Paris polyphylla ethanol extract and polyphyllin I ameliorate adenomyosis by inhibiting epithelial-mesenchymal transition.

Autor: Shi YX; First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China., Xu L; Department of reproductive medicine, Shandong University of Traditional Chinese Medicine Second Affiliated Hospital, Jinan 250001, China., Wang X; Department of Pharmacy, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan 250014, China., Zhang KK; Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu 610000, China., Zhang CY; Postgraduate Training Base of Linyi People's Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510000, China., Liu HY; Department of Gynecology, Linyi Central Hospital, Yishui 276400, China., Ding PP; Department of Gynecology, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan 250014, China., Shi W; First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China; Department of Gynecology, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan 250014, China. Electronic address: sw19781214@163.com., Liu ZY; Central Laboratory, Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan 250014, China; Shandong Key Laboratory of Dominant Diseases of Traditional Chinese Medicine, Jinan 250014, China. Electronic address: 71001968@sdutcm.edu.cn.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 May; Vol. 127, pp. 155461. Date of Electronic Publication: 2024 Feb 22.
DOI: 10.1016/j.phymed.2024.155461
Abstrakt: Background: The active ingredients of the Chinese medical herb Paris polyphylla, P. polyphylla ethanol extract (PPE) and polyphyllin I (PPI), potentially inhibit epithelial-mesenchymal transition (EMT) in tumors. However, the roles of these ingredients in inhibiting EMT in adenomyosis (AM) remain to be explored.
Purpose: The primary goal of the study was to uncover the underlying molecular processes through which PPE and PPI suppress EMT in AM, alongside assessing the safety profiles of these substances.
Methods: To assess the suppressive impact of PPE on adenomyosis-derived cells (AMDCs), we employed Transwell and wound healing assays. The polyphyllins (PPI, PPII, PPVII) contained in PPE were characterized using high-performance liquid chromatography (HPLC). Then, bioinformatics techniques were performed to pinpoint potential PPI targets that could be effective in treating AM. Immunoblotting was used to verify the key proteins and pathways identified via bioinformatics. Furthermore, we examined the efficacy of PPE and PPI in treating Institute of Cancer Research (ICR) mice with AM by observing the morphological and pathological features of the uterus and performing immunohistochemistry. In addition, we assessed safety by evaluating liver, kidney and spleen pathologic features and serum test results.
Results: Three major polyphyllins of PPE were revealed by HPLC, and PPI had the highest concentration. In vitro experiments indicated that PPE and PPI effectively prevent AMDCs invasion and migration. Bioinformatics revealed that the primary targets E-cadherin, N-cadherin and TGFβ1, as well as the EMT biological process, were enriched in PPI-treated AM. Immunoblotting assays corroborated the hypothesis that PPE and PPI suppress the TGFβ1/Smad2/3 pathway in AMDCs to prevent EMT from progressing. Additionally, in vivo studies showed that PPE (3 mg/kg and 6 mg/kg) and PPI (3 mg/kg and 6 mg/kg), successfully suppressed the EMT process through targeting the TGFβ1/Smad2/3 signaling pathway. Besides, it was observed that lower doses of PPE (3 mg/kg) and PPI (3 mg/kg) exerted minimal effects on the liver, kidneys, and spleen.
Conclusions: PPE and PPI efficiently impede the development of EMT by inhibiting the TGFβ1/Smad2/3 pathway, revealing an alternative pathway for the pharmacological treatment of AM.
Competing Interests: Declaration of competing interest There are no known conflicts of interest in this publication.
(Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)
Databáze: MEDLINE
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