Saleem Uzma, Iman Shafa, Ahmad Bashir, Shah Muhammad Ajmal, Bibi Shabana, Alqarni Mohammed, Khan Muhammad Saad, Shah Ghulam Mujtaba, Khan Haroon, Alhasani Reem Hasaballah, Althobaiti Norah A, Albalawi Aishah E
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, 38000, Pakistan.
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Pakistan.
Metab Brain Dis. 2023 Feb;38(2):483-505. doi: 10.1007/s11011-022-00955-0. Epub 2022 Mar 28.
Mangifera indica L., also known as mango, is a tropical fruit that belongs to the Anacardiaceae family and is prized for its juiciness, unique flavour, and worldwide popularity. The current study aimed to probe into antidepressant power (ADP) of MIS in animals and confirmation of ADP with in silico induced-fit molecular docking. The depression model was prepared by exposing mice to various stressors from 9:00 am to 2:00 pm during 42 days study period. MIS extract and fluoxetine were given daily for 30 min before exposing animals to stressors. ADP was evaluated by various behavioural tests and biochemical analysis. Results showed increased physical activity in mice under behavioural tests, plasma nitrite and malondialdehyde (MDA) levels and monoamine oxidase A (MAO-A) activity decreased dose-dependently in MIS treated mice and superoxide dismutases (SOD) levels increased in treated groups as compared to disease control. With the peculiar behaviour and significant interactions of the functional residues of target proteins with selected ligands along with the best absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, it is concluded that catechin could be the best MAO-A inhibitor at a binding energy of -8.85 kcal/mol, and two hydrogen bonds were generated with Cys406 (A) and Gly443 (A) residues of the active binding site of MAO-A enzyme. While catechin at -6.86 kcal/mol generated three hydrogen bonds with Ala263 (A) and Gly434 (A) residues of the active site of monoamine oxidase B (MAO-B) enzyme and stabilized the best conformation. Therefore, it is highly recommended to test the selected lead-like compound catechin in the laboratory with biological system analysis to confirm its activity as MAO-A and MAO-B inhibitors so it can be declared as one of the novel therapeutic options with anti-depressant activity. Our findings concluded that M. indica seeds could be a significant and alternative anti-depressant therapy.
芒果（Mangifera indica L.），又称杧果，是一种热带水果，属于漆树科，以其多汁、独特风味和全球知名度而备受赞誉。当前研究旨在探究芒果种子提取物（MIS）在动物体内的抗抑郁能力（ADP），并通过计算机诱导契合分子对接来确认其ADP。在为期42天的研究期间，从上午9:00至下午2:00让小鼠暴露于各种应激源来制备抑郁模型。在将动物暴露于应激源之前，每天给予MIS提取物和氟西汀30分钟。通过各种行为测试和生化分析来评估ADP。结果显示，在行为测试中，MIS处理的小鼠身体活动增加，血浆亚硝酸盐和丙二醛（MDA）水平以及单胺氧化酶A（MAO-A）活性呈剂量依赖性降低，与疾病对照组相比，处理组中超氧化物歧化酶（SOD）水平升高。鉴于目标蛋白的功能残基与所选配体具有独特的相互作用以及最佳的吸收、分布、代谢、排泄和毒性（ADMET）特性，得出结论：儿茶素可能是最佳的MAO-A抑制剂，结合能为-8.85千卡/摩尔，并且与MAO-A酶活性结合位点的Cys406（A）和Gly443（A）残基形成了两个氢键。而结合能为-6.86千卡/摩尔的儿茶素与单胺氧化酶B（MAO-B）酶活性位点的Ala263（A）和Gly434（A）残基形成了三个氢键，并稳定了最佳构象。因此，强烈建议在实验室中通过生物系统分析来测试所选类先导化合物儿茶素，以确认其作为MAO-A和MAO-B抑制剂的活性，这样它就可以被宣布为具有抗抑郁活性的新型治疗选择之一。我们的研究结果得出结论：芒果种子可能是一种重要的替代性抗抑郁疗法。
