Inhibition of Prostaglandin E₂ Production by Platycodin D Isolated from the Root of Platycodon grandiflorum

Abstract

Platycodin D, isolated from the root of Platycodon grandiflorum A. DC. (Campanulaceae) suppressed prostaglandin E₂ production at 10 and 30 μM in rat peritoneal macrophages stimulated by the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA). Platycodin D₃ and oleanolic acid showed no effect at these concentrations. Western blot analysis revealed that the induction of COX-2 protein by TPA was inhibited by platycodin D in parallel with the inhibition of prostaglandin E₂ production. Platycodin D showed no direct effect on COX-1 and COX-2 activities. TPA-induced release of [³ H]arachidonic acid from pre-labeled macrophages was also not inhibited by platycodin D.

References

• 1 Takagi K, Lee E B. Acute toxicity and central depressant activity of crude platycodin.  Nippon Yakugaku Zasshi. 1972;  92 951-60
• 2 Tada A, Kaneiwa Y, Shoji J, Shibata S. Isolation and the structure of platycodin D.  Chem. Pharm. Bull.. 1975;  23 2965-72
• 3 Yamada M, Niki H, Yamashita M, Mue S, Ohuchi K. Prostaglandin E₂ production dependent upon cyclooxygenase-1 and cyclooxygenase-2 and its contradictory modulation by auranofin in rat peritoneal macrophages.  J. Pharmacol. Exp. Ther.. 1997;  281 1005-12
• 4 Ishii H, Tori K, Tozyo T, Yoshimura Y. Structures of polygalacin D and D₂, platycodin D and D₂ and their monoacetates, saponins isolated from Platycodon grandiflorum A. D.C., determined by ¹³C nuclear magnetic resonance spectroscopy.  Chem. Pharm. Bull.. 1978;  26 674-7
• 5 Ohuchi K, Watanabe M, Yoshizawa K, Tsurufuji S, Fujiki H, Suganuma M, Sugimura T, Levine L. Stimulation of prostaglandin E₂ production by 12-O-tetradecanoylphorbol 13-acetate (TPA)-type and non-TPA-type tumor promoters in macrophages and its inhibition by cycloheximide.  Biochim. Biophys. Acta. 1985;  834 42-7
• 6 Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C.  Science. 1992;  258 607-14
• 7 Kim Y P, Yamada M, Lim S S, Lee S H, Ryu N, Shin K H, Ohuchi K. Inhibition by tectorigenin and tectoridin of prostaglandin E₂ production and cyclooxygenase-2 induction in rat peritoneal macrophages.  Biochim. Biophys. Acta. 1999;  1438 399-407