Methyl 9-Oxo-(10E,12E)-octadecadienoate Isolated from Fomes fomentarius Attenuates Lipopolysaccharide-Induced Inflammatory Response by Blocking Phosphorylation of STAT3 in Murine Macrophages

Fomes fomentarius is a fungus of the Polyporaceae family and is used in traditional oriental therapies. Although the anti-inflammatory activities of this species have been previously reported, the identity of the bioactive compounds responsible for this activity remains unknown. Here, we investigated whether methyl 9-oxo-(10E,12E)-octadecadienoate (FF-8) purified from F. fomentarius exerts anti-inflammatory activity in murine macrophages stimulated with lipopolysaccharide (LPS). FF-8 suppressed secretion of nitric oxide (NO) and prostaglandin E2 through downregulation of inducible NO synthase and cyclooxygenase-2 expression induced by LPS. In addition, pretreatment of cells with FF-8 led to a reduction in levels of secreted inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 in macrophages stimulated with LPS. Conversely, FF-8 did not affect nuclear factor kappaB, p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase pathways. Instead, FF-8 specifically interfered with signal transducer and activator of transcription 3 (STAT3) phosphorylation induced by LPS. Collectively, this study demonstrated that FF-8 purified from F. fomentarius suppresses inflammatory responses in macrophages stimulated with LPS by inhibiting STAT3 activation. Further studies will be required to elucidate the anti-inflammatory effect of FF-8 in vivo.

Differential Modulation of Lipopolysaccharide-Induced Inflammatory Cytokine Production by and Antioxidant Activity of Fomentariol in RAW264.7 Cells

Medicinal mushrooms have been used worldwide to treat cancer and modulate the immune system. Over the last several years, there has been increasing interest in isolating bioactive compounds from medicinal mushrooms and evaluating their health beneficial effects. Fomes fomentarius is used in traditional oriental medicine and is known to possess antioxidant, anti-inflammatory, antidiabetic, and antitumor effects. In the present study, we isolated fomentariol from Fomes fomentarius and investigated its anti-inflammatory effect in murine macrophages (RAW264.7 cells) stimulated with lipopolysaccharides. Fomentariol inhibited the production of nitric oxide and intracellular reactive oxygen species triggered by lipopolysaccharides. Interestingly, fomentariol differentially regulated cytokine production triggered by lipopolysaccharides. Fomentariol effectively suppressed the production of interleukin-1beta and interleukin-6 but not tumor necrosis factor-alpha. The inhibitory effect of fomentariol against nitric oxide, interleukin-1beta, and interleukin-6 production was possibly mediated by downregulation of the extracellular signal-regulated kinase signaling pathway. Taken together, our results suggest that fomentariol differentially modulated inflammatory responses triggered by lipopolysaccharides in macrophages and is one of the bioactive compounds that mediate the physiological effects of Fomes fomentarius.

Chemical constituents of Forties fomentarius (L. Ex. Fr.): Part (II) / 中国药学杂志

OBJECTIVE: To study the chemical constituents of Fomes fomentarius (L. Ex. Fr.). METHODS: The compounds were isolated by chromatography on silica gel column, Sephadex LH - 20 column, and their structures were elucidated by spectral analysis. RESULTS: Six compounds were obtained and identified as fomentarinin (1), 2-hydroxy hexacosanoic acid ethyl ester (2), syringic acid (3), syringyl alcohol (4), vanillin (5), and ergosta-7, 22-diene-3, 6-dione (6), respectively. CONCLUSION: Compound 1 is a new compound, and compound 2-6 are isolated from the fungus for the first time.