Yu Qinyao, Li Mengqing, Anayyat Umer, Zhou Cai, Nie Shenglan, Yang Hua, Chen Fengyi, Xu Shuling, Wei Yunpeng, Wang Xiaomei
School of Pharmacy, Shenzhen University, Shenzhen, Guangdong, 518061, China.
School of Basic Medical Sciences, Shenzhen University, Shenzhen, Guangdong, 518061, China.
Heliyon. 2024 Aug 10;10(16):e36063. doi: 10.1016/j.heliyon.2024.e36063. eCollection 2024 Aug 30.
Multiple sclerosis (MS) is a chronic autoimmune disease in the central nervous system. Forskolin (FSK) is a plant-derived diterpene with excellent immunomodulatory properties and has not been systematically reported for treating MS. This study investigated the therapeutic effects of FSK on cellular and animal MS models and preliminarily explored related mechanisms. The results showed that FSK suppressed the inflammatory response, reduced the expression of STEAP4, and relieved iron deposition in BV-2 cells pretreated by LPS at the cellular level. Meanwhile, at the animal level, FSK treatment halted the progression of experimental autoimmune encephalomyelitis (EAE), alleviated the damage at the lesion sites, reduced the concentration of proinflammatory factors in peripheral blood, and inhibited the immune response of peripheral immune organs in EAE mice. Besides, FSK treatment decreased the expression of STEAP4 in the spinal cord and effectively restored the iron balance in the brain, spinal cord, and serum of EAE mice. Further investigation showed that FSK can reduce IL-17 expression, prevent the differentiation of TH17 cells, and inhibit the calcium signaling pathway. Thus, these results demonstrate that FSK may have the potential to treat MS clinically.
多发性硬化症（MS）是一种中枢神经系统的慢性自身免疫性疾病。福斯可林（FSK）是一种植物来源的二萜，具有出色的免疫调节特性，尚未有关于其治疗MS的系统性报道。本研究调查了FSK对细胞和动物MS模型的治疗效果，并初步探索了相关机制。结果表明，在细胞水平上，FSK抑制了LPS预处理的BV-2细胞中的炎症反应，降低了STEAP4的表达，并减轻了铁沉积。同时，在动物水平上，FSK治疗阻止了实验性自身免疫性脑脊髓炎（EAE）的进展，减轻了病变部位的损伤，降低了外周血中促炎因子的浓度，并抑制了EAE小鼠外周免疫器官的免疫反应。此外，FSK治疗降低了EAE小鼠脊髓中STEAP4的表达，并有效恢复了脑、脊髓和血清中的铁平衡。进一步研究表明，FSK可降低IL-17表达，阻止TH17细胞分化，并抑制钙信号通路。因此，这些结果表明FSK可能具有临床治疗MS的潜力。
