Maltol (3-Hydroxy-2-methyl-4-pyrone) Slows d-Galactose-Induced Brain Aging Process by Damping the Nrf2/HO-1-Mediated Oxidative Stress in Mice

Abstract

Maltol, a maillard reaction product from ginseng (Panax ginseng C. A. Meyer), has been confirmed to inhibit oxidative stress in several animal models. Its beneficial effect on oxidative stress related brain aging is still unclear. In this study, the mouse model of D-galactose (D-Gal)-induced brain aging was employed to investigate the therapeutic effects and potential mechanisms of maltol. Maltol treatment significantly restored memory impairment in mice as determined by the Morris water maze tests. Long-term D-Gal treatment reduced expression of cholinergic regulators, i.e., the cholineacetyltransferase (ChAT) (0.456 ± 0.10 vs 0.211 ± 0.03 U/mg prot), the acetylcholinesterase (AChE) (36.4 ± 5.21 vs 66.5 ± 9.96 U/g). Maltol treatment prevented the reduction of ChAT and AChE in the hippocampus. Maltol decreased oxidative stress levels by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA) production in the brain and by elevating antioxidative enzymes. Furthermore, maltol treatment minimized oxidative stress by increasing the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), nuclear factor-erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1). The above results clearly indicate that supplementation of maltol diminishes D-Gal-induced behavioral dysfunction and neurological deficits via activation of the PI3K/Akt-mediated Nrf2/HO-1 signaling pathway in brain. Maltol might become a potential drug to slow the brain aging process and stimulate endogenous antioxidant defense capacity. This study provides the novel evidence that maltol may slow age-associated brain aging.

Anti-Ageing Effect of Physalis alkekengi Ethyl Acetate Layer on a d-galactose-Induced Mouse Model through the Reduction of Cellular Senescence and Oxidative Stress

“…Oxidative stress promoted cellular senescence [35]. A large number of studies have used the D-gal-induced ageing model for screening of anti-ageing compounds [26][27][28][29][32][33][34]. In our study, the D-gal-induced ageing model was well-established…”

“…d-Gal can cause systematic ageing-related changes, such as hepatic and brain injury, a decline in immune function [26][27][28][29], learning and memory impairment, and fatigue in behavior studies [26,27]. Parallel histopathological features of the liver, spleen, and hippocampus were observed similarly in the d-gal-induced ageing and naturally aging groups [30].…”

Serine Deficiency Exacerbates Inflammation and Oxidative Stress via Microbiota-Gut-Brain Axis in D-Galactose-Induced Aging Mice

“…After maintained on ice for 20 min, the samples were centrifuged at 4800 g for 20 min at 4°C. The supernatant was collected and analyzed by injection onto the chromatographic system as previously described [15].…”

Neuroprotection Against Oxidative Stress: Phytochemicals Targeting TrkB Signaling and the Nrf2-ARE Antioxidant System

“…For instance, naringenin, a polyphenol, protected against OS-induced aging in a D-galactose-induced male ICR mouse model of brain aging by activating the PI3K/Akt/Nrf2 pathway and increasing the nuclear translocation of Nrf2, the expressions of HO−1, NQO1, SOD, and CAT, and the phosphorylations of PI3K and Akt (Zhang et al, 2017). A similar study showed that maltol, a Maillard reaction product of ginseng, protected against brain aging (Sha et al, 2019), activating the PI3K/Akt-mediated Nrf2/HO-1 signaling pathway. In a D-galactose-induced male ICR mouse model of brain aging, maltol inhibited cell death and suppressed the productions of OS markers (ROS and MDA) by enhancing the phosphorylations of PI3K and Akt and increasing the nuclear translocation and phosphorylation of Nrf2 and the expression of antioxidative enzymes, such as HO-1, CAT, and GSH (Sha et al, 2019).…”