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. Cachet X1, Langrand J2, Riffault-Valois L3, Bouzidi C3, Colas C4,5, Dugay A3, Michel S3, Boucaud-Maitre D6,7. Author information 1 Laboratoire de Pharmacognosie, UMR 8638 COMETE CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, F-75006, France. xavier.cachet@parisdescartes.fr. 2 Centre Antipoison de Paris, AP-HP Hôpital Lariboisière-Fernand Widal, Paris, F-75010, France. 3 Laboratoire de Pharmacognosie, UMR 8638 COMETE CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, F-75006, France. 4 Institut de Chimie Organique et Analytique, ICOA UMR 7311 CNRS Université d'Orléans, Orléans, F-45071, France. 5 Centre de Biophysique Moléculaire, CBM UPR 4301 CNRS, Orléans, F-45071, France. 6 Dispositif de Toxicovigilance Antilles, Centre Hospitalier de la Basse-Terre, Basse-Terre, F-97100, France. 7 Direction de la Recherche Clinique et de l'Innovation, Centre Hospitalo-Universitaire de Guadeloupe, Pointe-à-Pitre, F-97110, France. 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. PMID: 30202067 PMCID: PMC6131512 DOI: 10.1038/s41598-018-31815-6 Free PMC Article