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Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats

Background and aims: Pelvic inflammatory disease (PID) is infection-induced inflammation of the female upper reproductive tract that results in high fever, ectopic pregnancy, infertility, and varying degrees of chronic pelvic pain. Recent clinical studies have shown that Kangfuxiaoyanshuan (KFXYS),...

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Autores principales: Fan, Linyuan, Liu, Zhaohui, Zhang, Zhan, Li, Ting, Zong, Xiaonan, Bai, Huihui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340273/
https://www.ncbi.nlm.nih.gov/pubmed/35924054
http://dx.doi.org/10.3389/fphar.2022.894149
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author Fan, Linyuan
Liu, Zhaohui
Zhang, Zhan
Li, Ting
Zong, Xiaonan
Bai, Huihui
author_facet Fan, Linyuan
Liu, Zhaohui
Zhang, Zhan
Li, Ting
Zong, Xiaonan
Bai, Huihui
author_sort Fan, Linyuan
collection PubMed
description Background and aims: Pelvic inflammatory disease (PID) is infection-induced inflammation of the female upper reproductive tract that results in high fever, ectopic pregnancy, infertility, and varying degrees of chronic pelvic pain. Recent clinical studies have shown that Kangfuxiaoyanshuan (KFXYS), a Traditional Chinese Medicine (TCM) formulation, may short the course of the disease and reduce the occurrence of PID sequelae, but its pharmacological action and potential mechanism have not been fully elucidated. Here, we aimed to investigate the therapeutic effects and mechanism of KFXYS in rats with PID. Materials and Methods: A PID rat model was constructed through endometrial mechanical injury and pathogen infection. The rectal temperature was measured during the 14-days course of treatment, and the white blood cell (WBC) count in the blood and the levels of cytokines (IFN-γ, IL-1β, IL-4, TNF-α) in the serum were evaluated by ELISA. Hematoxylin and eosin (HE) staining was performed to analyze pathological changes, and transmission electron microscopy (TEM) was used to observe ultrastructural changes. The p-p65/p65 protein expression was evaluated by western blotting and the levels of MMP-2 and TGF-β in adhesion tissues were assessed by immunohistochemistry. Results: KFXYS lowered the rectal temperature and the WBC counts in the blood in the acute stage of PID and alleviated inflammatory cell infiltration of the uterus, especially when combined with levofloxacin. KFXYS significantly decreased the levels of proinflammatory cytokines (IFN-γ, IL-1β, IL-4) and adhesion-related factors (TNF-α) and protected the ultrastructure of endometrial epithelial cells. Mechanistically, KFXYS inhibited the NF-κB activation by decreasing phosphorylation of p65, thus the alleviation of inflammation further reduced the expression of TGF-β and MMP-2, and inhibited the occurrence of uterine adhesions. Conclusion: These results revealed that KFXYS alleviated pelvic inflammation and effectively inhibits inflammation-associated adhesion, which indicated the potential role of KFXYS for treatment of PID and the prevention of PID sequelae.
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spelling pubmed-93402732022-08-02 Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats Fan, Linyuan Liu, Zhaohui Zhang, Zhan Li, Ting Zong, Xiaonan Bai, Huihui Front Pharmacol Pharmacology Background and aims: Pelvic inflammatory disease (PID) is infection-induced inflammation of the female upper reproductive tract that results in high fever, ectopic pregnancy, infertility, and varying degrees of chronic pelvic pain. Recent clinical studies have shown that Kangfuxiaoyanshuan (KFXYS), a Traditional Chinese Medicine (TCM) formulation, may short the course of the disease and reduce the occurrence of PID sequelae, but its pharmacological action and potential mechanism have not been fully elucidated. Here, we aimed to investigate the therapeutic effects and mechanism of KFXYS in rats with PID. Materials and Methods: A PID rat model was constructed through endometrial mechanical injury and pathogen infection. The rectal temperature was measured during the 14-days course of treatment, and the white blood cell (WBC) count in the blood and the levels of cytokines (IFN-γ, IL-1β, IL-4, TNF-α) in the serum were evaluated by ELISA. Hematoxylin and eosin (HE) staining was performed to analyze pathological changes, and transmission electron microscopy (TEM) was used to observe ultrastructural changes. The p-p65/p65 protein expression was evaluated by western blotting and the levels of MMP-2 and TGF-β in adhesion tissues were assessed by immunohistochemistry. Results: KFXYS lowered the rectal temperature and the WBC counts in the blood in the acute stage of PID and alleviated inflammatory cell infiltration of the uterus, especially when combined with levofloxacin. KFXYS significantly decreased the levels of proinflammatory cytokines (IFN-γ, IL-1β, IL-4) and adhesion-related factors (TNF-α) and protected the ultrastructure of endometrial epithelial cells. Mechanistically, KFXYS inhibited the NF-κB activation by decreasing phosphorylation of p65, thus the alleviation of inflammation further reduced the expression of TGF-β and MMP-2, and inhibited the occurrence of uterine adhesions. Conclusion: These results revealed that KFXYS alleviated pelvic inflammation and effectively inhibits inflammation-associated adhesion, which indicated the potential role of KFXYS for treatment of PID and the prevention of PID sequelae. Frontiers Media S.A. 2022-07-18 /pmc/articles/PMC9340273/ /pubmed/35924054 http://dx.doi.org/10.3389/fphar.2022.894149 Text en Copyright © 2022 Fan, Liu, Zhang, Li, Zong and Bai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Fan, Linyuan
Liu, Zhaohui
Zhang, Zhan
Li, Ting
Zong, Xiaonan
Bai, Huihui
Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats
title Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats
title_full Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats
title_fullStr Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats
title_full_unstemmed Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats
title_short Kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting NF-κB p65 and TGF-β/MMP-2 signaling pathway in pelvic inflammatory disease rats
title_sort kangfuxiaoyanshuan alleviates uterine inflammation and adhesion via inhibiting nf-κb p65 and tgf-β/mmp-2 signaling pathway in pelvic inflammatory disease rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340273/
https://www.ncbi.nlm.nih.gov/pubmed/35924054
http://dx.doi.org/10.3389/fphar.2022.894149
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