Bupleurum

• How It Works

  Bupleurum is used along with other herbs in traditional medicine formulas to treat colds, digestive issues, and liver problems, but studies in humans are lacking.  

  Bupleurum is an important herb used in traditional Chinese and Japanese medicine. It is frequently prescribed in combination with other herbs to treat colds, fever, digestive disorders, and chronic liver diseases. Herbal formulas such as Xiao Chai Hu Tang (Sho-saiko-to), contain bupleurum as a major ingredient.

  Compounds called saikosaponins in bupleurum have been identified as responsible for the plant’s medicinal activities. However, most studies on bupleurum have only been performed in the lab and human data are lacking. In addition, excess doses have been linked to a few cases of adverse effects.

• Purported Uses

  NOTE: The following uses and descriptions of effectiveness apply to bupleurum only. Please see our monograph on Sho-saiko-to for information regarding the effectiveness of bupleurum in combination with other herbs.

  • To treat liver diseases, including hepatitis and cirrhosis of the liver
    Although bupleurum is used in traditional Chinese medicine to treat liver diseases, human data are lacking.
  • To treat the common cold
    Bupleurum may have antiviral activity, but clinical trials have not been conducted.
  • As a fever reducer
    Although bupleurum is used in traditional Chinese medicine to reduce fever, there are no clinical data to back this claim.
  • To treat infections
    Bupleurum may have antibacterial activity, but human studies are lacking.
  • To reduce inflammation
    Laboratory studies show that components of bupleurum interfere with the processes that cause inflammation. Human studies are needed.
  • To treat malaria
    Bupleurum may have antiviral activity, but human data are lacking.
• Do Not Take If
  • You are taking drugs that are substrates of cytochrome P450 2C9: Lab studies suggest bupleurum extracts may increase the risk of side effects of these drugs. Clinical relevance has yet to be determined. Patients should check with their treating physician.
  • You are taking drugs that are substrates of cytochrome P450 2E1, 2D6, and 3A4:  Animal studies suggest that bupleurum can induce CYP2E1, CYP2D6 and CYP3A4 enzymes, but that herb-drug interactions are more likely at higher doses. Patients should check with their treating physician.
• Side Effects

  There have been a few case reports of liver damage with excess doses of bupleurum.

• Scientific Name

  Bupleurum chinense, Bupleurum scorzoneraefolium, Bupleurum falcatum, Radix Bupleuri

• Clinical Summary

  Bupleurum is an important herb used in traditional Chinese and Japanese medicine. It is frequently prescribed in combination with other herbs to treat colds, fever, malaria, digestive disorders, and chronic liver diseases. Herbal formulas such as Xiao Chai Hu Tang (Sho-saiko-to), contain bupleurum as a major ingredient.

  Preclinical studies suggest that bupleurum has antiviral ^(4) (7), hepatoprotective ⁽¹⁶⁾, anti-inflammatory ^(1) (17), immune-modulating ^(3) (14), antiproliferative ⁽¹¹⁾, and chemopreventive ^(12) (13) properties. Experiments suggest bupleurum might exert some influence over multidrug resistance in drug-resistant cells ⁽²⁾. Saikosaponins, a major constituent, enhanced cisplatin cytotoxicity against solid tumors ⁽¹⁵⁾.

  In animal studies, bupleurum demonstrated inhibitory effects against allergic asthma ⁽¹⁰⁾. Experiments in both chronic mildly stressed and healthy rats describe differential effective and toxic responses ⁽²¹⁾. Saikosaponins were identified as the compound which may be responsible for bupleurum-induced liver injury ⁽²²⁾.

  Studies of bupleurum in humans are lacking. Poor quality control is a concern with commercial herbal products. A sample of bupleurum was found contaminated with a nephrotoxic drug, aristolactone ⁽¹⁸⁾. In addition, the extent to which bupleurum is screened for levels of toxic compounds such as polyacetylenes in general is unclear ⁽²³⁾.

• Purported Uses
  • Common colds
  • Fever
  • Inflammation
  • Liver disease
• Mechanism of Action

  Saikosaponins in bupleurum are the main constituent to which medicinal activities are attributed. In vitro studies indicate they exert anti-inflammatory effects by inhibiting arachidonic acid metabolism ⁽⁴⁾. Bupleurum polysaccharides also have anti-inflammatory properties, attributed to their inhibitory effect on LPS-mediated Toll like receptor 4 (TLR4) signaling ⁽¹⁷⁾. Immunoregulatory activity of saikosaponin-d has been related to the promotion of interleukin-2 production and receptor expression as well as modulating T-lymphocyte function ^(3) (14). However, saikosaponins were also identified as the compound which may be responsible for dose-dependent bupleurum-induced liver injury ⁽²²⁾.

  Apoptotic effects of bupleurum may be partly mediated by increased c-myc and p53 mRNA levels along with decreased bcl-2 mRNA levels ⁽⁶⁾, and by inhibition of telomerase activity ⁽⁹⁾. In some solid tumor cells, bupleurum demonstrated antiadhesive and hemolytic effects.

• Adverse Reactions

  Case reports

  Increased risk of liver injury: In hepatitis B patients using Chinese herbal products containing >19 g of bupleurum ⁽²⁴⁾ .

  Reports of liver injuries and hepatitis: With use of the traditional medicine formula Sho-saiko-to, which contains bupleurum ^(25) (26).

• Herb-Drug Interactions

  Cytochrome P450 2C9 substrates: In vitro, bupleurum extracts inhibit CYPC29 and might affect the intracellular concentration of drugs metabolized by this enzyme ⁽²⁰⁾. Clinical relevance has yet to be determined.

  Cytochrome P450 2E1, 2D6, and 3A4 substrates:  Animal studies suggest that bupleurum can induce CYP2E1, CYP2D6 and CYP3A4 enzymes, but that herb-drug interactions are more likely at higher doses ⁽²⁷⁾.

• References

  1. Wang J, Wang W, Pang Y. Saikosaponin A Inhibits LPS-Induced Endometritis in Mice Through Activating Nrf2 Signaling Pathway. Inflammation. Aug 2018;41(4):1508-1514.

  2. Ye RP, Chen ZD. Saikosaponin A, an active glycoside from Radix bupleuri, reverses P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cells and HepG2/ADM cells. Xenobiotica. Feb 2017;47(2):176-184.

  3. Kato M, et al. Characterization of the immunoregulatory action of saikosaponin-d. Cell Immunol 1994;159:15-25.

  4. Bermejo Benito P, et al. In vivo and in vitro antiinflammatory activity of saikosaponins. Life Sci 1998;63:1147-56.

  5. Wu W, Hsu H. Involvement of p-15(INK4b) and p-16(INK4a) gene expression in saikosaponin a and TPA-induced growth inhibition of HepG2 cells. Biochem Biophys Res Commun 2001;285:183-7.

  6. Hsu M, et al. Effect of saikosaponin, a triterpene saponin, on apoptosis in lymphocytes: association with c-myc, p53, and bcl-2 mRNA. Br J Pharmacol 2000;131:1285-93.

  7. Ushio Y, Abe H. Inactivation of measles virus and herpes simplex virus by saikosaponin d. Planta Med 1992;58:171-3.

  8. Ahn B. et al. Inhibitory effect of bupleuri radix saponins on adhesion of some solid tumor cells and relation to hemolytic action: screening of 232 herbal drugs for anti-cell adhesion. Planta Med 1998;64:220-4.

  9. Cheng YL, et al. Acetone extract of Bupleurum scorzonerifolium inhibits proliferation of A549 human lung cancer cells via inducing apoptosis and suppressing telomerase activity. Life Sci. 2003 Sep 19;73(18):2383-94.

  10. Park KH, et al. Effect of saikosaponin-A, a triterpenoid glycoside, isolated from Bupleurum falcatum on experimental allergic asthma. Phytother Res. 2002 Jun;16(4):359-63.

  11. Cheng YL, Lee SC, Lin SZ, et al. Anti-proliferative activity of Bupleurum scrozonerifolium in A549 human lung cancer cells in vitro and in vivo. Cancer Lett. 2005 May 26;222(2):183-93.

  12. Chen YL, Lin SZ, Chang JY, et al. In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells. Biochem Pharmacol. 2006 Jul 28;72(3):308-19.

  13. Lee CY, Hsu YC, Wang JY, et al. Chemopreventive effect of selenium and Chinese medicinal herbs on N-nitrosobis(2-oxopropyl)amine-induced hepatocellular carcinoma in Syrian hamsters. Liver Int. 2008 Jul;28(6):841-55.

  14. Wong VK, Zhou H, Cheung SS, et al. Mechanistic study of saikosaponin-d (Ssd) on suppression of murine T lymphocyte activation. J Cell Biochem. 2009 May 15;107(2):303-15.

  15. Wang Q, Zheng XL, Yang L, et al. Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells. J Exp Clin Cancer Res. 2010 Dec 9;29:159.

  16. Lee TF, Lin YL, Huang YT. Protective effects of kaerophyllin against liver fibrogenesis in rats. Eur J Clin Invest. 2012 Jun;42(6):607-16.

  17. Wu J, Zhang YY, Guo L, Li H, Chen DF. Bupleurum Polysaccharides Attenuates Lipopolysaccharide-Induced Inflammation via Modulating Toll-Like Receptor 4 Signaling. PLoS One. 2013 Oct 22;8(10):e78051.

  18. Rueda DC, Zaugg J, Quitschau M, et al. Discovery of GABA(A) receptor modulator aristolactone in a commercial sample of the Chinese herbal drug “Chaihu” (Bupleurum chinense roots) unravels adulteration by nephrotoxic Aristolochia manshuriensis roots. Planta Med. 2012 Feb;78(3):207-10.

  19. Xie W, Yu YH, Du YP, et al. Saikosaponin a Enhances Transient Inactivating Potassium Current in Rat Hippocampal CA1 Neurons. Evid Based Complement Alternat Med. 2013;2013:413092.

  20. Yu T, Chen X, Wang Y, Zhao R, Mao S. Modulatory effects of extracts of vinegar-baked Radix bupleuri and saikosaponins on the activity of cytochrome P450 enzymes in vitro. Xenobiotica. 2014 Oct;44(10):861-7.

  21. Gao X, Liang M, Fang Y, et al. Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles. Front Pharmacol. 2017;8:995.

  22. Li X, Li X, Lu J, et al. Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study. BMC Complement Altern Med. Apr 19 2017;17(1):219.

  23. Lin M, Zhang W, Su J. Toxic polyacetylenes in the genus Bupleurum (Apiaceae) – Distribution, toxicity, molecular mechanism and analysis. J Ethnopharmacol. Dec 4 2016;193:566-573.

  24. Lee CH, Wang JD, Chen PC. Risk of liver injury associated with Chinese herbal products containing Radix bupleuri in 639,779 patients with hepatitis B virus infection. PLoS One. Jan 12 2011;6(1):e16064.

  25. Hsu LM, Huang YS, Tsay SH, et al. Acute hepatitis induced by Chinese hepatoprotective herb, xiao-chai-hu-tang. J Chin Med Assoc. Feb 2006;69(2):86-88.

  26. Itoh S, Marutani K, Nishijima T, et al. Liver injuries induced by herbal medicine, syo-saiko-to (xiao-chai-hu-tang). Dig Dis Sci. Aug 1995;40(8):1845-1848.

  27. Cheng Y, Huang Y, Tian Y, et al. Assessment of the effects of Radix bupleuri and vinegar-baked Radix bupleuri on cytochrome 450 activity by a six-drug cocktail approach. Chin J Nat Med. May 2013;11(3):302-308.