Salvianolic Acid A Protects the Peripheral Nerve Function in Diabetic Rats through Regulation of the AMPK-PGC1α-Sirt3 Axis

Abstract

Salvianolic acid A (SalA) is one of the main efficacious, water-soluble constituents of Salvia miltiorrhiza Bunge. This study investigated the protective effects of SalA on peripheral nerve in diabetic rats. Administration of SalA (0.3, 1 and 3 mg/kg, ig) was started from the 5th week after strepotozotocin (STZ60 mg/kg) intraperitoneal injection and continued for 8 weeks. Paw withdrawal mechanical threshold (PWMT) and motor nerve conduction velocity (MNCV) were used to assess peripheral nerve function. The western blot methods were employed to test the expression levels of serine-threonine liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), silent information regulator protein3 (sirtuin 3/Sirt3) and neuronal nitric oxide synthase (nNOS) in sciatic nerve. Results showed that SalA administration could increase PWMT and MNCV in diabetic rats; reduce the deterioration of sciatic nerve pathology; increase AMPK phosphorylation level, up-regulate PGC-1α, Sirt3 and nNOS expression, but had no influence on LKB1. These results suggest that SalA has protective effects against diabetic neuropathy. The beneficial effects of SalA on peripheral nerve function in diabetic rats might be attributed to improvements in glucose metabolism through regulation of the AMPK-PGC1α-Sirt3 axis.

Metformin attenuates hyperalgesia and allodynia in rats with painful diabetic neuropathy induced by streptozotocin

“…It was found that application of AICAR could activate AMPK, as well as decreasing oxidative stress and decreasing nociceptive response in diabetic rats. In addition, metformin and AICAR could not only activate AMPK, but also regulate the expression of AMPK target gents (PGC-1α, Sirt3 and nNOS), which has been shown to be to be involved in diabetic neuropathy (Yu et al, 2012). All those findings confirmed the involvement of AMPK activation in the decrease of oxidative stress and nociceptive response in diabetic rats.…”

PGC-1α regulation of mitochondrial degeneration in experimental diabetic neuropathy

“…A recent study reports that regulation of the AMPK- PGC-1α- sirtuin 3 axis protects peripheral nerve function in the diabetic rat (Yu et al, 2012). However, the current study presents novel evidence that loss of PGC-1α can directly cause neuropathy that is worsened by diabetes.…”

Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

“…We have summarized a few of new approaches in Table 2 [79–97]. Hopefully, some reviews in the recent years have proven positive effects of natural antioxidants and herbal products such as Satureja species and Urtica dioica in diabetes and its complications [111–116].…”