Efficiency of Biobran/MGN-3, an Arabinoxylan Rice Bran, in Attenuating Diabetes-Induced Cognitive Impairment of the Hippocampus via Oxidative Stress and IR/Akt/NF- κ B in Rats

Abstract

Type 2 diabetes mellitus (T2DM) is a common metabolic disease accompanied by cognitive impairment, hippocampal malfunctioning, and inflammation. Biobran/MGN-3, an arabinoxylan rice bran, has been shown to have an antidiabetic effect in streptozotocin-induced diabetic rats. The present study investigates Biobran's effect against diabetes-induced cognitive impairment and synaptotoxicity in the hippocampus via oxidative stress and the IR/A/NF-κB signaling pathway in rats. Diabetes was induced via i.p. injection of streptozotocin (STZ) (40 mg/kg BW); STZ-treated rats were then administered Biobran (100 mg/kg BW) for 4 wks. Biobran supplementation improved motor coordination and muscular strength, as assessed by Kondziella's inverted screen test. Biobran also improved concentration levels of glutathione (GSH), antioxidant enzymes, acetylcholine (ACh), dopamine, serotonin, insulin receptor (IR), and alpha serine-threonine protein kinase (Akt); it protected against elevated levels of glucose, total cholesterol, triglycerides, oxidative stress markers, TBARS, NO, AChE, and MAO; and it significantly decreased inflammatory cytokines levels of IL-1β, NF-κB, TNF-α, and amyloid β_1-42. Moreover, Biobran ameliorated hippocampal histological alterations. Immunohistochemical observations showed that Biobran reduced overexpression of hippocampal synaptophysin and Ki67 relative to untreated diabetic rats. Biobran may ameliorate hippocampal alterations in diabetic rats via its antidiabetic, antiproliferative, anti-inflammatory, antiapoptotic, and antioxidant effects.

Figure 1

Kondziella's inverted screen test. Values are mean ± S.E.; each group has n = 6. ^aSignificantly different relative to control group, p < 0.05. ^bSignificantly different relative to diabetic group, p < 0.05.

Figure 2

Photomicrographs of sections in the hippocampus of male rats. (a, b) control and Biobran-treated rats show normal polymorphic (plm), normal granular (g), and normal molecular (M) layers. (c) Section from diabetic rat showing degenerated neurons (red circle) with darkly stained pyknotic nuclei (green arrow) enveloped by large perinuclear spaces (black arrow), dilated blood vessels (black dotted arrow) in the molecular layer, and red neurons in polymorphic and granular layers (blue dotted arrow). (d) Diabetic + Biobran-treated rats show marked improvements with few cells with darkly stained nuclei and perinuclear space (red arrow) (H&E, X400).

Figure 3

Photomicrographs of rat hippocampi sections revealing immunoreactivity for synaptophysin (CYV). Control (a) and Biobran-treated rat (b) sections show positive reaction for CYV (red arrows). The hippocampus section from diabetic rats (c) reveals weak reaction for CYV. The section from diabetic + Biobran group (d) shows positive reaction for CYV (red arrows) (CYV, X400).

Figure 4

Photomicrographs of rat hippocampi sections revealing immunoreactivity for Ki67. Control (a) and Biobran-treated rat (b) sections showed positive reaction for Ki67 (red arrows). The hippocampus section from diabetic rats (c) revealed weak reaction for Ki67. The diabetic + Biobran group rats (d) showed positive reaction for Ki67 (red arrows) (Ki67, X400).