Neferine mediated TGF-β/ERK signaling to inhibit fibrosis in endometriosis

Yue Xia; Ying Guo; Jianhua Zhou; Limin Fan; Jiani Xie; Yili Wang; Huilan Du; Xiaorong Ni

Neferine mediated TGF-β/ERK signaling to inhibit fibrosis in endometriosis

Am J Transl Res. 2023 May 15;15(5):3240-3253. eCollection 2023.

Authors

Yue Xia¹, Ying Guo¹, Jianhua Zhou¹, Limin Fan², Jiani Xie¹, Yili Wang¹, Huilan Du³, Xiaorong Ni¹

Affiliations

¹ Department of Gynecology, Shanghai Traditional Chinese Medicine Hospital, Shanghai University of Traditional Chinese Medicine Shanghai 200071, China.
² The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine Shanghai 200092, China.
³ Department of Gynecology, Hebei University of Chinese Medicine Shijiazhuang 050200, Hebei, China.

PMID: 37303677
PMCID: PMC10250984

Abstract

Objective: To investigate the mechanism of Neferine in treating endometriosis fibrosis by TGF-β/ERK signaling pathway through a combination of network pharmacological analysis of Lotus embryos, in vivo animal experiments, and in vitro cell experiments.

Methods: The active ingredients of the drug lotus embryos, the drug targets and the targets of endometriosis were determined from the TCMSP database, the Swiss Target Prediction database and GeneCard and Online Mendelian Inheritance in Man. The String database and Cytoscape 3.6.3 software were used to construct the network of common target protein interactions between drug and disease, as well as the target network. GO and KEGG enrichment analysis of the common targets was performed. We designed endometriosis mouse models with Neferine to investigate the therapeutic effect of Neferine on the fibrosis model of endometriosis and its mechanism of action. Different methods were used to evaluate the treated endometriotic lesion tissue and the untreated ectopic lesion tissue. The 12Z cells (human endometriosis immortalized cells) were cultured in vitro and treated with Neferine to detect cell viability and the effects of invasion and metastasis.

Results: The results of GO function and KEGG enrichment analysis showed that the role pathways of lotus germ were TGF-β signaling pathway, ERK1/2 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway, and PI3K-Akt signaling pathway. Neferine which is one of the effective active ingredients of lotus germ, significantly inhibited the expression of fibronectin, collagen I, connective tissue growth factor, and smooth muscle actin by activating the TGF-β/ERK pathway in vivo, which is required for the fibrosis process of endometriosis. Neferine also significantly inhibited the proliferation, invasion and metastasis ability of 12Z cells.

Conclusion: Neferine inhibits the progression of endometriosis both in vitro and in vivo. Its mechanism of action may involve the regulation of the TGF-β/ERK signaling pathway, leading to the inhibition of fibrosis in endometriosis.

Keywords: Neferine; TGF-β/ERK signaling pathway; endometriosis; fibrosis.