Diabetic nephropathy is one of the microvascular complications of diabetes. This study is aimed at investigating the role and mechanisms of salvianolic acid B (Sal B) in diabetic nephropathy. High glucose (HG)-induced human renal tubular epithelial HK-2 cells were treated with Sal B, BAY-60-6583 (agonist of adenosine 2B receptor), or PSB-603 (antagonist of adenosine 2B receptor) for 24 h. Adenosine A2b receptor (ADORA2B), NACHT, leucine-rich repeat (LRR), and pyrin (PYD) domains-containing protein 3 (NALP3), and nuclear factor Kappa B (NFκB) expressions, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels were examined. Following 6 weeks of Sal B treatment, db/db mice blood and kidney tissue were harvested for biochemical detection with hematoxylin-eosin (H&E), Masson's, periodic acid schiff (PAS), and Sirius red staining and detection of ADORA2B, NALP3, NFκB, interleukin 1β (IL-1β), and toll-like receptor 4 (TLR4) activity. NFκB, NALP3, and ADORA2B were found to be downregulated in Sal B treated HK-2 cells exposed to high glucose (HG), accompanied by elevated levels of MMPs and reduced intracellular ROS production. Sal B-treated diabetic mice had the improvement in body weight, water intake, hyperglycemia, hyperlipidemia, and liver and kidney function. Altogether, Sal B attenuates HG-induced kidney tubule cell injury and diabetic nephropathy in diabetic mice, providing clues to other novel mechanisms by which Sal B is beneficial in diabetic nephropathy.
Keywords: ADORA2B; diabetic nephropathy; mitochondrial membrane potential; reactive oxygen species; salvianolic acid B.