Exploring the anti-obesity bioactive compounds of Thymelaea hirsuta and Ziziphus spina-christi through integration of lipase inhibition screening and molecular docking analysis.

Activity-guided fractionation of the ethanolic extracts of Thymelaea hirsuta and Ziziphus spina-christi furnished eight compounds with pancreatic lipase inhibitory activity. Six compounds were isolated from the chloroform fraction of T. hirsuta. It is worth mentioning that this is the first report for the isolation of 5,7,4'-trihydroxy-8-methoxycarbonyl flavanol (2), daphnodorin G-3''-methyl ether (4) and daphnodorin G (5) from genus Thymelaea. Moreover, daphnoretin (1), neochamaejasmin A (3) and daphnodorin B (6) were also isolated from the chloroform fraction of the same plant. On the other hand, quercetin 3-O-α-l-rhamnopyranosyl-(1 → 2)-[α-l-rhamnopyranosyl-(1 → 6)]-β-d-galactopyranoside (7) and 3-O-[α-l-fucopyranosyl-(1 → 2)-β-d-glucopyranosyl-(1 → 3)-α-l-arabinopyranosyl] jujubogenin (christinin A) (8) were isolated from the n-butanol fraction of Z. spina-christi. Structure elucidation of the isolated compounds was carried out by detailed analysis of 1D and 2D spectral data. These compounds showed percentage inhibitions of 72% (1), 52% (2), 61.8% (3), 39% (4), 69.5% (5), 3.5% (6), 68% (7) and 75% (8) at the concentration of 250 μM and XP-G scores of lipase inhibition were 11.40 (1), 8.71 (2), 6.13 (3), 8.23 (4), 6.22 (5), 9.76 (6), 14.66 (7) and 12.00 (8). This is the first report of the isolation of lipase inhibitors from both plants T. hirsuta and Z. spina-christi. In addition to that, this might result in presenting the biscoumarin, daphnoretin, and the dammarane saponin, christinin A, as potent lipase inhibitors.