Velumani Kadhirmathiyan, Rajan P Sundar, Shaik Mohammed Rafi, Hussain Shaik Althaf, Shaik Baji, Guru Ajay, Issac Praveen Kumar
Department of Medical Biotechnology, Institute of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India.
Department of Chemical Engineering, Saveetha Engineering College, Chennai, Tamil Nadu, India.
Cell Biochem Biophys. 2025 Apr 12. doi: 10.1007/s12013-025-01747-w.
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.
氧化应激在胰岛素抵抗（IR）的发展中起关键作用，胰岛素抵抗是糖尿病等代谢紊乱的关键因素。植物活性成分在保护生物体免受环境应激源影响方面发挥着至关重要的作用，并已显示出对各种代谢紊乱具有有前景的治疗潜力。青蒿素（ART）是一种从黄花蒿中获得的具有内酯环的倍半萜，具有有前景的治疗特性。本研究调查了青蒿素对鲁普洛克斯（LUP）诱导的斑马鱼幼体氧化应激及由此产生的胰岛素抵抗的作用潜力，特别研究了PI3K/AKT信号通路的参与情况。选择斑马鱼幼体是因为它们对氧化应激高度敏感、葡萄糖代谢特征明确且与人类代谢途径具有遗传相似性。它们暴露于LUP以诱导氧化应激，随后用青蒿素进行处理。通过生化测定、荧光染色和基因表达分析评估其效果。通过DCFDA和DPPP染色测定证实，青蒿素有效地恢复了关键抗氧化酶（超氧化物歧化酶、过氧化氢酶、谷胱甘肽）并减轻了氧化应激，细胞内活性氧和脂质过氧化的减少证明了这一点。此外，青蒿素改善了葡萄糖摄取并降低了血糖水平。基因表达分析进一步表明PI3K/Akt信号成分和抗氧化相关基因（核因子E2相关因子2、血红素加氧酶-1、谷胱甘肽过氧化物酶和谷胱甘肽还原酶）的水平升高。我们的结果表明，青蒿素通过降低活性氧水平和增强抗氧化酶活性显著减轻氧化应激。此外，青蒿素通过恢复葡萄糖代谢和上调PI3K/AKT途径成分来减轻胰岛素抵抗。这些发现突出了植物活性成分，特别是青蒿素，在开发针对胰岛素抵抗和氧化应激相关代谢紊乱的疗法方面的转化潜力。
