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油棕空果串木质素及其主要氧化产物对对硝基苯酚和4-甲基伞形酮肝和肾葡萄糖醛酸化的抑制作用

The Inhibition of Hepatic and Renal Glucuronidation of -Nitrophenol and 4-Methylumbelliferone by Oil Palm Empty Fruit Bunch Lignin and Its Main Oxidation Compounds.

作者信息

Salleh Norliyana Mohamad, Ismail Sabariah, Ibrahim Mohamad Nasir Mohamad

机构信息

Centre for Drug Research, Universiti Sains Malaysia, Penang, Malaysia.

Centre for Herbal Standardization, Sains@USM, Bayan Lepas, Penang, Malaysia.

出版信息

Pharmacogn Mag. 2017 Jan;13(Suppl 1):S102-S114. doi: 10.4103/0973-1296.203990. Epub 2017 Apr 7.

DOI:10.4103/0973-1296.203990
PMID:28479734
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5407101/
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 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 -nitrophenol (-NP) and 4-methylumbelliferone (4-MU) were employed as probe substrates in glucuronidation assays. The effect of soda oil palm EFB lignin on , , CL, , and mode of inhibition of 4-MU glucuronidation in RLM was also determined.

RESULTS

The inhibitory potency of oil palm EFB lignin for both -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 > -hydroxybenzaldehyde. Soda oil palm EFB lignin exhibited mixed-type inhibition against 4-MU glucuronidation in RLM, showing the change in apparent and with only a minor effect on compared with control.

CONCLUSIONS

The findings showed that effect of oil palm EFB lignin on both -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.

SUMMARY

The inhibitory potential of oil palm EFB lignin extracts for -NP and 4-MU glucuronidation in RLM and RKM can be listed in the following rank order: soda > kraft > organosolvThe inhibitory potential of oil palm EFB lignin main oxidation compounds for -NP and 4-MU glucuronidation in RLM and RKM can be listed in the following rank order: vanillin > syringaldehyde > p-hydroxybenzaldehydeResults suggested that the effect of oil palm EFB lignin on -NP and 4-MU glucuronidation activity in both RLM and RKM was enhanced by the presence of vanillin as well as total flavonoid contentResults also suggested that oil palm EFB lignin may inhibit glucuronidation of substrate by UGT enzymes, especially UGT1A6, particularly in rat liver -NP: -Nitrophenol, 4-MU: 4-Methylumbelliferone, EFB: Empty fruit bunch, DME: Drug-metabolizing enzymes, UGT: UDPglucuronosyltransferase, : Maximal reaction velocity, : Michaelis-Menten constant, CLint: Intrinsic clearance, : Dissociation constant of an inhibitor enzyme complex, 4-MUG: 4-Methylumbelliferone glucuronide, DMSO: Dimethyl sulfoxide, IC50: Half maximal inhibitory concentration, -NPG: -Nitrophenol glucuronide, RKM: Rat kidneys microsomes, RLM: Rat liver microsome, UDPGA: UDPglucuronic acid, TCA: trichloroacetic acid, MPA: mycophenolic acid.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4c6/5407101/efe59504f7b5/PM-13-102-g015.jpg
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摘要

背景

为了将油棕空果串（EFB）木质素开发为一种营养保健品和健康补充剂，研究其通过抑制药物代谢酶（DMEs）与其他药物相互作用的潜力将确保产品安全。

目的

本研究旨在调查油棕EFB木质素及其主要氧化化合物对大鼠肝和肾微粒体中Ⅱ相DME尿苷二磷酸葡萄糖醛酸转移酶（UGTs）的影响。

材料与方法

在葡萄糖醛酸化试验中使用对硝基苯酚（-NP）和4-甲基伞形酮（4-MU）作为探针底物。还测定了苏打油棕EFB木质素对大鼠肝微粒体（RLM）中4-MU葡萄糖醛酸化的(V_{max})、(K_m)、(CL_{int})、(K_i)和抑制模式的影响。

结果

发现油棕EFB木质素对大鼠肝微粒体（RLM）和大鼠肾微粒体（RKM）中-NP和4-MU葡萄糖醛酸化的抑制效力顺序为：苏打法>(硫酸盐)法>有机溶剂法。然而，其主要氧化化合物的抑制效力顺序为：香草醛>丁香醛>(对)-羟基苯甲醛。苏打油棕EFB木质素对RLM中4-MU葡萄糖醛酸化表现出混合型抑制，与对照相比，表观(K_m)和(V_{max})发生变化，而(K_i)影响较小。

结论

研究结果表明，香草醛和类黄酮的存在增强了油棕EFB木质素对RLM和RKM中-NP和4-MU葡萄糖醛酸化的影响。动力学研究表明，苏打油棕EFB木质素对RLM中UGT活性具有强烈抑制作用，呈混合型抑制模式。

总结

油棕EFB木质素提取物对RLM和RKM中-NP和4-MU葡萄糖醛酸化的抑制潜力可按以下顺序列出：苏打法>(硫酸盐)法>有机溶剂法

油棕EFB木质素主要氧化化合物对RLM和RKM中-NP和4-MU葡萄糖醛酸化的抑制潜力可按以下顺序列出：香草醛>丁香醛>(对)-羟基苯甲醛

结果表明，香草醛和总黄酮含量的存在增强了油棕EFB木质素对RLM和RKM中-NP和4-MU葡萄糖醛酸化活性的影响

结果还表明，油棕EFB木质素可能抑制UGT酶对底物的葡萄糖醛酸化作用，尤其是UGT1A6，特别是在大鼠肝脏中

-NP：对硝基苯酚，4-MU：4-甲基伞形酮，EFB：空果串，DME：药物代谢酶，UGT：尿苷二磷酸葡萄糖醛酸转移酶，(V_{max})：最大反应速度，(K_m)：米氏常数，(CL_{int})：内在清除率，(K_i)：抑制剂-酶复合物的解离常数，4-MUG：4-甲基伞形酮葡萄糖醛酸，DMSO：二甲基亚砜，IC50：半最大抑制浓度，-NPG：对硝基苯酚葡萄糖醛酸，RKM：大鼠肾微粒体，RLM：大鼠肝微粒体，UDPGA：尿苷二磷酸葡萄糖醛酸，TCA：三氯乙酸，MPA：霉酚酸

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2
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3
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