Saikosaponin d (SSD) alleviates diabetic peripheral neuropathy by regulating the AQP1/RhoA/ROCK signaling in streptozotocin-induced diabetic rats

Aims Diabetic peripheral neuropathy (DPN) is one of the most important complications of diabetes with a poor prognosis. Saikosaponin d (SSD) is a triterpenoid saponin isolated from Radix Bupleuri that has multiple pharmacological activities. However, whether SSD affects DPN is unclarified. Methods Sprague Dawley rats were treated with streptozotocin (STZ) and high-fat diet (HFD) to induce DPN, in the presence or absence of SSD, with or without transfection of lentivirus vectors carrying siRNA targeting aquaporin 1 (si-AQP1). The body weight, plasma glucose levels, mechanical and thermal hyperalgesia, and nerve conductive velocity (NCV) of rats were measured. Hematoxylin–Eosin staining was used for histopathological observation of sciatic nerves. RT-qPCR and western blotting were utilized for measuring expression levels of AQP1 and ras homolog family member A/Rho-associated protein kinase (RhoA/ROCK) signaling pathway-related markers in dorsal root ganglion (DRG) of rats. Results SSD increased the body weight, decreased plasma glucose levels, attenuated mechanical and thermal hyperalgesia, enhanced NCV and reduced proinflammatory cytokine levels in DPN rats. AQP1 displayed a high level in DPN rats and SSD treatment repressed the expression of AQP1. SSD enhanced the protective effect of AQP1 knockdown on the pathological changes of DPN. AQP1 depletion suppressed the activation of RhoA/ROCK signaling pathway in DPN rats. Conclusion SSD alleviates STZ/HFD-induced DPN in rats by inhibiting the AQP1/RhoA/ROCK signaling pathway.