Antiobesity and lipid lowering effects of Glycyrrhiza chalcones: experimental and computational studies.

Twelve flavonoids (1-12), isolated from Glycyrrhiza glabra roots were evaluated for their pancreatic lipase (PL) inhibitory activity in vitro. The structures of the isolated compounds were elucidated by spectroscopic methods. Amongst all the compounds 7, 8, 10 and 11 showed strong inhibition against PL with IC(50) values of 7.3 μM, 35.5 μM, 14.9 μM and 37.6 μM, respectively. Molecular docking studies on the most active compound 7 revealed that it binds with the key amino acid residues of the PL active site. In silico absorption, distribution, metabolism and excretion (ADME) parameters were also computed on the active compounds to determine their preliminary pharmacokinetic properties. Further, investigations were carried out to determine the antiobesity and lipid lowering effects of 7 and 10 in high fat diet (HFD) fed male SD rats. In the rats supplemented with compound 7 the body weight increase was only 23.2±3.6 g as compared to 64.2±0.5 g in the HFD control group while in the rats treated with compound 10 showed 23.2±3.6 g weight gain only. Compound 7 decreased the levels of plasma total cholesterol (TC) to 84.6±1.4 mg/dl and plasma total triglycerides (TG) to 128.8±6.0 mg/dl. Compound 10 also lowered the plasma TC and TG levels considerably. The results indicate the potential of the chalcone scaffold as a source of PL inhibitors for preventing obesity.