6‐Gingerdione Reduces Apoptotic Conditions in HepG2 Cells and Inhibits Inflammatory Cytokine Gene Expression in Alcoholic Liver Injured Zebrafish Larvae

Antioxidant natural products and their analogs especially phenolic compounds, exhibit diverse biological properties, including anti‐inflammatory, antioxidant, and anticancer activities. Ginger which is widely used worldwide for various beneficial effects also contains several phenolic antioxidants, and 6‐gingerol is one of the natural products studied extensively. However, the molecular mechanism of synthetically synthesized 6‐gingerdione (compound 1) from 6‐gingerol was not known. In this study, compound 1 and methylated 6‐gingerdione (compound 2) were obtained semi synthetically from 6‐gingerol. Compound 1 and 2 are subjected to SwissADME prediction. Then the protective effect of compound 1 was analyzed in 2 % EtOH induced HepG2 cells and zebrafish larvae. Hydroxyl and nitric oxide scavenging assays reveal that compound 1 showed more antioxidant activity than compound 2 at 50 μM. Moreover, compound 1 exhibited good anti‐inflammatory activity via lipoxygenase inhibition and proteinase inhibition. Apoptosis and oxidative stress in HepG2 cells were induced by 2 % EtOH and treated with compound 1. Compound 1 significantly inhibited the EtOH induced nitric oxide production, apoptosis, and ROS generation in HepG2 cells. Encouraged by the in‐vitro antioxidant and anti‐inflammatory activities, compound 1 was then investigated for its protective effect in 2 % EtOH induced ALD zebrafish larva. Compound 1 protected the zebrafish larvae from liver injury by suppressing inflammatory (COX‐2, TNF‐α, and IL‐1β) and lipogenic genes (C/EBP‐α, SREBP1, and IL‐1β) while upregulating the antioxidant gene. Our findings indicate that compound 1 synthesized from 6‐gingerol ameliorated liver injury that likely, contributes to its potential antioxidant and anti‐inflammatory properties.