糖尿病肾病(DN)是糖尿病最严重的并发症。以往的研究表明,在DN的发展过程中,核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)的活化与炎症有关。香雷醇,一种天然的二萜化合物,对炎症有有益作用。因此,我们假设香雷醇可能通过抗炎作用预防DN.本研究旨在探讨香雷酚在DN进展中的作用。并探讨了相关的分子机制。斯雷罗治疗显著缓解肾功能不全,纤维化,和炎症细胞因子水平在糖尿病小鼠中呈剂量依赖性。此外,香紫苏醇抑制糖尿病肾组织中MAPKs和NF-κB的激活。在SV40细胞中的高水平葡萄糖下,证实了香雷醇的治疗作用,和香雷醇预防高糖诱导的纤维化和炎症反应,这主要是由MAPK和NF-κB抑制驱动的。特别是,MAPKs抑制剂混合物可以抑制NF-κB途径和香紫苏醇参与的炎性细胞因子的释放。总之,香雷醇对糖尿病引起的肾功能障碍有好处,通过MAPK/NF-κB信号通路的介导部分与纤维化和炎症的改善有关。香雷醇可能是预防DN进展的有前途的药物。
Diabetic nephropathy (DN) represents the most serious complication of diabetes. Previous studies have shown that the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) are linked to inflammation in the development of DN.
Sclareol, a natural diterpene compound, has beneficial effects on inflammation. Thus, we hypothesized that
sclareol might prevent DN via anti-inflammatory actions. This study aimed to investigate the actions of sclareol in the progression of DN, and explored the related molecular mechanism. Sclareol treatment significantly alleviated renal dysfunction, fibrosis, and inflammatory cytokine levels in a dose-dependent manner in diabetic mice. Moreover,
sclareol inhibited the activations of MAPKs and NF-κB in diabetic kidney tissues. The therapeutic effects of
sclareol were confirmed under high levels of glucose in SV40 cells, and
sclareol prevented high glucose-induced fibrosis and inflammatory responses, which was largely driven by MAPKs and NF-κB inhibitions. In particular, MAPKs inhibitors mixture could suppress the NF-κB pathway and release of inflammatory cytokines that sclareol was involved in. In conclusion, sclareol has benefits for diabetes-induced renal dysfunction, which was partially associated with amelioration of fibrosis and inflammation via mediation of the MAPK/NF-κB signaling pathway.
Sclareol may be a promising agent for preventing the progression of DN.