Inhibition of leptin receptors through plant-derived ligands for liver fibrosis drug development

Background: Liver fibrosis is a common health problem worldwide. Several drug-targets have been identified from the fibrosis pathway namely leptin, leptin receptors, adiponectin, and PPAR ã agonist. Suitable antifibrotic drugs are needed.

Objective: Present plant-derived ligands inhibiting the leptin receptor mediated pathway as antifibrotic drugs.

Methods: Bioinformatics was used to generate 3D-structure of leptin receptor to explore binding grooves of therapeutic targets. A molecular library with bioactive compounds from SE Asian medicinal plants was developed by using the bioactive compounds, docking with leptin receptor.

Results: The homology model of leptin receptor has showed similarities with crystal structures and folds reported previously for other cytokine family members. The Ramachandran plot shows that 89.1% of the residues are most favored region. Besides, 15 possible active sites were identified with active residues such as Ser180, Gln463, Pro477, IIe482, Leu519, Asn550, Pro564, Val600, Glu643, Lys665, Asp671, Ser675, Leu767, Pro803, and Glu834.

Conclusion: This study provides data on surface cavity, binding groove, and active sites of the leptin receptor, which will be useful for researchers to understand leptin receptor/complex. We hope that the strandline serve as a potential drug candidate for liver fibrosis in the near future.