New Constituents with iNOS Inhibitory Activity from Mycelium of Antrodia camphorata

Abstract

In continuing our investigation on the bioactive constituents of mycelium of Antrodia camphorata, antroquinonol B (1), 4-acetyl-antroquinonol B (2), 2,3-(methylenedioxy)-6-methylbenzene-1,4-diol (3) and 2,4-dimethoxy-6-methylbenzene-1,3-diol (4) along with antrodin D (5) were isolated by the guidance of an inducible nitric oxide synthase (iNOS) inhibitory assay and identified on the basis of their spectroscopic analysis. The effect of these compounds on the inhibition of NO production in lipopolysaccharide (LPS)-activated murine macrophages was further evaluated. Compounds 4 and 5 significantly inhibited NO production without any cytotoxicity, the IC₅₀ values being 32.2 ± 0.1 and 26.3 ± 1.6 µg/mL, respectively. Compounds 1 and 2 possessed greater effects on NO inhibition, with IC₅₀ values of 16.2 ± 0.8 and 14.7 ± 2.8 µg/mL, respectively, but displayed cytotoxicity at considerably higher concentrations. Compound 3 showed the lowest percent cell viability of 45.5 ± 1.8 % as observed in treated cells at a concentration of 16.8 µg/mL.

Supporting information available online at http://www.thieme-connect.de/ejournals/toc/plantamedica

Key words

Antrodia camphorata - Polyporaceae - mycelium - antroquinonol B - iNOS

References

• 1 Chen C C, Shiao Y J, Lin R D, Shao Y Y, Lai M N, Lin C C, Ng L T, Kuo Y H. Neuroprotective diterpenes from the fruiting body of Antrodia camphorata.  J Nat Prod. 2006;  69 689-691
• 2 Wang G J, Tseng H W, Chou C J, Tsai T H, Chen C T, Lu M K. The vasorelaxation of Antrodia camphorata mycelia: involvement of endothelial Ca2+-NO-cGMP pathway.  Life Sci. 2003;  73 2769-2783
• 3 Cheng P C, Hsu C Y, Chen C C, Lee K M. In vivo immunomodulatory effects of Antrodia camphorata polysaccharides in a T1/T2 doubly transgenic mouse model for inhibiting infection of Schistosoma mansoni.  Toxicol Appl Pharmacol. 2008;  227 291-298
• 4 Shen Y C, Chou C J, Wang Y H, Chen C F, Chou Y C, Lu M K. 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;  231 137-143
• 5 Lee I H, Huang R L, Chen C T, Chen H C, Hsu W C, Lu M K. Antrodia camphorata polysaccharides exhibit anti-hepatitis B virus effects.  FEMS Microbiol Lett. 2002;  209 63-67
• 6 Liu D Z, Liang H J, Chena C H, Sub C H, Lee T H, Huanga C T, How W C, Lin S Y, Zhong W B, Lin P J, Hung L F, Liang Y C. Comparative anti-inflammatory characterization of wild fruiting body, liquid-state fermentation, and solid-state culture of Taiwanofungus camphoratus in microglia and the mechanism of its action.  J Ethnopharmacol. 2007;  113 45-53
• 7 Tatemichi M, Sawa T, Gilibert I, Tazawa H, Katoh T, Ohshima H. Increased risk of intestinal type of gastric adenocarcinoma in Japanese women associated with long forms of CCTTT pentanucleotide repeat in the inducible nitric oxide synthase promoter.  Cancer Lett. 2005;  217 197-202
• 8 Nagy G, Clark J M, Buzás E I, Gorman C L, Cope A P. Nitric oxide, chronic inflammation and autoimmunity.  Immunol Lett. 2007;  111 1-5
• 9 Rubbo H, Batthyany C, Radi R. Nitric oxide-oxygen radicals interactions in atherosclerosis.  Biol Res. 2000;  33 167-175
• 10 Wang G J, Chen S M, Chen W C, Chang Y M, Lee T H. Selective inducible nitric oxide synthase suppression by new bracteanolides from Murdannia bracteata.  J Ethnopharmacol. 2007;  112 221-227
• 11 Han H F, Hirakawa A, Zuo F, Nakamura N, Hattori M. Quantitative determination of maleic and succinic acid derivatives in the mycelium of Antrodia cinnamomea.  J Tradit Med. 2006;  23 19-23
• 12 Lee T H, Lee C K, Tsou W L, Liu S Y, Kuo M T, Wen W C. A new cytotoxic agent from solid-state fermented mycelium of Antrodia camphorata.  Planta Med. 2007;  73 1412-1415
• 13 Pihlaja K, Kleinpeter E. Carbon-13 NMR chemical shifts in structural and stereochemical analysis. New York; VCH Publishers, Inc. 1994: 231
• 14 Chiang H C, Wu D P, Cherng I W, Ueng C H. A sesquiterpene lactone, phenyl and biphenyl compounds from Antrodia cinnamomea.  Phytochemistry. 1995;  39 613-616
• 15 Chen J J, Lin W J, Liao C H, Shieh P C. Anti-inflammatory benzenoids from Antrodia camphorata.  J Nat Prod. 2007;  70 989-992
• 16 Zhang G L, Wang Y H, Teng H L, Lin Z B. Effects of aminoguanidine on nitric oxide production induced by inflammatory cytokines and endotoxin in cultured rat hepatocytes.  World J Gastroenterol. 2001;  7 331-334