Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Inflamamtion and Immunopharamcology

Modulation of inflammation-related genes of polysaccharides fractionated from mycelia of medicinal basidiomycete Antrodia camphorata

Abstract

Aim:

To investigate the effect of water soluble-ethanol precipitation fraction (AC-1) and alkaline extraction-isoelectric precipitation fraction (AC-2) from Antrodia camphorata (Polyporaceae, Aphyllophorales) on lipopolysaccharide (LPS)-induced gene activation in mouse macrophages.

Methods:

The AC-1 and AC-2 fractions were prepared, and their effects on LPS-induced gene expression were monitored by Western blotting and RT-PCR.

Results:

Our results indicated that AC-2, but not AC-1 dose-dependently (50–200 mg/L) inhibited LPS-induced nitric oxide production as well as the protein and the mRNA expression of the inducible nitric oxide synthase (iNOS) gene. Neither AC-1 nor AC-2 inhibited LPS-induced cyclooxygenase-2 gene expression. Using the cytokine array assay, it showed that AC-2 also had the ability to inhibit LPS-induced the protein expression of interleukin (IL)-6, IL-10, the monocyte chemoattractant protein (MCP)-5, and regulated upon activation, normal T-cell expressed, and presumably secreted (RANTES). Like iNOS, AC-2 inhibiting LPS-induced IL-6 and IL-10 secretion resulted from inhibiting their mRNA expression.

Conclusion:

It was suggested that alkaline extraction-isoelectric precipitated the polysaccharide fraction of A camphorata and had the ability to inhibit LPS-induced iNOS, IL-6, IL-10, MCP-5, and RANTES expression in mouse macrophages.

References

  1. Tsai Z, Liaw S . The use and the effect of Ganoderma. Taichung, Taiwan: Sheng-Tun Publishers; 1982.

    Google Scholar 

  2. Hseu YC, Chang WC, Hseu YT, Lee CY, Yech YJ, Chen PC, et al. Protection of oxidative damage by aqueous extract from Antrodia camphorata mycelia in normal human erythrocytes. Life Sci 2002; 71: 469–82.

    CAS  Article  Google Scholar 

  3. Song TY, Yen GC . Protective effects of fermented filtrate from Antrodia camphorata in submerged culture against CCl4-induced hepatic toxicity in rats. J Agric Food Chem 2003; 51: 1571–7.

    CAS  Article  Google Scholar 

  4. Hsiao G, Shen MY, Lin KH, Lan MH, Wu LY, Chou DS, et al. Antioxidative and hepatoprotective effects of Antrodia camphorata extract. J Agric Food Chem 2003; 51: 3302–8.

    CAS  Article  Google Scholar 

  5. Shen YC, Chou CJ, Wang YH, Chen CF, Chou YC, Lu MK . Anti-inflammatory activity of the extracts from mycelia of Antrodia camphorata cultured with water-soluble fractions from five different Cinnamomum species. FEMS Microbiol Lett 2004; 231: 137–43.

    CAS  Article  Google Scholar 

  6. Hseu YC, Wu FY, Wu JJ, Chen JY, Chang WH, Lu FJ, et al. Anti-inflammatory potential of Antrodia Camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-kappaB pathway. Int Immunopharmacol 2005; 5: 1914–25.

    CAS  Article  Google Scholar 

  7. Hseu YC, Yang HL, Lai YC, Lin JG, Chen GW, Chang YH . Induction of apoptosis by Antrodia camphorata in human premyelocytic leukemia HL-60 cells. Nutr Cancer 2004; 48: 189–97.

    Article  Google Scholar 

  8. Hsu YL, Kuo YC, Kuo PL, Ng LT, Kuo YH, Lin CC . Apoptotic effects of extract from Antrodia camphorata fruiting bodies in human hepatocellular carcinoma cell lines. Cancer Lett 2005; 221: 77–89.

    CAS  Article  Google Scholar 

  9. Song TY, Hsu SL, Yen GC . Induction of apoptosis in human hepatoma cells by mycelia of Antrodia camphorata in submerged culture. J Ethnopharmacol 2005; 100: 158–67.

    Article  Google Scholar 

  10. Song T Y, Hsu SL, Yeh CT, Yen GC . Mycelia from Antrodia camphorata in submerged culture induce apoptosis of human hepatoma HepG2 cells possibly through regulation of Fas pathway. J Agric Food Chem 2005; 53: 5559–64.

    CAS  Article  Google Scholar 

  11. Lee IH, Huang RL, Chen CT, Chen HC, Hsu WC, Lu MK . Antrodia camphorata polysaccharides exhibit anti-hepatitis B virus effects. FEMS Microbiol Lett 2002; 209: 63–7.

    CAS  Article  Google Scholar 

  12. Jong SC, Birmingham JM . Medicinal and therapeutic value of the shiitake mushroom. Adv Appl Microbiol 1993; 39: 153–84.

    CAS  Article  Google Scholar 

  13. Mizuno T, Wasa T, Ito H, Suzuki C, Ukai N . Antitumor-active polysaccharides isolated from the fruiting body of Hericium erinaceum, an edible and medicinal mushroom called yamabu-shitake or houtou. Biosci Biotechnol Biochem 1992; 56: 347–8.

    CAS  Article  Google Scholar 

  14. Liu JJ, Huang TS, Hsu ML, Chen CC, Lin WS, Lu FJ, et al. Antitumor effects of the partially purified polysaccharides from Antrodia camphorata and the mechanism of its action. Toxicol Appl Pharmacol 2004; 201: 186–93.

    CAS  Article  Google Scholar 

  15. Cheng JJ, Yang CJ, Cheng CH, Wang YT, Huang NK, Lu MK . Characterization and functional study of Antrodia camphorata lipopolysaccharide. J Agric Food Chem 2005; 53: 469–74.

    CAS  Article  Google Scholar 

  16. Green SJ, Nacy CA, Meltzer MS . Cytokine-induced synthesis of nitrogen oxides in macrophages: a protective host response to Leishmania and other intracellular pathogens. J Leukoc Biol 1991; 50: 93–103.

    CAS  Article  Google Scholar 

  17. Lorsbach RB, Murphy WJ, Lowenstein CJ, Snyder SH, Russell SW . Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide. J Biol Chem 1993; 268: 1908–13.

    CAS  PubMed  Google Scholar 

  18. Nussler AK, Billiar TR . Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol 1993; 54: 171–8.

    CAS  Article  Google Scholar 

  19. Sano H, Hla T, Maier JA, Crofford LJ, Case JP, Maciag T, et al. In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis. J Clin Invest 1992; 89: 97–108.

    CAS  Article  Google Scholar 

  20. Kargman SL, O'Neill GP, Vickers PJ, Evans JF, Mancini JA, Jothy S . Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancer. Cancer Res 1995; 55: 2556–9.

    CAS  PubMed  Google Scholar 

  21. O'Sullivan MG, Chilton FH, Huggins EM Jr, McCall CE . Lipopolysaccharide priming of alveolar macrophages for enhanced synthesis of prostanoids involves induction of a novel prostag-landin H synthase. J Biol Chem 1992; 267: 14547–50.

    CAS  PubMed  Google Scholar 

  22. Chen LC, Chen BK, Chang JM, Chang WC . Essential role of c-Jun induction and coactivator p300 in epidermal growth factor-induced gene expression of cyclooxygenase-2 in human epidermoid carcinoma A431 cells. Biochim Biophys Acta 2004; 1683: 38–48.

    CAS  Article  Google Scholar 

  23. Ker YB, Chen KC, Chyau CC, Chen CC, Guo JH, Hsieh CL, et al. Antioxidant capability of polysaccharides fractionated from sub-merge-cultured Agaricus blazei mycelia. J Agric Food Chem 2005; 53: 7052–8.

    CAS  Article  Google Scholar 

  24. Akira S, Takeda K . Toll-like receptor signalling. Nat Rev Immunol 2004; 4: 499–511.

    CAS  Article  Google Scholar 

  25. Kamimura D, Ishihara K, Hirano T . IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol 2003; 149: 1–38.

    CAS  PubMed  Google Scholar 

  26. Castell JV, Gomez-Lechon MJ, David M, Hirano T, Kishimoto T, Heinrich PC . Recombinant human interleukin-6 (IL-6/BSF-2/HSF) regulates the synthesis of acute phase proteins in human hepatocytes. FEBS Lett 1988; 232: 347–50.

    CAS  Article  Google Scholar 

  27. Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, et al. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 1994; 368: 339–42.

    CAS  Article  Google Scholar 

  28. Koss K, Satsangi J, Welsh KI, Jewell DP . Is interleukin-6 important in inflammatory bowel disease?*. Genes Immun 2000; 1: 207–12.

    CAS  Article  Google Scholar 

  29. Wong PK, Campbell IK, Egan PJ, Ernst M, Wicks IP . The role of the interleukin-6 family of cytokines in inflammatory arthritis and bone turnover. Arthritis Rheum 2003; 48: 1177–89.

    CAS  Article  Google Scholar 

  30. Fiorentino DF, Bond MW, Mosmann TR . Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 1989; 170: 2081–95.

    CAS  PubMed  Google Scholar 

  31. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O'Garra A . IL-10 inhibits cytokine production by activated macrophages. J Immunol 1991; 147: 3815–22.

    CAS  PubMed  Google Scholar 

  32. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE . Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 1209–20.

    CAS  Article  Google Scholar 

  33. Del Prete G, De Carli M, Almerigogna F, Giudizi MG, Biagiotti R, Romagnani S . Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol 1993; 150: 353–60.

    CAS  PubMed  Google Scholar 

  34. Takanaski S, Nonaka R, Xing Z, O'Byrne P, Dolovich J, Jordana M . Interleukin 10 inhibits lipopolysaccharide-induced survival and cytokine production by human peripheral blood eosinophils. J Exp Med 1994; 180: 711–5.

    CAS  Article  Google Scholar 

  35. Jenkins JK, Malyak M, Arend WP . The effects of interleukin-10 on interleukin-1 receptor antagonist and interleukin-1 beta production in human monocytes and neutrophils. Lymphokine Cytokine Res 1994; 13: 47–54.

    CAS  PubMed  Google Scholar 

  36. Beinhauer BG, McBride JM, Graf P, Pursch E, Bongers M, Rogy M, et al. Interleukin 10 regulates cell surface and soluble LIR-2 (CD85d) expression on dendritic cells resulting in T cell hyporesponsiveness in vitro. Eur J Immunol 2004; 34: 74–80.

    CAS  Article  Google Scholar 

  37. Cohen SB, Crawley JB, Kahan MC, Feldmann M, Foxwell BM . Interleukin-10 rescues T cells from apoptotic cell death: association with an upregulation of Bcl-2. Immunology 1997; 92: 1–5.

    CAS  Article  Google Scholar 

  38. Conti P, Kempuraj D, Kandere K, Di Gioacchino M, Barbacane RC, Castellani ML, et al. IL-10, an inflammatory/inhibitory cytokine, but not always. Immunol Lett 2003; 86: 123–9.

    CAS  Article  Google Scholar 

  39. Hobbs AJ, Higgs A, Moncada S . Inhibition of nitric oxide synthase as a potential therapeutic target. Annu Rev Pharmacol Toxicol 1999; 39: 191–220.

    CAS  Article  Google Scholar 

  40. Bogdan C . Nitric oxide and the immune response. Nat Immunol 2001; 2: 907–16.

    CAS  Article  Google Scholar 

  41. Dusting GJ . Nitric oxide in coronary artery disease: roles in atherosclerosis, myocardial reperfusion and heart failure. Exs 1996; 76: 33–55.

    CAS  PubMed  Google Scholar 

  42. Bor JY, Chen H Y, Yen GC . Evaluation of antioxidant activity and inhibitory effect on nitric oxide production of some common vegetables. J Agric Food Chem 2006; 54: 1680–6.

    CAS  Article  Google Scholar 

  43. Aktan F, Henness S, Roufogalis BD, Ammit AJ . Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating NF-kappaB-mediated iNOS protein expression. Nitric Oxide 2003; 8: 235–42.

    CAS  Article  Google Scholar 

  44. Wadsworth TL, Koop DR . Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide. Chem Biol Interact 2001; 137: 43–58.

    CAS  Article  Google Scholar 

  45. Sarafi MN, Garcia-Zepeda EA, MacLean JA, Charo IF, Luster AD . Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a structural and functional homologue of human MCP-1. J Exp Med 1997; 185: 99–109.

    CAS  Article  Google Scholar 

  46. Appay V, Rowland-Jones SL . RANTES: a versatile and controversial chemokine. Trends Immunol 2001; 22: 83–7.

    CAS  Article  Google Scholar 

  47. An SJ, Pae HO, Oh GS, Choi BM, Jeong S, Jang SI, et al. Inhibition of TNF-alpha, IL-1beta, and IL-6 productions and NF-kappa B activation in lipopolysaccharide-activated RAW 264.7 macrophages by catalposide, an iridoid glycoside isolated from Catalpa ovata G Don (Bignoniaceae). Int Immunopharmacol 2002; 2: 1173–81.

    CAS  Article  Google Scholar 

  48. Yan YJ, Li Y, Lou B, Wu MP . Beneficial effects of ApoA-I on LPS-induced acute lung injury and endotoxemia in mice. Life Sci 2006; 79: 210–5.

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yi-wen Liu.

Additional information

Project supported in part by grants (NSC 93-2320-B-415-002 and NSC 94-2313-B-241-004) from the National Science Council of Taiwan, China.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wu, Yy., Chen, Cc., Chyau, Cc. et al. Modulation of inflammation-related genes of polysaccharides fractionated from mycelia of medicinal basidiomycete Antrodia camphorata. Acta Pharmacol Sin 28, 258–267 (2007). https://doi.org/10.1111/j.1745-7254.2007.00500.x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1111/j.1745-7254.2007.00500.x

Keywords

  • Antrodia camphorata
  • cytokines
  • inducible nitric oxide synthase
  • cyclooxygenase-2
  • macrophages

Further reading

Search

Quick links