44 3
595th MEETING, MANCHESTER
The above results with plasma fractions also show that
albumin (Cohn V), which has been shown to inhibit prostaglandin biosynthesis in other biological systems (Collier et al.,
1980). had no effect on the lipid peroxidation observed in these
experiments. These paradoxical results may help to elucidate
further the mechanism of action of anti-inflammatory drugs and
plasma inhibitors of prostaglandin biosynthesis.
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113-1 17
The effect of ellagic acid and tannic acid on prostaglandin synthase activity in bovine
seminal-vesicle homogenates
SHEIKH A. SAEED, NAEEM M. BUTT and
WENDY J. McDONALD-GIBSON
Research Department, Miles Laboratories Limited, Stoke
Poges, Slough SL2 I L Y , Berks., U.K.
It has been posulated that the pharmacological actions of
non-steroidal anti-inflammatory drugs involves the inhibition of
prostaglandin synthase (Vane, 197 I). These drugs are diverse
chemically, yet they all share to some extent the anti-pyretic,
anti-inflammatory and analgesic activities of acetylsalicylate. On
the other hand, several phenolic drugs have been shown to
stimulate prostaglandin biosynthesis both in uitro and in vivo
(Collier et al., 1975, 1976; Beubler, 1978). Paradoxically
however, p-acetamidophenol, which is commonly used as an
anti-pyretic and analgesic drug, is phenolic in nature and both
stimulates as well as inhibits prostaglandin biosynthesis (Collier
& McDonald-Gibson, 1979). The present study examines the
effects of two other phenolic drugs, ellagic acid and tannic acid,
on prostaglandin synthase. Both compounds stimulated as well
as inhibited the enzymic activity in bovine seminal-vesicle
homogenates.
Prostaglandin synthase enzyme derived from bull seminalvesicle homogenate was used for the synthesis in uitro of
prostaglandins E, and FZo, prepared as described previously
(Collier el al., 1976). Each assay incubation mixture contained a
final concentration of SOmhi-phosphate buffer, pH 7.4,500pl of
bull seminal-vesicle homogenate, an appropriate amount of the
test drug with and without the cofactors 1.3m~-reduced
glutathioine and 0.09 1 mwhydroquinone and 0.06 1 mwarachidonic acid in a final volume of 2.0ml. The reaction was
allowed to proceed for 15min at 37OC before being terminated
with 0.2 M-CitriC acid. The prostaglandins were extracted with
ethyl acetate and assayed on rat or hamster stomach fundic strip
as described previously (Collier et al., 1976).
As Fig. 1 shows, both ellagic acid and tannic acid at lower
concentrations, when incubated with the enzyme without
cofactors, stimulated prostaglandin biosynthesis in a concentration-related manner. At higher concentrations however,
tannic acid strongly inhibited the enzyme activity. In the
presence of cofactors, both compounds were inhibitory (Fig. 1).
We conclude that these compounds in the investigated enzyme
system can substitute reduced glutathione and hydroquinone as
cofactors. This is consistent with our previous observations on
other phenolic drugs (Collier et al., 1976).
The present results may also explain the use of tannic acid for
VOl. 9
,x
r,
6058
0.58
58
58
580
IEllagic acidl or ltannic acidl (PM)
Fig. 1. Stimulation and inhibition of prostaglandin svnthase by
ellagic acid and tannic acid
Effect of ellagic acid in the absence (A) and presence (A)of the
cofactors 1.3 mM-reduced glutathione and 0.09 1 mwhydroquinone, and the effect of tannic acid in the absence (0)and
presence (r) of the cofactors was tested on bovine seminalvesicle prostaglandin synthase. ‘Prostaglandin production ratio’
is the ratio of prostaglandin produced in the presence of test
drug to that produced in its absence. Experimental details are
given in the text.
the symptomatic treatment of diarrhoea and relief of burns
(Swinyard, 1975) since both of these pathological conditions can
be mediated by prostaglandins.
Beubler, E. & Juan, H. (1978) Experientia 34,386-387
Collier, H. 0. J. & McDonald-Gibson,W. J. (1979) Eur. J . Pharmacol.
58,497-500
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Lancet i, 702
Collier, H. 0. J., McDonald-Gibson,W. J. & Saeed, S. A. (1976) Br. J .
Pharmacol. 58, 193-199
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(Goodman. L. S . & Gilman, A., eds), pp. 946-959. Macmillan. New
York
Vane, J. R. (1971) Nature (London)New Biol. 231,232-233