Aegle marmelos extract rich in marmelosin exacted ameliorative effect against chromium-induced oxidative stress and apoptosis through regulation of Gadd45 in HepG2 cell line.

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 K2 Cr2 O7 -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 K2 Cr2 O7 in HepG2 cell line as evidenced by cell morphology, MTT, LDH, and MMP assays. Pretreatment of MAR attenuated K2 Cr2 O7 -induced oxidative stress by downregulating intracellular ROS and RNS. Further, pretreatment of MAR significantly downregulated K2 Cr2 O7 -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 K2 Cr2 O7 -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.