Protective Effect of Artemisinin Against Luperox Induced Oxidative Stress and Insulin Resistance via Pi3k/Akt Pathway in Zebrafish Larvae.

Abstract

Oxidative stress plays a critical role in the development of insulin resistance (IR), a key factor in metabolic disorders such as diabetes. Plant active ingredients play a crucial role in protecting organisms from environmental stressors and have shown promising therapeutic potential against various metabolic disorders. Artemisinin (ART), a sesquiterpenoid with a lactone ring obtained from the herb Artemisia annua, exhibits promising therapeutic properties. This study investigates the potential of ART on Luperox (LUP)-induced oxidative stress and the resulting IR in zebrafish larvae, specifically investigating the involvement of the PI3K/AKT signaling pathway. Zebrafish larvae were chosen due to their high sensitivity to oxidative stress, well-characterized glucose metabolism, and genetic similarity to human metabolic pathways. They were exposed to LUP to induce oxidative stress, followed by treatment with ART. The effects were evaluated through biochemical assays, fluorescence staining and gene expression analysis. ART effectively restored key antioxidant enzymes (SOD, CAT, GSH) and mitigated oxidative stress evidenced by reduction in intercellular ROS and lipid peroxidation, as confirmed through DCFDA and DPPP staining assays. Additionally, ART improved glucose uptake and lowered blood glucose levels. Gene expression analysis further indicated increased levels of PI3K/Akt signalling components and antioxidant-related genes (NRF2, HO-1, GPx, and GSR). Our results indicate that artemisinin significantly alleviates oxidative stress by reducing ROS levels and enhancing antioxidant enzyme activity. Furthermore, artemisinin mitigates IR by restoring glucose metabolism and upregulating PI3K/AKT pathway components. These findings highlight the translational potential of plant active ingredients, particularly artemisinin, for the development of therapies targeting IR and oxidative stress-related metabolic disorders.