OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Ba Jiao Lian – Generic

DRUG CLASS

Herbal and Dietary Supplements

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Podophyllotoxin	518-28-5 ID: JW05850000	C22-H22-O8 Herbal mixture

ANNOTATED BIBLIOGRAPHY

References updated: 24 May 2022

• 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 Chinese 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 and teas, but not Ba Jiao Lian).
• Mayapple [Podophyllum peltatum]. In, PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007.

  (Compilation of short monographs on herbal medications and dietary supplements; has a section on mayapple, but not ba jiao or dysosma).
• Kao WF, Hung DZ, Tsai WJ, Lin KP, Deng JF. Podophyllotoxin intoxication: toxic effect of Bajiaolian in herbal therapeutics. Hum Exp Toxicol. 1992;11:480–7. [PubMed: 1361136]

  (5 patients with Bajiaolian toxicity presenting with nausea, diarrhea, abdominal pain, abnormal liver tests [bilirubin normal, ALT 43-66 U/L, AST 52-183, Alk P usually normal], thrombocytopenia, sensory and motor neuropathy consistent with podophyllotoxin intoxication).
• Stickel F, Seitz HK, Hahn EG, Schuppan D. Z Gastroenterol. 2001;39:225–32, 234-7. [Liver toxicity of drugs of plant origin] German. [PubMed: 11324140]

  (Review of hepatotoxicity of botanicals including pyrrolizidine alkaloids, germander, celandine, chaparral, Chinese herbs and pennyroyal; Ba Jiao Lian and podophyllum are not discussed).
• 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; Ba Jiao Lian is listed as hepatotoxic).
• Pittler MH, Ernest E. Systematic review: hepatotoxic events associated with herbal medicinal products. Aliment Pharmacol Ther. 2003;18:451–71. [PubMed: 12950418]

  (Systematic review of published cases of hepatotoxicity due to herbal medications, listing 52 case reports or case series, most common agents being celandine [3], chaparral [3], germander [8], Jin Bu Huan [3], kava [1], Ma huang [3], pennyroyal [1], skullcap [2], Chinese herbs [9], valerian [1]).
• 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]).
• 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 usnic acid; Ba Jiao Lian is not discussed).
• Chou SL, Chou MY, Kao WF, Yen DH, Yen LY, Huang CI, Lee CH. Bajiaolian poisoning-a poisoning with high misdiagnostic rate. Am J Emerg Med. 2010;28:85–9. [PubMed: 20006208]

  (Review of records of 4 poison centers in Taiwan from 1985 to 2003 identified 17 cases of Ba Jiao Lian toxicity, 15 were initially misdiagnosed; presenting with nausea, weakness, confusion, gastrointestinal bleeding, and abnormal liver tests followed by sensory-motor and autonomic neuropathy).
• 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 were attributed to drug induced liver injury, of which 12 were attributed to herbals, but none specifically to Ba Jiao Lian).
• 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; no mention of Ba Jiao Lian).
• 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, herbal drugs and supplements including 1 publication on Ba Jiao Lian [Kao 1992]).
• Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther. 2013;37:3–17. [PubMed: 23121117]

  (Systematic review of literature on HDS associated liver injury discusses Chinese and Asian herbs, but does not mention Ba Jiao Lian specifically).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–25. [PubMed: 23419359]

  (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, including 15 attributed to herbals or dietary supplements, but none to Ba Jiao Lian specifically).
• 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 130 cases of HDS associated liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to Ba Jiao Lian).
• Seeff LB, Bonkovsky HL, Navarro VJ, Wang G. Herbal products and the liver: a review of adverse effects and mechanisms. Gastroenterology. 2015;148:517–532.e3. [PubMed: 25500423]

  (Extensive review of herbal associated liver injury does not discuss Ba Jiao Lian specifically).
• Medina-Caliz I, Garcia-Cortes M, Gonzalez-Jimenez A, Cabello MR, Robles-Diaz M, Sanabria-Cabrera J, Sanjuan-Jimenez R, et al. Spanish DILI Registry. Herbal and dietary supplement-induced liver injuries in the Spanish DILI Registry. Clin Gastroenterol Hepatol. 2018;16:1495–1502. [PubMed: 29307848]

  (Among 856 cases of hepatotoxicity enrolled in the Spanish DILI Registry between 1994 and 2016, 32 were attributed to herbal products, the most frequent cause being green tea [n=8] and Herbalife products [n=6], while none were attributed to Ba Jiao Lian).
• Bessone F, García-Cortés M, Medina-Caliz I, Hernandez N, Parana R, Mendizabal M, Schinoni MI, et al. Herbal and dietary supplements-induced liver injury in Latin America: experience from the LATINDILI Network. Clin Gastroenterol Hepatol. 2022;20:e548–e563. [PubMed: 33434654]

  (Among 367 cases of hepatotoxicity enrolled in the Latin American DILI Network between 2011 and 2019, 29 [8%] were attributed to herbal products, the most frequent being green tea [n=7], Herbalife products [n=5] and garcinia [n=3], while none were attributed to Ba Jiao Lian).
• Ballotin VR, Bigarella LG, Brandão ABM, Balbinot RA, Balbinot SS, Soldera J. Herb-induced liver injury: Systematic review and meta-analysis. World J Clin Cases. 2021;9:5490–5513. [PMC free article: PMC8281430] [PubMed: 34307603]

  (Systematic review of the literature on herb induced liver injury identified 446 references describing 936 cases due to 79 different herbal products, the most common being He Shou Wu [91], green tea [90] Herbalife products [64], kava [62 and greater celandine [48]; only 4 were attributed to Ba Jiao Lian).