Cichoriin, a coumarin glycoside with antidiabetic effect and cardioprotective activity against H2O2 induced oxidative stress in H9c2 cells: in-vitro and in-silico study.

In this research, the therapeutic potential of cichoriin is examined, and for the first time, its antioxidant, hemocompatible, and cardioprotective properties against oxidative stress caused by H2O2 in H9c2 cardiac cells are reported. At 100 μg/mL, cichoriin exhibited potent in vitro activities, including DPPH radical scavenging (80.71 ± 0.33 %), metal chelation (74.60 ± 0.39 %), anti-lipid peroxidation (87.96 ± 1.01 %), and pancreatic lipase inhibition (84.88 ± 0.53 %). The IC50 for hemolysis test was 1211.37 μg/mL, indicating limited toxicity towards RBCs. In the MTT assay, cichoriin demonstrated minimal cytotoxicity toward 3T3-L1 and H9c2 cells, maintaining cell viability at 65.22 ± 0.2 % and 67.40 ± 0.82 %, respectively, at 100 μg/mL. Glucose uptake in yeast was significantly enhanced by 81.35 ± 0.53 % at 100 μg/mL with glucose (20 mM), alongside delayed glucose diffusion and inhibition of α-amylase (74.55 ± 0.46 %), α-glucosidase (84.08 ± 0.57 %), and DPP-IV (77.78 ± 0.67 %). Cell viability assay and DCFH-DA staining revealed that cichoriin preserved cellular integrity under oxidative stress in H9c2 cells. It restored the SOD and CAT activities while reducing lipid peroxidation and LDH release induced by H2O2. In-silico studies, including molecular docking, ADMET, and ProTox analyses, confirmed strong binding affinities to target proteins, favorable drug-likeness, and a low toxicity profile. Overall, cichoriin exhibits potent antidiabetic and cardioprotective properties, supporting its potential development as a natural lead compound for the treatment of diabetes-associated cardiovascular disorders.