Toxic phorbol esters from Chinese tallow stimulate protein kinase C.
Phorbol esters were isolated from the seeds of Chinese tallow (Sapium sebiferum L. Roxb.). These compounds were based on the tigliane nuclei, 4-deoxyphorbol, 12-deoxyphorbol and 4,20-dideoxy-5-hydroxyphorbol. The pro-inflammatory activity (ID50) of the pure compounds was between 0.042 and 2.6 nmoles per ear. Protein kinase C activation assays were carried out on samples of enzyme purified from mammalian brain and the activities (Ka) were in the range 76-176 nM. The 4,20-dideoxy-5-hydroxy analogue was inactive in both tests. Chinese tallow, which is used as a substitute for linseed oil, may represent an industrial toxic hazard in terms of both pro-inflammatory and tumour-promoting effects.
Department of Pharmacognosy and Pharmaceutical Chemistry, School of Pharmacy, University of London, U.K.
G
G
Brooks
N A
NA
Morrice
C
C
Ellis
A
A
Aitken
A T
AT
Evans
F J
FJ
Evans
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007249:Inflammation / Q000139:chemically induced; D008055:Lipids / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D010703:Phorbol Esters / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D010946:Plants, Medicinal / Q000032:analysis*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D013268:Stimulation, Chemical
D008055:Lipids; D010703:Phorbol Esters; D011493:Protein Kinase C