Moringa (Moringa oleifera) Leaf Attenuates the High-Cholesterol Diet-Induced Adverse Events in Zebrafish: A 12-Week Dietary Intervention Resulted in an Anti-Obese Effect and Blood Lipid-Lowering Properties

<b>Objective:</b> The study investigates the dietary effects of <i>Moringa oleifera</i> leaf powder on obesity, blood biochemical parameters, and organ health in hyperlipidemic zebrafish (<i>Danio rerio</i>). <b>Methodology</b>: Adult hyperlipidemic zebrafish (n = 56/group) were fed for 12 weeks either with a high-cholesterol diet (HCD, 4% <i>w</i>/<i>w</i>) or HCD supplemented with 0.5% (<i>w</i>/<i>w</i>) <i>M. oleifera</i> leaf powder (0.5% MO) or HCD with 1.0% (<i>w</i>/<i>w</i>) <i>M. oleifera</i> leaf powder (1.0% MO). At different time points (0 to 12 weeks), the survivability and body weight (BW) of zebrafish were measured, while various biochemical and histological evaluations were performed after 12 weeks of feeding the respective diets. Additionally, an in silico approach was used to assess the binding interactions of MO phytoconstituents with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. <b>Results</b>: Following 12-week supplementation, higher zebrafish survivability was observed in the MO-supplemented groups compared to the survivability of the HCD group. Relative to the initial BW, only 4% BW enhancement was observed post 12 weeks of dietary intake of 1.0% MO, in contrast to 27% BW gain in the HCD group. MO supplementation at both (0.5% and 1.0%) effectively mitigates the HCD-induced dyslipidemia and significantly minimizes the atherogenic coefficient and atherogenic index. Similarly, MO reduces elevated blood glucose levels, the ALT/AST ratio, and augments ferric ion reduction (FRA) and paraoxonase (PON) activity in a dose-dependent manner. Likewise, MO (particularly at 1.0%) effectively restrained HCD-induced steatosis, hepatic interleukin (IL)-6 production, and protected the kidneys, testes, and ovaries from oxidative stress and cellular senescence. The in silico findings underscore that the six phytoconstituents (chlorogenic acid, isoquercetin, kaempferol 3-<i>O</i>-rutinoside, astragalin, apigetrin, and myricetin) of MO exhibited a strong interaction with HMG-CoA reductase active and binding site residues via hydrogen and hydrophobic interactions. <b>Conclusions</b>: The findings demonstrated an antioxidant, anti-inflammatory, and hypoglycemic effect of MO, guiding the events to prevent HCD-induced metabolic stress and safeguard vital organs.