Honokiol attenuates high glucose‐induced peripheral neuropathy via inhibiting ferroptosis and activating AMPK/SIRT1/PGC‐1α pathway in Schwann cells

Abstract

Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC‐1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC‐1 staining results demonstrated that honokiol reduced HG‐induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT‐qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG‐induced inhibition of AMPK/SIRT1/PGC‐1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG‐induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin‐induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG‐induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.

Advances of traditional Chinese medicine preclinical mechanisms and clinical studies on diabetic peripheral neuropathy

“…This was accompanied by similar enhancements in the protein expression of downstream target genes (SOD1 and SOD2) (Hu M et al. 2023 ). Similarly, the Chinese medicine Tang Bi Kang has been shown to improve mitochondrial oxidative stress by activating the AMPK/SIRT3 pathway, promoting SOD expression, reducing MDA levels, and increasing the NAD + /NADH ratio, as well as ATP synthesis (Yu et al.…”

“…Hu M et al. ( 2023 ) indicated honokiol improvements in sciatic NCV, increased thermal and mechanical sensitivity in diabetic rats, and relief from neuropathy symptoms. Moreover, honokiol mitigated high glucose-induced damage in Schwann cells.…”

“…Recent studies have developed novel herbal products to address the growing prevalence of DPN (Hu M et al. 2023 ; Jiang et al. 2023 ; Liu Q et al.…”