Interaction Between Magnesium Lithospermate B And Gut Microbiota

Magnesium lithospermate B is an important component in danshen water extract,which is now an angina-marketed drug in China.However,low bioavailability and poor absorption limit its clinical application to intravenous r OTUe.Interestingly,orally administered low-dose MLB demonstrably alleviates chronic kidney disease,type 2 diabetes,hypertension,hepatic fibrosis and cerebral ischemia in animal models.In some in vitro experiments,researchers owe the efficacy to its antioxidant and vasodilative property,but such high effective concentration can hardly be reached by oral administration.Thus there might be new mechanisms of magnesium lithospermate B to explain this paradox.There are enormous microbial population inhabit in individuals' gut.Recent years,gut microbiota and its metabolites play important roles in diabetes,chronic kidney disease and obesity.And the physiological conditions of the hosts will impact the composition of gut microbiota.Resveratrol and berberine,low bioavailability components in Chinese traditional medicine,can alleviate disease through interacting with gut microbiota.In liver injury model,water extract of danshen can restore the composition of gut microbiota,while whether the magnesium lithospermate B was the active component is unknown.Furthermore,metabolic profiles of magnesium lithospermate B change with the gut environment.Thus we suppose that the cross-talk between lithoapermate B and gut microbiota might explain this paradox.We divide our research into three parts:1.Whether magnesium lithospermate B can act like a prebiotics to change the composition of gut microbiota in healthy mice model.2.Whether the interaction between magnesium lithospermate B and gut microbiota can be considered as a mechanism of chronic kidney disease treatment.3.Validate whether the gut microenvironment has impact on metabolic profiles of magnesium lithospermate B.To validate our three hypotheses,we used fecal 16 S r RNA gene sequencing,bioinformatic analysis,bile acids analysis,modeling diabetic nephropathy DBA/2J mice to reach our conclusion:1.Magnesium lithospermate B can increase the diversity of gut microbiota.2.Magnesium lithospermate B might modulate gut microbiota and metabolic profiles of bile acids to alleviate kidney injury.3.Magnesium lithospermate B hydrolyse in gut of healthy mice,but its metabolic profiles change significantly when gut microbiome disorder happened.These results shed a light on explaining the paradox between efficacy of magnesium lithospermate B and its poor bioavailability.