Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells

Toxicol Appl Pharmacol. 2014 Nov 1;280(3):434-42. doi: 10.1016/j.taap.2014.09.007. Epub 2014 Sep 16.

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.

Keywords: Anti-inflammatory effect; Ganoderma lucidum; Heme oxygenase-1; Lanostane triterpenes; Nrf2; PI3K/AKT pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / antagonists & inhibitors
  • Acetylcysteine / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Chromones / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / immunology*
  • Inflammation / enzymology
  • Inflammation / immunology*
  • Macrophages
  • Mice
  • Morpholines / pharmacology*
  • RNA / chemistry
  • RNA / genetics
  • Reishi / chemistry*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triterpenes / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • Triterpenes
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • RNA
  • Heme Oxygenase-1
  • Acetylcysteine