Hypolipidemic and Antioxidant Activities of <i>Leptadenia hastata</i> (Perse) Decne. Leaf and <i>Syzygium aromaticum</i> L. Bud Combination: In Vivo, In Vitro, and In Silico Evaluation

ABSTRACT For decades, the interest in the intake of mixture or combined plant‐based products to achieve maximum health benefits is increasing. Leptadenia hastata Vatke leaf and Syzygium aromaticum L. bud are popularly consumed as foods and have demonstrated potential to mitigate metabolic disorders associated with hyperlipidemia. However, effect of the L. hastata leaf and S. aromaticum bud combination has not yet been studied. Therefore, the study investigated the hypolipidemic and antioxidant activities of the L. hastata leaf and S. aromaticum bud in poloxamer 407‐induced hyperlipidemic rats. The combination of the plants in a 1:1 ratio was used and administered at 50 and 100 mg/kg bw for four (4) weeks. Molecular docking assessment of eight compounds found in the plants was carried out against HMG‐CoA reductase. From the results, the hyperlipidemic control group demonstrated increased body weight, fasting blood glucose (FBG), dyslipidemia, and oxidative stress. Oral administration of the combination of the two plants attenuated the biochemical alterations, restoring values toward normal levels. In addition, the combination inhibited HMG‐CoA reductase in a noncompetitive manner and could be the possible mechanism of hypolipidemic activity of the extract. Compounds detected by GC‐MS analysis revealed mostly phenolics as eugenol derivatives and others such as humulene, 9,12‐octadecadienoic acid, methyl ester, ( E, E )‐ and aspidospermidin‐17‐ol, and 1‐acetyl‐19,21‐epoxy‐15,16‐dimethoxy. Three compounds including aspidospermidin‐17‐ol, 1‐acetyl‐19,21‐epoxy‐15,16‐dimethoxy‐, phenol, and 2‐methoxy‐4‐(1‐propenyl)‐ and phenol, 4‐(2‐propenyl)‐ acetate had the best docking score (−8.3 kcal/mol, −5.8 kcal/mol, −6.3 kcal/mol) and formed binding complexes within the binding pocket of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase. The data demonstrate combination of the L. hastata leaf and the S. aromaticum bud in amelioration of dyslipidemia and oxidative stress and recommend further detailed molecular and toxicity studies to support the present data.