Salvianolic Acid A Alleviates Sciatic Nerve Injury in Rats Via Inhibiting NLRP3 Inflammasome Through the Activation of Schwann Cells Autophagy

Salvianolic acid A (SalA) is a phenolic acid of Salvia miltiorrhiza with the effects of anti-oxidant and immunoenhancing medicinal properties. In this study, we investigated the activities of SalA on the neurorestorative function and the autophagy-regulated NLRP3 inflammasome in sciatic nerve injury (SNI) rats and schwann cells. Sciatic nerve compression model rats were constructed, the sciatic nerve function index and gastrocnemius muscle mass ratio were used to detect the recovery of motor function. The effect of SalA on repairing pathological injured nerves was evaluated by H&E staining and masson staining, toluidine blue staining and TEM were used to analyze the myelin removal ability. Western blotting and immunohistochemistry were used to identify the expression of NLRP3 inflammasome, autophagy-related proteins and myelin proteins in the injured area. Moreover, the modulatory effects of SalA on cellular antioxidant capacity and damage were investigated by appending the autophagy inhibitor 3-MA based on LPS-treated RSC96 cells. SalA promoted the recovery of motor nerve function after injury, increased the number of myelinated nerve regeneration and improved the damaged myelin sheath structure. SalA administration could increase MBP, NF200 and Beclin-1 expression, reduce the NLRP3/pro-caspase1/ASC signaling pathway in SNI rats, up-regulate LC3 level in RSC96 cells. SalA increased cell survival and decreased inflammatory factors production, which was reversed by 3-MA. SalA restores neuromotor function after nerve crush injury by accelerating early myelin degradation and promoting proliferation. In addition, SalA inhibits neuroinflammation and apoptosis by reducing the activation of NLRP3 inflammasome, and autophagy-related signaling pathways may be potential regulatory targets (graphical abstract).