从[来源未提及]中分离和鉴定具有抗过氧化氢诱导的人视网膜色素上皮ARPE - 19细胞氧化应激保护作用的二氢菲衍生物。

Isolation and Identification of Dihydrophenanthrene Derivatives from with Protective Effects against Hydrogen-Peroxide-Induced Oxidative Stress of Human Retinal Pigment Epithelium ARPE-19 Cells.

作者信息

Panuthai Pongsawat, Phumsuay Rianthong, Muangnoi Chawanphat, Maitreesophone Porames, Kongkatitham Virunh, Mekboonsonglarp Wanwimon, Rojsitthisak Pornchai, Likhitwitayawuid Kittisak, Sritularak Boonchoo

机构信息

Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

出版信息

Antioxidants (Basel). 2023 Mar 2;12(3):624. doi: 10.3390/antiox12030624.

DOI:10.3390/antiox12030624

PMID:36978871

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10045308/

Abstract

Oxidative stress is a significant factor in the development of age-related macular degeneration (AMD), which results from cell damage, dysfunction, and death in the retinal pigmented epithelium (RPE). The use of natural compounds with antioxidant properties to protect RPE cells from oxidative stress has been explored in , a genus of orchid plants belonging to the family Orchidaceae. Two new compounds and seven known compounds from the MeOH extract of the whole plant of were successfully isolated and structurally characterized. Out of all the compounds isolated, 2-methoxy-9,10-dihydrophenanthrene-4,5-diol () showed the highest protective effect against hydrogen peroxide (HO)-induced oxidative stress in human retinal pigment epithelial (ARPE-19) cells. Therefore, it was selected to evaluate its protective effect and mechanism on oxidative-stress-induced ARPE-19 cells. Cells were pre-treated with compound 3 at 25, 50, and 100 µg/mL for 24 h and then induced with 400 µM HO for 1 h. The results demonstrated that compound significantly ( < 0.05) increased cell viability by 10-35%, decreased ROS production by 10-30%, and reduced phosphorylation of p38, ERK1/2, and SAPK/JNK by 20-70% in a dose-dependent manner without toxicity. Furthermore, compound significantly ( < 0.05) modulated the expression of apoptosis pathway proteins (cytochrome c, Bax and Bcl-2) by 20-80%, and enhanced SOD, CAT, and GPX activities, and GSH levels in a dose-dependent manner. These results suggest that compound protects ARPE-19 cells against oxidative stress through MAPKs and apoptosis pathways, including the antioxidant system. Thus, compound could be considered as an antioxidant agent for preventing AMD development by protecting RPE cells from oxidative stress and maintaining the retina. These findings open up new possibilities for the use of natural compounds in the treatment of AMD and other oxidative-stress-related conditions.

摘要

氧化应激是年龄相关性黄斑变性（AMD）发展的一个重要因素，AMD是由视网膜色素上皮（RPE）中的细胞损伤、功能障碍和死亡引起的。人们已经探索使用具有抗氧化特性的天然化合物来保护RPE细胞免受氧化应激，[该植物名称]是兰科的一种兰花植物。从[该植物名称]全株的甲醇提取物中成功分离并鉴定了两种新化合物和七种已知化合物。在所有分离出的化合物中，2-甲氧基-9,10-二氢菲-4,5-二醇（[化合物编号]）对过氧化氢（HO）诱导的人视网膜色素上皮（ARPE-19）细胞氧化应激显示出最高的保护作用。因此，选择它来评估其对氧化应激诱导的ARPE-19细胞的保护作用及其机制。细胞分别用25、50和100μg/mL的化合物3预处理24小时，然后用400μM HO诱导1小时。结果表明，化合物[编号]以剂量依赖性方式显著（<0.05）提高细胞活力10 - 35%，降低活性氧产生10 - 30%，并使p38、ERK1/2和SAPK/JNK的磷酸化降低20 - 70%，且无毒性。此外，化合物[编号]以剂量依赖性方式显著（<0.05）调节凋亡途径蛋白（细胞色素c、Bax和Bcl-2）的表达20 - 80%，并增强超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPX）的活性以及谷胱甘肽（GSH）水平。这些结果表明，化合物[编号]通过丝裂原活化蛋白激酶（MAPKs）和凋亡途径（包括抗氧化系统）保护ARPE-19细胞免受氧化应激。因此，化合物[编号]可被视为一种抗氧化剂，通过保护RPE细胞免受氧化应激并维持视网膜来预防AMD的发展。这些发现为天然化合物用于治疗AMD和其他氧化应激相关病症开辟了新的可能性。