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.

Antidiabetic; Antioxidants; Cardioprotective; Cichoriin; Oxidative stress.