Polydatin protects Schwann cells from methylglyoxal induced cytotoxicity and promotes crushed sciatic nerves regeneration of diabetic rats

Abstract

Oxidative stress plays the main role in the pathogenesis of diabetes mellitus and peripheral neuropathy. Polydatin (PD) has been shown to exhibit strong antioxidative and antiinflammatory effects. At present, no research has focused on the possible effects of PD on Schwann cells and impaired peripheral nerves in diabetic models. Here, we used an in vitro Schwann cell damage model induced by methylglyoxal and an in vivo diabetic sciatic nerve crush model to study problems in such an area. In our experiment, we demonstrated that PD potently alleviated the decrease of cellular viability, prevented reactive oxygen species generation, and suppressed mitochondrial depolarization as well as cellular apoptosis in damaged Schwann cells. Moreover, we found that PD could upregulate Nrf2 and Glyoxalase 1 (GLO1) expression and inhibit Keap1 and receptor of AGEs (RAGE) expression of damaged Schwann cells. Finally, our in vivo experiment showed that PD could promote sciatic nerves repair of diabetic rats. Our results revealed that PD exhibited prominent neuroprotective effects on Schwann cells and sciatic nerves in diabetic models. The molecular mechanisms were associated with activating Nfr2 and GLO1 and inhibiting Keap1 and RAGE.

Polydatin Alleviates Diabetes-Induced Hyposalivation through Anti-Glycation Activity in db/db Mouse

“…In this study, the accumulation of AGEs and the increased expression of RAGE in the DM group showed that the increase in glycation caused by hyperglycemia was related to salivary gland hyposalivation. There are reports about the accumulation inhibition of AGEs by resveratrol [46], the formation inhibition of polydatin's BSA-MGO reaction induced AGEs [47], and the expression inhibition of RAGE in Schwann cells of diabetic rats [48], and this study confirmed the reduction of AGEs and RAGE by polydatin in the DM + PD group, showing in addition that the improvement of diabetes-induced hyposalivation by polydatin treatment is related to the anti-glycation effect of polydatin.…”

Polydatin: Pharmacological Mechanisms, Therapeutic Targets, Biological Activities, and Health Benefits

“…As previously mentioned, polydatin exhibited analgesic effects on endometriosis, chronic pelvic pain, and dysmenorrhea [ 215 , 216 , 218 ]. In addition, polydatin ameliorated osteoarthritis [ 227 ], cystitis/bladder pain syndrome [ 231 ], and diabetic neuropathy [ 232 ]. Polydatin reduced inflammatory factors and matrix-degrading protease in osteoarthritis through anti-inflammatory and chondroprotective effects [ 227 ].…”

“…Polydatin reduced inflammatory factors and matrix-degrading protease in osteoarthritis through anti-inflammatory and chondroprotective effects [ 227 ]. Activation of the Nrf2 pathway is related to therapeutic and protective effects of polydatin on osteoarthritis [ 227 ] and diabetic neuropathy [ 232 ]. Polydatin also demonstrated protective effects on sciatic neurons and Schwann cells in animal models of diabetic neuropathy via inhibition of Keap 1, and activation of Nrf2/glyoxalase 1 [ 232 ].…”

Polydatin as a therapeutic alternative for central nervous system disorders: A systematic review of animal studies

“…Polydatin might also promote regeneration of sciatic nerve injury in diabetic rats. Animals treated with polydatin showed improvements in nerve morphology as well as myelinated axonal densities (L. Chen et al, 2021).…”