Inflammation contributes to the progression of numerous chronic diseases, and plants are a rich source of bioactive secondary metabolites. In this study, bioassay-guided isolation of the previously unexplored Australian native plant Beyeria viscosa (Labill.) Miq. yielded eleven known compounds (1–11). The chemical structures of these compounds were identified by detailed spectroscopic data analysis, and definitive structural confirmation was established using single-crystal X-ray crystallography for fritillebic acid (8) and herbacetin 3,7,8-trimethyl ether (5) for the first time. All compounds were first screened for nitric oxide (NO) inhibitory activity and cytotoxicity in lipopolysaccharide (LPS) and interferon (IFN)-γ-stimulated RAW 264.7 macrophages, and the active NO inhibitors were further assessed for tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) inhibition. Notably, compounds 5, 8, and 10 were evaluated for NO inhibitory activity for the first time, with compound 8 being the most potent (IC50 = 8.8 ± 1.3 μM), compound 10 showing moderate potency (IC50 = 12.2 ± 8.8 μM), and compound 5 being inactive. Among all tested compounds, fritillebic acid (8) emerged as the most active constituent, showing strong NO inhibition and moderate suppression of TNF-α and IL-6 production; therefore, it was further assessed in LPS-stimulated N-11 microglial cells, where it retained NO inhibitory activity (IC50 = 12.3 ± 0.5 μM) with a favorable activity–cytotoxicity profile (LC50 = 107.9 ± 1.9 μM). Consistent with the promising activity, molecular docking of compound 8 showed strong receptor-binding affinity with selected inflammation-related targets. Moreover, preliminary structure–activity relationship analysis of all isolated compounds suggested that substitution and oxygenation patterns may influence NO inhibitory potency. Overall, these findings identify fritillebic acid as the major anti-inflammatory lead from B. viscosa and highlight Australian native plants as a source of bioactive secondary metabolites.
Shahid et al. (Sun,) studied this question.