Apigenin attenuates hippocampal oxidative events, inflammation and pathological alterations in rats fed high fat, fructose diet

Biomed Pharmacother. 2017 May:89:323-331. doi: 10.1016/j.biopha.2017.01.162. Epub 2017 Feb 24.

Abstract

High calorie diet promotes oxidative stress and chronic low grade inflammation that predispose to brain dysfunction and neurodegeneration. Hippocampus region of the brain has been shown to be particularly sensitive to high calorie diet. We hypothesize that apigenin (API), a flavonoid could attenuate hippocampal derangements induced by high fat-high fructose diet (HFFD). In this study, we investigated the effects of API on oxidative stress and inflammation in the hippocampus, and compared with those of sitagliptin (STG), a standard drug with neuroprotective properties. The markers of oxidative stress and inflammation were examined using biochemical assays, western blotting and immunohistochemistry techniques. HFFD-fed rats showed severe pathological alterations and API treatment rescued the hippocampus from the derangements. API significantly improved the antioxidant machinery, reduced ROS levels and prevented the activation of the stress kinases, inhibitor of kappa B kinase beta (IKKβ) and c-Jun NH2 terminal kinase (JNK), and the nuclear translocation and activation of nuclear factor kappa B (NF-κB). The plasma levels of inflammatory cytokines were also reduced. Our findings suggest that hippocampal derangements triggered by HFFD feeding were effectively curtailed by API. Suppression of oxidative stress, NF-κB activation and JNK phosphorylation in the hippocampus are the mechanisms by which API offers neuroprotection in this model.

Keywords: Apigenin; High calorie diet; Hippocampus; Inflammation; Oxidative stress; Sitagliptin.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apigenin / pharmacology*
  • Biomarkers / metabolism
  • Diet, High-Fat / adverse effects
  • Flavonoids / pharmacology
  • Fructose / adverse effects
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects*
  • Phosphorylation / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • Biomarkers
  • Flavonoids
  • Insulin
  • NF-kappa B
  • Fructose
  • Apigenin
  • JNK Mitogen-Activated Protein Kinases