Anti-Inflammatory Ergostanes from the Basidiomata of Antrodia salmonea

Abstract

Three new anti-oxidative ergostanes, methyl antcinate L (1), antcin M (2), and methyl antcinate K (3), together with nine additional known compounds, 3-ketodehydrosulphurenic acid, sulphurenic acid, dehydrosulphurenic acid, 3β,15α-dihydroxylanosta-7,9(11),24-trien-21-oic acid, zhankuic acid A, zhankuic acid B, zhankuic acid C, antcin C, and antcin K were isolated from the basidiomata of Antrodia salmonea, a newly identified species of Antrodia (Polyporaceae) in Taiwan. These three new compounds were identified as methyl 3α,7α,12α-trihydroxy-4α-methylergosta-8,24(29)-dien-11-on-26-oate (1), 3α,12α-dihydroxy-4α-methylergosta-8,24(29)-dien-11-on-26-oic acid (2), and methyl 3α,4β,7β-trihydroxy-4α-methylergosta-8,24(29)-dien-11-on-26-oate (3) by spectroscopic analysis. We studied their antioxidative potential on the production of reactive oxygen species and nitric oxide (NO) in neutrophils and microglial cells, respectively. Compounds 1 - 3 displayed potent antioxidative activity with IC₅₀ values of around 2.0 - 8.8 μM that was partially due to inhibition (6 - 67 %) of NADPH oxidase activity but not through direct radical-scavenging properties. Compounds 1 - 3 also inhibited NO production with IC₅₀ values of around 1.7 - 16.5 μM and were more potent than a non-specific NOS inhibitor. We conclude that these three new compounds 1, 2, and 3 exhibit anti-inflammatory activities in activated inflammatory cells.

Polyporaceae - Antrodia salmonea - ergostane - lanostane - microglial cell - neutrophils - reactive oxygen species - nitric oxide (NO)

References

1 Y. H. Wang and T. T. Chang contributed to this work equally

• 1 Chang T T, Chou W N. Antrodia cinnamomea reconsidered and A. salmonea sp. nov. on Cunninghamia konishii in Taiwan.  Bot Bull Acad Sin. 2004;  45 347-52.
• 2 Tsai Z T, Liaw S L. The use and the effect of Ganoderma. Taichung; Sheng-Yun Publishers, Inc 1982.
• 3 Cherng I H, Chiang H C, Cheng M C, Wang Y. Three new triterpenoids from Antrodia cinnamomea .  J Nat Prod. 1995;  58 365-71.
• 4 Chen C H, Yang S W, Shen Y C. New steroid acids from Antrodia cinnamomea, a fungal parasite of Cinnamomum micranthum .  J Nat Prod. 1995;  58 1655-61.
• 5 Chiang H C, Wu D P, Cherng I W, Ueng C H. A sesquiterpene lactone, phenyl and biphenyl compounds from Antrodia cinnamomea .  Phytochemistry. 1995;  39 613-6.
• 6 Wu D P, Chiang H C. Constituents of Antrodia cinnamomea .  J Chin Chem Soc. 1995;  42 797-800.
• 7 Cherng I H, Wu D P, Chiang H C. Triterpenoids from Antrodia cinnamomea .  Phytochemistry. 1996;  41 263-7.
• 8 Yang S W, Shen Y C, Chen C H. Steroids and triterpenoids of Antrodia cinnamomea-a fungus parasitic on Cinnamomum micranthum .  Phytochemistry. 1996;  41 1389-92.
• 9 Shen Y C, Yang S W, Lin C S, Chen C H, Kuo Y H, Chen C F. Zhankuic acid F: a new metabolite from a formosan fungus Antrodia cinnamomea .  Planta Med. 1997;  63 86-8.
• 10 Huang K F, Huang W M, Chiang H C. Phenyl compounds from Antrodia cinnamomea .  Chin Pharm J. 2001;  53 327-31.
• 11 Shen C C, Kuo Y C, Huang R Y, Lin L C, Don M J, Chang T T. et al . New ergostanes and lanostanes from Antrodia camphorata .  J Chin Med. 2003;  14 247-58.
• 12 Shen Y C, Chen C F, Wang Y H, Chang T T, Chou C J. Evaluation of the immuno-modulating activity of some active principles isolated from the fruiting bodies of Antrodia camphorata .  Chin Pharm J. 2003;  55 313-8.
• 13 Huang R L, Huang Q L, Chen C F, Chang T T, Chou C J. Anti-viral effects of active compounds from Antrodia camphorata on wild-type and lamivudine-resistant mutant HBV.  Chin Pharm J. 2003;  55 371-9.
• 14 Shen Y C, Wang Y H, Chou Y C, Chen C F, Lin L C, Chang T T. et al . Evaluation of the anti-inflammatory activity of zhankuic acids isolated from the fruiting bodies of Antrodia camphorata .  Planta Med. 2004;  70 310-4.
• 15 Shen C C, Shen Y C, Wang Y H, Lin L C, Don M J, Liou K T. et al . New lanostanes and naphthoquinones isolated from Antrodia salmonea and their antioxidative burst activity in human leukocytes.  Planta Med. 2006;  72 199-203.
• 16 Anderson C G, Epstein W W, Van Lear G. Minor triterpenoids of Fomes officinalis .  Phytochemistry. 1972;  11 2847-52.
• 17 Yoshikawa K, Matsumoto K, Mine C, Bando S, Arihara S. Five lanostane triterpenoids and three saponins from the fruit body of Laetiporus versisporus .  Chem Pharm Bull. 2000;  48 1418-21.
• 18 Wang Y H, Wang W Y, Chang C C, Liou K T, Sung Y J, Liao J F. et al . Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation.  J Biomed Sci. 2006;  13 127-41.
• 19 Lin L C, Wang Y H, Hou Y C, Chang S, Liou K T, Chou Y C. et al . The inhibitory effect of phenylpropanoid glycosides and iridoid glucosides on free radical production and beta2 integrin expression in human leukocytes.  J Pharm Pharmacol. 2006;  58 129-35.
• 20 Williams F M. Role of neutrophils in respiratory injury. In: Hellewell PG, Williams TJ, editors Immunopharmacology of neutrophils. San Diego; Acedemic Press 1994: 245-57.
• 21 Nathan C. Points of control in inflammation.  Nature. 2002;  420 846-52.
• 22 Van den Worm E, Beukelman C J, Van den Berg A J, Kroes B H, Labadie R P, Van Dijk H. Effects of methoxylation of apocynin and analogs on the inhibition of reactive oxygen species production by stimulated human neutrophils.  Eur J Pharmacol. 2001;  433 225-30.
• 23 Li J, Baud O, Vartanian T, Volpe J J, Rosenberg P A. Peroxynitrite generated by inducible nitric oxide synthase and NADPH oxidase mediates microglial toxicity to oligodendrocytes.  Proc Natl Acad Sci USA. 2005;  102 9936-41.