A combined in vitro, in vivo and in silico approach for the discovery of bioactive molecules from Corchorus olitorius L as pancreatic lipase inhibitors, interleukin-6 and tumor necrosis factor alpha TNF-α.

This study aimed to evaluate the antioxidant, anti-inflammatory, and anti-obesity effects of bioactive compounds derived from Corchorus olitorius L., using a combined in vitro, in vivo, and in silico approach. The in vitro phase involved polyphenol extraction and antioxidant activity assays. The in vivo phase used a high-fat diet (HFD)-induced obesity model in Wistar rats divided into four groups: standard diet (STD), high-fat diet (HFD), STD with C. olitorius extract (STD + C. olitorius), and HFD with C. olitorius extract (HFD + C. olitorius). Rats received a daily oral administration of C. olitorius extract (100 mg/kg) throughout a 9-week treatment period. Plasma biochemical parameters and adipose tissue histology were assessed. The in silico phase involved molecular docking of previously identified and synthesized C. olitorius compounds against obesity- and inflammation-related targets (TNF-α, IL-6, PL), followed by ADMET predictions and analog design via bioisosteric replacement. C. olitorius treatment reduced body weight gain, visceral fat accumulation, and lipid parameters in HFD-fed rats. Histological analysis showed decreased fibrosis and inflammatory cell infiltration in adipose tissue, supporting its anti-inflammatory and anti-fibrotic effects. Molecular docking revealed that key compounds-particularly L7 (methyl-1,4,5-tri-O-caffeoylquinic acid) and L2 (3,5-dicaffeoylquinic acid)-demonstrated strong binding affinities to proinflammatory cytokines and pancreatic lipase. Analog compounds designed via bioisosteric modification retained favorable biological activity. ADME analysis indicated that the principal compounds possess favorable oral absorption properties and align with drug-likeness criteria. Compared to orlistat, these natural compounds offer a safer profile with reduced toxicity risks. This study highlights the multi-target therapeutic potential of C. olitorius derived compounds-particularly L7 and its analogs-as promising candidates for natural anti-obesity drug development. To fully establish their therapeutic value, comprehensive preclinical and clinical investigations are necessary to evaluate both efficacy and safety. Nonetheless, the current study is limited by the need for mechanistic validation and long-term toxicity assessments.