Salvianolic acid B attenuates diabetic nephropathy through alleviating ADORA2B, NALP3 inflammasome, and NFκB activity

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 hours. 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-week of Sal B treatment, db/db mice blood and kidney tissue were harvested for biochemical detection with H&E, Masson’s, PAS and Sirius red staining and detection of ADORA2B, NALP3, NFκB, interleukin 1β (IL-1β) and Toll-like receptor 4 (TLR4) activity. NFκB, IL-1β and TLR4 as well as increased MMP levels and decreased intracellular ROS generation in HK-2 cells with HG exposure. Sal B-treated diabetic mice had the improvement in body weight, water intake, hyperglycemia, hyperlipidemia, 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.