Curcumin improves D-galactose and normal-aging associated memory impairment in mice: In vivo and in silico-based studies

• Published in: PloS one Vol. 17; no. 6; p. e0270123
• Main Authors: Rahman, Md. Ashrafur, Shuvo, Arif Anzum, Bepari, Asim Kumar, Hasan Apu, Mehedi, Shill, Manik Chandra, Hossain, Murad, Uddin, Mohammed, Islam, Md. Rabiul, Bakshi, Monjurul Kader, Hasan, Javed, Rahman, Atiqur, Rahman, Ghazi Mohammad Sayedur, Reza, Hasan Mahmud
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 29-06-2022; Public Library of Science (PLoS)
• Subjects: Adenosine; Aging; Aging (artificial); Aging (natural); Alzheimer's disease; Analysis; Animal models; Animals; Antioxidants; Astaxanthin; Biology and Life Sciences; Biomarkers; Brain research; Catalase; Curcumin; D-Galactose; Demographic aspects; Enzymes; Fear conditioning; Flavin; Flavonoids; Freezing; Galactose; Gene expression; Glutathione; Glutathione transferase; Health aspects; Hippocampus; Impairment; In vivo methods and tests; Kinases; Lipid peroxidation; Lipids; Medicine and Health Sciences; Memory; Mitochondrial DNA; Molecular docking; Neurodegeneration; Nitric oxide; Oxidation; Oxidative stress; Peroxidation; Physiological aspects; Proteins; Research and Analysis Methods; Retention; Retention time; Secretase; Superoxide dismutase; Tonic immobility; β-Site APP-cleaving enzyme 1; Bangladesh
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0270123

Aging-induced memory impairment is closely associated with oxidative stress. D-Galactose (D-gal) evokes severe oxidative stress and mimics normal aging in animals. Curcumin, a natural flavonoid, has potent antioxidant and anti-aging properties. There are several proteins like glutathione S-transferase A1 (GSTA1), glutathione S-transferase omega-1 (GSTO1), kelch-like ECH-associated protein 1 (KEAP1), beta-secretase 1 (BACE1), and amine oxidase [flavin-containing] A (MAOA) are commonly involved in oxidative stress and aging. This study aimed to investigate the interaction of curcumin to these proteins and their subsequent effect on aging-associated memory impairment in two robust animal models: D-Gal and normal aged (NA) mice. The aging mice model was developed by administering D-gal intraperitoneally (i.p). Mice (n = 64) were divided into the eight groups (8 mice in each group): Vehicle, Curcumin-Control, D-gal (100mg/kg; i.p), Curcumin + D-gal, Astaxanthin (Ast) + D-gal, Normal Aged (NA), Curcumin (30mg/kg Orally) + NA, Ast (20mg/kg Orally) + NA. Retention and freezing memories were assessed by passive avoidance (PA) and contextual fear conditioning (CFC). Molecular docking was performed to predict curcumin binding with potential molecular targets. Curcumin significantly increased retention time (p < 0.05) and freezing response (p < 0.05) in PA and CFC, respectively. Curcumin profoundly ameliorated the levels of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation in mice hippocampi. In silico studies revealed favorable binding energies of curcumin with GSTA1, GSTO1, KEAP1, BACE1, and MAOA. Curcumin improves retention and freezing memory in D-gal and nature-induced aging mice. Curcumin ameliorates the levels of oxidative stress biomarkers in mice. Anti-aging effects of curcumin could be attributed to, at least partially, the upregulation of antioxidant enzymes through binding with GSTA1, GSTO1, KEAP1, and inhibition of oxidative damage through binding with BACE1 and MAOA.