Definition
Radix Bupleuri consists of the dried root of Bupleurum falcatum L. or B. falcatum L. var.scorzonerifolium (Willd.) Ledeb. (Apiaceae) (1, 2).
Synonyms
Bupleurum chinense D.C. and B. scorzonerifolium Willd. have been treated as different species (1) but are actually synonyms of B. falcatum L. var. scorzonerifolium (3). Apiaceae are also referred to as Umbelliferae.
Selected vernacular names
Beichaihu, bupleurum root, ch'ai hu, chaifu, chaihu, chaiku-saiko, Chinese thorowax root, juk-siho, kara-saiko, mishima-saiko, nanchaihu, northern Chinese thorowax root, radix bupleur, saiko, shi ho, shoku-saiko, wa-saiko, Yamasaiko (1–5).
Description
A perennial herb up to 1m tall; base woody and the rhizome branching. Stem slender, flexuous, branches spreading. Basal leaves lanceolate, upper lamina broad, lower narrowed into a petiole, veins 7, apex acute, mucronate; middle and upper leaves linear to lanceolate, gradually shorter, falcate, veins 7–9, base slightly amplexicaul, apex acuminate. Involucre of 1–3 minute bracts or lacking. Rays 5–8. Involucel of 5 minute, 3-veined bractlets, shorter than the flowering umbellet. Pedicels shorter than the fruits. Fruit oblong, 3–4 mm long; furrows 3- vittate (4, 6).
Plant material of interest: dried roots
General appearance
Single or branched root, of long cone or column shape, 10–20 cm in length, 0.5– 1.5 cm in diameter; occasionally with remains of stem on crown; externally light brown to brown and sometimes with deep wrinkles; easily broken, and fractured surface somewhat fibrous (2).
Organoleptic properties
Odour, characteristic, slightly aromatic to rancid; taste, slightly bitter (1, 2).
Microscopic characteristics
Transverse section reveals often tangentially extended clefts in cortex, the thickness reaching a third to a half of the radius, and cortex scattered with a good many intercellular schizogenous oil canals 1.5–3.5 cm in diameter; vessels lined radially or stepwise in xylem, with scattered fibre groups; in the crown pith also contains oil canals; parenchyma cells filled with starch grains and some oil drops. Starch grains composed of simple grains, 2–10µm in diameter, or compound grains (2).
Powdered plant material
Information not available. Description to be established by appropriate national authorities.
Geographical distribution
Indigenous to northern Asia, northern China, and Europe (4, 6).
General identity tests
Macroscopic and microscopic examinations (1, 2), microchemical detection for saponins (1, 2), and thin-layer chromatographic analysis for triterpene saponins with reference to saikosaponins (2).
Purity tests
Microbiology
The test for Salmonella spp. in Radix Bupleuri should be negative. The maximum acceptable limits of other microorganisms are as follows (7–9). For preparation of decoction: aerobic bacteria-not more than 107/g; fungi-not more than 105/g; Escherichia coli-not more than 102/g.
Chemical
Contains triterpene saponins (saikosaponins). Quantitative level to be established by appropriate national authorities, but should be not less than 1.5% according to literature data.
Foreign organic matter
Not more than 10% of stems and leaves (2). No roots of B. longiradiantum Turcz., which is toxic (1, 5). Not more than 1% of other foreign matter (2).
Total ash
Not more than 6.5% (2).
Acid-insoluble ash
Not more than 2% (2).
Dilute ethanol-soluble extractive
Not less than 11% (2).
Pesticide residues
To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin for Radix Bupleuri is not more than 0.05 mg/kg (9). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (7) and WHO guidelines for predicting dietary intake of pesticide residues (10).
Heavy metals
Recommended lead and cadmium levels are no more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (7).
Radioactive residues
For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (7).
Other tests
Tests for moisture and for water-soluble extractive to be established by national authorities.
Chemical assays
Total saikosaponins determination by colorimetric analysis (11), and highperformance liquid chromatography analysis for saikosaponins A, B1, B2, and D (12, 13).
Major chemical constituents
The major constituents are triterpene saponins, including saikosaponins A, B1–4, D, E, F and H and related compounds including saikogenins A–G (5, 14). Two biologically active polysaccharides, bupleurans 2IIb and 2IIc, have also been isolated from the roots of B. falcatum (15, 16). Representative structures of saikosaponins are presented in the figure.
Dosage forms
Decoction (5). Store crude plant material in a dry environment protected from moths, light, and moisture (1, 2).
Medicinal uses
Uses supported by clinical data
None.
Uses described in pharmacopoeias and in traditional systems of medicine
Treatment of fever, pain, and inflammation associated with influenza, and the common cold (1, 2, 5). The drug is also used as an analgesic for the treatment of distending pain in the chest and hypochondriac regions, and for amenorrhoea (1). Extracts have been used for the treatment of chronic hepatitis, nephrotic syndrome, and autoimmune diseases (1, 5).
Uses described in folk medicine, not supported by experimental or clinical data
Treatment of deafness, dizziness, diabetes, wounds, and vomiting (5).
Pharmacology
Experimental pharmacology
Antipyretic and analgesic activity
A number of in vivo studies have confirmed the antipyretic activity of Radix Bupleuri in the treatment of induced fevers in animals. Oral administration of a Bupleurum decoction (5 g/kg) to rabbits with a heat-induced fever decreased body temperature to normal levels within 1.5 hours (5). Subcutaneous injection of an aqueous ethanol extract of Bupleurum roots (2.2 ml/kg, 1.1 g crude drug/ml) significantly reduced fevers in rabbits injected with Escherichia coli (17).
Oral administration of saikosaponins to rats produced hypothermic and antipyretic effects (5). Furthermore, intraperitoneal injection of the volatile oil (300mg/kg) or saponins (380 and 635 mg/kg) isolated from B. chinense (B. falcatum) roots effectively decreased fever in mice induced by yeast injections (18). Oral administration of 200–800mg/kg of a crude saponin fraction to mice produced sedative, analgesic, and antipyretic effects, but no anticonvulsant effect or reduction in muscle tone was observed (14). Saikosaponins are believed to be the major active antipyretic constituents in Radix Bupleuri extracts.
Analgesic activity of Bupleurum extracts is also supported by in vivo studies. Injections of a crudeBupleurum extract or purified sapogenin A inhibited writhing induced by intraperitoneal injection of acetic acid in mice (5). The saikosaponins appear to be the active analgesic constituents of the drug. Intraperitoneal injection of mice with a total saponin fraction derived from B. chinense (B. falcatum) produced a marked analgesic effect on the pain induced by electroshock (5). Moreover, orally administered saikosaponins were reported to have an analgesic effect in mice (tail pressure test) (5).
Sedative effects
In vivo studies have also confirmed the sedative effects of Radix Bupleuri. Both the crude saikosaponin fraction and saikogenin A are reported to have signifi- cant sedative effects (5). In vivo studies, using the rod climbing test, demonstrated that the sedative effect of the saikosaponins (200–800mg/kg) in mice was similar to that of meprobamate (100mg) (5). Oral administration of saikosides extracted fromB. chinense (B. falcatum) or saikosaponin A has also been reported to prolong cyclobarbital sodium-induced sleep (5). Furthermore, intraperitoneal injection of saikogenin A inhibited rod climbing in mice and antagonized the stimulant effects of metamfetamine and caffeine (5).
Anti-inflammatory activity
Anti-inflammatory activity of Radix Bupleuri has been demonstrated by in vivo studies. Intraperitoneal injection of the saponin fraction, the volatile oil, or a crude extract from B. chinense (B. falcatum) significantly inhibited carrageenin-induced rat paw oedema (5). The saikosaponins are the active antiinflammatory constituents of the drug (19, 20). Oral administration of a crude saikosaponin fraction (2 g/kg) from B. falcatum inhibited dextran-, serotonin-, or croton oil-induced rat paw oedema (5, 21). Structure–activity correlations have revealed that saikosaponins A and D both have anti-inflammatory activity, while saikosaponin C does not (22). The potency of anti-inflammatory activity of the saikosaponins is similar to that of prednisolone (5).
Immune regulation activity
In vitro studies have demonstrated that a hot-water extract from the root of B. falcatum enhanced the antibody response and inhibited mitogen-induced lymphocyte transformation (23). An acidic pectic polysaccharide, bupleuran 2IIb, isolated from the roots of B. falcatum, was found to be a potent enhancer of immune complex binding to macrophages (24). The activity of this polysaccharide appeared to be due to its ability to enhance the Fc receptor function of macrophages. This study has shown that the binding of glucose oxidase– antiglucose oxidase complexes (a model of immune complexes) to murine peritoneal macrophages was stimulated by treatment with the polysaccharide (24). Bupleuran 2IIb appears to up-regulate both FcRI and FcRII receptor expression on the macrophage surface in a dose-dependent manner (25). The upregulation of the Fc receptor by bupleuran 2IIb depends on an increase in intracellular calcium and activation of calmodulin (25). Only saikosaponin D has been shown to enhance Fc receptor expression of thioglycollate-elicited murine peritoneal macrophages in vitro (26). This activity appears to be due to the translocation of FcR from the internal pool to the cell surface. In vitro studies with saikosaponin D have shown that this compound was able to control bidirectionally the growth response of T lymphocytes stimulated by concanavalin A, anti-CD3 monoclonal antibody, and calcium ionophore A23187 plus phorbol 12-myristate 13-acetate (27). Saikosaponin D also promoted interleukin-2 production and receptor expression, as well as c-fos gene transcription (28). The results of this study suggest that saikosaponin D exerts its immunostimulant effects by modification of T lymphocyte function (28).
Antiulcer activity
Antiulcer activity of Radix Bupleuri has been demonstrated both in vivo and in vitro. A polysaccharide fraction of a hot-water extract of the root of B. falcatum was reported to inhibit significantly hydrochloric acid- or ethanol-induced ulcerogenesis in mice (15). The polysaccharide fraction (BR-2, 100mg/kg) had potent antiulcer activity, and its activity was similar to that of sucralfate (100 mg/kg) (29). BR-2 significantly protected against a variety of gastric lesions, water-immersion stress ulcer and pylorus-ligation ulcer in mice and rats (29). By oral, intraperitoneal, or subcutaneous administration, BR-2 was further found to be effective against hydrochloric acid- or ethanol-induced gastric lesions suggesting that BR-2 acted both locally and systemically (29). The mechanism of antiulcer action appears to be due to a reinforcement of the protective mucosal barrier as well as an antisecretory action on acid and pepsin (30). Saponins isolated from B. falcatum root have also been reported to have weak antiulcer activity in the pylorus-ligation ulcer model (30).
Hepatoprotectant activity
Crude saponins of B. falcatum, administered orally to rats at a daily dose of 500mg/kg for 3 days, normalized liver functions as determined by serum alkaline phosphatase levels in rats treated with carbon tetrachloride (31). Treatment of rats with saikosaponins 2 hours before treatment with D-galactosamine inhibited the increase in serum aspartate aminotransferase and alanine aminotransferase levels produced by damage of liver tissues (31). Conversely, saikosaponins did not affect an increase in serum alanine aminotransferase and experimental cirrhosis in rats caused by carbon tetrachloride intoxication (32).
Clinical pharmacology
Antipyretic activity
The antipyretic activity of B. chinense (B. falcatum) has been investigated in patients with fevers caused by the common cold, influenza, malaria, and pneumonia (5). In one clinical study of 143 patients treated with the herb, fevers subsided within 24 hours in 98.1% of all cases of influenza, and in 87.9% of all cases of the common cold (5, 33). In another study, 40 patients with fever of pathological origin had a significant reduction in fever (1–2°C), but the antipyretic effect of Radix Bupleuri in these patients was transient unless combined with antibiotic therapy (5, 34).
Contraindications
No information available.
Warnings
Radix Bupleuri causes sedation when used in large doses (5); therefore, patients should be cautious when operating a motor vehicle or hazardous machinery.
Precautions
Drug interactions
The use of alcohol, sedatives and other central nervous system depressants in conjunction with Radix Bupleuri may cause synergistic sedative effects. No clinical studies have evaluated this possible interaction; however, patients should be cautioned about taking the drug with alcohol, sedatives, or other drugs known to cause depression of the central nervous system.
Carcinogenesis, mutagenesis, impairment of fertility
Methanolic extracts of B. chinense (B. falcatum) were not mutagenic in the modified Ames test usingSalmonella typhimurium TA 98 and TA 100, in the presence or absence of rat liver S-9 mix (35, 36). Furthermore, hot-water extracts of Bupleurum were shown to have antimutagenic activity in AFB1-induced mutagenesis in the mouse Salmonella typhi/mammalian microsomal system (Ames test) (strain TA 98) and in the in vivo mouse bone marrow cell chromosome aberration and mouse bone marrow eosinophil micronucleus test (37). There is one report that a hot-water extract of B. falcatum enhanced the mutagenic activity of Trp-P-1 with S9 mix in Salmonella typhimurium (38).
Pregnancy: teratogenic and non-teratogenic effects
No data available; therefore, B. falcatum should not be administered during pregnancy.
Nursing mothers
Excretion of the drug into breast milk and its effects on the newborn infant have not been established; therefore, Bupleurum should not be administered to nursing women.
Paediatric use
Guidelines for the administration of the drug to children are not available.
Other precautions
No information available concerning general precautions or drug and laboratory test interactions.
Adverse reactions
Mild lassitude, sedation, and drowsiness have been reported as frequent sideeffects (5). Large doses have also been reported to decrease appetite and cause pronounced flatulence and abdominal distension. Three incidents of allergic reactions were reported in patients given intramuscular injections of the drug (5).
Posology
Generally, doses of 3–9g/day (1).
References
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