title: Lucidenic acids-rich extract from antlered form of Ganoderma lucidum enhances TNFα induction in THP-1 monocytic cells possibly via its modulation of MAP kinases p38 and JNK.
abstract: The Ganoderma lucidum (G. lucidum) is one of the oriental fungi that has been reported to have immunomodulatory properties. Although effect of β-glucans from G. lucidum has been well documented, little is known about how other major bioactive components, the triterpenes, contribute to the immunomodulatory function of G. lucidum. Here, we showed that triterpenes-rich extract of antlered form of G. lucidum (G. lucidum AF) induces TNFα production in monocytic THP-1 cells. Furthermore, the extract also synergized with lipopolysaccharide (LPS) to induce TNFα production in THP-1 cells, suggesting an immunostimulatory role of triterpenes-rich extract of G. lucidum AF. Notably, the extract enhanced LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), while it suppressed LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK) MAPK. p38 Inhibitor suppressed TNFα production, while JNK inhibitor enhanced TNFα production, implying that synergistic effect of the extract may work by modulating p38 and JNK MAPKs. Moreover, we found that the triterpenes-rich extract of G. lucidum AF contains high amounts of lucidenic acids. Lucidenic acid-A, -F and -D(2), which seem to dominantly exist in the extract, were purified from the triterpenes-rich extract. We also identified Lucidenic acid-A and -F as modulators of JNK and p38, respectively. Thus, our data demonstrate that lucidenic acids-rich extract from G. lucidum AF enhances LPS-induced immune responses in monocytic THP-1 cells possibly via the modulation of p38 and JNK MAPKs activation.
authors: Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Global COE Cell Fate Regulation Research and Education Unit, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan.
authors: Kenji
authors: K
authors: Watanabe
authors: Tsuyoshi
authors: T
authors: Shuto
authors: Miki
authors: M
authors: Sato
authors: Kouhei
authors: K
authors: Onuki
authors: Shota
authors: S
authors: Mizunoe
authors: Shingo
authors: S
authors: Suzuki
authors: Takashi
authors: T
authors: Sato
authors: Tomoaki
authors: T
authors: Koga
authors: Mary Ann
authors: MA
authors: Suico
authors: Hirofumi
authors: H
authors: Kai
authors: Tsuyoshi
authors: T
authors: Ikeda
mesh_terms: D002460:Cell Line; D002793:Cholic Acids / Q000302:isolation & purification / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D020940:Reishi / Q000737:chemistry*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D002793:Cholic Acids; D004365:Drugs, Chinese Herbal; D007155:Immunologic Factors; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C481150:lucidenic acid A; C559644:lucidenic acid F; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases