Potent immunosuppressive principles, dimeric sesquiterpene thioalkaloids, isolated from nupharis rhizoma, the rhizoma of Nuphar pumilum (nymphaeaceae): structure-requirement of nuphar-alkaloid for immunosuppressive activity.
Potent immunosuppressants, the dimeric sesquiterpene thioalkaloids, 6-hydroxythiobinupharidine (2), 6,6'-dihydroxythiobinupharidine (3), 6-hydroxythionuphlutine B (5) and 6'-hydroxythionuphlutine B (6), were isolated from a natural medicine, Nupharis Rhizoma, the rhizoma of Nuphar pumilum (TIMM.) DC., through bioassay-guided separation together with five quinolizidine alkaloids (8, 9, 10, 11, 12). Dimeric sesquiterpene thioalkaloids (2, 3, 5, 6) were found to significantly inhibit anti-sheep erythrocyte plaque forming cell formation in mice spleen cells at 10(-6) M concentration. At this concentration, 2, 5 and 6 were found to exhibit no cytotoxicity to mice spleen cells, and 3 also showed only a little cytotoxicity. In addition, the inhibitory activity of several Nuphar alkaloids, dimeric sesquiterpene thioalkaloids (1, 4, 7, 8), and monomeric sesquiterpene alkaloids (9, 10, 11, 12) on anti-sheep erythrocyte plaque forming cell formation was examined and some structural requirement of Nuphar alkaloid for immunosuppressive activity was determined.
Yamahara
J
J
Research Institute for Production and Development, Kyoto, Japan.
Shimoda
H
H
Matsuda
H
H
Yoshikawa
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000302:isolation & purification* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D011807:Quinolizines / Q000302:isolation & purification* / Q000494:pharmacology; D012756:Sheep / Q000276:immunology; D013141:Spiro Compounds / Q000302:isolation & purification* / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000302:isolation & purification* / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D011807:Quinolizines; D013141:Spiro Compounds; D013876:Thiophenes; D016572:Cyclosporine; D006854:Hydrocortisone