In vitro inhibitory effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea, and Curcuma xanthorrhiza extracts and constituents on human liver glucuronidation activity

Abstract

Background:Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza are commonly consumed as herbal medicines. However their effects on human liver glucuronidation activity are not yet evaluated.Objective:In this study, we evaluate the inhibitory Effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza extracts and their constituents on human liver glucuronidation activity.Materials and Methods:Herbal extracts (aqueous, methanolic and ethanolic extracts) and their constituents were incubated with human liver microsomes with the addition of UDPGA to initiate the reaction. Working concentrations of herbal extracts and their constituents ranged from 10 μg/mL to 1000 μg/mL and 10 μM to 300 μM respectively. IC50 was determined by monitoring the decrement of glucuronidation activity with the increment of herbal extracts or phytochemical constituent's concentrations.Results:All herbal extracts inhibited human liver glucuronidation activity in range of 34.69 μg/mL to 398.10 μg/mL whereas for the constituents, only xanthorrhizol and curcumin (constituents of Curcuma xanthorrhiza) inhibited human liver glucuronidation activity with IC50 of 538.50 and 32.26 μM respectively.Conclusion:In the present study, we have proved the capabilities of Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza to interfere with in vitro glucuronidation process in human liver microsomes.SUMMARY This study documented the capabilities of Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza to inhibit human liver glucuronidation activity which may affect the metabolism of therapeutic drugs or hazardous toxicants that follow the same glucuronidation pathway. Abbreviations used: UGT: Uridine 5’-diphospho-glucuronosyltransferase; 4-MU: 4-methylumbelliferone; IC50: Half Maximal Inhibitory Concentration; Km: Michaelis constant; Vmax: Maximum velocity.

Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents

“…Our study found a comparable IC 50 value of 6.18 ± 1.27 µM. However in our previous study, andrographolide had shown weak inhibition in HLM when 4-methylumbelliferone (4MU) was used as a substrate [ 24 ]. This could be because 4MU is a nonspecific UGT substrate which is mainly conjugated by UGT1A6 in humans and rats [ 56 ], unlike ZDV which is a specific and selective substrate of UGT2B7 [ 57 ].…”

“…Flavonoids have been reported to possess a broad spectrum of health benefits due to their antioxidative, anti-inflammatory, anti-allergic, anti-mutagenic and anticancer properties, which are widely utilized in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications [ 75 ]. Similar to andrographolide and mitragynine, kaempferol-3-rutinoside did not significantly inhibit UGT enzymes in HLM when 4MU was used as a substrate [ 24 ]. On the other hand, it had inhibited UGT2B7-catalyzed glucuronidation of ZDV in HLM with an IC 50 value of 18.56 ± 8.62 µM in this study.…”