Deacetylepoxyazadiradione ameliorates diabesity in in-vivo zebrafish larval model by influencing the level of regulatory adipokines and oxidative stress.

Obesity and diabetes constitute significant global health issues associated with one another. In contrast to diabetes, which is characterised by oxidative stress that enhances cellular damage and the following complications. Obesity dynamics involve chronic inflammation that promotes insulin resistance and metabolic disruptions. Anti-inflammatory and antioxidant agents, therefore, hold promise for synergistic effects, addressing inflammation and oxidative stress, key factors in managing obesity and diabetes. These agents can be utilized in novel drug delivery approaches. The complex interactions between deacetylepoxyazadiradione (DEA) and zebrafish larva subjected to metabolic impairment due to a high-fat diet (HFD) are examined in this study. The survival assay showed a significantly lower rate (79% survival rate) in the larvae exposed to HFD. Contrastingly, DEA treatment showed significant results with survival rates increasing dose-dependently (84%, 89%, and 94% at concentrations of 50 μM, 100 μM, and 150 μM, respectively). Further investigations revealed that DEA could reduce hyperlipidemic and hyperglycemic conditions in zebrafish larvae. Glucose levels significantly dropped in the DEA treatment, which was associated with a decline in larval weight, lipid accumulation, oxidative stress and apoptosis. Enzyme assays revealed higher antioxidant enzyme concentrations in DEA treated in-vivo larval models, which were associated with reduced expression of pro-inflammatory genes. In conclusion, the results demonstrate that DEA can alleviate oxidative stress and inflammation, effectively easing the diabesity-like state in zebrafish larvae. This offers potential avenues for developing DEA as a valuable drug candidate to manage the intricate diabesity condition.