Study On The In Vivo Processes Of Main Effective Constituents Of Shenmai Injection

Shenmai injection consists of Ginseng radix et rhizoma rubra?Hongshen?and Ophiopogonis radix?Maidong?,which invigorates the Qi for relieving desertion and nourishes the Yin for replenishing bodily fluids.It is widely used for the treatment of cardiovascular disease,shock,cerebral infarction,and the adjuvant treatment of tumor,there has been no report on systematic research on the in vivo processes of main active constituents of Shenmai injection.In this work,with Shenmai injection as a research object,a LC-MS/MS method was developed for simultaneous determination of sixteen saponins in biological samples including seven protopapaxdiol?PPD?ginsenosides?ginsenosides Rb₁,Rb₂,Rb₃,Rc,Rd,S-Rg₃,and R-Rg₃?,six protopapaxtriol?PPT?ginsenosides?notoginsenoside R₁,ginsenosides Re,Rf,Rg₁,S-Rg₂,and R-Rg₂?,one oleanolic acid type ginsenoside?ginsenoside Ro?and two ophiopogonins?ophiopogonin D and ophiopogonin D'?.This method was used to investigage the pharmacokinetics,tissue distributions and excretions of these effective constituents of Shenmai injection in rats.This study could provide scientific basis for the studies on effective constituents,mechanism of action,and clinical rational application of Shenmai Injection.The main results of this article were as follows:1.The elimination characteristics of various types of saponins were different.Connection of the C-20 hydroxyl group to the glycoside and the chiral configuration of C-20 affected the metabolism of ginsenosides in vivo.PPT-type,oleanolic acid type ginsenosides,and steroidal saponins underwent a fast elimination in rat serum.PPD-type ginsenosides usually eliminated slowly in serum,but S-Rg₃ and R-Rg₃bearing a free hydroxyl group at C-20 exhibited a fast elimination.2.In tissue distribution studies,it was found that notoginsenoside R₁,ginsenoside Re,Rg₁,Rf,Ro,Rb₁,Rb₂,Rb₃,Rc,and Rd were most widely distributed in the kidney,while ginsenoside S-Rg₂,R-Rg₂,S-Rg₃,R-Rg₃,ophiopogonin D,and ophiopogonin D'had the largest distribution in the liver.PPD-type ginsenosides Rb₁,Rb₂,Rb₃,Rc,and Rd were found to have a long-term accumulation risk in some tissues,especially Rd in kidney.There were 10 ginsenosides?Re,Rg₁,Rf,Rb₁,Rc,Rb₂,Rd,S-Rg₃,R-Rg₃,and Ro?that could penetrate the blood-brain barrier.The elimination characteristics of various types of saponins in tissues were basically consistent with those in serum.3.Prototypes of S-Rg₂,R-Rg₂,S-Rg₃,R-Rg₃,ophiopogonin D,and ophiopogonin D'were excreted mainly in the feces,whereas prototypes of the remaining saponins were primarily excreted via urine.The cumulative excretion rate of prototypes of ginsenoside Rg₁,S-Rg₂,and ophiopogonin D were greater than 60%,indicating that they were mainly excreted in the prototype form,while the remaining 13 saponins were excreted mainly in the form of metabolites.