中國醫藥大學機構典藏 China Medical University Repository, Taiwan:Item 310903500/25887

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(3) Studies on the Active Constituents of Baphicacanthus cusia and Pandanus odorus NSC-88-2314-B-039-014 87 8 1

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(5) (Baphicacanthus cusia (Nees) Bremek.)(Acanthaceae).

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(8) !p-388 "# $ %&'()*+, -./01 234../%&'() 5 6*7

(9) 801 2 39:4../ ;./<=>?9@ . A Lupeol (H-1), Stigmasterol B β-sitosterol C @ (H-2), Betulin (H-3), Indigo (C-1), Indirubin (C-2), 2-Benzoxazolinone (E-1) 2-Hydroxy-1,4-benzoxazin-3-one (E-2), 4-Hydroxy-3-methoxy benzoic acid (E-3)D EFGH (Pandanus odorus Ridl.) IJK(Pandanaceae) LM+NO POQRS TUV WXYZ[\ ]^_`abc9defgShDE FGHijk ! p-388 A-549 "#$ l' mn*+,-./01 2 34../D'()./opq?9@ . A r-sitosterol and stigmasterol (NH-1) r -sitosterol-3-O- r -D-glucoside and stigmasterol-3-O- r -D-glucoside (NH-2)methylsuccic anhydride (NH-3) 1,3-dimethyl-pyrrolidine-2,5-dione (NH-4) p-hydroxycinnamic acid (NH-5)s[] tn u!vw9xy-z]. [\8SD {EFGH4. Abstract The plant Baphicacanthus cusia (Nees) Bremek. of Acanthaceae family has been used in traditional Chinese medicine for a long time. The plant has been used as anti-inflammatory, antibacterial and anti-carcinogenic agent. The extract of Baphicacanthus cusia root showed strong inhibitory effect on tumor cell lines such as p-388. Based on the cytotoxicity guided chemical fractionation, eight compounds were isolated: Lupeol (H-1), mixture of Stigmasterol and β-sitosterol (H-2), Betulin (H-3), Indigo (C-1), Indirubin (C-2), 2-Benzoxazolinone (E-1), 2-Hydroxy-1,4-benzoxazin-3-one (E-2), and 4-Hydroxy-3-methoxy benzoic acid (E-3). Panadus odorus Ridl. is one of the species of Pandanaceae family. It has been used as foods, flavoring or as a herb medicine effective in lowering blood sugar level, liver protection and inhibiting tumor growth. The methanolic extract of the leaves of Pandanus odorus Ridl. showed strong inhibitory effect on tumor cell lines such as P-388 and A-549. Based on the cytotoxicity guided chemical fractionation, five compounds were isolated: mixture of r -sitosterol and stigmasterol (NH-1) r -sitosterol-3-O- r -D-glucoside 1.

(10) { Lupeol (H-1)(10-16) ; m.p.: 214~215°C; IR (KBr) 3326.3 (OH), 948.1 (CH), 1458.6 (CH2), 1381.5 (CH3), 1041.9 (C-O) cm-1; EIMS m/z 426 [M]+; 1H-NMR ( CDCl3) δ 0.76, 0.79, 0.83, 0.95, 0.97, 1.03 (3H each, s, 5×CH3), 1.68 (3H, s, H-30), 2.38 (1H, ddd, J=10.96, 10.96, 5.46 Hz, H-19), 3.19 (1H, m, H-3), 4.57 (1H, d, J=2.4 Hz, H-29), 4.69 (1H, dd, J=2.4, 1.4 Hz, H-29).. and stigmasterol-3-O- r -D-glucoside (NH-2)methylsuccic anhydride (NH-3) 1,3-dimethyl-pyrrolidine-2,5-dione (NH-4) p-hydroxycinnamic acid (NH-5). The methanol extract of Pandanus odorus showed strong protective effect against carbon tetrachloride induced liver toxicity. Keywords: Baphicacanthus cusia, Pandanus odorus Ridl., active constituents.

(11) (Baphicacanthes cusia (Nees) Bremek.)(Acanthaceae)7|} ~ YDS a(1) ! 3¡¢](2-5) £ ¤¥¦ §¨©ª«5¬$® LD EFGH(Pandanus odorus Ridl.)I JK(Pandanaceae) IJK¯(Pandanus) ®°*±²³5´$µ³¶ ·¸ 7¯¹º±»¼½9¾± ¿ À~ Dúa thôm ±²³ÁÂu~ Pandan Wang(6)DÃÄ,2ÅÆ$Çe È ÉÊ=¿ËÇÌ º ÍÎEF RÏÐÑEÒRÓ l FGH P EFGH(Pandanus odorus Ridl.)(7-9)~D EFGH(Pandanus odorus Ridl.)Ô ³·¸Õ8OPOQRÖ ×Ø %ÙÚOÛÜÝ Þßà4Ûá7â| iã äåæçèéêS Pë4 ìíîïêð Tñ ¦òß L Móôõ~7 WYZ[\]^Wö ÷

(12) 8SD%&øU±Ûù ß Û¹úL ÅÆû·¸ ~ü iý þLµ~Y ÅÆ5u ~FFGHFý¹~(7)D '()./EFGH4.U 23ztn[]tnD. Betulin (H-3) (11,12,14-17) ; m.p.: 218~220°C; IR (KBr) 3344.8 (OH), 2943.6, 1458.3, 1374.0 cm-1; EIMS m/z 442 [M]+; 1H-NMR (CDCl3) δ 0.76, 0.82, 0.97, 0.98, 1.02 (3H each, s, 5×CH3), 1.66 (3H, s, H-30), 3.14 (1H, dd, J=10.4, 5.2 Hz, H-3), 3.33 (1H, d, J=10.7 Hz, H-28), 3.80 (1H, d, J=10.7 Hz, H-28), 4.58 (1H, br. s, H-29), 4.68 (1H, br. s, H-29). Indigo (C-1) (18-20) ; m.p.: 300

(13) * ; UV λ (CHCl3) 245, 284.5, 332.5, 600 nm; IR (KBr) 3267.6 (N-H), 1628 (C=O), 1300 (C-N), 760 (); EIMS m/z 262 [M]+(50), 205 (18), 158 (16), 130 (15), 103 (100), 75 (85). Indirubin (C-2) (18-21) ; m.p.: 352360

(14) ; UVλ (CHCl3) 242, 291, 361.5, 533.5 nm; IR (KBr) 3190.5 (N-H), 1666.6 (C=O), 1630.7 (C=C), 755.4 () cm-1; EIMS m/z 262 [M]+(8), 234 (4), 205 (4), 157 (16), 130 (6), 104 (31), 103 (27), 75 (100); 1H-NMR (DMSO) δ 6.90 (1H, d, J=7.64 Hz, H-7), 7.01 (2H, m, Hz, H-5, 5′), 7.24 (1H, ddd,J=7.60, 7.60, 0.88 Hz, H-6), 7.39 (1H, d, J=8.12 Hz, H-7′), 7.56 (1H, ddd, J=7.68, 7.68, 1.1 Hz, H-6′), 7.64 (1H, d, J=7.44 Hz, H-4′), 8.75 (1H, d, J=7.76 Hz, H-4), 10.88 (1H, s, H-1), 10.99 (1H, s, H-1′);13C-NMR. 2.

(15) (DMSO) δ 189.0 (C-3′), 171.3 (C-2), 152.8 (C-8′), 141.2 (C-8), 138.7 (C-2′), 137.5 (C-6′), 129.6 (C-6), 106.9 (C-3), 125.0 (C-4), 124.7 (C-4′), 121.7 (C-5), 121.7 (C-9), 121.7 (C-5′), 109.9 (C-7), 119.3 (C-9′), 113.7 (C-7′).. 123.7 (C-6), 121.8 (C-1), 114.4 (C-5), 112.3 (C-2), 55.2 (-OCH3). 'mnºop>? 9 @ 75 lupeol (H-1)phytosterol (stigmasterol, β-sitosterol $C@) (H-2) betulin (H-3)indigo (C-1)indirubin (C-2) 4. ¾ 2-benzoxazolinone (E-1)2-Hydroxy-1,4-benzoxazin-3-one (E-2) u'¯5./<=4.D ,-./¦ ! Ñ !£_`8SD. 2-Benzoxazolinone (BOA) (E-1) (22-24) ; m.p.: 139~141°C; IR (KBr) 3400~3500 (NH), 2600~3200 (OH), 1742.6 (C=O), 1318.1 (C-N), 1261.4 (C-O-C) cm-1; EIMS m/z 135 [M+] (100), 91 [M-CO2] + (27.14), 79 (70.05), 52 (77.01); 1H-NMR (CDCl3) δ 7.23~7.04 (m, 4H, H-4, H-5, H-6, H-7), 9.77 (br. s, 1H, NH); 13C-NMR (Acetone-d6,) δ 153.8 (C-2), 109.4 (C-4), 123.5 (C-5), 121.8 (C-6) , 109.2 (C-7) , 143.7 (C-8) , 130.2 (C-9). 2-Hydroxy-1,4-benzoxazin-3-one (HBOA) (E-2) (25,26) ; m.p.: 187~181°C; IR (KBr) 3300~2800 (OH P NH), 1679.5 (C=O) cm-1 ; EIMS m/z 165 [M]+(26.74), 136 (100), 108 (26.39), 80 (53.82), 63 (21.01), 52 (27.08); 1 H-NMR (DMSO) δ 5.45 (1H, br. s, H-2), 6.87~6.97 (1H, m, 4H, H-5, H-6, H-7, H-8), 7.95 (1H, br. s, 2-OH), 10.78 (1H, br. s, H-4); 13 C-NMR (CDCl3) δ162.8 (C-3), 140.9 (C-9), 126.9 (C-10), 123.3 (C-6), 122.7 (C-7), 117.6 (C-8), 115.8 (C-5), 90.5 (C-2).. EFGH{ Methylsuccinic anhydride (NH-3) (32,33) "#!; m.p.: 113.2~115.1

(16) ; IR (KBr) 1696 (-OH)cm-1; EI- MS m/z 114 (M+, 28.31); 1H- NMR (CDCl3) δ 1.30 (3H, d, J= 7.14Hz, -CH3), 2.56 (1H, dd, J1= 4.88, J2= 16.98Hz, H4-$), 2.74 (1H, dd, J1= 8.62, J2= 16.98Hz, H4-r), 2.93 (1H, m, H3); 13CNMR (CDCl3) δ 16.7 (-CH3), 35.5 (-CH, C-3), 37.2 (-CH2, C-4), 177.9 (C= O, C-2), 181.4 (C= O, C-5) 1,3-Dimethyl-pyrrolidine-2,5-dione. (NH-4). (34). % , m.p.:103~106

(17) ; IR (KBr)1697 (C= O), 3326 (-OH) cm-1; EI- MS m/z 127 (M+, 6.60); 1H- NMR (CDCl3) δ 1.22 (3H, d, J=6.96Hz, CH3), 2.44 (1H, dd, J1= 5.56, J2= 16.52 Hz, H-4$), 2.78 (1H, dd, J1= 8.08, J2= 16.26 Hz, H-4r), 2.95~ 2.82 (1H, m, H3), 3.68 (s, N- CH3); 13C- NMR (CDCl3) δ 16.9 (-CH3), 35.5 (-CH), 37.2 (-CH2), 252.1 (N-CH3), 175.7 (C= O), 177.1 (C= O). 4-Hydroxy-3-methoxy benzoic acid (vanillic acid) (E-3) (27-31) ; m.p.: 187~181°C; IR (KBr) 3486.7 (OH) 2990.7 (CH), 1683.9 C=O), 1242.4 (C-O-) cm-1; EIMS m/z 168 [M]+(100.00), 153 [M-Me]+(75.31), 151 (19.14), 125 (20.68), 97 (44.44), 79 (15.35), 51 (29.94); 1H-NMR (Acetone-d6) δ 3.90 (s, 3H, 3-OCH3), 6.91 (1H , d, J=8.08 Hz, H-5), 7.56 (1H, d, 1.94 Hz, H-2), 7.59 (1H, dd, 8.08, 1.96 Hz, H-6); 13C-NMR (Acetone-d6) δ 166.3 (C=O), 150.9 (C-4), 146.9 (C-3),. p-Hydroxycinnamic acid (NH-5) (34-37) &; m.p.188.4~194.8

(18) ;IR (KBr) 3388 (-OH), 1674 (C= O) cm-1; EI- MS m/z 167 (M+, 100); 1H- NMR (CDCl3) δ 6.26 (1H, d, J= 15.92Hz, CH-C-ph), 6.77 (2H, d, 3.

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(20) . J= 8.58Hz, H3, H5), 7.46 (1H, d, J= 15.98Hz, C= CH-ph), 7.49 (2H, d, J= 8.52Hz, H2, H6); 13C- NMR (CDCl3) δ 115.7 (C-3, C-5, C-8), 125.5 (C-1), 130.3 (C-2, C-6), 159.7 (C-4), 144.3 (C-7), 168.0 (C-9). DM*¦ob £+EFG8ÙÚOÛAÈWtu¾ Ñv ¾7w¥SjÈlmno()D 1. 5Àd;B©xy¬z{|}{5 Àd;B©¬z1990Ø~L Àd xy~ û 1995s171-172D 2. Yu J, Chen KJ: Clinical observations of AIDS treated with herbal formulas. Int J Orient Med 1989; 14 (4): 189-193D 3. Hsu B: Recent progress in antineoplastic drug research in China(Review). Cancer research in the People`s Republic of China and the United States of America-epidemiology, causation and approaches to therapy. P. A. Marks (ED.) 1980; 235-250D 4. Stao A: Studies on anti-tumor activity of crude drugs. I. The effects of aqueous extracts of some crude drugs in shortterm screening test. Yakugku Zasshi 1989; 109 (6) : 407- 423D 5. !{g Y` ¥ 4 . $() (I) 5¬ 1978s150-152D 6. {FGH Ø 1985s35(3){ 43-45 7. Ø {¬S-FG H !f¬ 1997s9{249D 8. Yanfg LL, Yen KY, Kikino H: Antihepatotoxic actions of formosan plant drugs. J Ethnopharmacol 1987; 19(1): 103-110. 9. -{FGH 5¬:Q 137-138D 10. Brandt Cortius TC, Hart PC: Native medicines from the East Indian Archipelago. Geneeskd Tijdschr Nederland Indie 1939; 79: 1735-.. 'EFGHi(5opq? 9@ 75r- sitosterol and stigmasterol (NH-1), β-sitosterol-3-O-β-D-glucoside stigmasterol-3-O- r -D-glucoside (NH-2), Methylsuccinic anhydride (NH-3), 1,3-dimethyl-pyrrolidine-2,5-dione (NH-4), p-hydroxycinnamic acid (NH-5).'¯ 5./<=4.D EFGH)*ztn ¦ £ + 7 " , - . Ö / LD50 0 1 10g/kg20g/kg 23=)*.456 77 89:H¬;Ñ<=>? È7z "X LM+8OÛ@SAÑBCD ED!vw9x(carbon tetrachloride)y sGOTsGPT FzGH IJ KL $_`8S(p< 0.01) M«N:(ANOVA N-K test).O Þs* 0.5g/kg ¥¦Ã P 7QRÖ/5* 0.5g/kg1g/kg [ ]¥¦S!TR £+EFGH!] ^ UV¥¦D W+4@S 7~7

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