Korean Journal of Medicinal Crop Science (한국약용작물학회지)

The Korean Society of Medicinal Crop Science (한국약용작물학회)
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A Cytotoxic Compound from Moutan Cortex Radicis

목단피의 세포독성 물질

  • Chu, Bo-Yeun (College of Pharmacy, Chungnam National University) ;
  • Jin, Wen-Yi (College of Pharmacy, Chungnam National University) ;
  • Choi, Su-La (College of Pharmacy, Chungnam National University) ;
  • Myung, Pyung-Keun (College of Pharmacy, Chungnam National University) ;
  • Seong, Yeon-Hee (College of Veterinary Medicine & Research Institute of Veterinary Medicine, Chungbuk Natl. Univ.) ;
  • Song, Kyung-Sik (College of Agriculture & Life Sci., Kyungpook Natl. Univ.) ;
  • Bae, Ki-Hwan (College of Pharmacy, Chungnam National University)
  • Published : 2004.06.30
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Abstract

The MeOH extracts from 21 species were tested for their cytotoxicity against SK-MEL-28 melanoma cell line and HaCat normal cell line in 5 g/ml by sulforrhodamine-B (SRB) method. Among them, the MeOH extract from Moutan Cortex Radicis showed the moderate activity with the growth rate of 74.3% in SK-MEL-28 cells and the high activity with the growth rate of 207.8% in HaCat cells. Activity-guided fractionation was performed and five compounds, paeonol (1), benzoylpaeoniflorin (2), benzoic acid (3), 2,5-dihydroxy-4-methoxy- acetophenone (4), paeonfliorin (5) were isolated from hexane and EtOAc fraction. The structures were established by physicochemical and spectrometric methods $(mp,\;UV,\;IR,\;^1H-NMR,\;^{13}C-NMR,\;spectram)$. All compounds were evaluated for their cytotoxicity, compound 4 showed the significant cytotoxic activity with $ED_50$ value of $5.92\;{\mu}g/ml$, but the other compounds no activity. These results suggest that compound 4 is a novel anticancer candidate against SK-MEL-28 melanoma cells.

21 종의 생약 추출물을 선정하여 $5\;{\mu}g/ml$의 농도에서 SK-MEL-28 cell 에 대한 세포독성을 조사한 결과 목단피의 메탄올 추출물이 74.3%의 성장율을 보였다. 활성 물질을 찾기 위하여 목단피로부터 silica gel column chromatography를 실시하여 hexane 분획과 EtOAc 분획에서 충 5개의 화합물을 분리하였고 $mp,\;UV,\;IR,\;^1H-NMR,\;^{13}C-NMR$ 등 각종 물리, 화학적 data로부터 그 구조를 paeonol (1), benzoylpaeoniflorin (2), benzoic acid (3), 2,5-dihydroxy-4-methoxy-acetophenone (4), paeoniflorin (5)으로 동정하였다. 분리한 물질을 human 피부 암세포인 SK-MEL-28 세포주에 대하여 $10\;{\mu}g/ml$의 농도에서 SRB방법으로 세포독성을 측정한 결과 compound 4가 $ED_50$ 값이 $5.92\;{\mu}g/ml$로 가장 좋은 세포독성을 나타내었다. 이결과는 compound 4가 SK-MEL-28 melanoma 세포주에 대한 새로운 항암 후보 물질임을 제시한다.

Keywords

References

  1. Aizan H (1994) Study on the mechanisms of antiplatelet and antiatherosclerotic effects of Sino - Japanese traditional medicines: focusing arachidonic acid cascade. Wakan Iyakugaku Zasshi 11:16-28
  2. Aizan H, Yasushi T, Hisashi Y (1985) Mechanism of antithrombotic and anti-inflammatoryactions of Moutan Cortex. Studies on arachidonic acid cascade. Wakan Iyaku Gakkaishi 2:63-65
  3. Aizan H, Yasushi T, Sho Y (1984) Moutan Cortex and prostaglandin metabolism. Gendai Toyo Igaku 5:62-68
  4. Archi S, Kubo M, Matsuda H, Tani T, Tsunagn K, Yoshiwaka M, Kitaga I (1979) Study on Moutan Cortex (III), on antiinflammatory activities. Shoyakugugaku Zasshi 33:178-184
  5. Asahina Y, Shirabe G (1915) Synthesis of peonolglucoside. Yakugaku Zasshi 35:1293
  6. Bae, K (2000) The Medicinal Plants of Korea, Kyo-Hak Publishing Co., Seoul, p. 170
  7. Bae K, Kim HM, Lee SM (1996) Isolation and evaluation of an antitumor constituent from Pyrolae Herba. Yakhak Hoechi 40:225-229
  8. Bae K, Min BS, Park KL, Ahn BZ (1994) Cytotoxic flavonoids from Scutellaria indica. Planta Med. 60:280-281 https://doi.org/10.1055/s-2006-959477
  9. Boo YC, Jeon CO (1993) Antioxidants of green tea leaves and Moutan Cortex. Han'guk Nonghwa Hakhoechi 36:326-331
  10. Chung JG (1999) Paeonol promotion of DNA adduct formation and arylamines N-acetyltransferase activity in human colon tumor cells. Food Chern. Toxicol. 37:327-334 https://doi.org/10.1016/S0278-6915(99)00011-3
  11. Dai M, Liu Q, Gu C, Zhang H (2000) Inhibitory effect of paeonol onlipid peroxidation reaction and oxidation decoration of low density lipoprotein. Zhongguo Zhongyao Zazhi 25:625-627
  12. Dai M, Zhi X, Peng D, Liu Q (1999) Inhibitory effect of paeonol on experimental atherosclerosis in quail. Zhongguo Zhongyao Zazhi 24:488-490
  13. Dool R, Peto R (1981) The causes of cancer: Quantitative estimates of avoidable risks of cancer in the Unitede States today. J. Natl. Cancer Inst. 66:1192
  14. Doyle A, Griffiths JB, Newell DG (1993) Cell & Tissue culture: Laboratoty procedures. Wiley
  15. Fukuhara Y, Yoshida D (1987) Paeonol; A bio-antimutagen isolated from a crude drug, Moutan Cortex. Agric. Chem. Bioi. Chem. 51:1441-1446 https://doi.org/10.1271/bbb1961.51.1441
  16. Hirai A, Teranto T, Hamazaki T, Sajiki J, Saito H, Tahara K, Tamura Y, Kumagai A (1983) Studies on the mechanism of antiaggregatory effect of Moutan Cortex. Thromb. Res. 31:29-40 https://doi.org/10.1016/0049-3848(83)90005-1
  17. Hu Q, Shi Y L (1994) Inhibition of voltage-gated $K^+$, $Na^+$and $Ca^{2+}$ currents in neuroblastoma X glioma hybrid cells by paeonol. Sheng Li Hsueh Pao 46:575-580
  18. Jeong SJ, Ahn NH, Kim YC (1988) Hyaluronidase inhibitors from Moutan Cortex Radicis. Saengyak Hakhoechi 29:44-47
  19. Jung HJ, Sok DE, Kim YH, Min BS, Lee JP, Bae K (2000) Potentiating effect of obacunone from Dictamnus dasycarpus on cytotoxicity of microtubule inhibitors, vincristine, vinblastine and taxol. Planta Med. 66:74-76
  20. Kim HJ, Le QK, Lee MH, Tae S, Lee HK, Kim YH, Bae K, Lee IS (2001) A cytotoxic secocycloartenoid from Abies koreana, Arch. Pharm. Res. 24:527-531 https://doi.org/10.1007/BF02975159
  21. Kim YH, Min BS, Bae K (1997) A cytotoxic constituent from Sophora flavescens. Arch. Pharm. Res. 20:342-345 https://doi.org/10.1007/BF02976197
  22. Kitagawa I, Yoshikawa M, Tsunaga K, Tani T (1979) Studies on Moutan cortex. II. On the chemical constituents. Shoyakugaku Zasshi 33:171
  23. Kubo M, Matsuda H, Izumi S, Tani T, Arichi S, Yoshikawa M, Kitagaw I (1982) Studies on Moutan Cortex (vI) Inhibitory effects on the intravascular coagulation. Shotakugaku Zasshi 36:70-77
  24. Kubo M, Matsuda H, Tani T, Arichi S, Kitagaw I (1984) Studies on Moutan Cortex (VII) Inhibitory effects on histamin release from rat peritoneal mast cells in vitro. Shoyakugaku Zasshi 38:276-278
  25. Kwon OG, Kim SH, Chun BY, Park CK, Son KH (1999) Isolation of antimicrobial components from Moutan Cortex. Korean J. Pharmacogn. 30:340-344
  26. Lee JS, Min BS, Lee SM, Na MK, Kwon BM, Lee CO, Kim YH, Bae K (2002) Cytotoxic sesquiterpene lactones from Carpesium abrotanoides. Planta Med. 68:745-747 https://doi.org/10.1055/s-2002-33789
  27. Li W, Wang Y, Cai S, Zhang H, Shi H, Hung F, Cao X (2000) Effects of paeonol in comparison with those of aspirin on the rheological parameters of blood in rats. Zhongcaoyao 31:29-31
  28. Masayukim Y, Emiko H, Atsuhiro K, Johji Y, Nobutoshi M, Isao K (1993) Absolute stereostructures of paeonisuffrone and paeonisuffral, two new labile monoterpenes, from Chinese Moutan Cortex. Chem. Pharm. Bull. 41:630-632 https://doi.org/10.1248/cpb.41.630
  29. Masayukim Y, Emiko H, Toshie M, Osamu M, Johji Y, Nobutoshi M, Isao K (1994) Absolute stereostructures of paeonisothujone, a novel skeletal monoterpene ketone, and deoxypaeonisuffron, and isopaeonisuffral, two new monoterpenes, from Moutan Cortex. Chem. Pharm. Bull. 42:736-738 https://doi.org/10.1248/cpb.42.736
  30. Min BS, Kim YH, Lee SM, Jung HJ, Lee JS, Na M, Lee CO, Lee JP, Bae K (2000) Cytotoxic triperpenes from Crataegus pinnatifida. Arch. Pharm. Res. 23:155-158 https://doi.org/10.1007/BF02975505
  31. Okubo T, Nagai F, Seto T, Satoh K, Ushiyama K, Kano 1(2000) The inhibition of phenylhydroquinone-induced oxidative DNA cleavage by constituents of Moutan Cortex and Paeoniae Radix. Biol. Pharm. Bull. 23:199-203. https://doi.org/10.1248/bpb.23.199
  32. Pan X, Yang LX (2000) Synthesis of five new paeonol derivatives with potential applications. Book of Abstracts, 219th ACS National Meeting, San Francisco, CA, March 26-30
  33. Satah K, Nagai F, Ushiyama K, Yasuda I, Seta T, Kana I (1997) Inhibition of Na', K'-ATPase by 1,2,3,4,6-penta-O-galloylbeta-D-glucose, a major constituent of both Moutan Cortex and Paeoniae Radix. Biochemical Pharmacology 53:611-614 https://doi.org/10.1016/S0006-2952(96)00828-3
  34. Sang TS, Wang BL (1994) Natural anti-acne creams. Riyaung Huaxue Gongye 6:283-285
  35. Tsuyoshi O (1997) Pharmacognostic composition for the treatment of atopic dermatitis. Jpn. Kokai Tokkyo Koho. p. 7.
  36. Yoshikawa M, uchida E, Kawaguchi A, Kitagawa I, Yamahara J (1992) Galloyl-oxypaeoniflorin, suffruticoside, A, B, C and D, five new antioxidative glucosides and suffruticoside E, apaeonol glycoside, from Chinese Moutan Cortex. Chem. Pharm. Bull. 40:2248-2250 https://doi.org/10.1248/cpb.40.2248
  37. YuJ, Lang HY, Xiao PG (1986) A new compound, apiopaeonoside, solated from the root of Paeonia suffruticosa. Acta Pharmaceutica Sinica 21:191-197
  38. Zhang G, Yu Z, Zaho H (1997) Inhibition of paeonol on arrhythmias induced by ischemia-reperfusion in rats. Zhongguo Yaoke Daxue Xuebao 28:225-227
  39. Zhang WG, Zhang ZS (1994) Anti-ischemia reperfusion damage and antilipid peroxidation effects of paeonol in rat heart. Yao Hsueh Hsueh Pao 29:145-148