antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»antibiotics-672Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSСкрининг продуцентов ингибиторов 15-липоксигеназы среди микромицетовScreening of Organisms Producing Inhibitors of 15-Lipoxygenase Among MicromycetesБибиковаМ. В.BibikovaM. V.noemail@neicon.ruСпиридоноваИ. А.SpiridonovaI. A.noemail@neicon.ruДаниленкоА. Н.DanilenkoA. N.noemail@neicon.ruКимЮ. А.KimYu. A.noemail@neicon.ruКорыстоваА. Ф.KorystovaA. F.noemail@neicon.ruШапошниковаВ. В.ShaposhnikovaV. V.noemail@neicon.ruКорыстовЮ. Н.KorystovYu. N.noemail@neicon.ruООО «ВИОРИН»РоссияViorinRussian FederationИнститут биохимической физики им. Н. М. Эммануэля РАНРоссияN.M. Emanuel Institute of Biochemical Physics RASRussian FederationИнститут биофизики клетки РАНРоссияInstitute of Cell Biophysics, Russian Academy of SciencesRussian FederationИнститут теоретической и экспериментальной биофизики РАНРоссияInstitute of Theoretical and Experimental Biophysics, Russian Academy of SciencesRussian Federation201613052020617-839Copyright © ООО «Издательство ОКИ», 20202020ООО «Издательство ОКИ»ООО «Издательство ОКИ»https://www.antibiotics-chemotherapy.ru/jour/about/submissions#copyrightNoticehttps://www.antibiotics-chemotherapy.ru/jour/article/view/672

Исследовали влияние экстрактов, выщеленных из мицелия грибов Lecanicilium lecanii №169, Beauveria fellina №7 и Beauveria bassiana №15 на активность 15-липоксигеназы (15-ЛО), выщеленной из ретикулоцитов крыс. Активность 15-ЛО определяли по окислению лииолевой кислоты. Показано, что экстракт из мицелиальиой массы комплекса грибов ингибирует 15-ЛО (IC50=12 мкг/мл). Ингибирующая 15-ЛО активность комплексного экстракта обусловлена веществами, экстрагируемыми из Lecanicillium lecanii №169. Быии определены фракции экстракта, ответственные за его активность и идентифицированы соединения, содержащиеся в этих фракциях. Ими оказались во фракции 10 - 4-гидроксибензойная кислота и 4-гидроксибензиловыш спирт, во фракции 11 - флавоновд генистеин. Рассмотрена возможная роль ингибирования этими соединениями 15-ЛО в аитиатеросклеротической активности экстракта грибов.

The effects of extracts from the mycelium of Lecanicilium lecanii No.169, Beauveria fellina No.7 and Beauveria bassiana No.15 on the activity of 15-lipoxygenase (15-LO) recovered from rat reticulocytes was investigated. The activity of 15-LO was determined by oxidation of linolic acid. The extract from the mycelium of the fungal complex was shown to inhibit 15-LO (IC50 of 12 mcg/ml). The inhibitory effect of the combined extract on 15-LO was due to the substances recovered from Lecanicilium lecanii No.169. The extract fractions responsible for the activity were determined and the compounds containing the fractions were identified. They proved to be 10 - 4-hydroxybenzoic acid and 4-hydroxybenzyl alcohol and genistein, a flavonoid from fraction 11. The possible role of the inhibitory effect of the compounds on 15-LO in the antiatherosclerotic activity of the fungal extract is discussed.

ингибиторы 15-липоксигеназымикромицетыгенистеин4-гидроксибензойная кислота15-lipoxygenase inhibitorsmicromycetes4-hydrobenzoic acidgenesteinReferencesЧмель Я.В., Бибикова М.В., Спиридонова И.А., Тертов В.В., Катлинский А.В. Скрининг природных соединений с гиполипидемической активностью. Антибиотики и химиотер 2004; 49: 8-12. / Chmel Ja.V, Bibikova M.V, Spiridonova I.A., Tertov V.V., Katlinskij A.V. Skrining prirodnykh soedinenij s gipolipidemicheskoj aktivnost'ju. Antibiotiki i khimioter 2004; 49: 8-12. [in Russian]Чмель Я.В., Бибикова М.В., Спиридонова И.А., Тертов В.В., Катлинский А.В. Скрининг природных соединений с гиполипидемической активностью. Антибиотики и химиотер 2004; 49: 8-12. / Chmel Ja.V, Bibikova M.V, Spiridonova I.A., Tertov V.V., Katlinskij A.V. Skrining prirodnykh soedinenij s gipolipidemicheskoj aktivnost'ju. Antibiotiki i khimioter 2004; 49: 8-12. [in Russian]Бибикова М.В., Пужевская Т.О., Грамматикова Н.Э., Катлинский А.В. Продуценты гиполипидемических соединений с антиоксидантной активностью. Антибиотики и химиотер 2009; 54: 3-7. / Bibikova M.V., Puzhevskaja T.O., Grammatikova N.Je., Katlinskij A.V. Producenty gipolipidemicheskikh soedinenij s antioksidantnoj aktivnost'ju.Antibiotiki i khimioter 2009; 54: 3-7. [in Russian]Бибикова М.В., Пужевская Т.О., Грамматикова Н.Э., Катлинский А.В. Продуценты гиполипидемических соединений с антиоксидантной активностью. Антибиотики и химиотер 2009; 54: 3-7. / Bibikova M.V., Puzhevskaja T.O., Grammatikova N.Je., Katlinskij A.V. Producenty gipolipidemicheskikh soedinenij s antioksidantnoj aktivnost'ju.Antibiotiki i khimioter 2009; 54: 3-7. [in Russian]Пужевская Т.О., Бибикова М.В., Грамматикова Н.Э., Катлинский А.В. Влияние природных гиполипидемических соединений на формирование биоплёнок штаммами рода pseudomonas. Антибиотики и химиотер 2009; 54: 10-13. / Puzhevskaja T.O., Bibikova M.V., Grammatikova N.Je, Katlinskij A.V. Vlijanie prirodnykh gipolipidemicheskikh soedinenij na formirovanie biopljonok shtammami roda pseudomonas. Antibiotiki i khimioter 2009; 54: 10-13. [in Russian]Пужевская Т.О., Бибикова М.В., Грамматикова Н.Э., Катлинский А.В. Влияние природных гиполипидемических соединений на формирование биоплёнок штаммами рода pseudomonas. Антибиотики и химиотер 2009; 54: 10-13. / Puzhevskaja T.O., Bibikova M.V., Grammatikova N.Je, Katlinskij A.V. Vlijanie prirodnykh gipolipidemicheskikh soedinenij na formirovanie biopljonok shtammami roda pseudomonas. Antibiotiki i khimioter 2009; 54: 10-13. [in Russian]Mertens A., Hobvoet P. Oxidized LDL and HDL: antagonists in atherothrombosis. FASEB J 2001; 15: 2073-2084.Mertens A., Hobvoet P. Oxidized LDL and HDL: antagonists in atherothrombosis. FASEB J 2001; 15: 2073-2084.Tsimikas S., Mallat Z., Talmud P.J., Kastelein J.J., Wareham N.J., Sandhu M.S. et al. Oxidation-specific biomarkers, lipoprotein(a), and risk of fatal and nonfatal coronary events. J Am Coll Cardiol 2010; 56: 946-955.Tsimikas S., Mallat Z., Talmud P.J., Kastelein J.J., Wareham N.J., Sandhu M.S. et al. Oxidation-specific biomarkers, lipoprotein(a), and risk of fatal and nonfatal coronary events. J Am Coll Cardiol 2010; 56: 946-955.Климов А.Н., Никульчева Н.Г. Обмен липидов и липопротеидов и его нарушения. С-Петербург: Питер Ком. 1999. / Klimov A.N., Nikul'cheva N.G. Obmen lipidov i lipoproteidov i ego narushenija. S-Peterburg: Piter Kom. 1999. [in Russian]Климов А.Н., Никульчева Н.Г. Обмен липидов и липопротеидов и его нарушения. С-Петербург: Питер Ком. 1999. / Klimov A.N., Nikul'cheva N.G. Obmen lipidov i lipoproteidov i ego narushenija. S-Peterburg: Piter Kom. 1999. [in Russian]Fogelman A.M., Schechter J.S., Hokom M., Child J.S., Edwards P.A. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages. Proc Natl Acad Sci USA 1980; 77: 2214-2218.Fogelman A.M., Schechter J.S., Hokom M., Child J.S., Edwards P.A. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages. Proc Natl Acad Sci USA 1980; 77: 2214-2218.Sparrow J.T., Parthasarathy S., Steinberg D. Enzymatic modification of low density lipoprotein by purified lipoxygenase plus phospholipase A2 mimics cell-mediated oxidative modification. J Lipid Res 1988; 29: 745-753.Sparrow J.T., Parthasarathy S., Steinberg D. Enzymatic modification of low density lipoprotein by purified lipoxygenase plus phospholipase A2 mimics cell-mediated oxidative modification. J Lipid Res 1988; 29: 745-753.Hiltunen T., Luoma J., Nikkari T., Ylä-Herttuala S. Induction of 15-lipoxygenase mRNA and protein in early atherosclerotic lesions. Circulation 1995; 92: 3297-3303.Hiltunen T., Luoma J., Nikkari T., Ylä-Herttuala S. Induction of 15-lipoxygenase mRNA and protein in early atherosclerotic lesions. Circulation 1995; 92: 3297-3303.Harats D., Shaish A., George J., Mulkins M., Kurihara H., Levkovitz H. et al. Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor-deficient mice. ATVB 2000; 20: 2100-2105.Harats D., Shaish A., George J., Mulkins M., Kurihara H., Levkovitz H. et al. Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor-deficient mice. ATVB 2000; 20: 2100-2105.Rapoport S.M., Schewe T., Wiesner R., Halangk W., Ludwig P., Janicke-Hone et al. The lipoxygenase of reticulocytes: purification, characterization and biological dynamics of the lipoxygenase; its identity with the respiratory inhibitors of the reticulocyte. Eur J Biochem 1979; 96: 545-561.Rapoport S.M., Schewe T., Wiesner R., Halangk W., Ludwig P., Janicke-Hone et al. The lipoxygenase of reticulocytes: purification, characterization and biological dynamics of the lipoxygenase; its identity with the respiratory inhibitors of the reticulocyte. Eur J Biochem 1979; 96: 545-561.Criswell K.A., Sulkanen A.P., Hochbaum A.F., Bleavins M.R. Effects of phenylhydrazine or phlebotomy on peripheral blood, bone marrow and erythropoietin in Wistar rats. J Appl Toxicol 2000; 20: 25-34.Criswell K.A., Sulkanen A.P., Hochbaum A.F., Bleavins M.R. Effects of phenylhydrazine or phlebotomy on peripheral blood, bone marrow and erythropoietin in Wistar rats. J Appl Toxicol 2000; 20: 25-34.Мешкова Н.П., Северина С.Е. Практикум по биохимии. М.: МГУ; 1979. / Meshkova N.P, Severina S.E. Praktikum po biokhimii. M.: MGU; 1979. [in Russian]Мешкова Н.П., Северина С.Е. Практикум по биохимии. М.: МГУ; 1979. / Meshkova N.P, Severina S.E. Praktikum po biokhimii. M.: MGU; 1979. [in Russian]Maccarone M., Salucci M.L., Melino G., Rosato N., Finazzi-Agro A. The early phase of apoptosis in human neuroblastoma chp100 cells is characterized by lipoxygenase-dependent ultraweak light emission. Biochem Biophys Res Com 1999; 265: 758-762.Maccarone M., Salucci M.L., Melino G., Rosato N., Finazzi-Agro A. The early phase of apoptosis in human neuroblastoma chp100 cells is characterized by lipoxygenase-dependent ultraweak light emission. Biochem Biophys Res Com 1999; 265: 758-762.Aoshima H., Kajiwara T., Hatanaka A. Kinetic study of lipoxygenase-hydroperoxylinoleic acid interaction. Biochim Biophys Acta 1976; 486: 121-126.Aoshima H., Kajiwara T., Hatanaka A. Kinetic study of lipoxygenase-hydroperoxylinoleic acid interaction. Biochim Biophys Acta 1976; 486: 121-126.Kopp E., Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 1994; 265: 956-959.Kopp E., Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 1994; 265: 956-959.Pierce J.W., Read M.A., Ding H., Luscinskas F.W., Collins T. Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration. J Immunol 1996; 156: 3961-3969.Pierce J.W., Read M.A., Ding H., Luscinskas F.W., Collins T. Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration. J Immunol 1996; 156: 3961-3969.Xia L., Pan J., Yao L., McEver R.P. A proteasome inhibitor, an antioxidant, or a salicylate, but not a glucocorticoid, blocks constitutive and cytokine-inducible expression of P-selectin in human endothelial cells. Blood 1998; 91: 1625-1632.Xia L., Pan J., Yao L., McEver R.P. A proteasome inhibitor, an antioxidant, or a salicylate, but not a glucocorticoid, blocks constitutive and cytokine-inducible expression of P-selectin in human endothelial cells. Blood 1998; 91: 1625-1632.Sagone A., Husney R. Oxidation of salicylates by stimulated granulocytes: evidence that these drugs act as free radical scavengers in biological systems. J Immunol 1987; 138: 2177-2183.Sagone A., Husney R. Oxidation of salicylates by stimulated granulocytes: evidence that these drugs act as free radical scavengers in biological systems. J Immunol 1987; 138: 2177-2183.Hermann M., Kapiotis S., Hofbauer R., Exner M., Seelos C., Held I.et al. Salicylate inhibits LDL oxidation initiated by superoxide/nitric oxide radicals. FEBS Letters 1999; 445: 212-214.Hermann M., Kapiotis S., Hofbauer R., Exner M., Seelos C., Held I.et al. Salicylate inhibits LDL oxidation initiated by superoxide/nitric oxide radicals. FEBS Letters 1999; 445: 212-214.Maron D. J. Flavonoids for reduction of atherosclerotic risk. Curr. Atherosclerosis Rep 2004; 6: 73-78.Maron D. J. Flavonoids for reduction of atherosclerotic risk. Curr. Atherosclerosis Rep 2004; 6: 73-78.Grassi D., Desideri G., Ferri C. Flavonoids: antioxidants against atherosclerosis. Nutrients 2010; 2: 889-902.Grassi D., Desideri G., Ferri C. Flavonoids: antioxidants against atherosclerosis. Nutrients 2010; 2: 889-902.Si H., Liu D. Genistein, a soy phytoestrogen, upregulates the expression of human endothelial nitric oxide synthase and lowers blood pressure in spontaneously hypertensive rats. J Nutr 2008; 138: 297-304.Si H., Liu D. Genistein, a soy phytoestrogen, upregulates the expression of human endothelial nitric oxide synthase and lowers blood pressure in spontaneously hypertensive rats. J Nutr 2008; 138: 297-304.Hodgson J.M., Croft K.D., Puddey I.B., Mori T.A., Beilin L.J. Soybean isoflavonoids and their metabolic products inhibit in vitro lipoprotein oxidation in serum. J Nutrit Biochem 1996; 7: 664-669.Hodgson J.M., Croft K.D., Puddey I.B., Mori T.A., Beilin L.J. Soybean isoflavonoids and their metabolic products inhibit in vitro lipoprotein oxidation in serum. J Nutrit Biochem 1996; 7: 664-669.Da Silva E. L., Tsushida T., Terao J. Inhibition of mammalian 15-lipoxygenase-dependent lipid peroxidation in low-density lipoprotein by quercetin and quercetin monoglucosides. Arch Biochem Biophys 1998; 349: 313-320.Da Silva E. L., Tsushida T., Terao J. Inhibition of mammalian 15-lipoxygenase-dependent lipid peroxidation in low-density lipoprotein by quercetin and quercetin monoglucosides. Arch Biochem Biophys 1998; 349: 313-320.

The authors declare that there are no conflicts of interest present.