Material Basis And Mechanism Of Shenfu Compatibility Attenattion

Formulation is a resplendent jewelry of traditional Chinese medicine, the material base and mechanism of action is still unclear for the reason of complex composition and interaction in formulation which made a big interference to convince worldwide colleague of traditional Chinese medicine and its modernization. Each herb played different roles in the formulation for synergism or attenuation. Shenfu Formulation was consisting of an equal ratio of Ginseng root (Radix Ginseng; Renshen) and Aconite root (Radix Aconiti Lateralis Preparata; Fu zi), and has an apparent therapeutic effect on cardiovascular diseases. The study intend to research the material base and mechanism of action by identify the modification of Shenfu formulation (Shenfu Injection) in vivo and alteration of endogenous to established a reliable method for component compatibility and synergism or attenuation.The modification of chemical fingerprint was firstly established by Ultra Performance Liquid Chromatography/Quadrupole Time-of-flight Mass Spectrometry. Then established an attenuation analysis method by analyze the metabolic procedure of main components in Shenfu Injection and research the attenuation material basis by different compatibility metabolic in rats. At last, analyze the difference of endogenous metabolic in rats and human by take different compatibility of Shenfu formulation. The study clarified the Attenuation material basis on serum and urine.There were 20 kinds of ginsenosides include protopanaxadiol, protopanaxatriol, octotillol, and oleanolic acid type and 16 kinds of alkaloids include monoester diterpenoid alkaloids, diester diterpenoid alkaloids and amine alcohol alkaloids general alkaloids in aconitum carmichaeli debx plants in Shenfu decoction and 16 kinds of ginsenosides and 10 kinds of alkaloids by analyze the fingerprints. The distribution half life of ginsenoside Rd, Rg1, Rb1, Ro, Re, Rb2 were 0.32±0.25,0.11±0.04,0.30±0.24, 0.11±0.02,0.24±0.19,0.23±0.12hours and elimination half life of Rd、Rb、Rc、Rb2 were 10.25±0.39,21.31±3.64,13.95±2.56,15.06±1.54hours by analyze the metabolic procedure of main components in Shenfu Injection. The distribution and elimination of Rg1 and Ro were fast while Rd, Rb1, Rc, and Rb2 were slow. Different compatibility experiment showed which monoester diterpenoid alkaloids and amine alcohol alkaloids apart from diester diterpenoid alkaloids were detectable. Co-decoction group compared with mixed-decoction group, the contents of 10-OH-benzoylmesaconine, dehydrated benzoylmesaconine, dehydrated benzoylhypaconine in mixed-decoction group were higher than co-decoction group. Co-decoction group and mixed-decoction group compared with Fuzi group, the contents of cammaconine, carmichaeline, fuziline, neoline, talatizamine, acetyltalatizamine in co-decoction group and mixed-decoction group were higher than Fuzi group, but benzoylaconine,10-OH-benzoylmesaconine, benzoylmesaconine, dehydrated benzoylmesaconine, dehydrated benzoylhypaconine were lower than Fuzi group and diester diterpenoid alkaloids were not detectable. The ginsenosides in co-decoction group and mixed-decoction group showed no significances difference. The study on the modification of endogenous in rats showed Fuzi in mixed-decoction group resulted that content of glutathione, phosphatidylcholine and citric acid decreased while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed Fuzi’s cardiotoxic and Shenfu compatibility could reduce cardiotoxic induced bu Fuzi. The study on the endogenous metabolite in urine of rats showed Shenfu co-decoction could alleviated Fuzi’s toxicity effectively compared with mixed-decoction, the contents of Ubiquinone Q2 and Hippuric acid decreased while L-Methionine increased. Ubiquinone Q2, Pantothenic acid, Riboflavin, L-Methionine could alleviated Fuzi’s toxicity by antioxidant and affected function of mitochondria.The biochemical indicator examination of acute myocardial infarction patients indicated the level of alanine aminotransferase, aspartate aminotransferase, phosphocreatine kinase, lactate dehydrogenase were high than normal. The results analyzed by UPLC-Q-TOF/MS indicated salicyluric acid, glycerophosphocholine and TG(16:1(9Z)/20:1(11Z)/20:4(5Z,8Z,11Z,14Z)) rise rapidly, LysoPE(0:0/18:0) and coproporphyrin Ⅲ decreased. After intravenously guttaed Shenfu injection, the level of PG(16:0/18:1(11Z)), PC(14:1(9Z)/22:6(4Z,7Z,10Z,13Z,19Z)), inosine diphosphate and DG(20:4(5Z,8Z,11Z,14Z)/22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0) increased, EET which was the metabolite of arachidonic acid metabolismed by cytochrome 450, PE(14:0/20:2(11Z,14Z)), PE(14:1(9Z)/P-18:1(11Z)), and PE(22:5(4Z,7Z,10Z,13Z,16Z)/22:6(4Z,7Z,10Z,13Z,16Z,19Z)) decreased and coproporphyrin III returned to normal.The research studied the chemical modification after compatibility in vivo and vitro, indicated key to attenuation was ginsenosides inhibited the absorption of toxiferous aconite alkaloids and different absorption and metabolism rate of ginsenosides was the material basis of effectiveness. Studied endogenous metabolite indicated cardiotoxic of Fuzi was likely to concerned with redox reaction in vivo and the attenuation method was anti-oxidant by compatibility, and the pathway was also related to mitochondria and contributed to energy metabolism.