Stilbenoids from the melinjo (Gnetum gnemon L.) fruit modulate cytokine production in murine Peyer's patch cells ex vivo.
Melinjo fruit ( Gnetum gnemon L.) has been used as a food in Southeast Asia. To investigate if this fruit has regulatory actions on ileal immune responses, we measured T-helper (Th) cytokine production, i.e., interleukin-2 (IL-2), IL-4, IL-5, and interferon-gamma (IFN- γ), in cultured Peyer's patch (PP) cells from mice orally treated with a methanol extract of melinjo fruit. Oral administration of the 50 % ethanol extract at 100 mg/kg/day significantly enhanced the production of the Th1 cytokines IL-2 and IFN- γ irrespective of concanavalin-A stimulation, whereas the production of the Th2 cytokines IL-4 and IL-5 was not affected. We also isolated seven active constituents accompanied with two new stilbenoids from the ethylacetate fraction of the extracts. The structure of the new stilbene glucosides gnemonoside L (5) and gnemonoside M (7) was determined by 1D and 2D NMR and MS analyses. Five known stilbenoids were identified as resveratrol (1), isorhapontigenin (2), gnemonoside D (4), gnetins C (3) and E (6). Among these tested compounds, only new stilbenoid 7 strongly enhanced Th1 cytokine production in cultured PP cells at 10 mg/kg/day. These results indicated that this melinjo extract and its active constituent 7 potentiated T-cell-dependent immune responses in the ileal mucosa.
Pharmacognosy and Chemistry of Natural Products, School of Pharmacy and Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan.
Hikaru
H
Kato
Masayuki
M
Samizo
Ryosuke
R
Kawabata
Fumihide
F
Takano
Tomihisa
T
Ohta
D000284:Administration, Oral; D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D000431:Ethanol / Q000737:chemistry; D005638:Fruit / Q000737:chemistry; D035684:Gnetum / Q000737:chemistry*; D007082:Ileum / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010581:Peyer's Patches / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D010936:Plant Extracts; D013267:Stilbenes; D003208:Concanavalin A; D015847:Interleukin-4; D000431:Ethanol; D007371:Interferon-gamma