| Summary: | <i>Mitrephora sirikitiae</i> Weeras., Chalermglin & R.M.K. Saunders has been reported as a rich source of lignans that contribute to biological activities and health benefits. However, cellular anti-inflammatory effects of <i>M. sirikitiae</i> leaves and their lignan compounds have not been fully elucidated. Therefore, this study aimed to investigate the anti-inflammatory activities of methanol extract of <i>M. sirikitiae</i> leaves and their lignan constituents on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 mouse macrophage cells. Treatment of RAW 264.7 cells with the methanol extract of <i>M. sirikitiae</i> leaves and its isolated lignans, including (−)-phylligenin (<b>2</b>) and 3′,4-<i>O</i>-dimethylcedrusin (<b>6</b>) significantly decreased LPS-induced prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and nitric oxide (NO) productions. These inhibitory effects of the extract and isolated lignans on LPS-induced upregulation of PGE<sub>2</sub> and NO productions were derived from the suppression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) production, respectively. In addition, treatment with 2-(3,4-dimethoxyphenyl)-6-(3,5-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane (<b>3</b>) and mitrephoran (<b>5</b>) was able to suppress LPS-induced tumor necrosis factor alpha (TNF-α) secretion and synthesis in RAW 264.7 cells. These results demonstrated that <i>M. sirikitiae</i> leaves and some isolated lignans exhibited potent anti-inflammatory activity through the inhibition of secretion and synthesis of PGE<sub>2</sub>, NO, and TNF-α.
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