Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetes Mellitus

Abstract

The aim of the study was to analyze the possible neuroprotective effect of hydroxytyrosol (HT) in diabetic animals in a model of hypoxia-reoxygenation. Rats (10 animals/group) were distributed in five groups: nondiabetic rats, control diabetic rats (DR), and DR rats treated for 2 months with 1, 5, or 10 mg/kg/day po HT. At the end of follow-up, an experimental model of hypoxia-reoxygenation in brain slices was tested. The DR group showed increased cell death, oxidative and nitrosative stress, and an increase in brain inflammatory mediators. These alterations were significantly greater in DR than in normoglycemic animals. HT significantly reduced oxidative (38.5-52.4% lipid peroxidation) and nitrosative stress (48.0-51.0% nitric oxide and 43.9-75.2% peroxynitrite concentration) and brain inflammatory mediators (18.6-40.6% prostaglandin E and 17.0-65.0% interleukin 1β concentration). Cell death was reduced by 25.9, 37.5, and 41.0% after the administration of 1, 5, or 10 mg/kg/day. The administration of HT in rats with experimental diabetes thus had a neuroprotective effect.

Comparison of the anti-angiogenic potential of hydroxytyrosol and five derivatives

“…Based on these grounds, diverse HT derivatives have been synthesized. [18][19][20][21][22] The bioactivities of these HT derivatives have been studied, including their antiplatelet aggregation capacity, 4,42,43 neuroprotective activity, 44 DNA oxidative damage protection, 30 cytoprotection, 45 antiinflammatory effects, 38,46 and anticancer activity. 12,47 Most of these derivatives have shown to maintain or even improve the diverse activities of free HT, mainly due to the better lipophilic/hydrophilic balance exhibited by these derivatives.…”

“…2 In the last years, scientific evidence has accumulated pointing to the pleiotropic effects of HT on multiple targets. In fact, demonstrated beneficial effects of HT for human health include its antidiabetic, 3,4 antifungal, 5 antiinflammatory, 6 antiparasitic, 7 cardio- 8 and neuroprotective 9 activities. HT has also beneficial effects on metabolic syndrome 10 and antitumoral effects of HT have been reported.…”

Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health

“…HTyr demonstrates hypoglycemic activity in various diabetic animal models by influencing the major biochemical processes leading to diabetic vasculopathy [67,68]. An animal model experiments showed that HTyr could effectively prevent diabetic neuropathy [69,70]. It was shown that HTyr improves insulin sensitivity and restores proper insulin-signaling [71].…”

Antidiabetic Effects of Hydroxytyrosol: In Vitro and In Vivo Evidence

“…It was concluded that HT may attenuate the vasculopathy or blood vessel inflammation induced by diabetes. Reyes et al (2017) administered HT to male Wistar rats via gavage at dosages of 1, 5 or 10 mg/kg for 7 days before inducing diabetes with intravenous STZ (50 mg/kg) [60]. HT treatments continued for 2 months following the induction of diabetes.…”