DRUGS AND SUPPLEMENTS

Bupleurum (Bupleurum chinense L., Bupleurum falcatum)

March 22, 2017

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Bupleurum (Bupleurum chinense, Bupleurum falcatum)

Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms

  • Apiaceae (family), bei chai hu, beichaihu, bupleuran 2IIc, Bupleurum chinese D.C., Bupleurum exaltatum, Bupleurum falcatum, Bupleurum falcatum L. var. scorzonerifolium, Bupleurum fruticosum L., Bupleurum ginghausenii, Bupleurum longifolium, Bupleurum multinerve, Bupleurum octoradiatum, bupleuri radix (Latin), bupleuri radix saponins, Bupleurum root, Bupleurum rotundifolium L., Bupleurum scorzonerifolium Willd, Bupleurum stewartianum, chaifu, chaihu (Chinese), chai hu, chai hu chaiku-saiko, Chinese thoroughwax root, echinocystic acid 3-O-sulfate, hare's ear root (English), He Jie Decoction, hydroxysaikosaponins, isochaihulactone, juk-siho, kara-saiko, Minor Bupleurum Decoction, mishima-saiko, nanchaihu, northern Chinese thorowax root, phenylpropanoids, radix bupleur, saiko (Japanese), saikospanonins, segl-hareore (Danish), shi ho, sho-saiko-to, shoku-saiko, shrubby hare's-ear, sickle-leaf hare's-ear, siho (Korean), thorowax, thoroughwax, TJ-9, triterpene saponins, Umbelliferae (family), wa-saiko, xiao chai hu tang, yamasaiko.

Background

  • Bupleurum (Bupleurum falcatum, Bupleurum fruticescens) has been widely used for over 2,000 years in Asia and is used today in Japan and China for hepatitis, cirrhosis, and other conditions associated with inflammation. Other traditional uses that are not supported by human scientific studies include the treatment of deafness, dizziness, diabetes, wounds, and vomiting. Bupleurum's root is an important ingredient in xiao-chai-hu-tan/sho-saiko-to, also known as Minor Bupleurum Decoction, a combination of nine herbs, including ginseng, ginger, and licorice, which is used in traditional Chinese and Japanese herbal medicine for hepatitis and cirrhosis.

  • Clinical studies have suggested that this combination may be effective in the treatment of hepatitis B and in the prevention of hepatocellular carcinoma. The mixture has also shown some promise as a liver-protecting agent and as an adjuvant in the treatment of HIV infection. The effect of Bupleurum is inseparable from the effects of the other ingredients in xiao-chai-hu-tan/sho-saiko-to, and thus it is difficult to make any firm conclusions based on studies of this combination product. However, because there is some promising early clinical evidence of efficacy for these formulae in the treatment and prevention of hepatitis-associated liver disease, a number of the studies of the combination preparations are included in this review.

Scientific Evidence

Uses

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Grade*

Brain damage (minimal, in children)

An herbal combination formula containing Bupleurum has been used as a treatment for children with minimal brain dysfunction. Early study is inconclusive, and additional study is needed to make a firm recommendation.

C

Fever

Chinese studies have suggested that Bupleurum may be helpful for reducing fever. However, additional study is needed to draw a firm conclusion about safety and effectiveness. In traditional Chinese medicine, Bupleurum is often used in combination with other herbs.

C

Hepatitis

Traditional use from China, as well preliminary human study, seems to suggest that Bupleurum and/or herbal combination formulas containing Bupleurum may be helpful in the treatment of chronic hepatitis. Further research is warranted to draw a firm recommendation.

C

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) arises predominantly in patients with cirrhosis, both hepatitis-associated and non-hepatitis associated. Sho-saiko-to, the Japanese version of the classical Bupleurum-based formula, has been examined for a possible role in preventing the development of HCC in patients with cirrhosis. Early study suggests that this formula may help prevent progression to HCC in patients with cirrhosis, although more study is needed for a strong recommendation.

C

Thrombocytopenic purpura

Primary thrombocytopenic purpura may respond in some cases to treatment with Bupleurum-containing herbal formulas. However, currently there is insufficient available evidence for or against the use of Bupleurum for this indication.

C

*Key to grades:A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).

Tradition/Theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

  • Adrenal insufficiency (stimulation), amenorrhea (absence of menstruation), analgesia (pain relief), angina (chest pain), anorexia, antibacterial, antifungal, anti-inflammatory, antioxidant, anti-pseudomonal, antiseptic, antitussive, antiviral, asthma, bronchitis, cancer, cirrhosis (liver disease), common cold, constipation, contraceptive, deafness, dementia, depression, diabetes, diaphoresis (excessive sweating), diarrhea, dizziness, dysmenorrhea (painful menstruation), epilepsy, fatigue, gastric ulcer, headache, hemorrhoids, herpes simplex virus infection, HIV, hot flashes, hypercholesterolemia (high cholesterol), hyperlipidemia (high cholesterol), immunosuppression, immune system enhancement, indigestion, influenza, kidney disease, kidney protection, lung cancer, lung congestion, malaria, melanoma, menstrual irregularities, muscle cramps, myalgia (muscle pain), nausea, pain, pain (epigastric), pancreatitis (inflammation of the pancreas), Parkinson's disease, premenstrual syndrome (PMS), pulmonary edema, rectal prolapse, rheumatoid arthritis, sedation, solid tumors, systemic lupus erythematosis (SLE), tinnitus, tuberculosis (pulmonary), ulcers, upper respiratory tract infection, uterine prolapse, vertigo, viral infections (poliovirus), vomiting, wounds.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • There is no proven safe or effective dose for Bupleurum. Bupleurum is typically taken in combination formulas with other herbs, and has not been well studied alone. Traditionally, 1.5-9 grams of Bupleurum root have been used per day. Also, 1.5-3 milliliters of a fluid extract have been used daily. For hepatitis, doses of 5.4 grams of combination therapy sho-saiko-to daily have been studied for 12 weeks. For prevention of hepatocellular carcinoma, sho-saiko-to has been administered at a dose of 7.5 grams daily in combination with conventional treatment.

Children (younger than 18 years)

  • There is no proven safe or effective dose for Bupleurum in children, and use is not recommended. Bupleurum is typically taken in combination formulas with other herbs, and has not been well studied alone.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in individuals with a known allergy or hypersensitivity to Bupleurum species, any of its constituents, the Apiaceae or Umbelliferae (carrot) families, snakeroot, cow parsnip, or poison hemlock. There are some reports that mention allergic reactions occurring in patients given intramuscular injections of Bupleurum.

Side Effects and Warnings

  • In recommended doses, many practitioners agree that Bupleurum is well tolerated. However, available safety data is lacking. Reports of adverse effects are largely theoretical and based on side effects from combination therapy; it is difficult to attribute the adverse effects to Bupleurum alone.

  • Reported side effects include decreased appetite, nausea, reflux, abdominal distension, gas, and increased bowel movements following large doses of Bupleurum. Rare instances of nausea, loss of appetite, and abdominal fullness have been reported following treatment with the combination therapy sho-saiko-to. Combinations containing Bupleurum have been associated with eosinophilic pneumonia, pulmonary edema, and multiple cases of pneumonitis (inflammation of the lungs). Use cautiously in patients with hypertension (high blood pressure), diabetes, or edema, due to possibility of adrenal stimulation.

  • Patients with autoimmune disease or in those taking immunosuppressants should use caution when taking Bupleurum, as saikosaponins in Bupleurum have been found to both stimulate and inhibit the immune system

  • There have been unverified reports of sedation, drowsiness, and lethargy, which are noted as frequent side effects. Rare instances of fatigue and paresthesia (abnormal sensations) were noted in one study that investigated the combination therapy sho-saiko-to. Use cautiously in patients operating motor vehicles or hazardous machinery, due to a possible risk of sedation.

  • Although not well studied in humans, Bupleurum may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.

  • Use cautiously in patients with diabetes. Saikosaponins, constituents of Bupleurum, may increase blood sugar levels.

Pregnancy and Breastfeeding

  • Bupleurum is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Bupleurum may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).

  • Saikosaponins, constituents of Bupleurum, may increase blood sugar levels. Caution is advised when using medications that may alter blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

  • Bupleurum may stimulate the adrenals and may decrease the effects of antihypertensives (drugs for high blood pressure). Patients taking blood pressure medications, including beta-blockers or ACE inhibitors, should use cautiously.

  • Although not well-studied in humans, Bupleurum may reduce cholesterol levels. Caution is advised in patients taking cholesterol-lowering agents.

  • Due to the possibility of adrenal stimulation, Bupleurum may decrease the effects of diuretics or increase the effects of corticosteroids (steroids).

  • Bupleurum may have immune inhibitory effects and might additively or synergistically enhance immunosuppressant effects.

  • Sho-saiko-to, a combination herbal formula that contains Bupleurum, was found to enhance the anti-HIV-1 activity of lamivudine in laboratory study. Consult a qualified healthcare professional, including a pharmacist, before combining Bupleurum or combination formulas containing Bupleurum with antiviral or hepatitis B agents.

  • Bupleurum may increase the amount of drowsiness caused by some drugs. Examples include benzodiazepines such as lorazepam (Ativan®) or diazepam (Valium®), barbiturates such as phenobarbital, narcotics such as codeine, some antidepressants, and alcohol. The use of Bupleurum in combination with alcohol might additively or synergistically enhance sedation. Caution is advised while driving or operating machinery.

  • In theory, Bupleurum may interact with medications metabolized by the liver. There are mixed reports of Bupleurum acting as both a protective agent for the liver, and also an agent that has toxic effects on the liver. Additionally, combination products containing Bupleurum may interact with any medication taken by mouth and may alter the way medications are absorbed in the body.

  • Although human evidence is lacking, Bupleurum may also interact with Alzheimer's disease medications, antibiotics, anticancer medications, or HIV medications (antiretrovirals). Consult with a qualified healthcare professional, including a pharmacist, to check for interactions.

Interactions with Herbs and Dietary Supplements

  • Bupleurum may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

  • Saikosaponins, constituents of Bupleurum, may increase blood sugar levels. Caution is advised when using herbs or supplements that may alter blood sugar. Patients should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

  • Sho-saiko-to, a combination herbal formula that contains Bupleurum, was found to enhance the anti-HIV-1 activity of lamivudine in laboratory study. Consult a qualified healthcare professional, including a pharmacist, before combining Bupleurum or combination formulas containing Bupleurum with antiviral herbs or supplements.

  • Saikosaponins, constituents of Bupleurum, may decrease triglyceride concentrations or decrease the effects of blood pressure-lowering agents. Caution is advised in patients taking cholesterol-lowering herbs or supplements, such as red yeast rice, or herbs or supplements that lower blood pressure. Consult with a qualified healthcare professional, including a pharmacist, to check for interactions.

  • Bupleurum may stimulate the adrenals and may have additive effects with corticosteroids (steroids) or decrease the effects of diuretics (agents that increase urine flow).

  • Bupleurum may have immune inhibitory effects and may additively or synergistically enhance herbs or supplements with immunosuppressant effects.

  • Bupleurum may increase the amount of drowsiness caused by some herbs or supplements.

  • In theory, Bupleurum may interact with herbs or supplements metabolized by the liver. There are mixed reports of Bupleurum acting as both a protective agent for the liver, and also an agent that has toxic effects on the liver. Additionally, combination products containing Bupleurum may interact with any medication taken by mouth and may alter the way medications are absorbed in the body.

  • Although human evidence is lacking, Bupleurum may interact with herbs and supplements taken for Alzheimer's disease, cancer, or HIV. Bupleurum may interact with herbs or supplements with antibacterial effects as well. Consult with a qualified healthcare professional, including a pharmacist, to check for interactions.

Author Information

  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Aiba T, Takahashi T, Suzuki K, et al. Liver injury induced by a Japanese herbal medicine, sairei-to (TJ-114, Bupleurum and Hoelen Combination, Chai-Ling-Tang) R1. J Gastroenterol Hepatol 2007;22(5):762-763. View Abstract

  2. Chen YL, Lin SZ, Chang J, et al. In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells. Biochem Pharmacol 7-28-2006;72(3):308-319. View Abstract

  3. Cheng BJ, Moritomo A, Yamasaki Y, et al. Preventive effect of traditional herbal formulae against experimental hypercholesterolemia in rats with special reference to blood lipoprotein cholesterol levels. J Ethnopharmacol. 2004;94(2-3):275-278. View Abstract

  4. Chiang LC, Ng LT, Liu LT, et al. Cytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species. Planta Med. 2003;69(8):705-709. View Abstract

  5. Chitturi S, Farrell GC. Hepatotoxic slimming aids and other herbal hepatotoxins. J Gastroenterol Hepatol. 2008 Mar;23(3):366-73. View Abstract

  6. Chou CC, Pan SL, Teng CM, et al. Pharmacological evaluation of several major ingredients of Chinese herbal medicines in human hepatoma Hep3B cells. Eur.J Pharm.Sci. 2003;19(5):403-412. View Abstract

  7. Estevez-Braun A, Estevez-Reyes R, Moujir LM, et al. Antibiotic activity and absolute configuation of 8S-heptadeca-2(Z),9(Z)-diene-4,6-diyne-1,8-diol from Bupleurum salicifolium. J Nat Prod. 1994;57(8):1178-1182. View Abstract

  8. Fernandez-Ocana AM, Gomez-Rodriguez MV, Velasco-Negueruela A, et al. In vivo antifungal activity of the essential oil of Bupleurum gibraltarium against Plasmopara halstedii in sunflower. J Agric.Food Chem 10-20-2004;52(21):6414-6417. View Abstract

  9. Hirayama C, Okumura M, Tanikawa K, et al. A multicenter randomized controlled clinical trial of Shosaiko-to in chronic active hepatitis. Gastroenterol Jpn 1989;24(6):715-719. View Abstract

  10. Ikegami F, Sumino M, Fujii Y, et al. Pharmacology and toxicology of Bupleurum root-containing Kampo medicines in clinical use. Hum.Exp Toxicol 2006;25(8):481-494. View Abstract

  11. Oka H, Yamamoto S, Kuroki T, et al. Prospective study of chemoprevention of hepatocellular carcinoma with Sho-saiko-to (TJ-9). Cancer 9-1-1995;76(5):743-749. View Abstract

  12. Tajiri H, Kozaiwa K, Ozaki Y, et al. Effect of sho-saiko-to(xiao-chai-hu-tang) on HBeAg clearance in children with chronic hepatitis B virus infection and with sustained liver disease. Am J Chin Med 1991;19(2):121-129. View Abstract

  13. Wu, S. J., Lin, Y. H., Chu, C. C., Tsai, Y. H., and Chao, J. C. Curcumin or saikosaponin a improves hepatic antioxidant capacity and protects against CCl4-induced liver injury in rats. J Med Food 2008;11(2):224-229. View Abstract

  14. Xie Y, Lu W, Cao S, et al. Preparation of Bupleurum nasal spray and evaluation on its safety and efficacy. Chem Pharm Bull.(Tokyo) 2006;54(1):48-53. View Abstract

  15. Zhang S, Cheng Z, Huang B, et al. [The effect of he jie decoction on the TCRV beta 7 of chronic hepatitis B patients]. Zhong.Yao Cai. 2002;25(6):451-453. View Abstract

Copyright © 2013 Natural Standard (www.naturalstandard.com)

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

Updated:  

March 22, 2017