Co-Supplementation of Policosanol and Banaba Leaf Extract Exhibited a Cooperative Effect Against Hyperglycemia and Dyslipidemia in Zebrafish: Highlighting Vital Organ Protection Against High-Cholesterol and High-Galactose Diet

The efficacy of <i>Lagerstroemia speciosa</i> (banaba) leaf extract (BLE), policosanol (POL), and their combination (BLE+POL) was evaluated in zebrafish (<i>Danio rerio</i>) against high cholesterol (HC)- and galactose (HG)-induced metabolic stress and organ toxicity. After 12 weeks of dietary intervention, BLE+POL significantly reduced HC+HG-augmented weight gain and improved hepatic and nephromegaly. Compared with BLE or POL alone, the combined intake of BLE+POL more effectively alleviated dyslipidemia and blood glucose levels. Likewise, BLE+POL effectively reduced blood malondialdehyde (MDA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and boosted plasma sulfhydryl content, ferric ion reduction ability (FRA), and paraoxonase (PON) activity. Histological outcomes suggest that BLE+POL has higher efficacy than either BLE or POL in mitigating HC+HG-induced fatty liver changes, hepatic inflammation, kidney senescence, and reactive oxygen species (ROS) production. Consistently, BLE+POL augmented the spermatozoa counts in the testes, enhanced mature vitellogenic oocytes in ovaries, and protected them from the HC+HG-induced oxidative stress. Compared with either BLE or POL, a combined intake of BLE+POL displayed a superior effect in inhibiting the apoptosis and accumulation of lipid peroxidation species 4-hyrdoxynonenal (4-HNE) in the brain. A combined intake of BLE+POL exhibited a pronounced impact than the BLE and POL alone and can be utilized as an effective formulation to counteract the HC+HG-induced events.