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.
Highlights
Tinospora crispa (L.) Hook. f. & Thomson belongs to the botanical family of Menispermaceae
We investigated whether borapetoside C (1) and other potentially toxic related clerodane furanoditerpenoids could be identified in an aqueous extract of fresh stems that mimics the traditional preparation
Among the large spectrum of traditional use of T. crispa reported in the literature, its anti-diabetic activity has raised a special interest for researchers all around the world considering the growing number of type 2 diabetes cases, all the more so as its use in South-Asia has been widespread for a long time
Summary
Among the large spectrum of traditional use of T. crispa reported in the literature, its anti-diabetic activity has raised a special interest for researchers all around the world considering the growing number of type 2 diabetes cases, all the more so as its use in South-Asia has been widespread for a long time. A potential mechanism of improvement of peripheral glucose uptake, notably via an increase in glucose utilization of skeletal muscle and liver, has been advanced following in vitro tests[24,25,26] To date, these promising non-clinical studies have not been confirmed by clinical trials applied especially to type 2 diabetic patients. There remain uncertainties on the efficacy on blood glucose control in real-life setting while the risk of hepatic trouble is established, both for an acute and for a chronic use and independently of the method of administration (stem in powder capsule or used as an aqueous extract). Toxic mechanisms may associate both dose-response relationship and idiosyncratic effects, making therapeutic use of T. crispa hazardous, in so far as diabetic patients are often treated simultaneously with statins, drugs known to potentially increase liver enzymes
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