Protective effect of 18β-glycyrrhetinic acid against H(2)O(2)-induced injury in Schwann cells based on network pharmacology and experimental validation.
Protective effect of 18β-glycyrrhetinic acid against H(2)O(2)-induced injury in Schwann cells based on network pharmacology and experimental validation.
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基于网络药理学和实验验证18β-甘草次酸对H2O2-诱导雪旺细胞损伤的保护作用
DOI：
10.3892/etm.2021.10676
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发表时间：
2021-11
影响因子：
2.7
通讯作者：
Zhao G
中科院分区：
文献类型：
--
作者：
Zhang D;Sun J;Chang S;Li X;Shi H;Jing B;Zheng Y;Lin Y;Qian G;Pan Y;Zhao G
本研究的目的是评估18β-GA对过氧化氢（H2 O2）诱导的损伤的保护作用。首先，使用18β-GA的SMILES注释来搜索PubChem，并在Swiss Target Prediction、Similarity Enhancement Approach Search Server和TargetNet数据库中进行反向分子对接以获得潜在靶标。从GeneCards数据库中获得损伤相关分子，通过韦恩图分析筛选18β-GA治疗损伤的预测靶点。随后，通过WebGestalt进行京都基因和基因组百科全书分析。将实验细胞分为对照组、模型组、10 μM SB 203580组、5 μM 18β-GA组和10 μM 18β-GA组。Hoechst 33258染色检测细胞内活性氧（ROS）水平、细胞凋亡、Bcl-xl、Bcl-2、Bad、Bax、切割型半胱天冬酶3、切割型半胱天冬酶7、瞬时受体电位锚蛋白1（TRPA 1）和瞬时受体电位香草素1（TRPV 1）水平以及p38 MAPK磷酸化。选择“TRP通道的炎症介质调节”通路进行实验验证。结果表明，与H2 O2处理的模型组相比，10 µM 18β-GA显著增加了细胞活力。细胞内ROS荧光强度的差异表明，18β-GA抑制H2 O2诱导的雪旺细胞ROS产生。Hoechst 33258染色显示18β-GA逆转了H2 O2处理后染色质浓缩和凋亡细胞核的增加。流式细胞仪检测结果显示，18β-GA显著抑制H_2O_2诱导的细胞凋亡。18β-GA预处理可明显降低H2 O2处理后Bad、Bax、cleaved-caspase 3、cleaved-caspase 7、TRPA 1和TRPV 1的表达及p38 MAPK的磷酸化水平，升高Bcl-2和Bcl-xl的表达。结论：18β-GA可抑制H2 O2诱导的雪旺细胞损伤和凋亡，可能是一种潜在的预防周围神经损伤的药物。
The aim of the present study was to assess the protective effects of 18β-GA against hydrogen peroxide (H2O2)-induced injury. First, the SMILES annotation for 18β-GA was used to search PubChem and for reverse molecular docking in Swiss Target Prediction, the Similarity Ensemble Approach Search Server and the TargetNet database to obtain potential targets. Injury-related molecules were obtained from the GeneCards database and the predicted targets of 18β-GA for injury treatment were selected by Wayne diagram analysis. Subsequently, Kyoto Encyclopedia of Genes and Genomes analysis was performed by WebGestalt. The experimental cells were assorted into control, model, 10 µM SB203580-treated, 5 µM 18β-GA-treated and 10 µM 18β-GA-treated groups. Hoechst 33258 staining was performed and intracellular reactive oxygen species (ROS) levels, cell apoptosis, Bcl-xl, Bcl-2, Bad, Bax, cleaved-caspase 3, cleaved-caspase 7, transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) levels, as well as p38 MAPK phosphorylation were measured. The ‘Inflammatory mediator regulation of TRP channels’ pathway was selected for experimental verification. The results indicated that 10 µM 18β-GA significantly increased cell viability as compared with the H2O2-treated model group. As suggested by the difference in intracellular ROS fluorescence intensity, 18β-GA inhibited H2O2-induced ROS production in Schwann cells. Hoechst 33258 staining indicated that 18β-GA reversed chromatin condensation and the increase in apoptotic nuclei following H2O2 treatment. Furthermore, flow cytometry suggested that 18β-GA substantially inhibited H2O2-induced apoptosis. Pre-treatment with 18β-GA obviously reduced Bad, Bax, cleaved-caspase3, cleaved-caspase 7, TRPA1 and TRPV1 levels and p38 MAPK phosphorylation after H2O2 treatment and increased Bcl-2 and Bcl-xl levels. In conclusion, 18β-GA inhibited Schwann cell injury and apoptosis induced by H2O2 and may be a potential drug to prevent peripheral nerve injury.
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影响因子：
6
作者：
Li, Zih-Ying;Tung, Yu-Tang;Yen, Gow-Chin
通讯作者：
Yen, Gow-Chin
影响因子：
5.1
作者：
Ma, Guixin;Luo, Weiwei;Chen, Xiuping
通讯作者：
Chen, Xiuping
影响因子：
4.3
作者：
Su, Li;Wang, Zeng;Hong, Jinsheng
通讯作者：
Hong, Jinsheng
基于网络药理学和实验验证的芍药苷对H_2O_2诱导雪旺细胞损伤的保护作用
影响因子：
4.6
作者：
Zhang Di;Yang Bing;Zhao Guo-Ping
通讯作者：
Zhao Guo-Ping
DOI：
10.1155/2012/650514
发表时间：
2012
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Ishida T;Mizushina Y;Yagi S;Irino Y;Nishiumi S;Miki I;Kondo Y;Mizuno S;Yoshida H;Azuma T;Yoshida M
通讯作者：
Yoshida M