Phellinsin A from Phellinus sp. PL3 Exhibits Antioxidant Activities

Abstract

Phellinsin A, which was isolated from the culture broth of Phellinus sp. PL3, exhibited significant low-density lipoproteins (LDL)-antioxidant activity. It inhibited the Cu²⁺-mediated oxidation of LDL (IC₅₀: 5.3 μM) and 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH)-mediated oxidation of LDL (IC₅₀: 2.8 μM) in the thiobarbituric acid-reactive substances (TBARS) assay as well as the macrophage-mediated LDL oxidation (73 % inhibition at 5 μM). In addition, it delayed LDL oxidation with a prolonged lag time (192 min at 2 μM, control: 44 min). This compound also showed a 10-fold more potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (IC₅₀: 1.7 μM) than trolox (IC₅₀: 18.6 μM), a known DPPH inhibitor. In addition, phellinsin A inhibited xanthine oxidase activity with an IC₅₀ value of 31.0 μM, whereas allopurinol, a xanthine oxidase inhibitor, showed an IC₅₀ value of 40.7 μM.

References

• 1 Steinberg D, Parthasarathy S, Carew T E, Khoo J C, Witztum J L. Beyond cholesterol; modifications of low-density lipoprotein that increase its atherogenecity.  N Engl J Med. 1989;  320 915-24
• 2 Regnstrom J, Nilsson J, Tornvall P, Landou C, Hamsten A. Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man.  Lancet. 1992;  339 1183-6
• 3 Carew T E, Schwenke D C, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit.  Proc Natl Acad Sci USA. 1987;  84 7725-9
• 4 Mashima R, Witting P K, Stocker R. Oxidants and antioxidants in atherosclerosis.  Curr Opin Lipidol. 2001;  12 411-8
• 5 Yun S S, Kim S H, Sa J H, Jin C, Lim C J, Park E H. Anti-angiogenic, antioxidant and xanthine oxidase inhibition activities of the mushroom Phellinus linteus .  J Ethnopharmacol. 2003;  88 113-6
• 6 Kim D H, Yang B K, Jeong S C, Park J B, Cho S P, Das S. et al . Production of a hypoglycemic, extracellular polysaccharide from the submerged culture of mushroom Phellinus linteus .  Biotechnol Lett. 2001;  23 513-7
• 7 Hwang E I, Yun B S, Kim Y K, Kwon B M, Kim H G, Lee H B. et al . Phellinsin A, a novel chitin synthases inhibitor produced by Phellinus sp. PL3.  J Antibiot. 2000;  53 903-11
• 8 Buege J A, Aust S D. Microsomal lipid peroxidation.  Methods Enzymol. 1978;  52 302-10
• 9 Lass A, Witting P, Stocker R, Esterbauer H. Inhibition of copper-and peroxy radical-induced LDL lipid oxidation by ebselen: antioxidant actions an in addition to hydroperoxide-reducing activity.  Biochim Biophys Acta. 1996;  1344 300-11
• 10 Thomas M J, Chen Q, Franklin C, Rudel L L. A comparison of the kinetics of low-density lipoprotein oxidation initiated by copper or by azobis(2-amidino-propane).  Free Radic Biol Med. 1997;  23 927-35
• 11 Brukdorfer K R. Non-enzymatic oxidation of lipid lipoproteins: the role of metals and nitric oxide.  Curr Opin Lipidol. 1993;  4 238-43
• 12 Markwell M AK, Hass S M, Tolbert N E, Bieber L L. Protein determination in membrane and lipoprotein sample: manual and automated procedure.  Methods Enzymol. 1981;  72 296-303
• 13 Ahn B T, Lee S K, Lee S B, Lee E S, Kim J G, Bok S H. et al . Low-density lipoprotein-antioxidant constituents of Saururus chinensis .  J Nat Prod. 2001;  64 1562-4
• 14 Esterbauer H, Striegi G, Puhl H, Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein.  Free Radic Res Commun. 1989;  6 67-75
• 15 Blios M S. Antioxidant determinations by the use of a stable free radical.  Nature. 1958;  26 1199-200
• 16 Lee S K, Mbwambo Z H, Chung H S, Luyengi L, Gamez E JC, Mehta R G. et al . Evaluation of the antioxidant potential of natural products.  Comb Chem High Throughput Screen. 1998;  1 35-46
• 17 Jeong T S, Kim K S, Kim J R, Cho K H, Lee S, Lee W S. Novel 3,5-diarylpyrazolines and pyrazole as low-density lipoprotein oxidation inhibitor.  Bioorg Med Chem Lett. 2004;  14 2719-23