Antidepressant activity of phytochemicals of Mangifera indica seeds assisted by integrated computational analysis.

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.

Pharmacological Screening of Mangifera indica Seeds for Antidepressant-like Action Along with a Mechanistic Study.

Depression is emerging as a major global issue. There are several antidepressants available in the market, but their efficacy is usually unpredictable. Therefore, there is a need to find an alternative therapeutic agent with better therapeutic efficacy and availability. In the current investigation, the antidepressant-like action of the aqueous methanolic extract of Mangifera indica seeds (25, 50, and 100 mg/kg) was evaluated by two predictive models like the tail suspension test and forced swimming test along with the determination of the mechanism of action working behind this action. The results of the acute treatment with the extract show a dose-dependent reduction in the duration of immobility in both models. The antidepressant-like action of the extract (100 mg/kg) was blocked by the administration of p-chlorophenyl alanine, α-methyl-p-tyrosine, prazosin, and sulpiride while remaining unaffected with propranolol. In contrast, the administration of d-serine along with the extract (a full agonist of glycine/N-methyl-d-aspartate, NMDA, receptors) diminished the anti-immobility action. The administration of the extract along with nitro-l-arginine-methyl ester synergizes into the anti-immobility action of the extract, and intake of l-arginine remained unable to effect this action, whereas sildenafil blocks the effect. The antidepressant-like action of the extract is probably due to the involvement of serotonergic and adrenergic (mainly α receptors are involved) systems, an NMDA receptor complex, and the nitric oxide pathway.

Chronopharmacology: Appraising the Influence of Biorhythms on the Efficacy and Safety of Antihypertensive Drugs.

This review is dedicated to chronopharmacology and chronotherapeutics of hypertension interventions. The aim of chronopharmacology is to determine the most suitable time for administration of a drug to enhance efficacy and safety, prevent tolerance, and minimize the untoward effects of the given therapy. In other words, chronotherapeutics and chronopharmacology optimize drug therapy through matching the disease rhythms to drug availability. Chronobiological principles to optimize the therapeutic effects of antihypertensive drugs attained significance a few decades ago. Circadian rhythm plays a pivotal role in the regulation of blood pressure and expresses as a contender for application of chronotherapeutics. Changes in the normal circadian rhythmic pattern of blood pressure also foretell the risk for developing cardiovascular events. This review highlights studies conducted on the chronopharmacology of different antihypertensive drug classes and prospective areas of chronotherapy to make it comprehensible for application in clinical practice to achieve optimum control of hypertension.