甘草酸(GA)通过阻断 ER 应激和 MAPK 通路抑制 UV-B 照射下人皮肤成纤维细胞中的活性氧物质介导的光损伤。

Glycyrrhizic acid (GA) inhibits reactive oxygen Species mediated photodamage by blocking ER stress and MAPK pathway in UV-B irradiated human skin fibroblasts.

机构信息

PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, Jammu and Kashmir, India.

PK-PD and Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu Tawi, Jammu and Kashmir, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.

出版信息

J Photochem Photobiol B. 2015 Jul;148:351-357. doi: 10.1016/j.jphotobiol.2015.05.003. Epub 2015 May 15.

Abstract

BACKGROUND

Previously we have reported that generation of reactive oxygen species is the prime event responsible for calcium mediated activation of PERK-eIF2α-CHOP pathway and apoptosis in UV-B irradiated human skin fibroblasts (Hs68). We have also reported that glycyrrhizic acid (GA) mediates potent photoprotective activity against UV-B - irradiation-induced photodamage in human skin fibroblast.

OBJECTIVE

In the present study, we aimed to investigate the role of GA in preventing oxidative stress mediated unfolded protein response (UPR) and mitogen activated protein kinases (MAPK) pathway.

METHODS

Human skin fibroblast (Hs68) cells were exposed to UV-B radiations in lab conditions. Different parameters of UVB induced cellular and molecular changes were analysed using western-blotting, microscopy and flow cytometry.

RESULTS

Our results show that GA has strong photoprotective action against UV-B induced cellular damage. It was observed that: (a) Oxidative disturbances and intracellular Ca(2+) imbalance induced by UV-B irradiation was significantly restored by GA treatment; (b) activation of PERK-eIF2α-CHOP and MAPK pathway induced by UV-B was significantly blocked by GA; (c) Loss of mitochondrial membrane potential and apoptosis induced by UV-B were reduced by GA treatment.

CONCLUSION

Based on the above findings we conclude GA has a highly significant ROS quenching activity, thereby blocking the cascade of events including release of calcium from ER and subsequent ER stress, MAPK pathway and cellular demise. GA offers highly potent anti photodamage effect and can be exploited for cosmetic or therapeutic purposes.

摘要

背景

我们之前曾报道过,活性氧的产生是导致钙介导的 PERK-eIF2α-CHOP 通路激活和 UV-B 照射下人皮肤成纤维细胞(Hs68)凋亡的主要事件。我们还报道过,甘草酸(GA)对 UV-B 照射诱导的人皮肤成纤维细胞光损伤具有很强的光保护活性。

目的

本研究旨在探讨 GA 在预防氧化应激介导的未折叠蛋白反应(UPR)和丝裂原活化蛋白激酶(MAPK)通路中的作用。

方法

在实验室条件下,将人皮肤成纤维细胞(Hs68)暴露于 UV-B 辐射下。使用 Western blot、显微镜和流式细胞术分析不同参数的 UVB 诱导的细胞和分子变化。

结果

我们的结果表明,GA 对 UV-B 诱导的细胞损伤具有很强的光保护作用。观察到:(a)GA 处理可显著恢复 UV-B 照射引起的氧化紊乱和细胞内 Ca(2+)失衡;(b)GA 显著阻断了 UV-B 诱导的 PERK-eIF2α-CHOP 和 MAPK 通路的激活;(c)GA 处理可减少由 UV-B 引起的线粒体膜电位丧失和凋亡。

结论

基于上述发现,我们得出结论,GA 具有很强的 ROS 清除活性,从而阻断了包括 ER 中钙释放和随后的 ER 应激、MAPK 通路和细胞死亡在内的一系列事件。GA 具有很强的抗光损伤作用,可用于美容或治疗目的。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索