Sclareol ameliorates hyperglycemia‐induced renal injury through inhibiting the MAPK/NF‐κB 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‐κB) and mitogen‐activated protein kinase (MAPK) are linked to inflammation in the development of DN. Sclareol, a natural diterpene compound, h...

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Bibliographic Details
Published in:Phytotherapy research 2022-06, Vol.36 (6), p.2511-2523
Main Authors: Han, Xue, Zhang, Jiajia, Zhou, Li, Wei, Jiajia, Tu, Yu, Shi, Qiaojuan, Zhang, Yi, Ren, Juan, Wang, Yi, Ying, Huazhong, Liang, Guang
Format: Article
Language:English
Subjects:
Cytokines
Diabetes
Diabetes mellitus
Diabetic nephropathy
Fibrosis
Glucose
Hyperglycemia
Inflammation
Kinases
MAP kinase
mitogen‐activated protein kinase
Nephropathy
nuclear factor kappa B
Protein kinase
Renal function
sclareol
Signal transduction
Signaling
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Summary: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.
ISSN:0951-418X
1099-1573
DOI:10.1002/ptr.7465