PROGRESS IN CHEMISTRY ,,, Zhao Qinshi. Sun Handong 3
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1 PROGRESS IN CHEMISTRY Vol. 21 No. 1 Jan., ( ), 20 80,( ), ,,, :1,52, 3,52 4,52, ,,98 %,,, ( ) : R284 ; R54 : A : X(2009) A Drug for Treating Cardio2Cerebrovascular Diseases Phenolic Compds of Erigeron breviscapus Sun Handong 3 Zhao Qinshi (State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming , China) medicine. Abstract Erigeron breviscapus (Vant. ) Hand.2Mazz. (compositae) is a well known drug as traditional Chinese The whole herb is used to treat a variety of paralysis and its sequelae originated from apoplexy and atherothrombotic of brain. Two kinds of drugs (injection liquid and tablets) developed from this medicine have been used in clinic for the cerebral embolism, cerebral thrombosis, paralysis arisen from cerebral embolism, coronary heart disease, angina pectoris, acute rend function failure, and nephritic syndrome etc., since 1980s. : ( ) 3 (No. YK98001) [2001 ]996 [2001 ] e2mail kib. ac. cn It has been collected in Pharmacopoeia of P. R. China (2005). Our research group have reinvestigated and recognized the chemical and bioactive constituents from E. breviscapus since As the results, we found a series of phenolic compds, such as 1,52, 3, 52 and 4, 52dicarffeoylquinic esters, and erigoster A and B, which also possessed same bioactivities with sculellarin isolated and identified by Guan and Zhang [4,5 ] in 1980s. Based on the above investigation, the new drug Injection of Dengzhanxixin Phenols developed by our research team has completed phase clinical trial in June 2007.
2 78 21 The production certificate is in application. This new drug, with clear bioactive ingredient composition, well2controlled quality, solid therapeutic effect, and complete intellectual property, is believed as new generation drug in the treatment of brain and heart vas related diseases. Key words traditional Chinese medicine ; Erigeron breviscapus ( compositae) ; cardio2cerebrovascular diseases ; components ; Dengzhanxixin phenols ; new type preparation of E. breviscapus Contents 2 1 Introduction 2 Medicinal history of Erigeron breviscapus 3 Bioactive ingredient composition of E. breviscapus 4 Investigation of the pharmacology and toxicology of Dengzhanxixin phenols 5 Comprehensive analysis and appraisal 6 Brief summary 1,,,,, 2005 :, 2112 %, 1719 % ; 2112 %, 1118 %,,,,,,,20 %;,15 %,,,,,,,, Erigeron breviscapus (Vant1) Hand12Mazz1,,2 300 :,,,,,,, [1 ] [2 ],,,, Erigeron breviscapus (Vant1) Hand. 2Mazz. (compositae)
3 1 79,,20 70,,, 2005 [3 ] 2, [4,5 ], (),, ( ) (breviscapin),,,,, ( Scutellaria altissima) ( S. baicalensis) ( S. barvata ) ( Oxoylum indicum) ( Sorbaria arborea) [6 ],1992, ( [7 ) 9 ],,3,52 (3,52dicaffeoyl quinic acid) 1,52 (1,52dicaffeoyl quinic acid) 4,52 ( 4, 52dicaffeoyl quinic acid ) (erigoster B) (, scutellarin) : ( ) ( 1), ; ADP ( 2) ; ( 3),, () The quality standards of E. breviscapus and its series products () 2005 QΠWS QΠWS ,WS ( ) QΠWS ,WS32B WS , QΠWS WS , QΠWS WS , QΠWS QΠWS ,WS32B WS2197 (Z258)291 WS32B QΠWS ,,,,
4 MDA ( in vitro) Table 1 The influences of the effective components of E. breviscapus on the MDA content of the rat liver homogenates ( in vitro) group dose ( gπml) N MDA content (nmolπg wet tissue) (black control) (scutellarin) (total caffeic acid esters) (erigeron phenol) ,52(3,52dicaffeoyl quinic acid) ,52(4,52dicaffeoyl quinic acid) (erigoster B) ,52(1,52dicaffeoyl quinic acid) P < 0105, 3 3 P < 0101 vs :, 3 P < 0105, 3 3 P < 0101 vs. black control group. inhibitory rate ( %) conclusion : The effective components of E. breviscapus show antioxidant activity based on the significant inhibition effect on the formation of lipid peroxidation in liver homogenates in vitro. 2 ADP Table 2 The effects of the effective components of E. breviscapus on platelet aggregation in rats induced by ADP group dose ( gπml) N maximal aggregation rate ( %) inhibition rate of maximal aggregation ( %) average aggregation rate ( %) (solvent control) (scutellarin) (total caffeic acid esters) (erigeron phenol) ,52(3,52dicaffeoyl quinic acid) ,52(4,52dicaffeoyl quinic acid) (erigoster B) ,52(1,52dicaffeoyl quinic acid) P < 0105, 3 3 P < 0101 vs. : ADP 3 P < 0105, 3 3 P < 0101 vs. black control group inhibition rate of average aggregation ( %) conclusion : The effective components of E. breviscapus exhibit certain inhibition effect on the rat platelet aggregation induced by adenosine diphosphate (ADP).
5 Table 3 The influence of the effective components of E. breviscapus on contractile response of aorta in rabbits induced by phenylephrine group concentration ( gπml) sample size vascular tension induced by phenylephrine (g) pre2administration post2administration (solvent control) (scutellarin) (total caffeic acid esters) (erigeron phenol) ,52(3,52dicaffeoyl quinic acid) ,52(4,52dicaffeoyl quinic acid) (erigoster B) ,52(1,52dicaffeoyl quinic acid) P < 0101 vs. :, 3 3 P < 0101 vs. pre2administration control percent relaxation ( %) conclusion : The effective components of E. breviscapus have the relaxant effect on contractile response of aorta in rabbits induced by phenylephrine. It shows that the effective components of E. breviscapus have the dilating vessel action.,,,3,52(3,52dicaffeoyl quinic acid) 1,52(1,52dicaffeoyl quinic acid) 4, 52 ( 4, 52dicaffeoyl quinic acid) (erigoster B) (, scutellarin) 5 80 %,,,, : : : ADP : : ; 1 (a), (b),(c) (HPLC) Fig. 1 HPLC fingerprint of Erigeron breviscapus (a),phenolic compds of Erigeron breviscapus (b),phenolic compds injection of Erigeron breviscapus (c)
6 : ;, : ( 5, 20mgΠkg) ; (100mgΠkg) (5,20mgΠkg) (100mgΠkg) 413 : Bliss LD mgΠkg, 95 % mgΠkg, MTD > 210gΠkg( 100 ) ; Bliss LD mgΠkg,95 % mgΠkg : SD (90mgΠkgΠd),,, SD 90 10mgΠkg ( 10 ) ; 30mgΠkg ( 30 ) ; 90mgΠkg(LD 50 1Π8, 90 ) ; Beagle (80mgΠkgΠd),,, Beagle 90 5mgΠkg ( 5 ) ; 20mgΠkg ( 20 ) ; 80mgΠkg ( LD 50 1Π7, 80 ) 414,,, (TBIL DBIL AST ALT) (BUN Scr), ;> +, > + ( Hb ) ; ; ALT > 2N(N ) ; ;< ΠL,< ΠL, 5 511, 80 %UV,HPLC 3,52 2, 5,,,, 512 : ( SD : 90mgΠkgΠd ;Beagle :80mgΠkgΠd),,,, AST ALT BUN,, ( 81, 598 ), ; ADL BARTHEL 72h 7d 14d,,,,,,,,,
7 (1) (2),,:,, 98 % (3) ( ), [ 1 ].,, 300 [ 2 ]., 1970, [ 3 ].,, 2005,, 100 [ 4 ] ( Guan B Q). ( Chinese Traditional and Herbal Drugs), 1980, 11 (10) : 480 [ 5 ] (Zhang R W), ( Yang S Y), (Lin Y Y). (Acta Pharmaceutica Sinica), 1981, 16 (1) : [ 6 ].,, 1986, 946 [ 7 ] ( Yue J M), (Lin Z W), (Sun H D). (Chinese Chemical Letters), 1997, 8 (3) : [ 8 ] ( Yue J M), (Lin Z W), ( Sun H D). Phytochemistry(), 1994, 36 (3) : [ 9 ] ( Yue J M), (Zhao Q S), (Lin Z W), (Sun H D). (Acta Botanica Sinica), 2000, 42 (3) :
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