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Studies On Anti-hepaticfibrosis Active Constituents In The Root Of Zanthoxylum Dimorphophylum Hemsl.var.spinifolum Rhed.et Wils.

Posted on:2003-01-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:C Y TaoFull Text:PDF
GTID:1104360092465067Subject:Pharmacognosy
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In order to investigate anti-hepaticalfibrosis active chemical constituents of Zanthoxylwn dimorphophyllum Hemsl. var. spinifolum Rhed. et Wils., which is widely used in the southwest country of China, compounds were isolated from the 85% EtOH extract of Zanthoxylum dimorphophyllum Hemsl. var. spinifolum Rhed. et Wils., 28compounds were obtained by using column chromatography of silica gel, non-polar macroreticular resin, Sephadex LH-20, ODS and HPLC. 25 of them were identified on the basis of spectral analysis (UV, IR, EI-MS, FAB-MS, 'H-NMR, 13C-NMR, 2.D-NMR) and phytochemical properties as: P -amyrin (l),aurepten (2), hexacosanoic acid (3), 1 -(4'-hydroxy-7'- isopropyl -4'-methyl - octahydro -inden-l-yl)-ethanone (4), 5-methoxy - 2',2'-dimethyl-[6, 7] pyran)-2H-l-benzopyran-2-one (5), p-sitosterol (6), p- sitosterol - 3 -O-p-?-glucopyranoside(7),6-(2',3l-dihydroxy- 3'-methybutyl) -7-acetoxy- 2H -1-benzopyran-2-one (8), asarinin (9), sesamin (10), Pluviatilol (11), 1, 4-Bis-(3, 4, 5-trimethoxy - phenyl) - tetrahydro -furo [3, 4-c]furan - lignan (12), 5,8- Dimethoxy -furo [6,7]- 2H -1- benzopyran -2- one (13), 6-(2', 3' -Dihydroxy -3'- methyl -butyl) -7-hydroxy-5 -methoxy-2H-1 -benzopyran-2-one( 14),6-(2',3 '-dihydroxy-3 '-methyl-buty 1)- 7-methoxy-8-(3'-methyl-but-2'-enyl)- 2H-l-benzopyran-2-one (15) , 6- (2',3'-Dihydroxy -3'- methyl-butyl) -7- hydroxy -2H -1- benzopyran -2- one (16), 6- (2',3'-oxiranyl -3'- methyl- butyl) -7- methoxy -8- (3-methyl -but -2- enyl)- 2H -1-benzopyran -2- one(17), 7-methoxy-8- (3-methyl -but-21-enyl)- 2H -1-benzopyran -2- one (18), behenic acid (19), 6-(2',3'-Dihydroxy-3'-methyl-butyl)-7-hydroxy -2H -l-benzopyran-2-one (20), 6-(4'-Pentyl-phenoxy)-hexanoic acid (21), spinifolumoside (22), 6-[6'-O-(-deoxy- a -I-mannopyranosyl)- P -?-benzopyran-4-one (23), 6-(2',3'-dihydroxy -3'- methybutyl)-7-(O- P - D- glucopyranosyloxy ) - 2H - 1 - benzopyran -2-one (24) ,6-(2'-0- P -D - glucopyranosyloxy, 3'-dihydroxy-3'-methybutyl)-7-hydroxy - 2H-1-benzopyran - 2 -one (25); All of these compounds were isolated from Zanthoxylum dimorphophyllum Hemsl. var. spinifolum Rhed.et Wils. for the first time.among them, compound 4,8and 22 are three new compounds.The effects of compounds obtained from Zanthoxylum dimorphophyllum Hemsl. var. spinifolum Rhed. et Wils.on proliferation of HSC-T6 were observed by MTT colorimetric assay and the effects of synthesis collaen were observed by the incorporation of 3H-proline.The results showed that 6-(2', 3'-dihydroxy -3'-methybutyl) -7-acetoxy-2H-l-benzopyran-2-one and 6-2', 3'-dihydroxy -3' -methyl -butyl )-7-hydroxy -2H-l-benzopyran-2-one inhibited proliferation and collagen synthesis of activated hepatic stellate cells stimulated by serum in vitro; It is the clear' recognition that the activation to MFB and proliferation of HSC stimulated by the fibrogenic mediators from the injury liver are critical and common events of hepatic fibrosis regardless of etiology. The increase of synthesis and the decrease of degradation of ECM result in the abnormal deposition of fibril and the "capillarization" of the sinusoid,which lead to the liver fibrosis. It was suggested that 6-( 2', 3'-dihydroxy-3'-methybutyl)-7-acetoxy-2H-l-benzopyran-2-one and 6 - (2', 3' -dihydroxy -3' -methyl -butyl )-7-hydroxy -2H-l-benzopyran-2-one have antifibrotic effects through the pathway mentioned above.Chemical components in samples of Zanthoxylum dimorphophyllum Hemsl. var. spinifolum Rhed. et Wils. from different districts were compared by means of HPLC. It was found that components are similar but contents vary greatly. According to the clustering analysis results of two kings of main active components (including active constituents), this herb was divided into two chemical types, represented respectively by: (1) Lieyang (Shanxi province), Laimeng (Sichuan province), Beichuan (Sichuan province ), Guarding (Guizhou province ); (2) Xirishan (Hubei province ), Hefeng (Hubei province) ,Longshan (Hunan province ) ,Pingli (Shanxi province). And 6-(2', 3' -dihydroxy -3' -methyl -but...
Keywords/Search Tags:Zanthoxylum dimorphophyllum Hemsl. var. spinifolum Rhed.et Wils., active constituents, coumarin, hepatic fibrosis, hepatic stellate cell, HPLC, content determination
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