Pharmacological Studies on the Anti-inflammatory Action of Phenolic Compounds

Abstract

The mechanism of the anti-inflammatory action of phenolic compounds was examined using neutrophil chemotaxis. Chemotactic activity of guinea pig peritoneal neutrophils to N-formylmethionyl-leucylphenylalanine (FMLP) was suppressed in a concentration-dependent manner. The order of drug potency in inhibiting the neutrophil chemotaxis was eugenol » thymol > guaiacol » phenol. The concentrations of phenolic compounds used in these experiments did not induce lactate dehydrogenase (LDH) release and did not affect neutrophil viability. There was a consistent positive relation between the ID₅₀ of superoxide anion generation in neutrophils and the inhibitory dose for neutrophil chemotaxis by phenolic compounds. A free phenolic hydroxyl group is essential for scavenging oxygen free-radicals and is also essential for inhibiting leukocyte chemotaxis, as was demonstrated in these experiments. These findings suggest that inhibition of leukocyte chemotaxis may be involved in the anti-inflammatory action of phenolic compounds, and that one of the anti-inflammatory actions of phenolic compounds is the prevention of the production of oxygen free-radicals by leukocytes.

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References

Azuma, Y. ; Hashizume, I. ; and Takagi, N. (1981): Participation of Free Radicals in Immediate Hypersensitivity Reaction, Proc Eighth Int Cong Pharmacol Tokyo: p. 427.

Azuma Y. ; Hashizume, I. ; and Takagi, N. (1983): The Anti-inflammatory Action of Superoxide Dismutase - Role of Superoxide Anions in Leukocyte Chemotaxis, Jpn J Inflamm 3 :355-356.

Bokoch, G.M. and Reed, P.W. (1979): Inhibition of the Neutrophil Oxidative Response to a Chemotactic Peptide by Inhibitors of Arachidonic Acid Oxygenation, Biochem Biophys Res Commun 90:481-487.

Dewhirst, F.E. (1980): Structure-Activity Relationship for Inhibition of Prostaglandin Cyclooxygenase by Phenolic Compounds, Prostaglandins 20:209-222.

Dewhirst, F.E. and Goodson, J.M. (1974): Prostaglandin Synthetase Inhibition by Eugenol, Guaiacol and Other Dental Medicaments, J Dent Res 53 (Sp Iss):No. 199.

Egan, R.W. ; Gale, P.H. ; Beveridge, G.C. ; Marnett, L.J. ; and Kuehl, F.A., Jr. (1980); Direct and Indirect Involvement of Radical Scavengers During Prostaglandin Biosynthesis, Adv Prostaglandin Thrombox Res 6:153-155.

Egan, R.W. ; Humes, J.L. ; and Kuehl, F.A., Jr. (1978): Differential Effects of Prostaglandin Synthetase Stimulators on Inhibition by Cyclooxygenase, Biochemistry 17:2230-2234.

Elferink, J.G.R. (1979): Chlorpromazine Inhibits Phagocytosis and Exocytosis in Rabbit Polymorphonuclear Leukocytes, Biochem Pharmacol 28:965-968.

Falk, W. ; Goodwin, R.H., Jr. ; and Leonard, E.J. (1980) : 48-well Micro Chemotaxis Assembly for Rapid and Accurate Measurement of Leukocyte Migration, J Immunol Methods 33 :239-247.

10.

Goldstein, I.M. ; Toos, D. ; Kaplan, H.B. ; and Weiss-Mann, G. (1975): Complement and Immunoglobulins Stimulate Superoxide Production by Human Leukocytes Independently of Phagocytosis, J Clin Invest 56:1155-1163.

11.

Harvath, L. ; Falk, W. ; and Leonard, E.J. (1980): Rapid Quantitation of Neutrophil Chemotaxis: Use of Polyvinylpyrrolidone-free Polycarbonate Membrane in a Multiwell Assembly , J Immunol Methods 37:39-45.

12.

Hashizume, I. ; Azuma, Y. ; Tokunaga, T. ; and Takagi, N. (1982): Possible Role of Free Radicals in Inflammation - Role of Free Radicals in Chemotaxis, Jpn J Oral Biol 24 (Suppl): p. 171.

13.

Kuehl, F.A., Jr. ; Humes, J.L. ; Egan, R.W. ; Ham, E.A. ; Beveridge, G.C. ; and Van Arman, C.G. (1977): Role of Prostaglandin Endoperoxide PGG2 in Inflammatory Processes, Nature 265:170-172.

14.

Lindgren, J.A. ; Claesson, H.-E. ; and Hammarstrom, S. (1977): Inhibition of Prostaglandin Synthesis in Mouse 3T3 Fibroblasts and Human Platelets by Substituted Phenols, Prostaglandins 13:1093-1100.

15.

Lund-Olesen, K. and Menander, K.B. (1974): Orgotein: a New Anti-inflammatory Metalloprotein Drug: Preliminary Evaluation of Clinical Efficacy and Safety in Degenerative Joint Disease, Current Therap Res 16:706-717.

16.

McCord, J.M. ; Stokes, S.H. ; and Wong, K. (1979): Superoxide Radicals as a Phagocyte-produced Chemical Mediator of Inflammation, Adv Inflamm Res 1:273-280.

17.

Oyanagui, Y. (1976): Participation of Superoxide Anions at the Prostaglandin Phase of Carrageenan Foot-oedema, Biochem Pharmacol 25:1465-1472.

18.

Petrone, W.F. ; English, D.K. ; Wong, K. ; and McCord, J.M. (1980): Free Radicals and Inflammation: Superoxide-dependent Activation of a Neutrophil Chemotactic Factor in Plasma , Proc Natl Acad Sci USA 77:1159-1163.

19.

Roos, D. and Loos, J.A. (1970): Changes in the Carbohydrate Metabolism of Mitogenically Stimulated Human Peripheral Lymphocytes. I. Stimulation by Phytohaemagglutinin, Biochim Biophys Acta 222:565-582.

20.

Schiffman, E. ; Corcoran, B.A. ; and Wahl, S.M. (1975): N-formyl-methionyl Peptides as Chemoattractants for Leukocytes, Proc Natl Acad Sci USA 72:1059-1062.

21.

Takeguchi, C. and Sih, C.J. (1972): A Rapid Spectrophotometric Assay for Prostaglandin Synthetase: Application to the Study of Non-steroidal Anti-inflammatory Agents , Prostaglandins 2 :169-184.

22.

Walravens, M. and Dequeker, J. (1976): Comparison of Gold and Orgotein Treatment in Rheumatoid Arthritis, Current Therap Res 20:62-69.