Treatment Of Vascular Cognitive Disorder With Kidney Yang Deficiency By Wenshenyizhi Formula Clinical Study And Pharmacological Analysis

ObjectsTo evaluate the clinical efficacy and safety of the Wenshenyizhi formula for the treatment of vascular cognitive disorders of the kidney-yang deficiency type systematically,and to conduct a network pharmacological analysis of this warm kidney puzzle formula for the treatment of vascular cognitive disorders based on differential mi RNA.Methods1.A multicentre,randomised,double-blind,controlled trial was used.One hundred patients with vascular cognitive disorder of kidney yang deficiency type from four medical institutions,namely Shanxi Provincial Hospital of Traditional Chinese Medicine,Oriental Hospital of Beijing University of Traditional Chinese Medicine,Beijing First Hospital of Integrative Medicine and Xiyuan Hospital of China Academy of Traditional Chinese Medicine,were selected and randomly divided into two groups,Treatment and Control.Treatment group was given Wenshenyizhi Formula granules + basic internal medicine treatment,while the control group was given simulants + basic internal medicine treatment,taking the medicine twice a day,1 bag each time,and the duration of treatment was all 90 days.Before and after treatment,cognitive function assessment(MMSE scale,MOCA scale),assessment of daily living ability(ADL scale),TCM identification scale score and safety assessment(blood routine,urine routine,liver function,blood and kidney function,ECG and other safety indicators and adverse drug events)were performed2.The GEO database was used to find the differential mi RNAs between VCI and cognitive normal,and the target genes were predicted by mir DIP,path DB,and Target Scan databases.TCMSP database was searched,BATMAN-TCM database was supplemented with the effective active ingredients and related proteins of the Wenshenyizhi formula,and the Uniport database was used to standardize the protein corresponding genes,and then the The drug-compound-target gene network was mapped using the Uniport database,which was then intersected with the mi RNA target genes,and the drug-compound-target gene data was imported into Cytoscape.The target genes were imported into the String platform and the results were imported into Cytoscape to obtain protein interaction networks and to screen key targets based on topological parameters.The Metascape database was used for GO and KEGG analysis and Autodock software for molecular docking.Results1.Eventually included 93 patients.There was no statistical difference between Treatment and Control grouo in terms of demographic data,past history,family history,cognitive level,ability to perform daily activities,and kidney yang deficiency score(P>0.05),and the two groups were comparable.2.Evaluation of the clinical efficacy of the Wenshenyizhi formula in treating patients with vascular cognitive disorder of the kidney yang deficiency type: after 90 days of intervention,(1)Cognitive function: there was no statistical difference between Treatment group and Control group in terms of total MMSE score after treatment compared with that before treatment(P>0.05),and there was no statistical difference between the two groups in terms of post-treatment scores(P>0.05);there was a statistical difference between Treatment group in terms of total Mo CA score after treatment compared with that before treatment(P<0.05)and the post-treatment scores improved compared to the pre-treatment scores,while the post-treatment Mo CA scores of patients in Control group were not statistically different compared to the pre-treatment scores(P>0.05),and the post-treatment improvement in the three areas of visuospatial and executive ability,attention and orientation was more pronounced in Treatment group.(2)Ability of daily living: the posttreatment ADL scores of patients in Treatment group and Control group were not statistically different compared to the pre-treatment scores(P>0.05).(3)Chinese Medicine Identification Scale scores: There was a statistical difference between Treatment group and Control group in terms of Chinese Medicine Identification Scale scores after treatment compared with those before treatment(P < 0.05),and there was a statistical difference between the two groups in terms of scores after treatment(P < 0.05).(4)Safety evaluation:No abnormalities were found in blood routine,urine routine,liver function,blood and kidney function and electrocardiogram of patients in Treatment group and Control group.There were no adverse drug events.3.The potential mechanism of the treatment of vascular cognitive disorders in patients with Wenshenyizhi Formula: 22 differential mi RNAs were obtained,corresponding to a total of 47 intersecting targets with the Wenshenyizhi formula,involving 42 active ingredients,which were shown to be involved in various biological processes such as inhibition of apoptosis,cellular response to hypoxia,estrogen and intracellular steroid hormone receptor signalling pathway,affecting PI3K-Akt,MAPK,Ras,Fox O,calcium signalling and other signalling pathways.Conclusions1.Wenshenyizhi Formula can effectively improve the cognitive level of patients with vascular cognitive disorder with kidney yang deficiency,especially in the areas of visuospatial and executive power,attention and orientation.2.Wenshenyizhi Formula can improve the symptoms of Chinese medicine in patients with Kidney-Yang deficiency vascular cognitive disorder,especially the symptoms of weakness in the waist and knees,cold hands and feet,cold knees and tinnitus,which can relieve patients’ adverse symptoms.3.Wenshenyizhi Formula has good clinical safety when treating vascular cognitive disorder of the kidney yang deficiency type.4.The treatment of vascular cognitive impairment with Wenshenyizhi Formula may be related to the regulation of various signaling pathways such as PI3K-Akt,MAPK,Ras,Fox O and calcium signaling,promoting oxidative stress,neuronal apoptosis,neural stem cell proliferation and differentiation,and vascular regeneration.