VVD-702

This study evaluated the cardioprotective potential of Vitex simplicifolia methanol extract (VSME) and explored its underlying mechanisms of action. Twenty‐five male rats were assigned to five groups (n = 5). Group 1 served as the normal control, while groups 2–5 were exposed to 5 mg/kg body weight of cadmium chloride (CdCl 2 ) daily. Group 2 received no treatment, whereas groups 3 and 4 were treated with 200 and 400 mg/kg VSME, respectively, and group 5 received 10 mg/kg propranolol (standard drug), all for 21 days via oral administration. Biochemical and histopathological analyses of the heart were conducted post‐treatment. Cadmium exposure significantly elevated cardiac malondialdehyde, triglycerides, cholesterol, low‐density lipoprotein, creatine kinase, lactate dehydrogenase, and C‐reactive protein, while reducing high‐density lipoprotein, superoxide dismutase (SOD), catalase, and glutathione peroxidase. VSME treatment reversed these changes, restoring antioxidant status, lipid profile, cardiac biomarkers, and myocardial architecture. Molecular docking revealed strong binding affinities of VSME phytochemicals (kaempferol, isorhamnetin, luteolin) with Kelch‐like ECH‐associated protein 1 (Keap1), primarily through hydrogen bonds. These compounds exhibited superior drug‐likeness, pharmacokinetics, and safety profiles compared to the standard Keap1 inhibitor, CPUY192018. These findings suggest that VSME may exert cardioprotective effects partly through antioxidant activity and potential interference with the Keap1‐Nrf2 interaction, as supported by molecular docking.

In this study, the biosynthesis, physicochemical properties and antioxidant activity of novel EPS from Limosilactobacillus fermentum A10 were investigated. Whole genome sequencing and functional annotation were employed to identify genes involved in the EPS synthesis and the Wzx/Wzy-dependent pathway. After being purified by a DEAE-52 cellulose column, the main component EPS-1, which consisted of rhamnose, galactose, glucose, mannose, and glucuronic acid, was isolated and prepared. Structural analysis indicated that EPS-1 was a heteropolysaccharide containing a pyranose ring with a zeta potential of -18 mV and a particle size of 146 nm. EPS-1 had a loose, porous, crystalline structure and had thermal stability of up to 257.80 °C. EPS-1 exhibited high radical scavenging activity and cytoprotective effect against H₂O₂-induced HepG2 cellular oxidative damage and significantly increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). Moreover, EPS-1 induced antioxidant mechanisms by activating the Keap1-Nrf2/ARE signaling pathway. Molecular docking results indicated that the main interactions between Keap1 protein and rhamnose, galactose, glucose, mannose, and glucuronic acid are hydrogen bonds (NH and OH) and electrostatic interactions (amide bonds). These results demonstrated that EPS-1 can potentially be used in functional food to target Keap1 inhibitors/Nrf2 activators.