--a flow cytometric study. J. Ethnopharmacol. 112,401-405.
Nunomura, R.C., Oliveira, V.G., Silva, S.L, da Nunomura, S.M., 2009. Characterization of bergenin in Endopleura uchi bark and its anti-inflammatory activity. J. Braz. Chem. Soc. 20,1060-1064.
Panossian, A., 2003. Adaptogens: tonic herbs for fatigue and stress. Altern. Complement. Ther. 9.327-332.
Panossian, A., Wikman, G., Wagner, H., 1999. Plant adaptogens. III. Earlier and more recent aspects and concepts on their mode of action. Phytomedicine 6 (4), 287-300.
Plant Resources of the USSR, 1987. Flowering plants, their chemical composition and use. In: Sokolov, P.D. (Ed.), Hydrangeaceae--Haloragaceae Families, vol. 3. Nauka, Leningrad, pp. 8-10 (in Russian).
Popov, S.V., Popova, G.Y., Nikolaeva, S.Y., Golovchenko, V.V., Ovodova, R.G., 2005. Immunostimulating activity of pectic polysaccharide from Bergenia crassifolia (L) Fritsch. Phytother. Res. 19, 1052-1056.
Popov, S.V., Ovodova, R.G., Popova, G.Y., Nikitina, I.R., Ovodov, Y.S.. 2007. Inhibition of neutrophil adhesion by pectic galacturonans. Russ. J. Bioorg. Chem. 33 (1), 175-180.
Pozharitskaya, O.N., Ivanova, SA, Shikov, A.N., Makarov, V.G., Galambosi, B., 2007. Separation and evaluation of free radical-scavenging activity of phenol components of green, brown, and black leaves of Bergenia crassifolia by using HPTLC-DPPH method. J. Sep. Sci. 30, 2447-2451.
Salminen, J.-P., Shikov, A.N., Karonen, M., Pozharitskaya, O.N., Kim, J., Makarov, V.G., Hiltunen, R., Galambosi, B., 2014. Rapid profiling of phenolic compounds of green and fermented Bergenia crassifolia L. leaves by UPLC-DAD-QqQ-MS and HPLC-DAD-ESI-QTOF-MS. Nat. Prod. Res., https://dx.doi.org/10.1080/14786419.2014.923999.
Seyfizadeh, N., Mahjoub, S., Zabihi, E., Moghadamnia, A., Pouramir, M., Mir, H., Khosravifarsani, M., Elahimanesh, F., 2012. Cytoprotective effects of arbutin against tert-butyl hydroperoxid induced toxicity in hep-G2 cell line. World Appl. Sci. J. 19(2), 163-167.
Shikov, A.N., Pozharitskaya, O.N., Dorman, H.J.D., Makarov, V.G., Tikhonov, V.P., Hiltunen, R., 2007. Chemical composition of extracts from green, brown and black leaves of Bergenia crassifolia L Planta Med. 73 (9), 897.
Shikov, A.N., Pozharitskaya, O.N., Kamenev, I.Y., Makarov, V.G., 2011. Arznei und Gewurzpflanzen in Russland. Zeitschrift fur Arznei & Gewurzpflanzen 16, 135-137.
Shikov, A.N., Pozharitskaya, O.N., Makarov, V.G., Wagner, H., Verpoorte, R., Heinrich, M., 2014. Medicinal plants of the Russian Pharmacopoeia; their history and applications. J. Ethnopharmacol. 154,481-536.
Shikov, A.N., Pozharitskaya, O.N., Makarova, M.N., Dorman, H.J.D., Makarov, V.G., Hiltunen, R., Galambosi, B., 2010. Adaptogenic effect of black and fermented leaves of Bergenia crassifolia L in mice. J. Funct. Foods 2,71 -76.
Shikov, A.N., Pozharitskaya, O.N., Makarova, M.N., Kovaleva, M.A., Laakso, L, Dorman, H.J.D., Hiltunen, R., Makarov, V.G., Galambosi, B., 2012. Effect of Bergenia crassifolia L extracts on weight gain and feeding behavior of rats with high-caloric diet-induced obesity. Phytomedicine 19,1250-1255.
Shilova, I.V., Pisareva, S.L, Krasnov, E.A., Bruzhes, M.A., Pyak, A.I., 2006. Antioxidant properties of Bergenia crassifolia extract. Pharm. Chem. J. 40 (11), 620-623.
Shnyakina, G.P., Sedel'nikova, V.A., Tsygankova, N.B., 1981. Arbutin content in the leaves of some plants grown at Dal'nyi Vostok. Rastitelnye Resursy 17 (4), 568-571.
Shutov, D.V., 2007. Hepatoprotective effect of Bergenia crassifolia extract and silymarin at experimental inhibition of (3-oxidation of fatty acids caused by 4-pentenioc acid. Bull. Siberian Med. 7, 64-70.
Sokolov. S.Y., 2000. Phytotherapy and Phytopharmacology: The Manual for Doctors. Medical News Agency, Moscow (in Russian).
Spiridonov, N.A., Konovalov, D.A., Arkhipov, V.V., 2005. Cytotoxicity of some Russian ethnomedicinal plants and plant compounds. Phytother. Res. 19,428-432.
Strapkova, A., Jahodar, L, Nosalova, G., 1991. Antitussive effect of arbutin. Pharmazie 46(8), 611-612.
Suslov, N.I., Churin, A.A., Skurikhin, E.G., Provalova, N.V., Stal'bovskii, A.O., Litvinenko, V.I., Dygai, A.M., 2002. Effect of the natural nootrope and adaptogen preparations on the bioelectric cortex activity in rats. Eksperimental'naya i Klinicheskaya Farmakologiya 65,7-10.
Taha, M.M.E., Salga, M.S., Ali, H.M., Abdulla, M.A., Abdelwahab, S.L, Hadi, A.H.A., 2012. Gastroprotective activities of Tumera diffusa Willd. ex Schult. revisited role of arbutin. J. Ethnopharmacol. 141 (1), 273-281.
Tamura, S., Yang, G.-M., Yasueda, N., Matsuura, Y., Komoda, Y., Murakami, N., 2010. Tellimagrandin I, HCV invasion inhibitor from Rosae Rugosae Flos. Bioorg. Med. Chem. Lett. 20 (5), 1598-1600.
The State Pharmacopoeia of the USSR, 11th ed., part 2,1990. Rhizomata bergeniae. Medizina, Moscow, pp. 357-358.
Thieme, H., Walewska, E., Winkler, H.J., 1969. Isolierung von Rhododendrin aus Bergenia-Arten. Pharmazie 24 (10), 648.
Tschitschibabin, A.E., Kirssanow, A.W., Korolew, A.J., Woroschzow, N.N., 1929. Uber nichtgerbende Substanzen des Extraktes aus dem Wurzelstock des Badans (Saxifraga crassifolia) I. Bergenin. Justus Liebigs Annalen der Chemie 469(1),93-127.
Tschitschibabin, A.E., Kirssanow, A.W., Rudenko, M.G., 1930. Liber nicht gerbende Substanzen aus Badan (Saxifraga crassifolia). II. Arbutin. Justus Liebigs Annalen der Chemie 479 (1), 303-306.
Tsyrenzhapova, O.D., Lubsandorzhieva, P.B., Bryzgalov, G.Y., 1996. Badaton and rantakrin--new adaptogenic preparations, vol. 2. Sokhranenie biologicheskogo raznoobrazia v Baikalskom regione: problemy, podkody, praktika, Ulan-Ude, pp. 157-158 (in Russian).
Turova, A.D., Sapozhnikova, E.N., 1989. Medicinal Plants of USSR and Their Applications. Medizina, Moscow (in Russian).
Utkin, LA., 1931. Traditional Medicinal plants of Siberia. In: Proceedings of Scientific Research Institutes of Industry, p. 434, vypusk 24 (in Russian).
Vereschagin, V.I., Sobolevskaya, K.A., Yakubova, A.I., 1959. Useful Plants of West Siberia. Publishing of Academy of Science of USSR, Moscow-Leningrad (in Russian).
Vityazev, F.V., Paderin, N.M., Golovchenko, V.V., 2012. In vitro binding of human serum low density lipoproteins by sulfated pectin derivatives. Russ. J. Bioorg. Chem. 38,319-323.
Voloboy. N.I., Smirnov, I.V., Bondarev, A.A., 2012. Features of diuretic activity of arbutin and hydroquinone. Siberian Med. J. 27 (3), 131 -134.
Williams, G.M., latropoulos, M.J., Jeffrey, A.M., Duan, J.-D., 2007. Inhibition by dietary hydroquinone of acetylaminofluorene induction of initiation of rat liver carcinogenesis. Food Chem. Toxicol. 45,1620-1625.
Yeo, P.F., 1966. A revision of the genus Bergenia Moench (Saxifragaceae). Kew Bull. 20(1), 113-148.
Zenk, M.H., 1964. Incorporation of p-hydroxybenzoic acid in the hydroquinone components of arbutin in Bergenia crassifolia. Zeitschrift fur Naturforschung B 19, 856-857.
Zhao, J., Liu, J., Zhang, X., Liu, Z., Tsering, T., Zhong, Y., Nan, P., 2006. Chemical composition of the volatiles of three wild Bergenia species from western China. Flavour Fragr. J. 21 (3),431-434.
Zhou, J., Xie, G., Yan, X., 2011. Encyclopedia of Traditional Chinese Medicines--Molecular Structures, Pharmacological Activities, Natural Sources and Applications. Isolated Compounds T-Z, vol. 5. Springer-Verlag Berlin Heidelberg, pp. 601.
Zuo, G.-Y., Li, Z.-Q., Chen, L-R., Xu, X.-J., 2005. In vitro anti-HCV activities of Saxifraga melanocentra and its related polyphenolic compounds. Antivir. Chem. Chemother. 16 (6), 393-398.
ARTICLE INFO
Article history:
Received 26 February 2014
Received in revised form 12 May 2014
Accepted 19 June 2014
Alexander N. Shikov (a),*, Olga N. Pozharitskaya (a), Marina N. Makarova (a), Valery G. Makarov (a), Hildebert Wagner (b)
(a) Saint-Petersburg Institute of Pharmacy, Leningrad Region, Vsevolozhsky District, 188663, Kuzmolovo P245, Russia
(b) Institute of Pharmacy, Pharmaceutical Biology, Ludwig Maximilian University, D-81377 Munich, Germany
* Corresponding author. Tel.: +7 812 3225605; fax: +7 812 3225605.
E-mail addresses: [email protected], [email protected] (A.N. Shikov).
Table 1
The compounds isolated from B. crassifolia. (The structure
of main compounds illustrated in Fig. 1).
N Compound Reference
Aldehydes
1 2,4-Heptadienal Chernetsova et al. (2014)
2 Benzaldehyde Zhao et al.(2006)
3 Benzeneacetaldehyde Zhao et al. (2006)
4 Decadienal Chernetsova et al. (2014)
5 Decanal Zhao et al. (2006)
6 Dimethyl cyclohexene Zhao et al. (2006)
acetaldehyde
7 E-2-decenal Zhao etal. (2006)
8 E-2-nonenal Chernetsova et al. (2014)
9 Nonanal Zhao etal. (2006)
10 p-Menthenal Chernetsova et al. (2014)
Terpenes
11 (E)-([beta]-Damascenone Zhao etal. (2006)
12 (E)-([beta]-Damascone Zhao etal. (2006)
13 3-Thujen-2-one Zhao et al. (2006)
14 Caryophyllene Zhao et al. (2006)
15 Cedranol Zhao et al. (2006)
16 E-2-Decenol Zhao etal. (2006)
17 Farnesol Chernetsova et al. (2014)
18 Farnesyl acetone Chernetsova et al. (2014)
19 Geraniol Zhao et al. (2006)
20 Geranyl acetone Chernetsova et al. (2014)
21 Hexahydrofarnesyl acetone Zhao et al. (2006)
22 Ionone Chernetsova et al. (2014)
23 Linalool Zhao etal. (2006)
24 m-Cymene Zhao et al. (2006)
25 Nerolidol Chernetsova et al. (2014)
26 Phytol Zhao etal. (2006)
27 p-Menth-l-en-4-ol Zhao etal. (2006)
28 Prenol Zhao etal. (2006)
29 Thymol Zhao etal. (2006)
30 [alpha]-Bisabolol Chernetsova et al. (2014)
31 [alpha]-Bisabololoxide B Chernetsova et al. (2014)
32 [alpha]-Cadinol Zhao et al. (2006)
33 [alpha]-Terpineol Zhao et al. (2006)
34 [beta]-Elemene Zhao etal. (2006)
35 [beta]-Eudesmol Zhao etal. (2006)
36 [beta]-Cadinene Chernetsova et al. (2014)
Flavonoids
37 11-O-(p-hydroxybezoyi)bergenin Janar etal. (2012)
38 3,11-di-O-galloylbergenin Janar etal. (2012)
39 4,11-di-O-galloylbergenin Janar etal. (2012)
40 Bergapten Chernetsova et al. (2012)
41 Bergenin Tschitschibabin et
al. (1929)
42 Kaempferol 3-O- Bohm et al. (1986)
xylosylgalactoside
43 Kaempferol 3-O- Bohm et al. (1986)
xylosylglucoside
44 Kaempferol 3-O-arabinoside Bohm et al. (1986)
45 Kaempferol 3-O-rutinoside Bohm et al. (1986)
46 Norathyriol Chernetsova et al. (2012)
47 Norbergenin Chernetsova et al. (2012)
48 Quercetin 3-O- Bohm etal. (1986)
xyiosylgalactoside
49 Quercetin 3-O-xyIosyiglucoside Bohm etal. (1986)
50 Quercetin 3-O-arabinoside Bohm etal. (1986)
51 Quercetin 3-O-galactoside Bohmet al. (1986)
52 Quercetin 3-O-glucoside Bohm etal. (1986)
53 Quercetin 3-O-rhamnoside Bohmet al.(1986)
54 Quercetin 3-O-rutinoside Bohm et al. (1986)
55 Quercetin 3-O-xyloside Bohm et al. (1986)
56 Trihydroxycoumarin Chernetsova et al. (2012)
Hydrolysable tannins
57 (+)-Catechin 3,5-di-O-gallate Ivanov etal. (2011)
58 (+)-Catechin 3-O-gallate Haslam (1969)
59 1,2,3,4,6-penta-O- Salminen etal. (2014)
galloylglucose
60 1,2,4,6-tetra-O-galloy-P-D- Haddock etal. (1982)
glucopyranose
61 1,2,6-tri-O-galloylglucose Salminen etal. (2014)
62 1-O-galloylglucose Salminen et al. (2014)
63 Monogalloyl quinic acid Salminen etal. (2014)
64 Pedunculagin Salminen et al. (2014)
65 Tellimagrandin I Salminen et al. (2014)
Phenolics
66 2-O-caffeoylarbutin Britton and Haslam (1965)
67 6-O-galloylarbutin Britton and Haslam (1965)
68 Arbutin Tschitschibabin
et al. (1930)
69 Ellagic acid Plant Resources of the
USSR (1987)
70 Hydroquinone Zenk(1964)
71 p-galloyloxyphenyl Britton and Haslam (1965)
([beta]-D-glucoside
72 Pyrogallol Phenolic acids Chernetsova et al. (2012)
73 Acetylsalicylic acid. Chernetsova et al. (2012)
74 Caffeoyl quinic acid Salminen et al. (2014)
75 Fumaric acid Chernetsova et al. (2012)
76 Furancarboxylic acid Chernetsova et al. (2012)
77 Gallic acid Shikov et al. (2007)
78 Malic acid Chernetsova et al. (2012)
79 Protocatechuic acid Shikov et al. (2007)
80 Quinic acid Other compounds Chernetsova et al. (2012)
81 4-Methoxystyrene Chernetsova et al. (2014)
82 9,12-Octadecadienoic acid Zhao et al. (2006)
83 9-Octadecenoic acid Chernetsova et al. (2014)
84 Bergenan BC Popov et al. (2005)
85 Carotenoids Fedoseeva and
Maloletkina (1999)
86 Chlorophyll Fedoseeva and
Maloletkina (1999)
87 Decanoic acid Chernetsova et al. (2014)
88 Dodecanoic acid Zhao et al. (2006)
89 Hexadecanoic acid Zhao et al. (2006)
90 n-Cetyl alcohol Zhao etal.(2006)
91 n-Eicosanol Zhao et al. (2006)
92 n-Hentriacontane Zhao etal.(2006)
93 n-Heptacosane Zhao et al. (2006)
94 n-Nonacosane Zhao et al. (2006)
95 Nonanoic acid Chernetsova et al. (2014)
96 n-Pentacosane Zhao et al. (2006)
97 Pentadecanoic acid Chernetsova et al. (2014)
98 Rhododendrin Thiemeetal. (1969)
99 Stearic acid Zhao et al. (2006)
100 Tetradecanoic acid Zhao et al. (2006)
101 Tetramethyl hexadecenol Zhao et al. (2006)
102 Trimethyl dihydronaphthalene Zhao et al. (2006)
103 Trimethyl-3-methylene Chernetsova et al. (2014)
hexadecatetraene
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