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消症丸通过Raf/ERK/ELK和HIF-1α/bFGF信号通路发挥抗乳腺增生作用。

Xiaozheng pill exerts an anti-mammary hyperplasia effect through Raf/ERK/ELK and HIF-1α/bFGF pathways.

作者信息

Liu Yu-Fei, An Tian, Yu Hong, Fan Ying-Yi, Pei Xiao-Hua

机构信息

Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China.

Department of General Surgery, Tsinghua University Yuquan Hospital, Beijing, China.

出版信息

J Tradit Complement Med. 2023 Jun 7;13(6):600-610. doi: 10.1016/j.jtcme.2023.05.002. eCollection 2023 Nov.

DOI:10.1016/j.jtcme.2023.05.002
PMID:38020551
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10658343/
Abstract

BACKGROUND AND AIM

The purpose of this study is to explore whether the Xiaozheng pill (XZP) has the effect of anti-hyperplasia of mammary glands (HMG) and to identify the related signaling pathways.

EXPERIMENTAL PROCEDURE

We analyzed the effective chemical components of the XZP, as well as the key chemical components, key proteins, main biological processes, and pathways in the treatment of HMG; Secondly, the levels of Estradiol (E2), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Progesterone (P), Raf/ERK/ELK and HIF-1α/bFGF pathways related proteins were detected; Finally, the effect of XZP on metabolites was analyzed by metabolomics.

RESULTS AND CONCLUSION

In this study, we identified key targets and pathways for XZP therapy of HMG, including EGFR, VEGFA, ER, and Ras signaling pathways. Animal experiments show that XZP can reduce the levels of E2, LH, and FSH and increase the expression of P in HMG mice. XZP can restore the normal structure of breast tissue and reduce ERα, ERβ, and PR expression in breast tissue. In addition, metabolomics results show that XZP also regulates HMG metabolites, including HIF-1α and metabolic pathways. The Western blot results showed that XZP intervention can reduce the protein expression of -Raf1, Raf1, -ERK1/2, ERK1/2, ELK, HIF-1α, and bFGF in the breast tissue of HMG mice. XZP may eliminate abnormal breast hyperplasia through inhibition of apoptosis and angiogenesis, which may be linked with the regulation of the Raf/ERK/ELK and HIF-1α/bFGF signaling pathways in HMG mice. These results suggest that XZP treatment may be beneficial for the management of HMG.

摘要

背景与目的

本研究旨在探讨消症丸(XZP)是否具有抗乳腺增生(HMG)的作用,并确定相关信号通路。

实验过程

我们分析了XZP的有效化学成分,以及治疗HMG的关键化学成分、关键蛋白、主要生物学过程和通路;其次,检测雌二醇(E2)、促卵泡激素(FSH)、促黄体生成素(LH)、孕酮(P)、Raf/ERK/ELK和HIF-1α/bFGF通路相关蛋白的水平;最后,通过代谢组学分析XZP对代谢物的影响。

结果与结论

在本研究中,我们确定了XZP治疗HMG的关键靶点和通路,包括表皮生长因子受体(EGFR)、血管内皮生长因子A(VEGFA)、雌激素受体(ER)和Ras信号通路。动物实验表明,XZP可降低HMG小鼠体内E2、LH和FSH的水平,并增加P的表达。XZP可恢复乳腺组织的正常结构,并降低乳腺组织中雌激素受体α(ERα)、雌激素受体β(ERβ)和孕激素受体(PR)的表达。此外,代谢组学结果表明,XZP还可调节HMG代谢物,包括HIF-1α和代谢通路。蛋白质免疫印迹结果显示,XZP干预可降低HMG小鼠乳腺组织中-Raf1、Raf1、-ERK1/2、ERK1/2、ELK、HIF-1α和bFGF的蛋白表达。XZP可能通过抑制细胞凋亡和血管生成来消除异常乳腺增生,这可能与调节HMG小鼠体内的Raf/ERK/ELK和HIF-1α/bFGF信号通路有关。这些结果表明,XZP治疗可能对HMG的治疗有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/852e/10658343/79f952df9168/gr8.jpg
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