Protective effect of 18β‑glycyrrhetinic acid against H<sub>2</sub>O<sub>2</sub>‑induced injury in Schwann cells based on network pharmacology and experimental validation

Zhang,Di; Sun,Jianxin; Chang,Shiquan; Li,Xing; Shi,Huimei; Jing,Bei; Zheng,Yachun; Lin,Yi; Qian,Guoqiang; Pan,Yuwei; Zhao,Guoping

doi:10.3892/etm.2021.10676

Protective effect of 18β‑glycyrrhetinic acid against H₂O₂‑induced injury in Schwann cells based on network pharmacology and experimental validation

Authors:
- Di Zhang
- Jianxin Sun
- Shiquan Chang
- Xing Li
- Huimei Shi
- Bei Jing
- Yachun Zheng
- Yi Lin
- Guoqiang Qian
- Yuwei Pan
- Guoping Zhao
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Affiliations: College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China, College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China, Preventive Treatment of Disease, Tianhe Traditional Chinese Medicine Hospital, Guangzhou, Guangdong 510665, P.R. China
Published online on: September 1, 2021 https://doi.org/10.3892/etm.2021.10676
Article Number: 1241
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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