A Preliminary Study On The Integrated Pharmacokinetics Of Anti-virus Components From Shuang-Huang-Lian Oral Liquid

Shuang-huang-lian(SHL),a traditional Chinese formula composed of Lonicerae Japonicae Flos(LJF),Scutellariae Radix(SR)and Forsythiae Fructus(FF),which was widely used to treat fever and acute upper respiratory tract infection caused by viruses or bacteria.Phenolic acids(neochlorogenic acid,chlorgenic acid and cryptochlorogenic acid)and flavonoids(baicalin,wogonoside,oroxylin A-7-O-glucuronide,baicalein,wogonin and oroxylin A)are considered to be the main active constituents contributed to antiviral and antipyretic effect of Shuang-Huang-Lian preparations.Due to the multi-components resulted in multi-activities of Chinese medicine preparations,it is difficult to evaluate the bio-effectives and quality.Nine recipes of Shuang-Huang-Lian based on the official prescription were prepared for HPLC analysis and pharmacological experiment separately(CPE method was used for observing the TCID50 of influenza A virus and MTT method was used for selecting drug concentration and analyzing cell viability).The results suggested that Shuang-Huang-Lian except recipe 1 demonstrate protecting effect on MDCK cell injury induced by influenza A virus(p<0.01,p<0.001).Stepwise regression analysis was used for analyzing the relationships between HPLC fingerprint and the protecting effect of Shuang-Huang-Lian on influenza A virus induced MDCK cell injury.Peak X2、X3、X5、X6、X8、X12、X13 and X17 were found to be related with anti-influenza A virus efficacy.HPLC peaks were identified through comparing the retention time between the standard and Shuang-Huang-Lian,caffeic acid derivatives and flavonoid glycosides were found to be correlated with anti-influenza A virus efficacy and maybe the substance basis of Shuang-Huang-Lian.A HPLC-UV method was developed to simultaneously determination 10 bioactive compounds recognized by relationship between fingerprint-effect,then the method was used to quantification 6 batches Shuang-Huang-Lian oral liquid manufactured by Harbin Pharmaceutical Group and Henan Taloph Pharmaceutical Stock Co.,Ltd.We select Shuang-Huang-Lian oral liquid as the model drug and a fast UPLC-MS/MS method for simultaneously determination multiple components in Shuang-Huang-Lian oral liquid and blood samples in rats after oral administration of Shuang-Huang-Lian preparations.After oral administration of Shuang-Huang-Lian,a remarkable increase(p<0.05,p<0.01)in values of A UC(0-t)and AUC(0-∞)of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,baicalin,oroxylin A-7-O-β-D-glucuronide and wogonoside was observed compared with LJF(Lonicerae Japonicae Flos)extract group or SR(Scutellariae radix)extract group.A study was designed to develop and validate an integrated pharmacokinetic approach to assess the holistic pharmacokinetic properties of traditional Chinese medicines(TCM)based on the results of the correlation between fingerprint and effect,taking Shuang-Huang-Lian as example.The coefficients were sorted in descending order:wogonoside>neochlorogenic acid>chlorogenic acid>cryptochlorogenic acid>baicalin>oroxylin A-7-O-D-glucopyranosid.The integrated plasma concentration(cT)of multi effective components was calculated by means of self-defined weighing coefficient based on IC50 to obtain the holistic pharmacokinetic profiles of Shuang-Huang-Lian.