Network pharmacology-based study on the mechanism of scutellarin against zearalenone-induced ovarian granulosa cell injury

• Main Authors: Panpan Hu, Na Sun, Ajab khan, Xinyue Zhang, Panpan Sun, Yaogui Sun, Jianzhong Guo, Xiaozhong Zheng, Wei Yin, Kuohai Fan, Jianzhong Wang, Huizhen Yang, Hongquan Li
• Format: Article
• Language: English
• Published: Elsevier 2021-12-01
• Series: Ecotoxicology and Environmental Safety
• Subjects: Scutellarin; Zearalenone; Granulosa cell injury; Network pharmacology; Molecular docking
• Online Access: http://www.sciencedirect.com/science/article/pii/S0147651321009775

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.