Bupleurum root (Bupleurum chinense, Bupleurum scorzoneraefolium, Bupleurum falcatum, Radix Bupleuri)

Bupleuri Radix, the dried roots of Bupleurum falcatum L. (Umbelliferae), which is a perennial medicinal herb distributed mainly in China, Korea, and Japan, is one of the most important ingredients in traditional Japanese Kampo and Chinese medicines. It is frequently prescribed in combination with other herbs to treat colds, fever, malaria, digestive disorders, chronic liver diseases, and depression

Bupleurum root (Bupleurum chinense, Bupleurum scorzoneraefolium, Bupleurum falcatum, Radix Bupleuri)

Uses

According to TCM theory, Radix Bupleuri is thought to regulate the exterior and interior metabolisms, disperse evil heat from superficies, soothe the liver, and promote yang and qi. Radix Bupleuri was initially recorded in Shennong Bencao Jing, a famous monograph of traditional Chinese medicine written in China in 200 AD. According to a record of traditional Chinese medicine dated 2000 years ago, Radix Bupleuri had mainly been used for the treatment of mouth bitterness, throat-drying, and eyes-dazzling. In other monographs of Materia Medica, such as Jin Kui Yao Lue, Kaibao Bencao, Bencao Gangmu, and Xinbian Bencao, this plant was described to be used for the treatment of common cold with fever, influenza, hepatitis, malaria, menoxenia, and hyperlipidemia. Currently, Radix Bupleuri exerts other pharmacological effects, such as balancing different organs and energies within the body, strengthening the action of the digestive tract, improving liver and circulatory system function, and relieving liver tension. Therefore, it is also used as a popular tonic herb in China. In Korea and Japan, this plant is commonly used for the treatment of fever, pain, and inflammation associated with influenza and the common cold. In addition, this plant is also used as an analgesic in the treatment of distending pain in the hypochondriac region of the chest and against amenorrhea. Important traditional Chinese herbal formulas such as Xiao Chai Hu Tang and Xiao Yao San contain bupleurum as a major ingredient.

Chemistry/Pharmacology

More than 281 components have been isolated from Radix Bupleuri, including 15 flavonoids, 430 lignins, 12 phenyl propanol derivatives, 66 triterpenoid saponins, and 158 volatile oils all with diverse pharmacological effects

Clinical Studies

Preclinical studies suggest that bupleurum has antiviral, hepatoprotective, anti-inflammatory, immune-modulating, antiproliferative, and chemopreventive properties. Experiments suggest bupleurum might exert some influence over multidrug resistance in drug-resistant cells. Saikosaponins, a major constituent, enhanced cisplatin cytotoxicity against solid tumors.

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

Biomechanical Mechanism

The major pharmaceutical constituents of BF, including saikosaponin-a, saikosaponin-c, and saikosaponin-d aglycones, are in the roots, and are known to have immunological, anti-inflammatory, analgesic, anti-allergic, and plasma cholesterol-lowering effects. Several studies have demonstrated the pharmacological effects of BF on the central nervous system (CNS) through modulation of the HPA axis. Some studies have also reported potent anti-hypertensive or vasodilator activities of BF in animal models of hypertension. BF was shown to affect the central dopaminergic and serotoninergic systems and to have a neuroprotective effect against excitotoxic neural death.

Saikosaponins in bupleurum appears to be the main constituent to which medicinal activities are attributed. In vitro studies indicate they exert anti-inflammatory effects by inhibiting arachidonic acid metabolism. Bupleurum polysaccharides also have anti-inflammatory properties, attributed to their inhibitory effect on LPS-mediated Toll-like receptor 4 (TLR4) signaling. The 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. However, saikosaponins were also identified as the compound which may be responsible for dose-dependent bupleurum-induced liver injury.

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

Sources/Articles

Abe, Hiroko, Machiko Sakaguchi, Shizuo Odashima, and Shigeru Arichi. "Protective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl 4-induced liver injury in the rat." Naunyn-Schmiedeberg's archives of pharmacology 320, no. 3 (1982): 266-271. https://link.springer.com/article/10.1007/BF00510139

ae-Hyun Hahm. "Antidepressant-like effect of the methanolic extract from Bupleurum falcatum in the tail suspension test." Progress in Neuro-Psychopharmacology and Biological Psychiatry 34, no. 2 (2010): 265-270. https://www.sciencedirect.com/science/article/abs/pii/S0278584609004011

Ahmadimoghaddam, Davoud, Mohammad Zarei, Saeed Mohammadi, Zohreh Izadidastenaei, and Iraj Salehi. "Bupleurum falcatum L. alleviates nociceptive and neuropathic pain: Potential mechanisms of action." Journal of Ethnopharmacology 273 (2021): 113990. https://www.sciencedirect.com/science/article/abs/pii/S0378874121002178

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.

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

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.

Chen, S-M., N. Sato, M. Yoshida, N. Satoh, and S. Ueda. "Effects of Bupleurum scorzoneraefolium, Bupleurum falcatum, and saponins on nephrotoxic serum nephritis in mice." Journal of ethnopharmacology 116, no. 3 (2008): 397-402. http://libir.tmu.edu.tw/bitstream/987654321/1587/2/181.pdf

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.

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.

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.

Ebata, Naobumi, Kaoru Nakajima, Koji Hayashi, Minoru Okada, and Masao Maruno. "Saponins from the root of Bupleurum falcatum." Phytochemistry 41, no. 3 (1996): 895-901. https://www.sciencedirect.com/science/article/abs/pii/0031942295007202

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.

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.

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

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.

Jang, Myoung-Jun, Ye Sol Kim, Eun Young Bae, Tae-Seok Oh, Hwa-Jung Choi, Jung-Hee Lee, Hyun-Mee Oh, and Seung Woong Lee. "Saikosaponin D isolated from Bupleurum falcatum inhibits selectin-mediated cell adhesion." Molecules 19, no. 12 (2014): 20340-20349. https://www.mdpi.com/1420-3049/19/12/20340/htm

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

Kim, Seong-Mo, Sang-Chan Kim, In-Kwon Chung, Woo-Hyun Cheon, and Sae-Kwang Ku. "Antioxidant and protective effects of Bupleurum falcatum on the L-thyroxine-induced hyperthyroidism in rats." Evidence-Based Complementary and Alternative Medicine 2012 (2012). https://www.hindawi.com/journals/ecam/2012/578497/

Kwon, Sunoh, Bombi Lee, Myunghwan Kim, Hyejung Lee, Hi-Joon Park, and D https://www.hindawi.com/journals/ecam/2012/578497/

Lee, Bom-Bi, Hye-Yeon Yun, In-Sop Shim, Hye-Jung Lee, and Dae-Hyun Hahm. "Bupleurum falcatum prevents depression and anxiety-like behaviors in rats exposed to repeated restraint stress." Journal of microbiology and biotechnology 22, no. 3 (2012): 422-430.
https://www.koreascience.or.kr/article/JAKO201224237129290.pdf

Lee, Bombi, Insop Shim, Hyejung Lee, and Dae-Hyun Hahm. "Effect of Bupleurum falcatum on the stress-induced impairment of spatial working memory in rats." Biological and Pharmaceutical Bulletin 32, no. 8 (2009): 1392-1398. https://www.jstage.jst.go.jp/article/bpb/32/8/32_8_1392/_pdf

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.

Lee, Jee Youn, Hwang Soo Kim, Tae Hwan Oh, and Tae Young Yune. "Ethanol extract of Bupleurum falcatum improves functional recovery by inhibiting matrix metalloproteinases-2 and-9 activation and inflammation after spinal cord injury." Experimental neurobiology 19, no. 3 (2010): 146. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214781/

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.

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.

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.

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.

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

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.

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.

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.

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.

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.
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.

Yamamoto, M., A. Kumagai, and Y. Yamamura. "Structure and actions of saikosaponins isolated from Bupleurum falcatum LI Anti-inflammatory action of saikosaponins." Arzneimittel-forschung 25, no. 7 (1975): 1021-1023. https://europepmc.org/article/med/1174407

Yang L, Shergis JL, Di YM, et al. Managing Depression with Bupleurum chinense Herbal Formula: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Altern Complement Med. Jan 2020;26(1):8-24.

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.

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.