Bioactive constituents of Zingiber Cassumunar and Inula Britannica Var. Chinensis

Abstract

Zingiber cassumunar Roxb. (생강과)의 근경의 CHCI_(3),분획추출물은 여러 사람암세포에 대한 시험에서 세포독성을 보였다. 이러한 활성에 따른 분획을 실시하여, 새로운 유효 물질인 (±)-trans-3-(3'-methoxy-4'-hydroxyphenyl)-4-[(E)-3"',4"'-dimethoxystyryl]cyclohexene (7) (A549,8.4; Col2, 11.2; SNU638, 6.6; HT-1080, IC_(50) 7.8 ㎍/㎖)와 4개의 알려진 유효 물질들, curcumin (1) (A549,12.3; Col2,2.3; SNU638,18.8; HT-1080, IC_(50) 2.9㎍/㎖),4- (3',4'-dimethoxyphenyl)but-1,3-diene (3) (SNU638,8.5;HT-1080, IC_(50) 1.5㎍/㎖) 4-(2',4',5'-trimethoxy-phenyl)but-1,3-diene (4) (SNU638, IC_(50) 13.2 ㎍/㎖), (±)- trans-3-(3',4'-dimethoxyphenyl)-4- [(E)-3"',4"'-dimethoxystyryl]cyclohexene (6) (A549, 4.8; Col2, 5.9; SNU638, 3.3; HT-1080, IC_(50) 6.1㎍/㎖)를 분리하였다. 추가적으로 분리된, 2개의 알려진 물질, (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol (2)와 (E)-3-hydroxy-1-(3',4'-dimethoxy-phenyl)but-3-en-1-yl acetate (5)은 활성은 나타내지 않았다. Inula britannica L. var. chinensis (Rupr.) Reg. (선복화, 국화과)의 꽃의 EtOAc 분획 추출물은 강력한 iNOS 효소 저해 활성을 보였다. 그리고 이 EtOAc 분획 추출물로부터 새로운 입체이성질체인 1-O-acetyl-4R,6S-britannilactone가 분리되었다. 이 물질의 iNOS 효소 저해 활성은 IC_(50) 22.1 ㎍/㎖로 나타났고, 이 값은 positive control인 L-N^(6)-(1-iminoethyl) Iysine(IC_(50) 33.7㎍/㎖)보다 더 우수한 저해 활성을 나타내었다.;A CHCl_(3) extract of the rhizomes of Zingiber cassumunar Roxb. (Zingiberaceae) showed significant cytotoxic activity against several human cancer cell lines. Bioassay-guided fraction led to the isolation of a new compound, (±)-trans3-(3'-methoxy-4'-hydroxypheny1)-4-[(E)-3''',4'''-dimethoxystyryl] cyclohexene (7) (A549, 8.4; Co12, 11.2; SNU638, 6.6; HT-1080, IC_(50) 7.8 ㎍/ml) and four known compounds, curcumin (1) (A549, 12.3; Co12,2.3; SNU638, 18.8; HT-1080, IC_(50) 2.9 ㎍/ml), 4-(3',4'-dimethoxyphenyl)but-1,3-diene (3) (SNU638, 8.5; HT-1080, IC_(50) 1.5 ㎍/ml), 4-(2',4',5'-trimethoxyphenyl)but-1,3-diene (4) (SNU638, IC_(50) 13.2 ㎍/ml), and (±)-trans-3-(3',4'-dimethoxypheny1)-4-[(E)-3''',4'''-dimethoxystyryl]cyclohexene (6) (A549, 4.8; Co12, 5.9; SNU638, 3.3; HT- 1080, IC_(50) 6.1 ㎍/ml) as cytotoxic constituents of Z. cassumunar. In addition, two known compounds, (E)-4-(3',4'-dimethoxyphenyl)but-3-en-l-ol (2) and (E)-3- hydroxy-l-(3',4'-dimethoxy-phenyl)but-3-en-l-yl acetate (5), were isolated as inactive constituents, in the present study. An EtOAc extract of the flowers of lnula britannica L. var. chinensis (Rupr.) Reg (Compositae) exhibited significant inhibitory activity against the lipopolysaccharide (LSP)-induced iNOS in murine macrophage RAW 264.7 cells. A new stereoisomer of britannilactone, l-O-acetyl-4R,6S-britannilactone, was isolated as a iNOS inhibitory constituent with an IC_(50) value of 22.1 ㎍/ml which is more potent than a positive control, LN^(6)-(l-iminoethyl)lysine (IC_(50) 33.7㎍/ml).