Int J Biol Sci 2021; 17(10):2449-2460. doi:10.7150/ijbs.60167

Research Paper

Combination of Ferulic Acid, Ligustrazine and Tetrahydropalmatine attenuates Epithelial-mesenchymal Transformation via Wnt/β-catenin Pathway in Endometriosis

Chengling Zhang1,2,3,4*, Ying Zhang1,2,3,4*, Haiying Pan5*, Yi Tan1,2,3,4, Qinghua Wei1,2,3,4, Xueshan Dai1,2,3,4, Jiahui Wei1,2,3,4, Yi Chen1,2,3,4✉

1. College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing, China.
2. Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, China.
3. Pharmacology of Chinese Materia Medica - the Key Discipline Constructed by the state Administration of Traditional Chinese Medicine, Chongqing, China.
4. National Demonstration Center for Experimental Pharmacy Education (Southwest University), Chongqing, China.
5. Sichuan Jinxin Women & Children Hospital, Chengdu 610066, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Zhang C, Zhang Y, Pan H, Tan Y, Wei Q, Dai X, Wei J, Chen Y. Combination of Ferulic Acid, Ligustrazine and Tetrahydropalmatine attenuates Epithelial-mesenchymal Transformation via Wnt/β-catenin Pathway in Endometriosis. Int J Biol Sci 2021; 17(10):2449-2460. doi:10.7150/ijbs.60167. Available from

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Previously the potential therapeutic action of ferulic acid, ligustrazine and tetrahydropalmatine (FLT) are discovered with unclear mechanism in rat autograft endometriosis. However, the effect of FLT on endometrial cells and allograft endometriosis is still unclear. This study is designed to elucidate the influence of FLT on epithelial-mesenchymal transformation in allograft endometriosis and endometrium cells. In vivo, fluorescent xenogeneic endometriosis model was established. In vitro, invasion and metastasis were analyzed after treating FLT. Epithelial-mesenchymal transformation and Wnt/β-catenin pathway were inspected in vitro and in vivo. Activator or inhibitor of Wnt/β-catenin signaling was performed to inspect mechanism of epithelial-mesenchymal transformation. In vivo, FLT not only decreased fluorescent intensity and volume of ectopic lesion, but also ameliorated pathological morphology. E2 and PROG levels in serum were reduced by FLT. In endometrial cells, FLT significantly inhibited the invasion and metastasis. Meantime, epithelial-mesenchymal transformation was reversed, accompanied by suppression of Wnt/β-catenin pathway. In-depth study, activation of Wnt/β-catenin pathway lead to promotion of epithelial-mesenchymal transformation, which was reversed by FLT. FLT prevented fluorescent allograft endometriosis and endometrium cells, which was related to suppress epithelial-mesenchymal transformation through inactivating Wnt/β-catenin pathway. The findings disclose molecular mechanism of epithelial-mesenchymal transformation in endometriosis by FLT, and contribute to further application.

Keywords: Ferulic acid, Ligustrazine, Tetrahydropalmatine, Allograft endometriosis, Epithelial-mesenchymal transformation, Wnt/β-catenin pathway