Acacetin Prevents Renal Damage Induced by Streptozotocin via Altering the NF‐κB/ASC/NLRP3 and AMPK/SIRT1 Pathways in Mice

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease. Its pathogenesis includes inflammation, an excess of reactive oxygen species, and kidney damage. The present study intended to explore the nephroprotective effects of acacetin (ACN) in streptozotocin-induced diabetic animals. The following are the experimental groups: One millilitre of 0.9% saline was given to Group I (control), Streptozotocin (STZ) (diabetic animals) + 0.9% saline to Group II (DN group) (negative control), DN + ACN (15 mg/kg body weight [bw]) to Group III, and DN + Valsartan (150 mg/kg bw) to Group IV. According to the findings, ACN decreased the levels of glucose, serum creatinine (Scr), blood urea nitrogen (BUN), malondialdehyde (MDA), and proinflammatory cytokines while increasing the bw, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in comparison to the DN animals. The histopathological analysis revealed that the animals treated with ACN showed recovery of renal damage in the tissues caused by STZ. In the STZ-induced DN mice, ACN reduced renal damage by upregulating the proteins of 5' adenosine monophosphate-activated protein kinase (AMPK), p-AMPK, and SIRT1 and downregulating the proteins of TGF-β, COL-1, COL-IV, NF-κB, ASC, NLRP3, and GSDMD, according to western blot analysis. Hence, the current study demonstrated that the regulation of the AMPK/SIRT1 and NF-κB/ASC/NLRP3 inflammasome pathways in DN mice was responsible for the protective effects of ACN. ACN may therefore be a viable treatment option for DN.