Caraway (Carum carvi L.) Agro-industrial Waste; Anti-obesity Effect and Chemical Characterization.

Roots and aerial parts are the agricultural by-products of caraway (Carum carvi L.) fruit production. Hereto, the anti-obesity and hypolipidemic effects of caraway waste were assessed using different in vitro and in vivo tests performed on total ethanol extract (TEE), as well as its fractions. The ethyl acetate fraction (EtOAc fr.) exhibited the highest inhibitory activity on pancreatic lipase (PL), a-amylase and DPPH free radical. Accordingly, it showed the highest ameliorative activity against dyslipidaemia among other fractions and the total extract when tested on a high fat diet-fed mice model. It attenuated hepatic steatosis, reduced adipocyte size, ameliorated the lipid profile, and suppressed leptin concentrations as revealed by the histopathological and biochemical examinations. Umbelliferone, p-coumaric acid and isoquercitrin were isolated from the bioactive EtOAc fr. and quantified in both, the EtOAc fr. and TEE, using HPLC. Isoquercitrin displayed the highest inhibitory activity towards DPPH and PL (IC50: 10 ± 2.50 and 93.54± 2.62 µg/mL, respectively), whereas umbelliferone was the most active against a-amylase (IC50: 50.70 ± 2.83 µg/mL). Molecular docking was carried out to uncover the binding affinities to the enzymes' active sites. Isoquercitrin demonstrated strong interaction in the binding site of lipase (-130.87 kcal·mol-1), via H-bonding with Asp79, Ile78, Arg256, Ser152 and Tyr114, whereas, umbelliferone formed H-bonding with Tyr59 and Leu142 and H-Pi interaction with Gln63 in the amylase enzyme's active site (-65.99 kcal·mol-1). The current research highlights the great potential for caraway waste as a multitarget remedy against obesity, which incites further molecular and clinical studies. [ABSTRACT FROM AUTHOR]