| Co-Investigator(Kenkyū-buntansha) |
OKAWA Masafumi Fukuoka Univ., Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (70332872)
AKAHANE Hiroshige Fukuoka Univ., School of medicine, Associated Professor, 医学部, 助教授 (30020754)
HIGO Hiroo Kyushu Univ., Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究院, 助手 (80117225)
MAKI Jun Kitasato Univ., School of Medicine, Lecturer, 医学部, 講師 (60050697)
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| Research Abstract |
Protozoan Trypanosoma cruzi is the etiologic agent of Chagas' disease (American trypanosomiasis), one of the most serious infectious diseases in Latin America. In order to seek new chemotherapeutic agents from natural resources, we studied trypanocidal constituents in plants. The life cycle of T cruzi is divided into three stages: epimastigote in the insect gut ; trypomastigote, an infectious form in the mammalian blood stream; and amastigote, a proliferative form in mammalian cells. The activity was expressed as the MC100 value, which was defined as the minimum concentration at which all the epimastigotes or trypomastigotes become immobilized after 24 h incubation. In the case of epimastigotes, IC_<50> value was also estimated using Cell Counting Kit-8. IC_<50> value was defined as the concentration of sample necessary to inhibit the growth to 50% of the control. Cytotoxicity of isolated compounds against human uterine carcinoma (HeLa) cells was examined using a modified MTT assay for estimation of selective toxicity. For preliminary screening test we examined 288 extracts, which are comprised of 70 families and 197 species including Mexican medicinal plants. As active components, lignans from the roots of Aristolochia taliscana, ursolic acid from the aerial parts of Rosmarius officinalis, xanthones from some Guttiferae plants, bisbenzylisoquinoline alkaloids from the roots of Stephania tetrandra and withanolides from the aerial parts of Physalis angulata, were obtained, respectively. Among them, subelliptenone A [xanthone, MC_<100>(trypo.) ; 54 μM, IC50(HeLa); 77 μM], physagulin F [withanolide, MC_<100>(trypo.) ; 9 μM, IC50(HeLa) ; 92 μM], tetrandrine [bisbenzylisoquinoline alkaloid, MC_<100>(trypo.) ; 10 μM, IC50(HeLa) ; 59 μM] and berberine [benzylisoquinoline alkaloid, MC_<100>(trypo.) ; 19 μM, IC_<50>(HeLa) ; 121 μM] showed rather high selective toxicity and aroused interest in further in vivo investigation.
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