Anti-inflammatory activity of Pogostemon cablin: Bioactive components and their modulation of MAPK and NF-κB...

Pogostemon cablin is a well-known Lamiaceae plant and widely utilized in Traditional Chinese Medicine (TCM) for its neuroprotective, anti-inflammatory, and anxiolytic properties. In this study, 16 known compounds (1-15 and 17) and one semi-synthesized new compound, 5-hydroxy-3-isoprenyloxy-7,3',4'-trimethoxyflavone (16), including flavonoids, pyranones, sesquiterpenes, and benzenoids, were obtained and characterized from aerial parts of P. cablin and investigated for their anti-inflammatory properties through the MAPK and NF-κB signaling pathways in LPS-induced RAW264.7 macrophages. Among the isolated compounds, rhamnazin (4), pachypodol (5), and (E)-2-methyl-6-(p-tolyl)hept-3-en-2-ol (15) exhibited potent anti-inflammatory activities in LPS-induced RAW264.7 macrophages. Rhamnazin (4) significantly modulated IκBα levels and reduced the expressions of phosphorylation of JNK and p38, indicating its effects on suppressing NF-κB activation and mitigating inflammation via MAPK signaling. Pachypodol (5) selectively inhibited iNOS and p-JNK expressions, showing specificity in its anti-inflammatory activity. (E)-2-Methyl-6-(p-tolyl)hept-3-en-2-ol (15) downregulated iNOS, p-Erk, and p-JNK expressions, demonstrating a broader inhibitory profile on pro-inflammatory mediators. Further molecular docking results demonstrated bioactive compounds 4, 5, and 15 possessed strong binding affinities with key residues, particularly Hem901, Pro344, and Glu371, consistent with their NO inhibition effects. In addition, in silico prediction of physicochemical properties confirmed favorable oral bioavailability and drug-likeness, supporting their potential as lead compounds for anti-inflammatory drug development. These findings provide comprehensive molecular insight into the anti-inflammatory effects and reveal the therapeutic potential of P. cablin constituents as natural plant-derived NF-κB and MAPK-targeting anti-inflammatory agents, offering promising candidates for managing inflammatory diseases.