Effect of Neiyi Prescription of QIU on autophagy and angiogenic ability of endometriosis via the PPARγ/NF-κB signaling pathway

Objectives Neiyi Prescription of QIU (NYPQ) is a traditional Chinese medicine prescription for the treatment of endometriosis (EMS). Here, we aimed to examine the effects and mechanisms of NYPQ on angiogenic ability in EMS. Study design EMS rats were established with estradiol valerate and autologous transplantation. EMS rats were intraperitoneally injected with chloroquine (CQ, 40 mg/kg), rapamycin (RAPA, 1 mg/kg), and monoclonal antibody VEGF (anti-VEGF, 3 mg/g/d) or administered 5, 10, 20 mg/g/d NYPQ decoction through oral gavage for 4 weeks, respectively. By the before and end of the treatment period, the volume of the endometriotic lesions was measured. The pathological morphology, angiogenesis, and the number of autophagosomes of the endometriotic lesion were observed by hematoxylin and eosin staining, immunohistochemistry, and transmission electron microscope, respectively. The cell viability, apoptosis, and angiogenesis of HUVECs were detected by MTT, flow cytometry, and lumen formation experiment, respectively. The expression levels of VEGF, autophagy-/apoptosis-/PPARγ/NF-κB- pathway-related proteins in endometrium tissues or HUVECs were detected by western blot assays.

The autophagy agonist rapamycin reduced the lesion size, the microvessel density, and VEGF expression, and promoted the production of autophagosomes and the expression of autophagy-related proteins, while the autophagy inhibitor chloroquine had the opposite effects. In vivo, NYPQ could dose-dependently reduce lesion volume and microvessel density, ameliorate histopathological features and promote autophagosome production of ectopic endometrium. Moreover, serum-containing NYPQ could significantly inhibit the cell viability and tube formation of HUVECs and elevate HUVECs apoptosis. Besides, NYPQ significantly reduced VEGF and promoted autophagy-/apoptosis-related protein expressions. Also, NYPQ might promote autophagy and inhibit angiogenesis by activating the PPARγ/NF-κB pathway.

Collectively, these findings indicate that NYPQ has therapeutic potential in experimentally induced peritoneal endometriosis, and its mechanism may be related to the activation of the PPARγ/NF-κB signaling pathway. Similar content being viewed by others

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Cancer Cell Int 21(1):188. https://doi.org/10.1186/s12935-021-01892-1 Funding This study was supported by the Natural Science Foundation of Zhejiang Province, China (no. LQ20H270003); National Natural Science Foundation of China (no. 82104909); Traditional Chinese Medicine Administration Project of Zhejiang Province, China (no. 2022ZB128); Health Commission Project of Zhejiang Province, China (no. 2020ZY664) and Science and Technology Project of Jinhua, Zhejiang province, China (2019-4-159). Author information Authors and Affiliations Contributions YG and HDY: initiated this study and designed the experiments. HDY, QFZ, HL, XQX: performed experiments and XLJ analyzed the data. HDY and HL: wrote the manuscript. YG reviewed the manuscript. All authors read the manuscript and approved it. Corresponding author Ethics declarations Conflict of interest All authors declare that they have no conflicts of interest. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Yang, HD., Zhu, QF., Li, H. et al. Effect of Neiyi Prescription of QIU on autophagy and angiogenic ability of endometriosis via the PPARγ/NF-κB signaling pathway. Arch Gynecol Obstet 306, 533–545 (2022). https://doi.org/10.1007/s00404-022-06537-w Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00404-022-06537-w