Study On Synergistic Antipyretic Mechanism Of The Extract And Volatile Oil Of Forsythia Forsytha

Objective: This study mainly investigated the antipyretic effect of the extract(EFF)and volatile oil(VOFF)of Forsythiae Fructus(FF)on yeast-induced pyrexia rats.The synergistic antipyretic mechanisms of EFF and VOFF were also discussed.Methods: 1.Three rats fever models were established by subcutaneously injection of dry yeast,subcutaneously injection of 2,4-dinitrophenol and intraperitoneal injection of lipopolysaccharide(LPS)to estimate the antipyretic effects.The most suitable model to investigate the antipyretic effects of EFF and VOFF was screened by comparing the effects of the three models.2.Yeast-induced pyrexia rats model was established.The EFF,VOFF and EFF&VOFF were administrated while the rats' body temperature increased by 0.8?.The temperature was measured every half hour after the administration,and lasted for 4h.2h after administration,the serum taken from the orbit was used to measure the IL-1 beta,IL-6 and TNF-alpha.Another group of pyrexia rats were killed after 2h of the administration of EFF,VOFF and EFF&VOFF.The hypothalamus was used to determine the level of PGE2 and c AMP.3.The blood was collected from the femoral artery after 2h of the administration of EFF and VOFF on yeast-induced pyrexia rats.UPLC-Q-TOF-MS/MS combined with multivariate statistical analysis and pattern recognition technology were used to analyze the serum metabolites in pyrexia rats,after they were treated by EFF and VOFF.The potential metabolic markers were selected and metabolic pathways were analyzed.Results:1.Compared with 2,4-dinitrophenol model and lipopolysaccharide(LPS)model,the thermal process of yeast-induced fever was long and stable.So the yeastinduced pyrexia rats model was selected to investigate the antipyretic effects of EFF and VOFF.2.Compared with the model group,the EFF,VOFF and EFF&VOFF Significantly inhibited the temperature rise of the rats(*P<0.05 or **P<0.01).Among them,the inhibitory effects of EFF and EFF&VOFF on body temperature were significantly faster than VOFF,and EFF&VOFF had a better inhibitory effect than EFF and VOFF.It can be seen from the serum index that VOFF could reduce the content of IL-1 beta in rats serum and EFF reduced IL-1 beta and IL-6 while the content of IL-1 beta,IL-6 and TNF-alpha were significantly reduced by EFF&VOFF.In rats' hypothalamus,EFF significantly decreased the content of PGE2 and c AMP(*P<0.05)while the EFF&VOFF showed the similar effect(**P<0.01).3.Compared with the fever rats,it was found that EFF and VOFF can significantly reverse the disturbance of metabolic profile in fever rat.Eight metabolites were screened out,including Sphingosine,Cytosine,L-Leucine,L-Methionine,Lyso PC(16:1(9Z)),L-Lactic acid,Adipic acid and 3-Hydroxybutyric acid.These results suggested that the antipyretic mechanisms of FF may involve in Cysteine and methionine metabolism,Valine leucine and isoleucine biosynthesis/degradation,Synthesis and degradation of ketone bodies,Butanoate metabolism.Conclusions: The results showed that the antipyretic effect of EFF&VOFF was better than that of the two given alone.It suggested that the different components of Forsythia forsythia might have a synergistic antipyretic effects.It also embodied the characteristics of multiple-components and targets in the treatment of TCM.