Ding Jie, Mei Shanshan, Cheng Wen, Ni Zhexin, Yu Chaoqin
Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital Affiliated to Navy Medical University (Second Military Medical University) Shanghai 200433, China.
Department of Gynecology of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine Shanghai 201203, China.
Am J Transl Res. 2022 Apr 15;14(4):2184-2198. eCollection 2022.
The aim of this study was to investigate whether curcumin has a therapeutic effect on endometriosis (EM) and to determine the specific mechanism.
Network pharmacology was used to obtain the core targets of curcumin for the treatment of EM and the specific biologic processes involved. A mouse model of EM was constructed and divided into different groups, as follows: control, negative control, curcumin, and denogestrel. The number, volume, and degree of adhesions of the lesions in each group were measured. The levels of IL-1β, IL-6, and VEGFA in the peritoneal cavity were measured by enzyme-linked immunosorbent assay (ELISA). Western blot and Q-PCR were used to detect HIF-1α and VEGFA proteins and gene expression levels in the lesion tissues.
Network pharmacology suggested that curcumin treated EM through the HIF signaling pathway, of which IL-6, HIF-1α, and VEGFA are key targets. The number of lesions, volume, and degree of adhesions were significantly reduced in the curcumin group compared to the negative control group and the control group (P < 0.05). IL-6, IL-1β, and VEGFA levels were reduced in the peritoneal fluid (P < 0.05). HIF-1α and VEGFA protein and gene levels were significantly reduced in the lesions (P < 0.05). No modulation of HIF-1α was shown by denogestins.
Curcumin played a role in the treatment of EM by modulating the HIF signaling pathway, improving the local hypoxia of the lesion, and reducing the inflammatory state of EM.
本研究旨在探讨姜黄素对子宫内膜异位症（EM）是否具有治疗作用，并确定其具体机制。
采用网络药理学方法获取姜黄素治疗EM的核心靶点及涉及的具体生物学过程。构建EM小鼠模型并分为不同组，如下：对照组、阴性对照组、姜黄素组和地诺孕素组。测量每组病变的数量、体积和粘连程度。采用酶联免疫吸附测定（ELISA）法检测腹腔中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和血管内皮生长因子A（VEGFA）的水平。采用蛋白质免疫印迹法（Western blot）和实时荧光定量聚合酶链反应（Q-PCR）检测病变组织中缺氧诱导因子-1α（HIF-1α）和VEGFA蛋白及基因表达水平。
网络药理学提示姜黄素通过HIF信号通路治疗EM，其中IL-6、HIF-1α和VEGFA是关键靶点。与阴性对照组和对照组相比，姜黄素组的病变数量、体积和粘连程度均显著降低（P<0.05）。腹腔液中IL-6、IL-1β和VEGFA水平降低（P<0.05）。病变组织中HIF-1α和VEGFA蛋白及基因水平显著降低（P<0.05）。地诺孕素未显示对HIF-1α有调节作用。
姜黄素通过调节HIF信号通路、改善病变局部缺氧状态及减轻EM的炎症状态，在EM治疗中发挥作用。
