Inhibition of prostaglandin and leukotriene generation by the plant alkaloids tetrandrine and berbamine.
We compared the effects of two bisbenzylisoquinoline compounds on leukotriene and prostaglandin generation by human monocytes and neutrophils. The results show that tetrandrine had a much greater effect than berbamine on leukotriene generation. However, both compounds were equally potent in suppression of prostaglandin generation. This inhibitory effect on prostaglandin generation can be overcome by exogenous arachidonic acid (AA), suggesting that the site of inhibition is not on the cyclooxygenase enzyme complex, but more proximally on the phospholipase-mediated release of AA from the cell membrane, similar to the action of corticosteroids. These results, together with previous findings of inhibitory effects on other inflammatory mediators such as histamine, platelet-activating-factor (PAF) and interleukin 1 (IL-1) indicate that these plant alkaloids may be useful lead compounds for the development of a new class of anti-inflammatory drugs.
Teh
B S
BS
Department of Child Health, University of Queensland, Mater Children's Hospital, South Brisbane, Australia.
Seow
W K
WK
Li
S Y
SY
Thong
Y H
YH
D000470:Alkaloids / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D044182:Benzylisoquinolines; D003208:Concanavalin A / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis; D006801:Humans; D015289:Leukotrienes / Q000032:analysis / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis*
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D044182:Benzylisoquinolines; D015289:Leukotrienes; D011453:Prostaglandins; D003208:Concanavalin A; D016718:Arachidonic Acid; C009438:tetrandrine; D015232:Dinoprostone; C027870:berbamine