Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka, Bangladesh.
Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Science Center (TTUHSC), Amarillo, TX, United States of America.
PLoS One. 2022 Jun 29;17(6):e0270123. doi: 10.1371/journal.pone.0270123. eCollection 2022.
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.
衰老引起的记忆障碍与氧化应激密切相关。D-半乳糖（D-gal）引起严重的氧化应激，并在动物中模拟正常衰老。姜黄素是一种天然类黄酮，具有强大的抗氧化和抗衰老特性。有几种蛋白质，如谷胱甘肽 S-转移酶 A1（GSTA1）、谷胱甘肽 S-转移酶 omega-1（GSTO1）、kelch 样 ECH 相关蛋白 1（KEAP1）、β-分泌酶 1（BACE1）和胺氧化酶[黄素]A（MAOA），通常参与氧化应激和衰老。本研究旨在研究姜黄素与这些蛋白质的相互作用及其对两种强大的动物模型（D-gal 和正常老化（NA）小鼠）中与衰老相关的记忆障碍的后续影响。衰老小鼠模型通过腹腔内注射 D-gal 建立。将小鼠（n=64）分为 8 组（每组 8 只）：对照组、姜黄素对照组、D-gal（100mg/kg；腹腔注射）、姜黄素+D-gal、虾青素（Ast）+D-gal、正常老化（NA）、姜黄素（30mg/kg 口服）+NA、虾青素（20mg/kg 口服）+NA。通过被动回避（PA）和情境恐惧条件反射（CFC）评估记忆保持和冻结记忆。进行分子对接以预测姜黄素与潜在分子靶标的结合。姜黄素显著增加了 PA 和 CFC 中的记忆保持时间（p<0.05）和冻结反应（p<0.05）。姜黄素显著改善了小鼠海马组织中谷胱甘肽、超氧化物歧化酶、过氧化氢酶、高级氧化蛋白产物、一氧化氮和脂质过氧化水平。计算研究表明，姜黄素与 GSTA1、GSTO1、KEAP1、BACE1 和 MAOA 的结合具有有利的结合能。姜黄素改善 D-gal 和自然诱导衰老小鼠的记忆保留和冻结记忆。姜黄素可改善小鼠氧化应激生物标志物的水平。姜黄素的抗衰老作用可能至少部分归因于通过与 GSTA1、GSTO1、KEAP1 结合上调抗氧化酶，以及通过与 BACE1 和 MAOA 结合抑制氧化损伤。
