Probing PXR activation and modulation of CYP3A4 by Tinospora crispa and Tinospora sinensis
Ethnopharmacological relevance: The two Tinospora species, T. crispa and T. sinensis, native to
Southeast Asia, are integral components of various traditional preparations with structurefunctional claims to treat various disorders, including diabetes and inflammation.
Aim of the study: To assure the safety of the botanical finished products, herb-drug interaction
potential of T. crispa and T. sinensis were investigated by testing their extracts and compounds for
potential in vitro activation of the pregnane X-receptor (PXR) and the modulation of CYP3A4
isozyme, selectively.
Materials and methods: A total of sixteen fully characterized phytochemicals from T. crispa and
T. sinensis were initially evaluated for PXR activation by luciferase reporter gene assay. CYP3A4
inhibition studies were carried out for eleven compounds. In addition, docking studies were
performed to elucidate the possible binding modes to the PXR by the compounds using
computational methods.
Results: Significant activation of PXR (2-fold) was observed for both extracts and non-polar
fractions of T. crispa. Columbin showed significant activation of PXR (3-fold), which was
comparable with the positive control, rifampicin. Vital interactions were predicted with docking
simulation of PXR-columbin complex with critical amino acid residues (Trp-299) that are known
for the activation of PXR. The methanolic extracts of T. crispa and T. sinensis also showed
considerable CYP3A4 inhibition.
Conclusion: T. crispa and T. sinensis, both demonstrated the potential to mediate herb-drug
interaction through PXR activation and inhibition of CYP3A4 isozyme. Moreover, the elucidation
of the potential to induce herb-drug interaction, by the phytochemicals of these Tinospora plants,
thereby supports the need for further investigation to establish the clinical relevancy of these
constituents for possible adverse interactions with pharmaceutical drugs.
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