From the Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China, XL.
Department of Chemistry and Biochemistry, University of Arizona, Tucson, USA, ZKL.
J Ethnopharmacol. 2021 Apr 6;269:113717. doi: 10.1016/j.jep.2020.113717. Epub 2020 Dec 24.
Epimedium brevicornu Maxim as a Chinese herb, is recommended for the treatment of menopausal women with hypertension for 50 years. Icariin, as the main hydrophilic ingredient of Epimedium brevicornu Maxim, has been proven to be a plant sex hormone and lower blood pressure down. Here, we hypothesized that Icariin can regulate T cells differentiation which leads to the blood pressure decrease in castrated SHR rats.
The present study aimed to investigate the effects of the exogenous estrogen, androgen and Icariin on T-cell modulation in hypertension.
Two weeks after castration, both male and female SHR rats were given estradiol, testosterone, and Icariin intervention respectively. Body weight, blood pressure, and heart rate were tested weekly. After six weeks, proportion of T helper cells (Th), cytotoxic T cells (Tc), and regulatory T cells (Tregs) in both peripheral blood mononuclear cells (PBMCs) and splenocytes were tested by flowcytometry. Serum levels of estrogen, testosterone, AngII, TNF-α, IL-17 were tested by Elisa. Aortic arches were isolated for HE and Masson staining. The expressions of ERβ and AR in aorta were tested by Western-blot.
In both male and female SHR rats, we found that Icariin and estradiol lower blood pressure, but testosterone elevates blood pressure. Similar as testosterone, Icariin can attenuate Tc and Th proportions and elevate Tregs proportion in both peripheral blood and splenocyte in male SHR, which can be blunt by flutamide. Besides, Icariin performs similar function as estradiol that attenuates Tc proportions and elevates Tregs proportion in both peripheral blood and splenocytes in female SHR, which leads to the lower blood pressure and can be partly blunt by fulvestrant. Testosterone increases AngII and TNF-α levels in serum, leading to the higher blood pressure in both male and female SHR rats.
These results verified that Icariin, as a plant sex hormone, can regulate T cells differentiation related to blood pressure decrease in SHR rats.
淫羊藿作为一种中药，被推荐用于治疗患有高血压的绝经后女性已有 50 年的历史。淫羊藿苷作为淫羊藿的主要亲水性成分，已被证明是一种植物性激素，具有降血压作用。在这里，我们假设淫羊藿苷可以调节 T 细胞分化，从而导致去势 SHR 大鼠血压下降。
本研究旨在探讨外源性雌激素、雄激素和淫羊藿苷对高血压中 T 细胞调节的影响。
去势 2 周后，雄性和雌性 SHR 大鼠分别给予雌二醇、睾酮和淫羊藿苷干预。每周测试体重、血压和心率。6 周后，通过流式细胞术检测外周血单个核细胞（PBMCs）和脾细胞中 T 辅助细胞（Th）、细胞毒性 T 细胞（Tc）和调节性 T 细胞（Tregs）的比例。通过 Elisa 检测血清中雌激素、睾酮、AngII、TNF-α、IL-17 的水平。分离胸主动脉进行 HE 和 Masson 染色。通过 Western blot 检测主动脉中 ERβ和 AR 的表达。
在雄性和雌性 SHR 大鼠中，我们发现淫羊藿苷和雌二醇可降低血压，而睾酮可升高血压。与睾酮相似，淫羊藿苷可降低雄性 SHR 大鼠外周血和脾细胞中 Tc 和 Th 的比例，升高 Tregs 的比例，该作用可被氟他胺阻断。此外，淫羊藿苷具有与雌二醇相似的功能，可降低雌性 SHR 大鼠外周血和脾细胞中 Tc 的比例，升高 Tregs 的比例，从而降低血压，该作用可被氟维司群部分阻断。睾酮可增加血清中 AngII 和 TNF-α 的水平，导致雄性和雌性 SHR 大鼠血压升高。
这些结果验证了淫羊藿苷作为一种植物性激素，可调节 T 细胞分化，与 SHR 大鼠的血压下降有关。
