探討發酵蓮霧葉萃取物對乙醯胺酚誘導肝細胞損傷之保護機制

The protective mechanism of fermented wax apple leaf extract against acetaminophen-induced hepatocyte injury

黃思翰(SSU-HAN HUANG)

指導教授 ： 蘇正元

中原大學/理學院/生物科技學系/碩士(2023年)

https://doi.org/10.6840/cycu202301021

摘要

肝臟是人體內負責代謝和解毒功能的重要器官，有些民眾若誤食過量的止痛藥成分乙醯胺酚(acetaminophen, APAP)，容易引發藥物性肝損傷 (drug-induced liver injury，簡稱 DILI)。故本研究擬探討發酵蓮霧葉 (wax apple leaf tea, WAT) 對APAP誘導肝細胞損傷之保護作用與可能機制。首先，製備發酵蓮霧葉乙醇粗萃物 (WAT-ethanolic extract, WAT-EE)，其含有gallic acid、EGCG、ellagic acid、myricetin等主要酚類化合物，對APAP誘導小鼠AML-12肝細胞死亡有保護效果，並減少APAP所造成的肝細胞內氧化壓力。WAT-EE可增加AML-12肝細胞內Nrf2與其下游抗氧化/解毒酵素HO-1、NQO1和UGT1A等mRNA和蛋白質表現量，並減少與發炎反應相關cox-2的mRNA表現量。WAT-EE亦降低表觀遺傳學相關酵素HDAC1、HDAC2、HDAC3、HDAC4、DNMT1和DNMT3b等蛋白質表現量，以及提升Nrf2 promoter未甲基化DNA相對量。因此，由目前結果得知WAT-EE對APAP誘導肝細胞損傷之保護機制，可能是藉由調控表觀遺傳學機制以活化Nrf2抗氧化系統，進而降低細胞內氧化壓力所造成的傷害；故WAT-EE具有開發成護肝機能性食品的潛力。

關鍵字：乙醯胺酚、表觀遺傳學、肝臟、Nrf2、氧化壓力、蓮霧

關鍵字

乙醯胺酚 ； 表觀遺傳學 ； 肝臟 ； Nrf2 ； 氧化壓力 ； 蓮霧

並列摘要

The liver is an important organ for metabolizing and detoxifying. However, people are prone to ingesting excessive amounts of acetaminophen (APAP), which is an analgesic ingredient, which leads to drug-induced hepatic damage. The objective of this study is to investigate the protective effect and potential mechanism of fermented apple leaf tea (WAT) on APAP-induced lesion of mouse AML-12 hepatocytes. We prepared an ethanol extract of WAT (WAT-EE) containing major phenolic compounds, including gallic acid, EGCG, ellagic acid, and myricetin. WAT-EE recovered the death ratio and reduced oxidative stress in AML-12 cells caused by APAP. WAT-EE increased mRNA and protein levels of Nrf2 and its downstream HO-1, NQO1, and UGT1A enzymes and decreased mRNA level of inflammatory cox-2. It can also reduce protein expression of epigenetic enzymes such as HDAC1, HDAC2, HDAC3, HDAC4, DNMT1 and DNMT3b, while the level of unmethylated DNA of Nrf2 promoter is increased. Therefore, it suggested that WAT-EE could suppress liver damage due to APAP-induced oxidative stress by regulating epigenetic mechanisms to activate the Nrf2 antioxidant system. WAT-EE might be used as a functional food for liver protection.

Keywords: Acetaminophen, epigenetics, liver, Nrf2, oxidative stress Syzygium samarangense

並列關鍵字

Acetaminophen ； epigenetics ； liver ； Nrf2 ； oxidative stress ； Syzygium samarangense

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