Clerodane furanoditerpenoids as the probable cause of toxic hepatitis induced by Tinospora crispa

Sci Rep. 2018 Sep 10;8(1):13520. doi: 10.1038/s41598-018-31815-6.

Abstract

Tinospora crispa is a popular traditional herbal plant commonly used throughout the world for treatment of various diseases, in particular type 2 diabetes mellitus. We report here a new case of toxic hepatitis in a 57-year old male patient in the French West Indies following the consumption of two aqueous extracts of fresh Tinospora crispa stems. It thus differs from two previously reported cases that concerned the chronic intake of powdered dry stems delivered in solid oral dosage forms (i.e. pellets and tablets). Liquid Chromatography-Diode Array Detection-Mass Spectrometry (LC/DAD/MS) analyses were performed on an aqueous extract of the offending sample that mimics the swallowed preparation. They revealed the presence of species-specific molecular marker borapetoside C (1) and thus enabled an unambiguous phytochemical identification. The exploration of tandem MS/MS data obtained by ultra-high performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-HRMS) allowed the identification of 17 additional cis-clerodane-type furanoditerpenoid lactones, analogues of 1. These results support the hypothesis that the mechanisms underlying hepatotoxicity of Tinospora crispa are the same as those encountered with furanoditerpenoids-containing plants such as Teucrium chamaedrys or Dioscorea bulbifera. In the context of type 2 diabetes treatment, we recommend that Tinospora crispa intake should be more closely monitored for signs of hepatotoxicity.

Publication types

  • Case Reports

MeSH terms

  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / etiology*
  • Diterpenes, Clerodane / toxicity*
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Liver Function Tests
  • Male
  • Middle Aged
  • Plant Extracts / adverse effects*
  • Plant Stems / chemistry
  • Plant Stems / toxicity
  • Tinospora / chemistry
  • Tinospora / toxicity*

Substances

  • Diterpenes, Clerodane
  • Plant Extracts