The inhibition of hepatic and renal glucuronidation of p-Nitrophenol and 4-Methylumbelliferone by oil palm empty fruit bunch lignin and its main oxidation compounds

Norliyana Mohamad Salleh; Sabariah Ismail; Mohamad Nasir Mohamad Ibrahim

Articles

Abstract

Pharmacognosy Magazine,2017,13,49s,s102-s114.

DOI:10.4103/0973-1296.203990

Published:April 2017

Type:Original Article

Authors:

Author(s) affiliations:

Norliyana Mohamad Salleh¹, Sabariah Ismail¹, Mohamad Nasir Mohamad Ibrahim²
¹Centre for Drug Research, Universiti Sains Malaysia, Penang; Centre for Herbal Standardization, Sains@USM, Bayan Lepas, Penang, Malaysia
²School of Chemical Sciences, Universiti Sains Malaysia, Penang, Malaysia

Abstract:

Background: In order to develop oil palm empty fruit bunch (EFB) lignin as a nutraceutical and health supplement, the investigation of its potential in interacting with other drugs via inhibition of drug-metabolizing enzymes (DMEs) would ensure product safety. Objective: The study was aimed to investigate the in vitro effect of oil palm EFB lignin and its main oxidation compounds on phase II DME UDP-glucuronosyltransferases (UGTs) in rat liver and kidney microsomes. Materials and Methods: The p-nitrophenol (p-NP) and 4-methylumbelliferone (4-MU) were employed as probe substrates in glucuronidation assays. The effect of soda oil palm EFB lignin on V_max, K_m, CL_int, K_i, and mode of inhibition of 4-MU glucuronidation in RLM was also determined. Results: The inhibitory potency of oil palm EFB lignin for both p-NP and 4-MU glucuronidation in rat liver microsome (RLM) and rat kidneys microsomes (RKM) was found to be in the rank order of soda > kraft > organosolv. However, the inhibitory potency of its main oxidation compounds were in the rank order of vanillin > syringaldehyde > p-hydroxybenzaldehyde. Soda oil palm EFB lignin exhibited mixed-type inhibition against 4-MU glucuronidation in RLM, showing the change in apparent V_max and with only a minor effect on K_m compared with control. Conclusions: The findings showed that effect of oil palm EFB lignin on both p-NP and 4-MU glucuronidation in RLM and RKM was enhanced by the presence of vanillin as well as flavonoids. Kinetic study showed that soda oil palm EFB lignin exhibited strong inhibition on UGT activity in RLM with mixed-type inhibition mode.