Study On The Effect Of Jie-geng-tang On Staphylococcus Aureus-induced Acute Lung Injury And Its Efficacy Constituents

Acute lung injury is a kind of life-threatening disease characterized by non-cardiogenic pulmonary edema,respiratory distress and severe hypoxemia.Bacterial infection is the most common cause of acute lung injury.Staphylococcus aureus,the most important gram-positive cocci in the clinic,has a strong virulence and a high mortality rate.It is the main pathogen causing the infection.Antibiotics are commonly used drugs to treat infectious diseases.As the largest producer of antibiotics in the world,our country is also one of the countries where the abuse of antibiotics is the most serious.As many as 80,000 people die of antibiotic abuse each year.To improve the status of antibiotics abuse,people begin to look for alternatives to antibiotics.The development of natural antibiotics from Chinese herbal medicines with antibacterial activity has become a hot spot for research.Jie-geng-tang,a classical TCM formula from Shang-Han-Lun,composed of Platycodon grandiflorum(Jacq.)A.DC.(PG)and Glycyrrhiza uralensis Fisch.(GU),is well known for "clearing heat and relieving toxicity" and its ability to "diffuse the lung and relieve sore throat".It is often used with "clearing heat and relieving toxicity" drug to treat throat inflammation and lung diseases such as lung abscess,lobar pneumonia,chronic bronchitis and so on.In the thesis,we focused on the rapid discovery of anti-bacterial constituents in Jie-geng-tang,and presented in detail as follows:Acute lung injury induced by S.aureus was administered by intratracheal instillation in mice.Jie-geng-tang could significantly improve the S.aureus-induced lung tissue pathological damage,reduce the amount of bacteria in the lungs and decrease the level of inflammatory cytokines.A rapid approach integrating liquid cromatography-iontrap-mass spectrometry with liquid chromatography-quadrupole-time-of-flight-mass spectrometry was established to analyze the chemical profiling of Jie-geng-tang.A total number of 120 constituents were observed,96 of them were identified unambiguously or tentatively,mainly including organic acids,flavonoids,triterpene saponins and the other type.31 constituents were confirmed by comparison with the standards.Five compounds with good antibacterial activity were screened by the method of micro broth dilution among the 23 compounds compared with anthentic standards.They were namely licochalcone A,licoisoflavone B,glyasperin A,isoliquiritigenin,and licochalcone B.A preliminary study of the bacteriostatic mechanism of licochalcone A and isoliquiritigenin showed that they could destroy bacterial cell walls and thus inhibit bacterial growth.In vivo pharmacodynamics results showed that licochalcone A and isoliquiritigenin could improve the survival rate of infected mice,reduce the bacteria load of lungs and improve the pathology of lung injury.What's more,the antibacterial effect of licochalcone A in vivo was first reported in this study.