Defence Food Research Laboratory (DFRL), Defence Research and Defence Organization (DRDO), Mysore, India.
Department of Biology, Indian Institute of Science Education and Research, Tirupati, India.
J Food Biochem. 2021 Apr;45(4):e13704. doi: 10.1111/jfbc.13704. Epub 2021 Mar 14.
Hexavalent chromium [Cr (VI)] is highly toxic compared to other valence states of chromium. In the process of metabolic reduction, Cr (VI) converts to trivalent chromium. Aegle marmelos (Bael), a sacred plant of India and its fruits are being consumed as traditional formulations against various diseases such as ulcer, gastric mucosal damage, inflammations, febrile delirium, acute bronchitis, anxiety, etc. The present study assessed the protective effects of marmelosin (MAR) from Aegle marmelos against K Cr O -induced toxic effects in HepG2 cell line through its antiapoptotic mechanism. Results of the study revealed that pretreatment of MAR ameliorated cell viability, mitochondrial damage, and DNA damage induced by K Cr O in HepG2 cell line as evidenced by cell morphology, MTT, LDH, and MMP assays. Pretreatment of MAR attenuated K Cr O -induced oxidative stress by downregulating intracellular ROS and RNS. Further, pretreatment of MAR significantly downregulated K Cr O -induced apoptotic markers, such as Bax, Caspase 3, and Gadd45. Our results suggested that application of marmelosin could be beneficial in ameliorating chromium-induced apoptotic cell death by suppressing oxidative stress and regulating excessive DNA damage. PRACTICAL APPLICATIONS: The study focused on protective mechanism of marmelosin from Aegle marmelos against chromium-induced oxidative stress for the first time. In this research, we reported that marmelosin effectively ameliorated K Cr O -induced morphological changes such as oxidative stress and apoptotic cell death by regulating Gadd45, Bcl-2, Bax, and Caspase 3 gene expressions, and inhibition of intracellular ROS and RNS. The study provides a better understanding of the pharmacological mechanisms of Aegle marmelos and its bioactive compound, that is, marmelosin in the management of intoxication of heavy metals associated with excessive DNA damage.
六价铬（Cr(VI)）的毒性比其他价态的铬高得多。在代谢还原过程中，Cr(VI)转化为三价铬。印度的神圣植物酸橙（Aegle marmelos）及其果实被用作传统制剂，用于治疗各种疾病，如溃疡、胃黏膜损伤、炎症、发热性谵妄、急性支气管炎、焦虑等。本研究评估了酸橙素（MAR）对 HepG2 细胞系中 KCrO4 诱导的毒性作用的保护作用，其机制为抗细胞凋亡作用。研究结果表明，MAR 的预处理通过细胞形态学、MTT、LDH 和 MMP 测定，改善了 HepG2 细胞系中由 KCrO4 诱导的细胞活力、线粒体损伤和 DNA 损伤。MAR 的预处理通过下调细胞内 ROS 和 RNS 减轻了 KCrO4 诱导的氧化应激。此外，MAR 的预处理显著下调了 KCrO4 诱导的凋亡标志物，如 Bax、Caspase 3 和 Gadd45。我们的结果表明，应用酸橙素可能通过抑制氧化应激和调节过度的 DNA 损伤，有利于改善铬诱导的细胞凋亡死亡。实际应用：本研究首次关注了酸橙素从 Aegle marmelos 中对铬诱导的氧化应激的保护机制。在这项研究中，我们报告说，酸橙素通过调节 Gadd45、Bcl-2、Bax 和 Caspase 3 基因的表达，以及抑制细胞内 ROS 和 RNS，有效地改善了 KCrO4 诱导的形态变化，如氧化应激和凋亡细胞死亡。该研究为了解酸橙及其生物活性化合物酸橙素在管理与过度 DNA 损伤相关的重金属中毒方面的药理机制提供了更好的认识。
