Abstract
The present study demonstrates the alternative source for pseudoalkaloids as well as the utilization of the agricultural wastes of Piper longum (PiL) as possible antiobesity agents. HPLC-based bioactivity-guided micro-fractionation of PiL root has resulted in five known compounds, piplartine (1), piperlonguminine (2), piperine (3), piperanine (5), pellitorine (6), and a new compound, piperdardine (4). Isolated compounds (1–6) were evaluated for their pancreatic lipase (PL) inhibitory potential. Pellitorine (PTR) was the most active component with IC50 = 3.35 μg/mL, which inhibited PL reversibly and in a mixed-type manner. The synergistic effect of PTR with orlistat (0.17 μM) was also observed at a concentration lower than 15.70 μM. The findings of Fourier transform infrared spectral studies demonstrated the structural compactness of PL with PTR. The thermodynamic studies have confirmed the binding interaction of PTR with PL as hydrophobic. Furthermore, molecular docking studies showed that PTR interacted in the catalytic active amino side residue (Ser153-Asp80-His264) of the protein (1ETH) by hydrogen bonds with affinity (ΔG = −7.0 kcal/mol). The findings of the study support PTR as a potential lead for further validation in animal studies to lead toward clinical translation as an anti-obesity supplement.
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