- Email: [email protected]
Triterpenoid acids from Schisandra propinqua with cytotoxic effect on rat luteal cells and human decidual cells in vitro
Fitoterapia 72 Ž2001. 435᎐437
Short report
Triterpenoid acids from Schisandra propinqua with cytotoxic effect on rat luteal cells and human decidual cells in vitro Ye-Gao Chena,U , Guo-Wei Qin b, Lin Cao b, Ying Leng b, Yu-Yuan Xie b a
Department of Chemistry, Yunnan Normal Uni¨ ersity, Kunming, Yunnan 650092, PR China b Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, PR China
Received 18 September 2000; accepted in revised form 4 January 2001
Abstract Three triterpenoid acids, nigranoic acid (1), manwuweizic acid (2), schisandronic acid (3), and other four compounds were isolated from the stems of Schisandra propinqua. Compounds 1 and 2 showed significant cytotoxic effect against human decidual cells and rat luteal cells in vitro. 䊚 2001 Elsevier Science B.V. All rights reserved. Keywords: Schisandra propinqua; Triterpenoids; Cytotoxicity; Flavonoids; Phenolics; Sterols
Plant. Schisandra propinqua ŽWall.. Hook. f. et Thoms ŽSchisandraceae . stems were collected in April 1997, from Tonghai County of Yunnan province, China and identified by Mr Bangtao Yue, botanist of Tonghai Institute of Drugs Control in Yunnan, China, where a voucher specimen ŽNo. 9703012. is deposited. Uses in traditional medicine and other reported activities. Indigenous to Yunnan, S. propinqua was used in folk medicine as a substitute of S. chinesis ŽYurcz.. Baill, a famous traditional Chinese medicine for over 2000 years as a tonic and sedative w1x. U
Corresponding author. E-mail address: [email protected] ŽY. Chen.. 0367-326Xr01r$ - see front matter 䊚 2001 Elsevier Science B.V. All rights reserved. PII: S 0 3 6 7 - 3 2 6 X Ž 0 1 . 0 0 2 6 9 - 6
436
Y. Chen et al. r Fitoterapia 72 (2001) 435᎐437
A herbal medicine preparation in which the stems and roots of S. propinqua are a major component has been used for treatment of lung carcinoma in several hospitals in Yunnan. The water extract of the stems and roots of S. propinqua showed activity against Lewis lung cancer in animal tests w2x. Previously isolated constituents. Two triterpenoid acids, anwuweizonic acid and manwuweizic acid (2). Compound 2 exhibited significant inhibitory activity against Lewis lung cancer, brain tumor-22 and solid hepatoma in mice w3x. New-isolated constituents. Nigranoic acid (1) w4,5x Žyield: 0.04% from dried stems., schisandronic acid (3) w6x Ž0.003., p-Ž2⬘-hydroxylethyl.-phenol (4) w7x Ž0.0008., p-Ž2⬘-hydroxylethyl.-phenol -D-pyranoglucoside (5) w8x Ž0.003., Žq.-catechin (6) Ž0.0003. and -sitosterol (7) Ž0.03..
Nigranoic acid (1). Mp 125᎐126⬚C; IR bands ŽKBr.: 3050᎐2870, 2600, 1701, 1690, 1635, 1458, 1413, 1373, 1254, 1218, 1163, 1077, 933 and 891 cmy1 ; 1 H-NMR Ž400 MHz, CDCl 3 .: ␦ 6.07 Ž1H, t, H-24., 4.80, 4.72 Žeach 1H, br s, H-28., 1.89 Ž3H, s, H-27., 1.64 Ž3H, s, H-29., 0.94 Ž3H, s, H-18., 0.92 Ž3H, s, H-30., 0.89 Ž3H, d, H-21., 0.73, 0.37 Žeach 1H, d, H-19.; MS mrz Žrel. int..: 470wMxq ŽC 30 H 46 O4 ., 455 Ž100., 406, 397, 371, 329, 235, 135, 121, 107, 95, 55. Schisandronic acid (3). Mp 165᎐166⬚C; IR bands ŽKBr.: 3200᎐2500, 1712, 1682, 1637, 1456, 1379 and 1263 cmy1 ; 1 H-NMR Ž400 MHz, CDCl 3 .: ␦ 6.07 Ž1H, t, H-24., 1.90 Ž3H, d, H-27., 1.10 Ž3H, s, H-29., 1.03 Ž3H, s, H-28., 0.98 Ž3H, s, H-30., 0.89 Ž3H, s, H-18., 0.89 Ž3H, d, H-21., 0.77, 0.56 Žeach 1H, d, H-19.. Tested material. Compounds 1, 2 Žyield: 0.0002% from dried stems., 3 and 5. Studied activity. Cytotoxic activity in vitro on human decidual cells and rat luteal cells w9x. Used organisms and procedure. Ža. Rat lutel cells. Both ovaries were excised from Sprague᎐Dawley pseudopregnant rats Žweighing 220᎐250 g; provided by the Shanghai Experimental Animal Center, Chinese Academy of Sciences.. Corpora lutea were dissected out under a microscope, seeded at a density of 2᎐3 = 10 5 cellsrwell
Y. Chen et al. r Fitoterapia 72 (2001) 435᎐437
437
Table 1 In vitro cytotoxic effect of constituents from Scisandra propinqua stems on human decidual cells and rat luteal cells a Treatment
Control Solventb 1 2 3 5
Conc. Žgrml.
Human decidual cells
40 40 40 40
0 0 99.3 " 0.5 100 " 0.0 41.2 " 1.0 69.4 " 0.7
Conc. Žgrml.
20 20 20 20
Rat luteal cells
0 0 100 " 0.0 98.5 " 1.3 55.3 " 4.3 48.9 " 1.8
a
Values Žpercentage of inviable cells after 24 h. are mean " S.D. Ž n s 4.. 1, nigranoic acid; 2, manwuweizic acid; 3, schisandronic acid; 5, p-Ž2⬘-hydroxylethyl.-phenol -D-pyranoglucoside. Effective inviable rate:) 90%. b Solvent: MeOH.
in 0.5 ml of McCoy’s 5A medium, and supplemented with 30% bovine serum albumin ŽBSA., benzylpenicillin potassium 2 = 10 5 IUrl, streptomycin 2 = 10 5 IUrl. Žb. Human decidual cells Žderived from human ovary. were dispersed and seeded at 2᎐3 = 10 5 cellsrwell in 0.5 ml of F12 Dulbecco’s modified Eagle’s medium, and supplemented with 10% BSA, benzylpenicillin potassium 2 = 10 5 IUrl, streptomycin 2 = 10 5 IUrl. Both kinds of cells were cultured at 37⬚C in air with 5% CO 2 for 24 h. After culturing for 24 h, the cells were exposed to two concentrations Ž20 grml for rat lutel cells and 40 grml for human decidual cells. of the tested compounds for 24 h. The quantity of MeOH added in each well was 25 l. Cell viability was assessed with trypan blue dye w9x. Results. Reported in Table 1. Conclusions. Nigranoic acid (1) and manwuweizic acid (2) showed significant inhibitory activity against human decidual cells and rat luteal cells in vitro. This is the first report that compounds from plants of Schisandraceae possess cytotoxic activity on these two kinds of cells.
References w1x Yunnan Provincinal Crude Drugs Company. Name lists of Chinese herbal medicine resources in Yunnan. Beijing: Science Press, 1993. p. 151. w2x Xu GH, Yang Z, Zhou GH, He TH. Chin Tradit Herb Drugs 1984;15:432. w3x Liu JS, Huang MF, Tao Y. Can J Chem 1988;66:414. w4x Kikuchi M, Yoshikoshi A. Chem Lett 1972: 725. w5x Sun HD, Qiu SX, Lin LZ et al. J Nat Prod 1996;59:525. w6x Takahashi K, Takani M. Chem Pharm Bull 1975;23:538. w7x Ayer WA, Browne LM, Feng MC, Orszanska H, Saeedi-Ghomi H. Can J Chem 1986;64:904. w8x Tanahashi T, Takenaka Y, Akimoto M et al. Chem Pharm Bull 1997;45:367. w9x Yang B, Cao L, Xu Y, Su ZX, Gu ZP. Acta Pharm Sin 1997;32:573.
Short report
Triterpenoid acids from Schisandra propinqua with cytotoxic effect on rat luteal cells and human decidual cells in vitro Ye-Gao Chena,U , Guo-Wei Qin b, Lin Cao b, Ying Leng b, Yu-Yuan Xie b a
Department of Chemistry, Yunnan Normal Uni¨ ersity, Kunming, Yunnan 650092, PR China b Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031, PR China
Received 18 September 2000; accepted in revised form 4 January 2001
Abstract Three triterpenoid acids, nigranoic acid (1), manwuweizic acid (2), schisandronic acid (3), and other four compounds were isolated from the stems of Schisandra propinqua. Compounds 1 and 2 showed significant cytotoxic effect against human decidual cells and rat luteal cells in vitro. 䊚 2001 Elsevier Science B.V. All rights reserved. Keywords: Schisandra propinqua; Triterpenoids; Cytotoxicity; Flavonoids; Phenolics; Sterols
Plant. Schisandra propinqua ŽWall.. Hook. f. et Thoms ŽSchisandraceae . stems were collected in April 1997, from Tonghai County of Yunnan province, China and identified by Mr Bangtao Yue, botanist of Tonghai Institute of Drugs Control in Yunnan, China, where a voucher specimen ŽNo. 9703012. is deposited. Uses in traditional medicine and other reported activities. Indigenous to Yunnan, S. propinqua was used in folk medicine as a substitute of S. chinesis ŽYurcz.. Baill, a famous traditional Chinese medicine for over 2000 years as a tonic and sedative w1x. U
Corresponding author. E-mail address: [email protected] ŽY. Chen.. 0367-326Xr01r$ - see front matter 䊚 2001 Elsevier Science B.V. All rights reserved. PII: S 0 3 6 7 - 3 2 6 X Ž 0 1 . 0 0 2 6 9 - 6
436
Y. Chen et al. r Fitoterapia 72 (2001) 435᎐437
A herbal medicine preparation in which the stems and roots of S. propinqua are a major component has been used for treatment of lung carcinoma in several hospitals in Yunnan. The water extract of the stems and roots of S. propinqua showed activity against Lewis lung cancer in animal tests w2x. Previously isolated constituents. Two triterpenoid acids, anwuweizonic acid and manwuweizic acid (2). Compound 2 exhibited significant inhibitory activity against Lewis lung cancer, brain tumor-22 and solid hepatoma in mice w3x. New-isolated constituents. Nigranoic acid (1) w4,5x Žyield: 0.04% from dried stems., schisandronic acid (3) w6x Ž0.003., p-Ž2⬘-hydroxylethyl.-phenol (4) w7x Ž0.0008., p-Ž2⬘-hydroxylethyl.-phenol -D-pyranoglucoside (5) w8x Ž0.003., Žq.-catechin (6) Ž0.0003. and -sitosterol (7) Ž0.03..
Nigranoic acid (1). Mp 125᎐126⬚C; IR bands ŽKBr.: 3050᎐2870, 2600, 1701, 1690, 1635, 1458, 1413, 1373, 1254, 1218, 1163, 1077, 933 and 891 cmy1 ; 1 H-NMR Ž400 MHz, CDCl 3 .: ␦ 6.07 Ž1H, t, H-24., 4.80, 4.72 Žeach 1H, br s, H-28., 1.89 Ž3H, s, H-27., 1.64 Ž3H, s, H-29., 0.94 Ž3H, s, H-18., 0.92 Ž3H, s, H-30., 0.89 Ž3H, d, H-21., 0.73, 0.37 Žeach 1H, d, H-19.; MS mrz Žrel. int..: 470wMxq ŽC 30 H 46 O4 ., 455 Ž100., 406, 397, 371, 329, 235, 135, 121, 107, 95, 55. Schisandronic acid (3). Mp 165᎐166⬚C; IR bands ŽKBr.: 3200᎐2500, 1712, 1682, 1637, 1456, 1379 and 1263 cmy1 ; 1 H-NMR Ž400 MHz, CDCl 3 .: ␦ 6.07 Ž1H, t, H-24., 1.90 Ž3H, d, H-27., 1.10 Ž3H, s, H-29., 1.03 Ž3H, s, H-28., 0.98 Ž3H, s, H-30., 0.89 Ž3H, s, H-18., 0.89 Ž3H, d, H-21., 0.77, 0.56 Žeach 1H, d, H-19.. Tested material. Compounds 1, 2 Žyield: 0.0002% from dried stems., 3 and 5. Studied activity. Cytotoxic activity in vitro on human decidual cells and rat luteal cells w9x. Used organisms and procedure. Ža. Rat lutel cells. Both ovaries were excised from Sprague᎐Dawley pseudopregnant rats Žweighing 220᎐250 g; provided by the Shanghai Experimental Animal Center, Chinese Academy of Sciences.. Corpora lutea were dissected out under a microscope, seeded at a density of 2᎐3 = 10 5 cellsrwell
Y. Chen et al. r Fitoterapia 72 (2001) 435᎐437
437
Table 1 In vitro cytotoxic effect of constituents from Scisandra propinqua stems on human decidual cells and rat luteal cells a Treatment
Control Solventb 1 2 3 5
Conc. Žgrml.
Human decidual cells
40 40 40 40
0 0 99.3 " 0.5 100 " 0.0 41.2 " 1.0 69.4 " 0.7
Conc. Žgrml.
20 20 20 20
Rat luteal cells
0 0 100 " 0.0 98.5 " 1.3 55.3 " 4.3 48.9 " 1.8
a
Values Žpercentage of inviable cells after 24 h. are mean " S.D. Ž n s 4.. 1, nigranoic acid; 2, manwuweizic acid; 3, schisandronic acid; 5, p-Ž2⬘-hydroxylethyl.-phenol -D-pyranoglucoside. Effective inviable rate:) 90%. b Solvent: MeOH.
in 0.5 ml of McCoy’s 5A medium, and supplemented with 30% bovine serum albumin ŽBSA., benzylpenicillin potassium 2 = 10 5 IUrl, streptomycin 2 = 10 5 IUrl. Žb. Human decidual cells Žderived from human ovary. were dispersed and seeded at 2᎐3 = 10 5 cellsrwell in 0.5 ml of F12 Dulbecco’s modified Eagle’s medium, and supplemented with 10% BSA, benzylpenicillin potassium 2 = 10 5 IUrl, streptomycin 2 = 10 5 IUrl. Both kinds of cells were cultured at 37⬚C in air with 5% CO 2 for 24 h. After culturing for 24 h, the cells were exposed to two concentrations Ž20 grml for rat lutel cells and 40 grml for human decidual cells. of the tested compounds for 24 h. The quantity of MeOH added in each well was 25 l. Cell viability was assessed with trypan blue dye w9x. Results. Reported in Table 1. Conclusions. Nigranoic acid (1) and manwuweizic acid (2) showed significant inhibitory activity against human decidual cells and rat luteal cells in vitro. This is the first report that compounds from plants of Schisandraceae possess cytotoxic activity on these two kinds of cells.
References w1x Yunnan Provincinal Crude Drugs Company. Name lists of Chinese herbal medicine resources in Yunnan. Beijing: Science Press, 1993. p. 151. w2x Xu GH, Yang Z, Zhou GH, He TH. Chin Tradit Herb Drugs 1984;15:432. w3x Liu JS, Huang MF, Tao Y. Can J Chem 1988;66:414. w4x Kikuchi M, Yoshikoshi A. Chem Lett 1972: 725. w5x Sun HD, Qiu SX, Lin LZ et al. J Nat Prod 1996;59:525. w6x Takahashi K, Takani M. Chem Pharm Bull 1975;23:538. w7x Ayer WA, Browne LM, Feng MC, Orszanska H, Saeedi-Ghomi H. Can J Chem 1986;64:904. w8x Tanahashi T, Takenaka Y, Akimoto M et al. Chem Pharm Bull 1997;45:367. w9x Yang B, Cao L, Xu Y, Su ZX, Gu ZP. Acta Pharm Sin 1997;32:573.