*Article* **Anti-Inflammatory Effects of** *Mitrephora sirikitiae* **Leaf Extract and Isolated Lignans in RAW 264.7 Cells**

**Supachoke Mangmool 1, Chayaporn Limpichai 2, Khine Kyi Han 3, Vichai Reutrakul 4,5 and Natthinee Anantachoke 2,5,\***


**Abstract:** *Mitrephora sirikitiae* 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 antiinflammatory effects of *M. sirikitiae* leaves and their lignan compounds have not been fully elucidated. Therefore, this study aimed to investigate the anti-inflammatory activities of methanol extract of *M. sirikitiae* 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 *M. sirikitiae* leaves and its isolated lignans, including (−)-phylligenin (**2**) and 3 ,4-*O*-dimethylcedrusin (**6**) significantly decreased LPS-induced prostaglandin E2 (PGE2) and nitric oxide (NO) productions. These inhibitory effects of the extract and isolated lignans on LPS-induced upregulation of PGE2 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 (**3**) and mitrephoran (**5**) was able to suppress LPS-induced tumor necrosis factor alpha (TNF-α) secretion and synthesis in RAW 264.7 cells. These results demonstrated that *M. sirikitiae* leaves and some isolated lignans exhibited potent anti-inflammatory activity through the inhibition of secretion and synthesis of PGE2, NO, and TNF-α.

**Keywords:** *Mitrephora sirikitiae*; anti-inflammation; lignans; polyphenols; mRNA expression; cytokines
