New Lanostanes and Naphthoquinones Isolated from Antrodia salmonea and their Antioxidative Burst Activity in Human Leukocytes

Abstract

Four new compounds were isolated from the basidiomata of the fungus Antrodia salmonea, a newly identified species of Antrodia (Aphyllophorales) in Taiwan. These new compounds are named as lanosta-8,24-diene-3β,15α,21-triol (1), 24-methylenelanost-8-ene-3β,15α,21-triol (2), 2,3-dimethoxy-5-(2′,5′-dimethoxy-3′,4′-methylenedioxyphenyl)-7-methyl-[1] [4]-naphthoquinone (3), and 2,3-dimethoxy-6-(2′,5′-dimethoxy-3′,4′-methylenedioxyphenyl)-7-methyl-[1] [4]-naphthoquinone (4), respectively. Their structures were elucidated by spectroscopic methods. An in vitro cellular functional assay was performed to evaluate their anti-oxidative burst activity in human leukocytes. They showed inhibitory effects against phorbol 12-myristate-13-acetate (PMA), a direct protein kinase C activator, induced oxidative burst in neutrophils (PMN) and mononuclear cells (MNC) with 50 % inhibitory concentration (IC₅₀) ranging from 3.5 to 25.8 μM. The potency order of these compounds in PMA-activated leukocytes was as 1 > 3 > 4 > 2. They were relatively less effective in formyl-Met-Leu-Phe (fMLP), a G-protein coupled receptor agonist, induced oxidative burst, except for compounds 3 and 4 in fMLP-activated PMN. These results indicated that three (1, 3, and 4) of these four newly identified compounds displayed anti-oxidative effect in human leukocytes with different potency and might confer anti-inflammatory activity to these drugs.

Key words

Polyporaceae - Antrodia salmonea - lanostane - naphthoquinone - anti-oxidative activity

References

• 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, Taiwan; 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 micrantham .  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, Chou C J. New ergostane and lanostane 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. Evalution 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 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
• 14 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 71-9
• 15 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
• 16 Williams F M. Role of neutrophils in respiratory injury. In: Immunopharmacology of Neutrophils, Hellewell PG, Williams TJ, editors San Diego; Academic Press 1994: p. 245-57
• 17 Nathan C. Points of control in inflammation.  Nature. 2002;  420 846-52