title: Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells.
abstract: Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE2, butyl lucidenateD2 (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting the involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Solip
authors.initials: S
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan 712-702, Republic of Korea.
authors.forename: Van Thu
authors.initials: VT
authors.lastname: Nguyen
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Nara
authors.initials: N
authors.lastname: Tae
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Suhyun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Ryoo
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan 712-702, Republic of Korea.
authors.forename: Byung-Sun
authors.initials: BS
authors.lastname: Min
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701, Republic of Korea. Electronic address: jhlee36@kangwon.ac.kr.
authors.forename: Jeong-Hyung
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000111:Acetylcysteine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000201:enzymology / Q000276:immunology*; D008264:Macrophages; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020940:Reishi / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D014315:Triterpenes; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D012313:RNA; D051547:Heme Oxygenase-1; D000111:Acetylcysteine
keywords: Anti-inflammatory effect; Ganoderma lucidum; Heme oxygenase-1; Lanostane triterpenes; Nrf2; PI3K/AKT pathway