Andrographis Paniculata And Curcuma Xanthorrhiza Extracts And Active Constituents Inhibit Morphine Glucuronidation
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Date
2016-08
Authors
Husni, Zulhilmi
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Abstract
A resurgence in the widespread popularity of herbal product in its supplement forms has recently attracted global attention concerning to herb-drug interaction. The inhibitory effects of selected Malaysian medicinal plant herbs namely Andrographis paniculata and Curcuma xanthorrhiza on morphine glucuronidation were evaluated on recombinant UGT2B7 protein and human liver microsomes. Ethanolic and aqueous extracts of Andrographis paniculata as well as andrographolide inhibited morphine glucuronidation at various degrees except for neoandrographolide. Aqueous extract moderately inhibited morphine glucuronidation compared to andrographolide and ethanolic extract. Andrographolide is the main perpetrator that contributes to the potent inhibitory action of ethanolic extract and kinetic analysis has suggested that andrographolide and Andrographis paniculata ethanolic extract competitively (mixed competitive) inhibited morphine glucuronidation featuring competitive inhibition constant, Kic values ranging from 1.35 to 15.06 μM for andrographolide and 3.22 to 17.94 μg/mL for Andrographis paniculata ethanolic extract on both recombinant UGT2B7 protein and human liver microsomes. Meanwhile, ethanolic extract of Curcuma xanthorrhiza strongly inhibited morphine glucuronidation while that of aqueous extract had displayed moderate inhibition trend on both recombinant UGT2B7 protein and human liver microsomes. Xanthorrhizol inhibited morphine metabolism not as potent as ethanolic extract whereas curcumin did not pose any significant inhibitory trend on morphine glucuronidation. Kinetic assessment has shown that xanthorrhizol competitively (pure and mixed competitive) inhibited morphine glucuronidation with Kic values ranging from 1.07 to 116.74 μM whereby Curcuma xanthorrhiza ethanolic extract inhibited morphine glucuronidation through various modes of
inhibition (pure competitive, mixed competitive and non-competitive) with Kic values ranging from 3.22 up to 14.30 μg/mL on both recombinant UGT2B7 protein and human liver microsomes. Data generated from this study is expected to provide supplementary information particularly for researchers with intention to conduct clinical study in humans and for the clinicians who routinely deal with patients that are prescribed with morphine.
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Keywords
The inhibitory effects of Andrographis paniculata and Curcuma xanthorrhiza , on morphine glucuronidation.