Study On Mechanism Of Jiedu Yizhi Formula Regulating Intestinal Microecology And Intervening Cognitive Impairment Based On The Theory Of "Shang Xia Jiao Sun,Dang Zhi Qi Zhong"

Objective: In this study,we clarified the medication experience and summary of previous generations in treating cognitive disorders.Based on Shang Xia Jiao Sun,Dang Zhi Qi Zhong,we explored the traditional medical connotation of Jiedu Yizhi Formula(JDYZF)in the treatment of cognitive impairment,explored the main components of JDYZF and the basis of the clinical syndrome,explored the protective effect and target of JDYZF on cognitive function,analyzed the mechanism of JDYZF regulating intestinal microecology.Methods:1 Literature research: Dictionary of Traditional Chinese Medicine Prescriptions was used as the retrieval object to explore the characteristics of the drug in the treatment of dementia by physicians in previous dynasties.2 Clinical research: Retrieved the outpatient medical records of Li mingquan professor,and explored the patient’s general condition,formula characteristics,and drug symptom relationship of JDYZF treatment for dementia.3 Experimental study: Analyze the Xing,Wei,and channel tropism of JDYZF.UHPLC-Q-Exactive mass spectrometry system was used to detect qualitative and quantitative.Morris water maze experiments were used to observe the influence of JDYZF on behavioral changes of APP/PS1 mice.H&E staining and IHC were used to observe the effect of JDYZF on the hippocampus tissue of APP/PS1 mice.The multi-omics analysis was used to detect the flora tissue of model mice.The differential flora,differential metabolites,and metabolic pathways among the groups were analyzed.Western Blot was used to detect the effect of JDYZF on the expression level of TLR4/NF-κB signaling pathway-related proteins in the hippocampus of APP/PS1 mice.H&E staining was used to observe the effect of JDYZF on the Hepatotoxicity and Nephrotoxicity of APP/PS1 mice.Results:1 Section Literature ResearchResearch on the medication rule for Dictionary of Traditional Chinese Medicine Prescriptions treating cognitive disorders based on the ancient and modern medical record cloud platform.Analysis of 215 prescriptions in the Dictionary of Traditional Chinese Medicine Prescriptions,involving 187 species of drugs,and the total medication frequency was 1970 times.Based on the main features of Wen,Ping,Gan and Xin,belonging to the heart,spleen and kidney meridians.The cluster analysis screened out two classical prescriptions of Kaixin San and Zhusha anshen pill,as well as three new combination formulas.2 Section Clinical ResearchResearched on the formula syndrome for JDYZF treating cognitive disorders based on the ancient and modern medical record cloud platform.Analysis of 154 medical cases,the incidence of female patients was higher than that of males,compared with 0.81:1.Age of onset was mainly concentrated in the 60-69 years,and clinical manifestations insomnia,fidgety,constipation,anxiety,palpitations,sluggish expression,fatigue,lethargy,dry mouth,reticence,decreased attention,mania,dizziness,depression,bitter mouth,abdominal distension,dreaminess,diarrhea,abdominal distension,red or dark red tongue,yellow and greasy fur,string pulse or several pulses.This prescription was often compatible with Qingre medicine(23.72%),Buxu medicine(16.49%),Huoxue huayu medicine(13.31%),Pinggan xifeng medicine(12.73%).The total frequency of plus drugs was 66.25%.The cluster analysis showed that JDYZF should have three types of syndromes,Rerao xinshen syndrome,Shenxu huowang syndrome and Tanshi pixu syndrome.Complex network analysis showed that the core syndromes of dementia were composed of insomnia,palpitations,irritability,silence and constipation.3 Section Experimental Research415 compounds were identified in JDYZF,and Berberine,Bis(2-ethylhexyl)adipate,N-Methylhernagine were the major components in JDYZF.The pharmacodynamic analysis of JDYZF could relieved the behaviors of fights and biting,and stabilized their status of body weight and eating.The pharmacodynamic results suggested that JDYZF improved the learning and memory ability of APP/PS1 mice,improved the neuronal cells and inhibited p-tau deposition in histopathology tissues.The multi-omics analysis revealed the regulation of gut microecology by JDYZF found favorable changed in the composition of the fecal microflora in mice administered JDYZF,including the increased of probiotics(Limosilactobacillus,Rikenellaceae and Prevotellaceae),the decreased of inflammatory pathogenic bacteria(Muribaculum and Alistipes),and improved the content of D-Glutamine,glutamate,Lyso PC(14:1(9Z),19-Oxotestosterone,Ganoderma lucidum acid and 1-(sn-glycoro-3-phospho)-1D myo inositol.The mechanism may be inhibited the expression of TLR4,p65/p-p65,iκB/p-iκB and IL-1βin hippocampus tissue of APP/PS1 mice.It showed that oral administration of JDYZF for 8 weeks will not cause significant changed in the structure of the liver and kidney in mice.Conclusion:Doctors in previous generations mostly used Zibu suixu to Anshen yizhi.JDYZF followed the perspective of Naosui theory,and regulated intestinal microecology based on Shang Xia Jiao Sun,Dang Zhi Qi Zhong,inhibited the TLR4/NF-κB signaling pathway,improved learning and memory ability and hippocampus tissue.