Neuroprotective Efficacy of Polyphenols of Marine Brown Macroalga Ecklonia cava in Diabetic Peripheral Neuropathy

Abstract

Objectives: In this study, the neuroprotective effect of polyphenols isolated from the brown marine macroalga Ecklonia cava (EC) was evaluated in experimental diabetic peripheral neuropathy (DPN).Materials and Methods: The polyphenolic fraction from EC was isolated. DPN was induced in animals by intraperitoneal injection of streptozotocin (45 mg/kg, b. w) and maintained for 6 weeks followed by treatment with EC polyphenols (ECPP) or epalrestat for 30 days. Nerve conduction velocity (NCV) of sciatic nerves and the compound muscle action potential (CMAP) of the gastrocnemius muscle were measured using a non-invasive method followed by neuropathic thermal analgesia and muscular grip strength. Sciatic nerve aldose reductase (AR) activity, intraneural sorbitol accumulation, Na+K+‑ATPase activity, production of proinflammatory cytokines (interleukin‑6 [IL‑6], IL‑1 β, and tumor necrosis factor alpha [TNF‑α]), and expression of AR and protein kinase C (PKC) were assessed.Results: The ECPP were found to inhibit AR activity as well as their expression in diabetic animals, thereby improving the NCV, CMAP, muscle grip strength, hot plate, and tail‑flick response time. Improvements in the sciatic nerve Na+K+‑ATPase activity and intraneural accumulation of sorbitol, an index of AR overactivity, were evident with ECPP treatment. The production of proinflammatory cytokines (IL‑6, IL‑1 β, and TNF‑α) and expression of PKC were also diminished.Conclusion: The data suggest that the polyphenols of EC have neuroprotective potential against experimental DPN.

Keywords: Aldose reductase; antidiabetic activity; Ecklonia cava; macroalgae; peripheral neuropathy; polyphenols