Ergothioneine (ET) is a naturally occurring antioxidant that is synthesized by non-yeast fungi and certain bacteria. ET is not synthesized by animals, including humans, but is avidly taken up from the diet, especially from mushrooms. In the current study, we elucidated the effect of ET on the hCMEC/D3 human brain endothelial cell line. Endothelial cells are exposed to high levels of the cholesterol oxidation product, 7-ketocholesterol (7KC), in patients with cardiovascular disease and diabetes, and this process is thought to mediate pathological inflammation. 7KC induces a dose-dependent loss of cell viability and an increase in apoptosis and necrosis in the endothelial cells. A relocalization of the tight junction proteins, zonula occludens-1 (ZO-1) and claudin-5, towards the nucleus of the cells was also observed. These effects were significantly attenuated by ET. In addition, 7KC induces marked increases in the mRNA expression of pro-inflammatory cytokines, IL-1β IL-6, IL-8, TNF-α and cyclooxygenase-2 (COX2), as well as COX2 enzymatic activity, and these were significantly reduced by ET. Moreover, the cytoprotective and anti-inflammatory effects of ET were significantly reduced by co-incubation with an inhibitor of the ET transporter, OCTN1 (VHCL). This shows that ET needs to enter the endothelial cells to have a protective effect and is unlikely to act via extracellular neutralizing of 7KC. The protective effect on inflammation in brain endothelial cells suggests that ET might be useful as a nutraceutical for the prevention or management of neurovascular diseases, such as stroke and vascular dementia. Moreover, the ability of ET to cross the blood-brain barrier could point to its usefulness in combatting 7KC that is produced in the CNS during neuroinflammation, e.g. after excitotoxicity, in chronic neurodegenerative diseases, and possibly COVID-19-related neurologic complications.

麦角硫因 (ET) 是一种天然存在的抗氧化剂，由非酵母真菌和某些细菌合成。ET 不是由包括人类在内的动物合成，而是从饮食中大量摄取，尤其是从蘑菇中摄取。在目前的研究中，我们阐明了 ET 对 hCMEC/D3 人脑内皮细胞系的影响。心血管疾病和糖尿病患者的内皮细胞暴露于高水平的胆固醇氧化产物 7-酮胆固醇 (7KC)，这一过程被认为可介导病理性炎症。7KC 诱导细胞活力的剂量依赖性丧失以及内皮细胞凋亡和坏死的增加。还观察到紧密连接蛋白 zonula occludens-1 (ZO-1) 和 claudin-5 向细胞核的重新定位。ET显着减弱了这些影响。此外，7KC 诱导促炎细胞因子、IL-1β、IL-6、IL-8、TNF-α 和环氧合酶-2 (COX2) 的 mRNA 表达以及 COX2 酶活性显着增加，这些均显着增加。由 ET 减少。此外，通过与 ET 转运蛋白 OCTN1 (VHCL) 抑制剂共孵育，ET 的细胞保护和抗炎作用显着降低。这表明 ET 需要进入内皮细胞才能发挥保护作用，并且不太可能通过细胞外中和 7KC 发挥作用。对脑内皮细胞炎症的保护作用表明，ET 可能可用作预防或管理神经血管疾病（如中风和血管性痴呆）的营养品。而且，