Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, 48 Wojska Polskiego St., 60-627 Poznan, Poland.
Department of Cancer Immunology, Poznan University of Medical Sciences, Garbary 15 St., 61-866 Poznan, Poland.
Nutrients. 2024 Oct 14;16(20):3483. doi: 10.3390/nu16203483.
Inflammation and immune cell dysfunction are critical facilitators of endometriosis pathophysiology. Macrophages are renowned for stimulating lesion growth, vascularization, innervation, and pain generation. By combining macrophages and endometriotic cells, we determined if resveratrol and its natural analogs can target the immune dysregulation and oxidative imbalance in endometriosis. After treatment with compounds (5, 10, 25 µM), we evaluated the expression of key inflammatory and oxidative stress markers, cytokines release, and ROS production by applying q-PCR, ELISA, Cytometric Beads Array, and multiplexed fluorogenic staining and flow cytometry analysis with bioimaging. The results showed that endometriosis-related macrophages treated with stilbenes have impaired expression of pro-inflammatory markers (, , , , , , ). The effect of resveratrol, pterostilbene, and piceatannol was observed, especially in reducing , , and genes up to 3.5-, 5-, and 7.7-fold at 25 µM, respectively. Also, with piceatannol or polydatin exposure, the IL-6 decrease was noticeable. This study reported an antioxidant effect by reducing ROS-positive cells from 96% to 48% by pterostilbene. Results from flow cytometry correlated with the transcript activation of detoxification enzymes (, ). Prospects for potential therapy based on regulating the immune microenvironment and reducing the accumulation of free radicals with stilbenes application were described in the article.
炎症和免疫细胞功能障碍是子宫内膜异位症病理生理学的关键促进因素。巨噬细胞以刺激病变生长、血管生成、神经支配和疼痛产生而闻名。通过将巨噬细胞和子宫内膜异位细胞结合，我们确定白藜芦醇及其天然类似物是否可以靶向子宫内膜异位症中的免疫失调和氧化失衡。在用化合物（5、10、25 μM）处理后，我们通过 q-PCR、ELISA、流式细胞术分析和生物成像的 Cytometric Beads Array 和多重荧光染色评估了关键炎症和氧化应激标志物的表达、细胞因子释放和 ROS 产生。结果表明，用白藜芦醇类似物处理的与子宫内膜异位症相关的巨噬细胞表现出促炎标志物（、、、、、）表达受损。观察到白藜芦醇、紫檀芪和白皮杉醇的作用，尤其是在 25 μM 时，分别将、和基因的表达降低至 3.5、5 和 7.7 倍。此外，用白皮杉醇或虎杖苷处理可显著降低 IL-6。本研究报道了一种抗氧化作用，通过紫檀芪将 ROS 阳性细胞从 96%减少至 48%。流式细胞术的结果与解毒酶的转录激活（、）相关。文章描述了基于调节免疫微环境和减少白藜芦醇类似物应用中自由基积累的潜在治疗前景。
