Elucidation of anti-inflammatory activity of a new cyclic alkaloid compound from root bark of ziziphus nummularia (aubrev.): in vitro, in silico and in vivo studies

Inflammatory diseases present a significant burden to global health, often requiring targeted and specific therapeutic agents for effective management. Ziziphus nummularia (Aubrev.), a traditional medicinal plant, offers a potential source for these agents. This article aims to explore the anti-inflammatory potential of a novel cyclic alkaloid compound isolated from the root bark of Ziziphus nummularia. The cyclic alkaloid compound, [(16-methoxy-10-(3-methyl-butyl)-2-oxa-6, 9, 12-triaza-tricyclo [13.3.1.03, 7] nonadeca-1(18), 13, 15(19), 16-tetraene-8, 11-Dione], exhibited promising anti-inflammatory properties. The potential of this isolated compound (IC) was evaluated in vitro by measuring the levels of nitric oxide (NO), prostaglandin-E2 (PGE2), and tumor necrosis factor-alpha (TNF-α). Additionally, Absorption, Distribution, Metabolism, and Excretion (ADME) simulations and molecular docking to the TNF-α receptor were carried out for IC. In vivo evaluations of both the IC and its ethanolic extract (EE) were performed using carrageenan-induced paw oedema and arachidonic acid/xylene-induced ear oedema tests. The IC showed a higher inhibition of TNF-α compared to other compounds, reaching a maximum inhibition of 88.00% at a concentration of 50.11 μM. In silico analysis revealed that IC formed hydrogen bonds with residues, aspartate at position 45 (ASP 45) and glutamine at position 47 (GLN 47). The IC significantly attenuated oedema induced by carrageenan, xylene, and arachidonic acid. Hence, this compound may offer a potential therapeutic approach for treating inflammation in future clinical applications.