OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Sho-Saiko-To – Generic

DRUG CLASS

Herbal and Dietary Supplements

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 15 August 2020

• Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott,1999: pp. 731-4.

  (Expert review of hepatotoxicity published in 1999; hepatotoxicity of Asian herbal products and teas are discussed generally without focus on any specific product or herb).
• Seeff L, Stickel F, Navarro VJ. Hepatotoxicity of herbals and dietary supplements. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 631-58.

  (Review of hepatotoxicity of herbal and dietary supplements [HDS] discusses Chinese and other Asian herbal medicines including Sho-saiko-to).
• PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007.

  (Compilation of short monographs on herbal medications and dietary supplements, including sections on ma huang, but not specifically on Sho-saiko-to).
• Mizoguchi Y, Miyajima K, Sakagami Y, Yamamoto S. Nippon Naika Gakkai Zasshi. 1986;75:1453–6. [A severe case of drug-induced allergic hepatitis in herbal medicine] Japanese. [PubMed: 3805846]

  (A 27 year old developed jaundice 6 weeks after taking Kinshigan, a Kampo herb with rapid recovery, but recurring with a more severe course 2 weeks after restarting [bilirubin 28.5 mg/dL, ALT 166 U/L, Alk P 1.5 times ULN, 1% eosinophils]; among 18 ingredients, Scutellariae radix).
• Satake I, Maeda M, Koyama W, Sakamoto S, Koizumi S, Kanayama M. A case of hepatic injury caused by an herb drug. Acta Hepatol Jpn. 1986;27:238–41.
• Carlsson C. Herbs and hepatitis. Lancet. 1990;336:1068. [PubMed: 1977040]

  (Analysis of laboratory results from 395 patients found higher ALT levels among 53 patients taking herbals [55 U/L] than among those who did not [12 U/L]).
• Marutani K, Matsuo S, Nishijima T, Watanobe T, Ishida Y, Sasaki K, Kameda C, Itoh S. Light and electron microscopic findings in the liver of five patients with syo-saiko-to-induced hepatitis. Jpn J Gastroenterol. 1990;87:640.
• Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL. Unconventional medicine in the United States. Prevalence, costs, and patterns of use. N Engl J Med. 1993;328:246–52. [PubMed: 8418405]

  (Among 1539 adults interviewed by telephone, 34% used an unconventional therapy during the previous 12 months, including 3% using herbal medicines).
• Itoh S, Marutani K, Nishijima T, Matsuo S, Itabashi M. Liver injuries induced by herbal medicine sho-saiko-to (xiao-chai-hu-tang). Dig Dis Sci. 1995;40:1845–8. [PubMed: 7648990]

  (4 cases, 42-58 year old women, taking Sho-saiko-to for 3-7 weeks, developed liver test elevations, 2 with jaundice, 2 with recurrence on restarting [peak ALT 135 to 1335 U/L], with resolution within 2 to 3 months upon stopping).
• Kamiyama T, Nouchi T, Kojima S, Murata N, Ikeda T, Sato C. Autoimmune hepatitis triggered by administration of an herbal medicine. Am J Gastroenterol. 1997;92:703–4. [PubMed: 9128330]

  (55 year old woman with chronic hepatitis developed jaundice one month after starting Dai-saiko-to [bilirubin 11.2 mg/dL, ALT 390 U/L, ANA 1:2560], responding rapidly to prednisone therapy).
• Matsuda R, Takahashi D, Chiba E, Kawana I, Tomiyama M, Ebira H, Ikegami T, et al. Nihon Shokakibyo Gakkai Zasshi. 1997;94:787–91. [A case of drug induced hepatitis and interstitial pneumonia caused by a herbal drug, Dai-saiko-to] Japanese. [PubMed: 9396337]

  (65 year old man developed dyspnea and interstitial pneumonitis with abnormal liver tests 4 weeks after starting Dai-saiko-to for autoimmune dermatitis, stopping at 6 weeks [bilirubin 1.2 mg/dL, ALT 675 U/L, Alk P 1070 U/L], resolving within a month of stopping).
• Shimizu I. Sho-saiko-to: Japanese herbal medicine for protection against hepatic fibrosis and carcinoma. J Gastroenterol Hepatol. 2000;15 Suppl:D84–90. [PubMed: 10759225]

  (Review of composition, clinical efficacy and mechanism of action of Sho-saiko-to; contains 7 herbs, including Bupleurum root, Pinellia tuber, and Scutellaria root, and Glycyrrhiza root; active components likely to be saikosaponins and the antioxidants, baicalin and baicalein, which resemble silybinin).
• Stedman C. Herbal hepatotoxicity. Semin Liver Dis. 2002;22:195–206. [PubMed: 12016550]

  (Review and description of patterns of liver injury associated with hepatotoxicity from herbal products, including discussion of risk factors and herb-drug interactions).
• Ernst E. Adulteration of Chinese herbal medicines with synthetic drugs: a systematic review. J Intern Med. 2002;252:107–13. [PubMed: 12190885]

  (Systematic review of literature on adulteration of herbals with conventional medications, in 15 case reports and 2 cases series of 21 patients; contaminants identified in up to 24% of products were NSAIDs, corticosteroids, benzodiazepines, diuretics and diabetes medications).
• Schiano TD. Hepatotoxicity and complementary and alternative medicines. Clin Liver Dis. 2003;7:453–73. [PubMed: 12879994]

  (Comprehensive review of herbal associated hepatotoxicity, including common patterns of presentation with discussion of Chinese herbal medicines, including Jin Bu Huan, Ma Huang, Shou Wu Pian, and Sho-saiko-to).
• Hsu LM, Huang YS, Tsay SH, Chang FY, Lee SD. Acute hepatitis induced by Chinese hepatoprotective herb, xiao-chai-hu-tang. J Chin Med Assoc. 2006;69:86–8. [PubMed: 16570576]

  (52 year old woman developed jaundice 1.5 months after starting Xiao Chai Hu Tang, known in Japan as Syo-saiko-to [bilirubin 1.9 mg/dL, ALT 2028 U/L, Alk P 213 U/L], resolving within 2 months of stopping).
• Yuen MF, Tam S, Fung J, Wong DK, Wong BC, Lai CL. Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: a 1-year prospective study. Aliment Pharmacol Ther. 2006;24:1179–86. [PubMed: 17014576]

  (Among 45 patients with chronic hepatitis B hospitalized because of liver dysfunction at Queen Mary Hospital, Hong Kong during 2004, 7 appeared to have liver injury caused by traditional Chinese herbal medications, marked by worsening of liver tests, lack of IgM anti-HBc and low or no detectable HBV DNA; 2 died and two underwent liver transplantation).
• Wai CT, Tan BH, Chan CL, Sutedja DS, Lee YM, Khor C, Lim SG. Drug-induced liver injury at an Asian center: a prospective study. Liver Int. 2007;27:465–74. [PubMed: 17403186]

  (Prospective survey of drug induced liver injury presenting over 26 months at a single hospital in Singapore identified 31 cases, ages 18-9 years, 55% male, Chinese traditional medicines being implicated in 17 [55%] and Malay agents in 5 cases [16%], adulterants were found in 9 of 31 tested traditional agents [codeine, corticosteroids, metformin, mercury, nonsteroidal antiinflammatory agents]).
• Seeff LB. Herbal hepatotoxicity. Clin Liver Dis. 2007;11:577–96. [PubMed: 17723921]

  (Review of herbal induced hepatotoxicity, including Chinese herbal medicines such as Sho-saiko-to, Chaso, Onshido, Jin Bu Huan, Ma Huang and Shou Wu Pian).
• García-Cortés M, Borraz Y, Lucena MI, Peláez G, Salmerón J, Diago M, Martínez-Sierra MC, et al. Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry. Rev Esp Enferm Dig. 2008;100:688–95. [PubMed: 19159172]

  (Among 521 cases of drug induced liver injury submitted to Spanish registry, 13 [2%] were due to herbals, including Camellia sinensis [green tea], Cassia angustifolia [senna], kava, valerian, Rhamnus purshianus [cascara], fitosoja [soy plant], biosoja [soy extract], Aesculus hippocatanum [horse chestnut], chitosan [deacetylated chitin], and Couterea latifloral [Copalchi]).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, 9% of cases were attributed to herbal medications and dietary supplements [HDS] but none specifically to Sho-saiko-to).
• Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis. 2009;29:373–82. [PubMed: 19826971]

  (Overview of the regulatory environment, clinical patterns, and future directions in research with HDS including traditional Chinese herbal medicines and Sho-saiko-to).
• Wang YP, Shi B, Chen YX, Su J, Jiang CF, Xie WF. Drug-induced liver disease: an 8-year study of patients from one gastroenterological department. J Dig Dis. 2009;10:195–200. [PubMed: 19659787]

  (Among 30 patients with drug induced liver disease seen at a single medical university in Shanghai between 2000 and 2008, 12 were due to Chinese herbs, but specific agents were not discussed; 9 patients were jaundiced and 6 had hepatocellular, 3 cholestatic and 2 mixed patterns of injury).
• Reuben A, Koch DG, Lee WM., Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 [11%] were attributed to drug induced liver injury of which 12 [9%] were due to herbals, but none were attributed specifically to Sho-saiko-to).
• Lee JK, Kim JH, Shin HK. Therapeutic effects of the oriental herbal medicine Sho-saiko-to on liver cirrhosis and carcinoma. Hepatol Res. 2011;41:825–37. [PubMed: 21682829]

  (Review of the efficacy and safety of Sho-saiko-to as therapy of liver disease, mentions side effects of interstitial pneumonitis and 3 case reports of hepatic injury).
• Stickel F, Kessebohm K, Weimann R, Seitz HK. Review of liver injury associated with dietary supplements. Liver Int. 2011;31:595–605. [PubMed: 21457433]

  (Review of current understanding of liver injury from herbals and dietary supplements focusing upon Herbalife and Hydroxycut products, green tea, usnic acid, Noni juice, Chinese herbs, vitamin A and anabolic steroids; Sho-saiko-to is not discussed).
• Deng G, Kurtz RC, Vickers A, Lau N, Yeung KS, Shia J, Cassileth B. A single arm phase II study of a Far-Eastern traditional herbal formulation (sho-sai-ko-to or xiao-chai-hu-tang) in chronic hepatitis C patients. J Ethnopharmacol. 2011;136:83–7. [PubMed: 21527335]

  (Among 42 patients with chronic hepatitis C who were treated with Sho-saiko-to [2.5 g three times daily] for 12 months, ALT levels decreased in 67% and increased in 29%, while liver histology did not change overall; side effects were not mentioned).
• Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a tabular compilation of reported cases. Liver Int. 2012;32:1543–56. [PubMed: 22928722]

  (A systematic compilation of all publications on the hepatotoxicity of specific herbals identified 185 publications on 60 different herbs, including 2 reports of Xiao Chai Hu Tang: [Itoh 1995] and Hsu [2005]).
• Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, Reddy KR, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014;60:1399–408. [PMC free article: PMC4293199] [PubMed: 25043597]

  (Among 85 cases of HDS associated liver injury [not due to anabolic steroids] enrolled in a US prospective study between 2004 and 2013, none were attributed to Sho-saiko-to but two cases were due to Move Free, a product that contains Scutellaria baicalensis).
• Douros A, Bronder E, Andersohn F, Klimpel A, Kreutz R, Garbe E, Bolbrinker J. Herb-Induced Liver Injury in the Berlin Case-Control Surveillance Study. Int J Mol Sci. 2016;17:E114. pii. [PMC free article: PMC4730355] [PubMed: 26784183]

  (Among 198 patients with suspected drug induced liver injury seen at Berlin Hospitals and enrolled in a prospective database, 10 were attributed to herbal supplements but none were attributed to Sho-saiko-to or Scutellaria radix).
• Brown AC. Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series. Food Chem Toxicol 2017; 107(Pt A): 472-501. [PubMed: 27402097]

  (Description of an online compendium of cases of liver toxicity attributed to HDS products, does not list Sho-saiko-to but lists two cases of liver injury attributed to skullcap [Estes 2003, Hullar 1999]).
• Hsueh TP, Lin WL, Tsai TH. Pharmacokinetic interactions of herbal medicines for the treatment of chronic hepatitis. J Food Drug Anal. 2017;25:209–18. [PMC free article: PMC9332521] [PubMed: 28911662]

  (Discussion of herbal medications used to treat chronic liver disease including Sho-saiko-to and their interactions with other medications; does not discuss hepatotoxicity).
• Enomoto Y, Nakamura Y, Enomoto N, Fujisawa T, Inui N, Suda T. Japanese herbal medicine-induced pneumonitis: A review of 73 patients. Respir Investig. 2017;55:138–44. [PubMed: 28274529]

  (Review of the literature on pneumonitis caused by Japanese herbal medications identified 73 cases in 59 articles, including 19 cases attributed to Sho-saiko-to; no mention of liver injury).
• Shimada Y, Fujimoto M, Nogami T, Watari H, Kitahara H, Misawa H, Kimbara Y, et al. Recurrent drug-induced liver Injury caused by the incidental readministration of a Kampo formula containing Scutellariae radix. Intern Med. 2018;57(12):1733–40. [PMC free article: PMC6047989] [PubMed: 29434136]

  (67 year old woman with depression developed liver test abnormalities within 4 days of starting 4 medications including Sho-saiko-to [bilirubin 1.1 mg/dL, ALT 139 U/L, Alk P 362 U/L], which resolved within 2-3 months of stopping all medications and arose again 1 year later when she restarted Sho-saiko-to [bilirubin 1.3 mg/dL, ALT 800 U/L, GGT 373 U/L], resolving within a month of stopping; attributed to Scutellariae radix based upon lymphocyte stimulation tests).
• Zhao T, Tang H, Xie L, Zheng Y, Ma Z, Sun Q, Li X. Scutellaria baicalensis Georgi. (Lamiaceae): a review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. J Pharm Pharmacol. 2019;71:1353–69. [PubMed: 31236960]

  (Review of the chemistry, clinical uses and toxicity of Scutellaria baicalensis, a major ingredient in many traditional Chinese medicines, which contains more than 40 compounds including flavonoids [baicalin, mogonin], terpenoids, volatile acids and polysaccharides; the herb is used for liver protection, and treatment of diarrhea, vomiting, and high blood pressure, known as Huang Qin [yellow reed]; “there is no obvious adverse reaction in the oral preparation of Scutellaria baicalensis”, but it may cause stomach discomfort, diarrhea and other minor symptoms in some patients).