Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway

Abstract

Context Kirenol possesses anti-inflammatory, antifibrotic and anti-arthritic effects. However, its reno-protective effects against diabetic nephropathy (DN) have not been evaluated. Objective This study explores the reno-protective effects of kirenol against DN and clarifies the potential mechanisms. Materials and methods The mesangial cells were treated with 20 µM kirenol and 10 ng/mL human recombinant TGF-β1 or 30 mM glucose for 24 h. Then the cells were harvested to assay the expression of the target genes or proteins. Thirty C57BL/6J male mice were given high-fat diet with streptozotocin injection to induce diabetes and then were randomized into three groups ( n = 10): vehicle administration (DM group), 2 mg/kg kirenol (DM + kirenol group) and 200 mg/kg metformin (Met group) for 3 months, orally. A healthy group (Con, n = 10) was included as the control. Results Compared to the DM group, kirenol treatment decreased the phosphorylation of Smad2/3 and NF-κB (0.64- and 0.43-fold) as well as the accumulation of FN and Col IV (0.58- and 0.35-fold); moreover, the expression of IκBα was restored to normal level by kirenol treatment both in vivo and in vitro . After kirenol treatment, IL-6 expression was decreased 0.35- and 0.57-fold, and TNF-α expression was decreased 0.34- and 0.46-fold, in vitro and in vivo , respectively. Furthermore, kirenol alleviated the glomerular basement membrane thickness and foot process fusion. Discussion and conclusions Kirenol could alleviate DN by downregulating the TGF-β/Smads and the NF-κB signal pathway. Our study provides a potential mechanism for the treatment of DN with kirenol.

Astragalus Polysaccharide Ameliorates Renal Inflammatory Responses in a Diabetic Nephropathy by Suppressing the TLR4/NF-κB Pathway

“…Recent evidence has indicated that some inflammatory cytokines such as IL-1β, IL-6, MCP-1, TNF-α, and TGF-β1 played a critical role in hyperglycaemia-induced renal injury. 14 , 15 Therefore, inhibiting inflammatory responses and reducing the expression of cytokines will effectively improve renal injury and enhance renal function in DN. Previous researches have demonstrated that TLR4/NF-κB as crucial pathway had played crucial role in the DN by mediating immune inflammatory response.…”