Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

A Prolyl Endopeptidase-lnhibiting Antioxidant from Phyllanthus ussurensis

  • Chung, Shin-kyo (Department of Food Technology, Kyungpook National University) ;
  • Nam, Ji-Ae (Division of Applied Biology and Chemistry, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Jeon, So-Young (Division of Applied Biology and Chemistry, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Kim, Sang-ln (Division of Applied Biology and Chemistry, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Lee, Hee-Ju (Division of Applied Biology and Chemistry, College of Agriculture and Life Sciences, Kyungpook National University) ;
  • Chung, Tai-Ho (School of Medicine, Kyungpook National University) ;
  • Song, Kyung-Sik (Division of Applied Biology and Chemistry)
  • Published : 2003.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

A prolyl endopeptidase inhibitor was isolated from the ethyl acetate soluble fraction of Phyllanthus ussurensis. The active compound was identified as an ellagitannin, corilagin. It was shown to non-competitively inhibit prolyl endopeptidase (PEP) with the $IC_{50}$ value of $1.17 \times $10^{-6}\mu$M. The Ki value was $6.70 \times 10^{-7}$ M. Corilagin was less inhibitory to other serine proteases such as chymotrypsin, trypsin, and elastase, indicating that it was relatively a specific inhibitor of PEP. Corilagin also effectively inhibited reactive oxygen species such as hydroxide and superoxide anion radical, hydrogen peroxide, and DPPH. Especially, corilagin showed potent scavel1ging activity on the superoxide anion radical in the ESR method ($IC_{50} =3.79 \times 10^{-6}$M) as well as xanthine oxidase system.

Keywords

References

  1. Aoyagi, T., Nagai, M., Ogawa, K, Kojima, F., Okada, M., Ikeda, T., Hamada, M., and Takeuchi, T., Poststatin, a new inhibitor of prolyl endopeptidase produced by Streptomyces viridochromogenes MH534-30F3. I. Taxonomy, production, isolation, physico-chemical properties and biological activities. J. Antibiotics, 44, 949-955 (2002)
  2. Aoyagi, T., Wada, T., Nagai, M., Kojima, F., Harada, S., Takeuchi, T., Takahashi, H., Hirokawa, K., and Tsumita, T., Deficiency of kallikrein-like enzyme activities in cerebral tissue of patients with Alzheimer's disease. Experientia, 46, 94-97 (1990) https://doi.org/10.1007/BF01955428
  3. Arai, H., Nishioka, H., Niwa, S., Yamanaka, T., Tanaka, Y., Yoshinaga, K., Kobayashi, N., Miura, N., and Ikeda, Y., Synthesis of prolyl endopeptidase inhibitors and evaluation of their structure-activity relationships: In vitro inhibition of prolyl endopeptidase from canine brain. Chem. Pharm. Bull., 41, 1583-1588 (1993) https://doi.org/10.1248/cpb.41.1583
  4. Bakker, A. V., Jung, S., Spencer, R. W., Vinick, F. J., and Faraci, W. S., Slow tight-binding of prolyl endopeptidase by benzyloxycarbonyl-prolyl-prolinal. Biochem. J., 271, 559-562 (1990) https://doi.org/10.1042/bj2710559
  5. Blois, M. S., Antioxidant determination by the use of a stable free radical. Nature, 181, 1199-1201 (1958) https://doi.org/10.1038/1811199a0
  6. Checler, F., Processing of the beta-amyloid precursor protein and its regulation in Alzheimer's disease. J. Neurochem., 65, 1431-1444 (1995) https://doi.org/10.1046/j.1471-4159.1995.65041431.x
  7. Chung, S. K., Osawa, T., and Kawakishi, S., Hydroxyl radical-scavenging effect of spices and scavengers from brown mustard (Brassica nigra). Biosci. Biotech. Biochem., 61, 118-124 (1997) https://doi.org/10.1271/bbb.61.118
  8. Fan, W., Tezuka, Y., Komatsu, K., Namaba, T., and Kadota, S., Prolyl endopeptidase inhibitors from the underground part of Rhodiola sacra S. H. Fu. Biol. Pharm. Bull., 22, 157-161 (1999) https://doi.org/10.1248/bpb.22.157
  9. Glenner, G. G. and Wong, C. W., Alzheimers disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun., 120, 885-890 (1984) https://doi.org/10.1016/S0006-291X(84)80190-4
  10. Ham, I., Wang, T., Cho, E.-S., Cho, H.-K., and Whang, W.-K., Phenolic compounds from Phyllanthus ussuriensis. Yakhak Hoeji, 45, 237-244 (2001)
  11. Hwang, J.-S., Song, K.-S., Kim, W.-G., Lee, T.-H., Koshino, H., and Yoo, I.-D., Polyozellin, a new inhibitor of prolyl endopeptidase from Polyozellus multiplex. J. Antibiotics, 50, 773-777 (1997) https://doi.org/10.7164/antibiotics.50.773
  12. Iio, M., Moriyama, A., Matsumoto, Y., Takai, N., and Fukumoto, M., Inhibition of xanthine oxidase by flavonoids. Agric. Biol. Chem., 49, 2173-2182 (1985) https://doi.org/10.1271/bbb1961.49.2173
  13. Ishiura, S., Tsukahara, T., Tabira, T., Shimizu, T., Arahata., and Sugita, H., Identification of a putative amyloid A4-generating enzyme as a prolyl endopeptidase. FEBS, 260, 131-134 (1990) https://doi.org/10.1016/0014-5793(90)80084-V
  14. Kim, S.-I. and Song, K.-S., 1,2,3,4,6-Pentagalloyl-$\beta$-D-glucopyranose, a prolyl endopeptidase inhibitor from Moutan cortex. J. Korean Soc. Agric. Chem. Biotechnol., 43, 158-161 (2000)
  15. Kimura, K., Kawaguchi, N., Yoshihama, M., and Kawanishi, G., Staurosporine, a prolyl endopeptidase inhibitor. Agric. Biol. Chem., 54, 3021-3022 (1990) https://doi.org/10.1271/bbb1961.54.3021
  16. Kwak, J.-Y., Rhee, I.-K., Lee, K.-B., Hwang, J.-S., Yoo, I.-D., and Song, K.-S., Thelephoric acid and kynapcin-9 from mushroom Polyozellus multiplex inhibit prolyl endopeptidase in vitro. J. Microbiol. & Biotechnol., 9, 798-803 (1999)
  17. Lee, H.-J., Rhee, I.-K., Lee, K.-B., Yoo, I.-D., and Song, K.-S., Kynapcin-12, a new p-terphenyl derivative from Polyozellus multiplex, inhibits prolyl endopeptidase. J. Antibiotics, 53, 714-719 (2000) https://doi.org/10.7164/antibiotics.53.714
  18. Lee, K.-H., Kwak, J.-H., Lee, K.-B., and Song, K.-S., Prolyl endopeptidase inhibitors from Caryophylli Flos. Arch. Pharm. Res., 21, 207-211 (1998) https://doi.org/10.1007/BF02974029
  19. Liu, Y., Qin, L., Wilson, B., An, L., Hong, J.-S., and Liu, B., Inhibition by naloxone stereoisomers of $\beta$-amyloid peptide (1-42)-induced superoxide production in microglia and deqeneration of cortical and mesencephalic neurons. J. Pharmacol. & Exp. Therap., 320, 1212-1219 (2002)
  20. Mattson, M. P., Involvement of superoxide in pathogenic action of mutations that cause Alzheimer's disease. Methods in Enzymology, 352 (Redox Cell Biology and Genetics, Part A), 455-474 (2002) https://doi.org/10.1016/S0076-6879(02)52040-1
  21. Mattson, M. P., Barger, S. W., Lieberburg, I., Smith-Swintosky, V. L., and Rydel, R. E., $\beta$-Amyloid precursor protein metabolites and loss of neuronal $Ca^{2+}$ homeostasis in Alzheimer's disease. Trends Neurosci., 16, 409-414 (1993) https://doi.org/10.1016/0166-2236(93)90009-B
  22. Muller, H. E., Detection of hydrogen peroxide produced by microorganism on ABTS-peroxidase medium. Zentralbl Bakteriol. Mikrobio. Hyg., 259, 151-158 (1985)
  23. Portevin, B., Benoist, A., Remond, G., Herve, Y., Vincent, M., Lepagnol, J., and De Nanteuil, G., New prolyl endopeptidase inhibitors: in vitro and in vivo activities of azabicyclo[2.2.2] octane, azabicyclo[2.2.1]heptane, and perhydroindole derivatives. J. Med. Chem., 39, 2379-2391 (1996) https://doi.org/10.1021/jm950858c
  24. Prasad, K. N., Hovland, A. R., Cole, W. C., Prasad, K. C., Nahreini, P., Edwards-Prasad, J., and Andreatta, C. P., Multiple antioxidant in the prevention and treatment of Alzheimer disease: analysis of biologic rationale. Clin. Neuropharmacol., 23, 2-13 (2000) https://doi.org/10.1097/00002826-200001000-00002
  25. Qin, L., Liu, Y., Cooper, C., Liu, B., Wilson, B., and Hong, J.-S., Microglia enhance $\beta$-amyloid peptide-induced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species. J. Neurochemistry, 83, 973-983 (2002) https://doi.org/10.1046/j.1471-4159.2002.01210.x
  26. Rennex, D., Hemmings, B. A., Hofsteenge, J., and Stone, S. R., cDNA cloning of porcine brain prolyl endopeptidase and identification of the active-site seryl residue. Biochemistry, 30, 2195-2203 (1991) https://doi.org/10.1021/bi00222a025
  27. Sisodia, S. S. and Price, D. L., Role of the $\beta$-amyloid protein in Alzheimers disease. FASEB J., 9, 366-370 (1995) https://doi.org/10.1096/fasebj.9.5.7896005
  28. Song, K.-S. and Raskin, I., A prolyl endopeptidase-inhibiting benzofuran dimer from Polyozellus multiplex. J. Nat. Prod., 65, 76-78 (2002) https://doi.org/10.1021/np010194b
  29. Toda, S., Obi, Y., Numata, K., Hamagishi, Y., Tomita, K., Komiyama, N., Kotake, C., Furumai, T., and Oki, T., Eurystatins A and B, new prolyl endopeptidase inhibitors. I. taxonomy, production, isolation and biological activities. J. Antibiotics, 45, 1573-1579 (1992) https://doi.org/10.7164/antibiotics.45.1573
  30. Yaron, A. and Naider, F., Proline-dependent structural and biological properties of peptides and proteins. Critic. Rev. Biochem. Mol. Biol., 28, 31-81, (1993) https://doi.org/10.3109/10409239309082572
  31. Yoshimoto, T., Kado, K., Matsubara, F., Koriyama, N., Kaneto, H., and Tsuru, D., Specific inhibitors for prolyl endopeptidase and their anti-amnesic effect. J. Pharmacobio-Dyn.,10, 730-735 (1987) https://doi.org/10.1248/bpb1978.10.730
  32. Yoshimoto, T., Nishimura, T., Kita, T., and Tsuru, D., Post-proline cleaving enzyme (prolyl endopeptidase) from bovine brain. J. Biochem., 94, 1179-1190 (1983) https://doi.org/10.1093/oxfordjournals.jbchem.a134463