Mori Cortex Radicis Attenuates High Fat Diet-Induced Cognitive Impairment via an IRS/Akt Signaling Pathway

Abstract

Present study was conducted to investigate ameliorating effects of Mori Cortex radicis on cognitive impair and neuronal defects in HFD-induced (High Fat Diet-Induced) obese mice. To induce obesity, C57BL/6 mice were fed an HFD for 8 weeks, and then mice were fed the HFD plus Mori Cortex radicis extract (MCR) (100 or 200 mg/kg/day) for 6 weeks. Prior to sacrifice, body weights were measured, and Y-maze test and oral glucose tolerance test were performed. Serum lipid metabolic biomarkers (TG, LDL, and HDL/total cholesterol ratio) and antioxidant enzymes (glutathione, superoxide dismutase, and catalase), malondialdehyde (MDA), and acetylcholinesterase (AChE) levels were measured in brain tissues. The expressions of proteins related to insulin signaling (p-IRS, PI3K, p-Akt, and GLUT4) and neuronal protection (p-Tau, Bcl-2, and Bax) were examined. MCR suppressed weight gain, improved serum lipid metabolic biomarker and glucose tolerance, inhibited AChE levels and MDA production, and restored antioxidant enzyme levels in brain tissue. In addition, MCR induced neuronal protective effects by inhibiting p-Tau expression and increasing Bcl-2/Bax ratio, which was attributed to insulin-induced increases in the expressions p-IRS, PI3K, p-Akt, and GLUT4. These indicate MCR may reduce HFD-induced insulin dysfunction and neuronal damage and suggest MCR be considered a functional material for the prevention of T2DM-associated neuronal disease.

Biological and Pharmacological Characterization of Ascorbic Acid and Nicotinamide Chitosan Nanoparticles against Insulin-Resistance-Induced Cognitive Defects: A Comparative Study

“…59 In addition, the brain is regarded as an insulin-sensitive organ since insulin is crucial for normal brain functioning as well as for stimulating the release of neurotransmitters like catecholamines. 62 The binding of insulin to receptors induces a complex intracellular signaling cascade affecting several neural functions such as learning and memory. Development of brain-insulin resistance has been confirmed to be a major contributor in cognitive disorders.…”

Abelmoschus Esculentus (L.) Moench’s Peel Powder Improves High-Fat-Diet-Induced Cognitive Impairment in C57BL/6J Mice

“…In a recent study, 14 weeks of HFD intake reduced the phosphorylation of insulin receptor substrate (IRS), increased the production of MDA and reduced antioxidant enzyme levels (superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT)) in the brain of adult male C57BL/6 mice. Reduced phosphorylation of IRS leads to a decrease in the activation of PI3K and Akt, causing an increase in Tau-phosphorylation and the expression of Bax (pro-apoptotic protein) and a decrease in the expression of Bcl-2 (anti-apoptotic protein), resulting in neurodegeneration [ 14 , 15 ]. Prolonged consumption of HFD also increases the expression of TREM2 (primarily present in microglia) along mRNAs of IL-1β, TNF-α, TLR-4, iNOS and phosphorylation of p65 and Ilkβ in the C57BL/6J mice hippocampus [ 16 , 17 ], suggesting the crucial role of microglia in HFD-induced neuroinflammation.…”

“…Furthermore, aqueous extract of okra seed, which mainly consists of catechin and quertin derivatives, reduced MDA, and increased antioxidant activities, and elevated neurotransmitter levels such as dopamine, norepinephrine, acetylcholine, serotonin, and epinephrine in the hippocampus of depressed mice [ 43 ]. Based on existing literature, insulin/PI3K/Akt/Tau/Bax [ 14 , 15 ], microglia-driven neuroinflammatory [ 57 ], and oxidative stress-neurogenesis [ 10 ] pathways in the hippocampus were associated with HFD-induced neuronal injury, which are coinciding with the neuroprotective property of okra against non-HFD-model-induced neuronal injury in the hippocampus. Therefore, it is likely that any of the aforementioned mechanisms could have mediated the effects of okra in the present study.…”

“…HFD causes an excessive production of reactive oxygen species (ROS), such as malondialdehyde (MDA), and reduces the antioxidant enzyme levels, leading to increased insulin resistance [ 13 ]. Reduced activation of insulin causes a decrease in the activities of phosphoinositide 3-kinase (PI3K), and Akt, consequently increasing the Tau phosphorylation and the expression of pro-apoptotic protein and decreasing the expression of anti-apoptotic proteins, contributing to neurodegeneration in the hippocampus [ 14 , 15 ]. HFD also causes neuroinflammation in the hippocampus via a microglia-mediated pathway [ 16 , 17 ].…”

Phenolic Compounds from Mori Cortex Ameliorate Sodium Oleate-Induced Epithelial–Mesenchymal Transition and Fibrosis in NRK-52e Cells through CD36

“…The dry root bark of the dicotyledonous plant Morus alba L is called Mori Cortex after removing the cork [14]. It is cold in nature, sweet in taste [15].…”