Objective: To evaluate the therapeutic potential and underlying mechanisms of action of propolis in db/db mice. Methods: The chemical composition of propolis was analyzed using UHPLC-MS/MS. Thirty mice, including six wt/wt and 24 db/db mice, were randomly assigned to four groups (n = 6 per group): control, model, metformin (250 mg/kg), low dose propolis (100 mg/kg), and high dose propolis (HDP; 400 mg/kg). Treatments were administered orally for four weeks. Body weight and FBG levels were recorded weekly, and an oral glucose tolerance test was conducted on the 25th day. Serum levels of FIN, GSP, connecting peptide, AST, ALT, HDL, LDL, TG, and TC were quantified using ELISA. Liver histopathology was assessed using H&E and PAS staining. Western blotting was performed to examine the expression levels of NF-κB, phosphorylated NF-κB, IκBα, pIκBα, and AKT in liver tissues. Results: The top 10 metabolites of propolis were identified in positive and negative ion modes. The HDP group exhibited a significant reduction in FBG levels, body weight, connecting peptide levels, homeostatic model assessment of β-cell function scores, and homeostasis model assessment of insulin resistance scores (all P < .05). GSP levels were significantly reduced in both treatment groups (all P < .001). The HDP group also exhibited a reduction in TC and LDL levels (both P < .05), whereas HDL levels increased in both treatment groups (all P < .05). Liver weight, AST levels, and ALT levels were reduced in both treatment groups (all P < .05). Histological analysis revealed improved liver morphology. Protein analysis demonstrated downregulation of phosphorylated NF-κB and phosphorylated IκB, alongside upregulation of AKT. Conclusion Propolis exhibited significant antihyperglycemic effects in db/db mice, potentially by modulating the AKT and NF-κB signaling pathways, highlighting its potential as a therapeutic agent for diabetes management.

Diabetic nephropathy （DN） is a serious complication of diabetes， a major risk factor for chronic renal failure and end-stage renal disease， a major cause of deaths of diabetic patients， and a major cause of noncommunicable disease-associated deaths in the world. Pyroptosis and inflammasome activation are closely associated with the occurrence and development of DN. They can mediate a variety of pathological changes such as the loss and fusion of podocytes， up-regulated expression of inflammatory cytokines， macrophage infiltration， glomerular mesangial matrix expansion， and increased urinary albumin-to-creatinine ratio， eventually leading to nephron loss and kidney injury. The available studies have reported that the active ingredients in Chinese medicinal herbs or classical prescriptions play a role in the treatment of DN by lowering blood glucose and lipid levels， mitigating insulin resistance， reducing inflammation， alleviating oxidative stress， and regulating immunity. Moreover， the active ingredients can inhibit the activation of inflammasomes and the pyroptosis of renal cells， repair the inflammation-induced damage， improve renal function， and slow the progression of DN， demonstrating definite therapeutic effect. Chinese medicines can treat DN in a multi-target， multi-pathway， and multi-system manner， possessing broad prospects in the prevention and treatment of DN. Despite the extensive studies about the traditional Chinese medicine （TCM） intervention of DN in vivo and in vitro， a comprehensive summary of experimental studies on the TCM intervention of DN model remains to be carried out. This paper reviews the research progress in pyroptosis， inflammasomes， roles of pyroptosis and inflammasomes in DN， and TCM intervention of DN， aiming to provide ideas and reference for the research and development of drugs for this disease.