期刊
PHYTOTHERAPY RESEARCH
卷 36, 期 6, 页码 2511-2523出版社
WILEY
DOI: 10.1002/ptr.7465
关键词
diabetic nephropathy; inflammation; mitogen-activated protein kinase; nuclear factor kappa B; sclareol
资金
- National Natural Science Foundation of China [21961142009, 31900381]
- Basic Scientific Research Project of Hangzhou Medical College [KYYB202114, KYZD202102]
- Natural Science Foundation of Zhejiang Province [LGJ18H310002]
- Wenzhou Science and Technology Key Project [2018ZY009]
- Zhejiang Provincial Key Scientific Project [2021C03041]
Sclareol may prevent and ameliorate diabetic nephropathy through its anti-inflammatory effects, which involve the regulation of the MAPK/NFKB signaling pathway.
Diabetic nephropathy (DN) represents the most serious complication of diabetes. Previous studies have shown that the activation of nuclear factor kappa B (NF-kappa B) 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-kappa B 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-kappa B inhibitions. In particular, MAPKs inhibitors mixture could suppress the NF-kappa B 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-kappa B signaling pathway. Sclareol may be a promising agent for preventing the progression of DN.
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