6‐Gingerol and Semisynthetic 6‐Gingerdione Counteract Oxidative Stress Induced by ROS in Zebrafish

Abstract

Abstract 6‐Gingerol ( 1 ) is one of the major components in ginger and developing new synthetic methodologies could bring semisynthetic analogs with improved therapeutic properties. Towards this, multigram scale isolation of 6‐gingerol with excellent purity was optimized using a simple and robust extraction, followed by column purification. Synthesis of 6‐gingerdione, 7 from 6‐gingerol was then achieved through selective –OTBDMS protection, DMP oxidation and deprotection reaction sequence for the first time. Compounds 1 , 7 and 8 (dehydrozingerone) exhibited excellent cell‐free antioxidant properties in DPPH, ABTS, superoxide radical scavenging assay and H 2 O 2 assay at 10–50 μM concentrations. The hemolytic study suggests that up to 50 μM, all three compounds did not exhibit toxicity to human erythrocytes. When H 2 O 2 treated zebrafish larvae groups (96hpf) were exposed to compounds 1 , 7 and 8 , it increases the SOD (19, 19.1 and 18.7 U/mg protein), CAT (18.1, 16.5, and 15.8 μmol/mg levels and decreases the lipid peroxidation level (13, 15 and 18 nmol/mg protein), respectively. In vivo ROS levels and degree of cell death were studied using DCFDA and Acridine orange assays. Compounds 1 , 7 and 8 decreases the ROS and cell death level significantly. Taken together, compounds 1 , 7 and 8 exhibit excellent antioxidant properties, counteract H 2 O 2 induced oxidative stress, reduces cell death in zebrafish larvae.