Study On The Chemical Synthesis And Anti-inflammatory Pharmacodynamics Of Ergosterone

Objective: Ergosterone is the main component of a variety of medicinal fungi,and has a variety of biological activities such as diuresis,treatment of chronic kidney disease,and antitumor.However,the content of ergosterone in fungi is low,which limits its development and application.Therefore,in this study,ergosterone was synthesized by chemical synthesis,simplifying the synthesis steps,optimizing the synthesis process,solving its resource problems,and explored its protective effect on lung injury,gastric ulcer and liver injury and its anti-inflammatory mechanism.This provides a theoretical basis for the development and application of ergosterone and fungal Chinese medicine.Methods: Using ergosterol as a substrate,a single redox agent was added to synthesize ergosterone.After separation and purification of ergosterone,the synthetic compounds were determined by thin-layer chromatography,high performance liquid chromatography-ultraviolet detection,and nuclear magnetic resonance technology.Then by examining the conditions such as the redox agent,solvent,temperature,time and other conditions,the optimal synthesis process was determined by high performance liquid chromatography.Ergosterone separated by column chromatography,and its protective effects on lung injury,gastric ulcer,liver injury,and NLRP3 inflammation were established by establishing mouse models of lipopolysaccharide-induced acute lung injury,alcohol-induced acute gastric ulcer,and alcohol-induced acute liver injury,and 16 S rRNA gene sequencing technology was used to study its effect on gut microbiota of mice with alcohol-induced acute liver injury.Results: The best synthetic process of ergosterone was as follows: take 100 mg of ergosterol and 114.5 mg of DDQ in a molar ratio of 1: 2,put it in a 50 mL round bottom flask,add 20 mL of dichloromethane,and heat and reflux at 60 ° C for 15 min.The ergosterone synthesis rate was determined to be about 64% by high performance liquid chromatography.Lipopolysaccharide-induced acute lung injury in mice shown that ergosterone can significantly reduce W/D,TNF-α,IL-1β,IL-6,P-selectin,ICAM-1,MDA,MPO And NO levels,significantly increased the level of SOD,and significantly inhibited the expression of NLRP3,ASC,Pro-caspase-1,Caspase-1,Pro-IL-1β and IL-1β.Alcohol-induced acute gastric ulcer experiments in mice shown Ergosterone can significantly reduce the levels of TNF-α,MTL,SP,MPO,MDA,AST and ALP,significantly increase the levels of VIP and SOD,and significantly inhibit NLRP3,ASC,Pro-caspase-1,Caspase-1,Pro-IL-1β and IL-1β protein expression.Alcohol-induced acute liver injury in mice shown that ergosterone can significantly down-regulate AST,ALT,γ-GT,TNF-α,IL-1β,IL-18,and MDA Levels,significantly upregulate the levels of PA and SOD,significantly inhibit the expression of NLRP3,ASC,Pro-caspase-1,Caspase-1,Pro-IL-1β and IL-1β,and regulate the changes of gut microbiota caused by alcohol.Conclusion: The optimal synthetic process of ergosterone was determined,and a method for detecting the content of ergosterone in this process by high performance liquid chromatography was established.Ergosterone can protect lipopolysaccharide-induced acute lung injury,alcohol-induced acute gastric ulcer in mice,and alcohol-induced acute liver injury by inhibiting NLRP3 inflammasome signaling pathway activation,and it can also regulate alcohol-induced changes of gut microbiota in mice with acute liver injury.