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

• Main Authors: Jialin Li (Author), Jiawen Zhang (Author), Meng Yang (Author), Xiaocui Huang (Author), Meng Zhang (Author), Xiansong Fang (Author), Suzhen Wu (Author)
• Format: Book
• Published: Taylor & Francis Group, 2022-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1080/13880209.2022.2112239; 1744-5116; 1388-0209
• Keywords: TNF-α; IL-6; mesangial cells; fibronectin; collagen IV; Therapeutics. Pharmacology; RM1-950
• Source: Pharmaceutical Biology, Vol 60, Iss 1, Pp 1690-1700 (2022)

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.