The Network Pharmacology Calculation And Experimental Study Of The Antipyretic Effect And Mechanism Of Ginseng Cubaihu Decoction

Background:Fever is a common clinical manifestation of many diseases,and high fever is clinically critical.In the clinical practice of traditional Chinese medicine,Baihu Decoction is suitable for yang brightness heat,and Baihu with Ginseng Decoction is suitable for yang brightness heat,and healthy qi and body fluid injury.Modern experimental studies have shown that Baihu Decoction has significant antipyretic effects,but its mechanism of action is not clear.Reports on Baihu with Ginseng Decoction are rare.To provide experimental basis for the clinical application of Baihu with Ginseng Decoction,we researched the antipyretic effect and mechanism of Baihu with Ginseng Decoction.Objective:To study the promoting antipyretic effect of ginseng for Baihu Decoction,the application of network pharmacology to predict its antipyretic mechanism,and then verify it.Methods:Using network pharmacology method that was mainly to find the“Ginseng-Targets-Fever”network for predicting the antipyretic mechanism of ginseng promoting Baihu Decoction through TCMSP database,human phenotypic database?HPO database?,and so on.The method of creating rat model with body imaginary and fever as follows:dwarf and glauber decoction was intragastrically administered for 3 days,twice daily,and the rats were intraperitoneally injected with LPS to induce body imaginary and fever model after the last intragastrically 5 h.Experimental study on antipyretic effects of Baihu with Ginseng Decoction:48 SD rats were divided into8 groups,including the control group,the model group,the aspirin group,the Baihu Decoction group,the half-dose Baihu with Ginseng Decoction group,the 1 times Baihu with Ginseng Decoction group,the 4 times Baihu with Ginseng Decoction group and the ginseng group.The serum level of IL-6,TNF-?and the levels of PGE₂,cAMP in hypothalamus tissue were determined by ELISA;RT-qPCR and Western Blot were used separately to measure the TLR4 mRNA and protein levels in lung tissue.Results:1.Network pharmacology predicts that the antipyretic effects mechanism of Baihu with Ginseng Decoction have nine signaling pathway that includes Toll-like receptor signaling pathway.2.Model rats had the symptoms of increasing drinking water,apathetic,decreased activity and unshaped stool,and its body temperature increased significantly?P<0.01?.The body temperature appeared double peak phenomenon at 6 h and 8 h.3.After administration 1 h,the temperature of aspirin and1 times Baihu with Ginseng Decoction group reduced significantly?P<0.01?.4.ELISA results of serum and hypothalamus in each group show that compared with the model group,the levels of serum IL-6 and TNF-?and hypothalamic cAMP and PGE₂ levels were decreased in the aspirin group and the 4 times the Baihu with Ginseng Decoction group,and the levels of IL-6,TNF-?and cAMP in the Baihu Decoction group,1 times Baihu with Ginseng Decoction group and ginseng group were decreased,and the data were statistically different.5.The results of RT-qPCR and Western Blot in lung tissue of each group show that compared with the model group,the aspirin group?P<0.05?and Baihu Decoction group?P<0.05?could increase the TLR4 mRNA level in lung tissue;the half-dose Baihu with Ginseng Decoction group?P<0.01?,1 times Baihu with Ginseng Decoction group?P<0.01?,4 times Baihu with Ginseng Decoction group?P<0.01?and ginseng group?P<0.05?can increase TLR4 mRNA and protein levels.6.The Linear Regression Equation of Decoction Content and TLR4 mRNA Level of Baihu with Ginseng Decoction:Y^{^}=1.494*X+10.07?R²=0.7542?.Conclusions:1.Rat model with body imaginary and fever was successful created by intragastrically administered warf and glauber decoction for 3 days and intraperitoneally injected with LPS.2.The clinically equivalent amount of Baihu with Ginseng Decoction?1 times Baihu with Ginseng Decoction?has significant antipyretic effect among these designed drug groups.3.Apirin,Baihu Decoction,1 times Baihu with Ginseng Decoction,4 times Baihu with Ginseng Decoction and ginseng can reduce the serum levels of IL-6 and TNF-?in rat with body imaginary and fever.4.The Baihu Decoction,half-dose Baihu with Ginseng Decoction group,1 times Baihu with Ginseng Decoction and ginseng can reduce c AMP levels in hypothalamus tissues of rats with body imaginary and fever.Apirin and 4 times Baihu with Ginseng Decoction can inhibit the levels of cAMP and PGE₂.5.The half-dose Baihu with Ginseng Decoction,1 times Baihu with Ginseng Decoction,4 times Baihu with Ginseng Decoction and ginseng can improve TLR4 mRNA and protein levels in lung tissues,Baihu Decoction increases TLR4 mRNA levels.6.The level of TLR4 mRNA increased with the increase of dose in each dose group of Baihu with Ginseng Decoction,and there was a good linear regression effect.