Neuroprotective effects of Vitis vinifera extract on prediabetic mice induced by a high-fat diet

Background/Aims: Vitis vinifera grape seed extract (VVE) contains oligomeric proanthocyanidins that show antioxidant and free radical-scavenging activities. We evaluated VVE for its neuroprotective effect in prediabetic mice induce by a high-fat diet (HD). Methods: Mice were divided into four groups according to VVE dose: those fed a normal diet (ND; n = 10), HD (n = 10), HD with 100 mg/kg VVE (n = 10), and HD with 250 mg/kg VVE (n = 10). After 12 weeks, immunohistochemical analyses were carried out using a polyclonal antibody against antiprotein gene product 9.5 (protein-gene-product, 9.5), and intraepidermal innervation was subsequently quantified as nerve fiber abundance per unit length of epidermis (intraepidermal nerve fiber, IENF/mm). Results: Daily administration of VVE at doses of 100 or 250 mg/kg for 12 weeks protected HD mice from nerve fiber loss compared to untreated mice, as follows (IENF/mm): controls ($40.95{\pm}5.40$), HD ( $28.70{\pm}6.37$), HD with 100 mg/kg ($41.14{\pm}1.12$), and HD with 250 mg/kg ($48.98{\pm}7.01$ ; p < 0.05, HD with VVE vs. HD). Conclusions: This study provides scientific support for the therapeutic potential of VVE in peripheral neuropathy in an HD mouse model. Our results suggest that VVE could play a role in the management of peripheral neuropathy, similar to other antioxidants known to be beneficial for diabetic peripheral neuropathy.