Synergistic role of resveratrol and exercise training in management of diabetic neuropathy and myopathy via SIRT1/NGF/GAP43 linkage

Reem Essam Ghoweba; Akef Abdelhalim Khowailed; Basma Emad Aboulhoda; Laila Ahmed Rashed; Asmaa Selmy

doi:10.1016/j.tice.2023.102014

Synergistic role of resveratrol and exercise training in management of diabetic neuropathy and myopathy via SIRT1/NGF/GAP43 linkage

Tissue Cell. 2023 Apr:81:102014. doi: 10.1016/j.tice.2023.102014. Epub 2023 Jan 5.

Authors

Reem Essam Ghoweba¹, Akef Abdelhalim Khowailed¹, Basma Emad Aboulhoda², Laila Ahmed Rashed³, Asmaa Selmy¹

Affiliations

¹ Department of Physiology, Faculty of Medicine, Cairo University, Egypt.
² Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Egypt. Electronic address: basma.emad@kasralainy.edu.eg.
³ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Egypt.

PMID: 36621294
DOI: 10.1016/j.tice.2023.102014

Abstract

Aims: Oxidative stress also plays an important role in the pathogenesis of diabetic neuropathy (DN). Both resveratrol (RES) and exercise (EX) have potent anti-oxidative benefits. Low levels of nerve growth factor (NGF) and SIRT1 (a member of sirtuin family) have been reported in patients with DN. The current study has been designed to investigate the role of serum NGF and SIRT1 on DN-induced hyperalgesia and motor incoordination and to evaluate the possible protective role of RES and/or EX.

Main methods: A total of 40 male adult albino rats divided into five groups; control, DN, DN + RES, DN + EX, and DN + RES and EX. DN was confirmed by sensorimotor disturbance and diminished nerve conduction velocity (NCV). NGF and SIRT1 levels were measured by western blot. Calcitonin gene-related peptide (CGRP) was measured by PCR. Myofibrillar degeneration and inflammation scores were revealed via H&E microscopic analysis of the gastrocnemius muscle. Immunohistochemical evaluation of caspase3 and TNF-α was performed in the lumber segment of spinal cord and gastrocnemius muscle sections. Ultrastructural evaluation of sciatic nerve axonal degeneration has also been assessed.

Key findings: DN group showed decreased SIRT1 level, decreased NGF level and correlated with CGRP level and Na+/K+ ATPase. Treatment with RES and/or EX resulted in improvement of sensorimotor disturbance. DN characterized by reduced SOD level, whereas RES and/or EX could limit oxidative damage by up-regulation Bcl2, Akt and GAP-43 and down-regulation of caspase3 and TNF-α. In conclusion, increased level of SIRT1and NGF by incorporation of RES (natural supplementation) and EX (life style modification) could improve the neuroinflammatory state in DN.

Keywords: Diabetic neuropathy; Exercise; GAP-43; NGF; Resveratrol; SIRT1.

MeSH terms

Animals
Calcitonin Gene-Related Peptide
Diabetes Complications / drug therapy
Diabetes Complications / metabolism
Diabetes Complications / therapy
Diabetic Neuropathies* / drug therapy
Diabetic Neuropathies* / metabolism
Diabetic Neuropathies* / therapy
Exercise*
GAP-43 Protein / metabolism
Male
Muscular Diseases* / drug therapy
Muscular Diseases* / therapy
Nerve Growth Factor / metabolism
Rats
Resveratrol* / pharmacology
Sirtuin 1 / metabolism
Tumor Necrosis Factor-alpha

Substances

Calcitonin Gene-Related Peptide
Nerve Growth Factor
Resveratrol
SIRT1 protein, human
Sirtuin 1
Tumor Necrosis Factor-alpha
GAP-43 Protein