Xanthones from Garcinia pedunculata and Garcinia nujiangensis and their anti-inflammatory activity

Ten new xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), and sixteen known analogues (9-24) were isolated from Garcinia pedunculata Roxb. and G. nujiangensis C. Y. Wu & Y. H. Li. Their structures were established based on their HRESIMS data, extensive NMR spectroscopic analyses, and ECD calculations. All compounds without cytotoxicity were evaluated for their anti-inflammatory properties by measuring the inhibition ratio of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 displayed substantial anti-inflammatory activity with the IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μM, respectively. Enzyme-linked immunosorbent assay (ELISA) revealed that compounds 7b, 19, and 21 inhibited the expression of proinflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory rate of compound 21 on IL-6 at 20 μM was similar to that of the positive control. In the network pharmacology studies, the potential targets of compounds and inflammation were obtained from PharmMapper and GeneCards database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were closely related to the major pathogenic processes linked to inflammation, such as positive regulation of MAPK cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance.