Inhibitory Effects of Active Constituents and Extracts of Andrographis Paniculata on Ugt1a1, Ugt1a4, and Ugt2b7 Enzyme Activities

Objective: The present investigation addresses the inhibitory potential of five Andrographis paniculata (AP) extracts of different polarity and its three active constituents on UGT1A1, UGT1A4 and UGT2B7. Methods: Bioluminescent assay with luciferin as a substrate was used to determine IC50 values for all extracts and constituents. The kinetic enzyme inhibition experiments were subsequently performed to determine Ki values and inhibition modes for extracts and constituents having IC50 Results: Our results in general exhibit that AP extracts and constituents potently inhibited UGT1A1 and UGT2B7 with varying degrees of inhibition featuring Ki values from 1.0 upto 7.5 μg/mL. On the other hand, none of them showed significant inhibitory effect on UGT1A4. Of the extracts tested, AP ethanolic, AP aqueous (root) and AP aqueous (leaf) were found to inhibit UGT1A1, while the remaining, were devoid of any potent interaction. In contrast, AP ethanolic was found to exclusively and competitively inhibit UGT2B7. Of the constituents examined, andrographolide and 14-Deoxy11,12-didehydroandrographolide were found to inhibit the activity of UGT2B7, while neo andrographolide and 14-Deoxy-11,12didehydroandrographolide inhibited UGT1A1, partially implying their relative content in the extracts, consequently representing correlation with inhibition seen in the corresponding extracts. values less than 10 μg/mL. Conclusion: These findings suggest that AP extracts could cause herb-drug interactions via inhibition of UGT iso forms. An in vivo study is needed to examine this further.