Analgesic Effect And Pharmacokinetics Of Physalin A

The calyces of Physalis alkekengi var.franchetii are a well-known traditional Chinese medicine?Jindenglong,Chinese Lantern?.Beginning in the"Shen Nong's Materia Medica",creat cold and bitter,for lung,has qingrejiedu.It is used for sore throat,cough with phlegm and heat,astringent with hot leaching,and external treatment for pemphigus and eczema.Physalin A?Physalin A?is a steroidal ester compound isolated from the lantern.As a representative chemical component of Physalins,Physalin A has good antitumor and anti-inflammatory effects,has great development prospects.This thesis provides scientific basis for its further development and application of analgesic effects and in vivo processes.This article first used mouse acetic acid twist and hot plate method to conduct pharmacodynamic study of physalin A,and used virtual screening method to the 7 major protein targets(PLA_2,COX-1,COX-2,5-LOX,LTA₄H,CYP450?different subtypes?)of physalin A on the metabolic pathways of arachidonic acid were molecularly docked to explore the analgesic mechanism of physalin A.The results show that physalin A has analgesic effect,and its mechanism may be related to its involvement in regulating LTA₄H activities in the arachidonic acid metabolism pathway.In addition,based on the early degradation of physalin A found by the research team,the effects of temperature,p H and light on the stability of physalin A were investigated.The results of the study on the stability of physalin A.solution will provide guidance for the biological sample collection,storage,and pretreatment processes during subsequent studies on the in vivo absorption kinetics of physalin A.The results suggest that physalin A is easily decomposed under strong alkaline conditions and relatively stable under acidic conditions at low temperatures and dark.Therefore,the collection,processing,and storage of experimental animal biological samples after physalin A should be performed at low temperature,and avoid contact with strong alkali as much as possible during the whole process and quantitative acidification to stabilize it.UPLC-MS/MS was used to establish a sensitive and reliable analytical method for the the analysis of physalis A in plasma samples and it was applied to rats after intragastric administration of physalin A in vivo pharmacokinetic studies.Detection of drug exposure in rat plasma at different time points after administering different doses of physalin A CMC-Na suspension to rats by a single intragastric administration,then DAS software was used to calculate the pharmacokinetic parameters.Pharmacokinetic data showed that different concentrations of physalin A were rapidly absorbed after intragastric administration.The dose was linearly correlated with AUC?r²=0.9?,indicating that the pharmacokinetic behavior of physalin A was a linear process.The apparent volume of distribution is 841-1706 L/kg,which exceeds the total water in the rat?0.15 L/kg at 0.25 kg body weight?,suggesting that physalin A can be widely distributed in rat tissues.The research team conducted a systematic research on the metabolism of physalis A in rats in the early stage,and found a relatively special metabolic pathway,sulfonation metabolism.This project uses UPLC-Q-TOF/MS technology to study the metabolic process of physalin A in liver microsomes and intestinal flora,in order to clarify the mechanism of its sulfonation metabolism.The results show that the sulfonation metabolism of physalin A can occur in the liver and intestine,and non-enzymatic sulfonation metabolism can occur in liver microsomes with cysteine as a sulfur donor.The sulfonation metabolism of physalin A in the intestinal flora does not depend on the sulfur provided by the exogenous substrate,and the sulfur-containing substances existing in the intestinal flora can provide the sulfur as a substrate.This project first studied the analgesic effect of physalin A and its mechanism of action.At the same time,a series of studies have been carried out on the solution stability of physalin A in different chemical conditions in vitro,absorption kinetics in rats,and the mechanism of sulfonation metabolism.This study enriched the pharmacological effects and in vivo processes of physalin A,and provided valuable reference for its further development and clinical rational application.