Clinical efficacy of Modified Shuyu Pill for mild and moderate Alzheimer’s disease and its effects on expressions of IL-1β/NF-κB/miR-146a in peripheral blood

Objective To explore the clinical efficay of Modified Shuyu Pill(MSP)for treatment of mild and moderate Alzheimer’s disease(AD)and its effect on the expressions of interleukin-1β(IL-1β)/nuclear factor-kappa B(NF-κB)/microRNA-146a(miR-146a)in peripheral blood.Methods Totally 52 patients with mild and moderate AD were randomly assigned to the treatment group and the control group,26 in each group.Patients in the treatment group took MSP,15 mL each time,twice a day,while those in the control group took Donepezil,5 mg each time,once before bedtime.The therapeutic course for all was 12 weeks.Mini-mental State Examination(MMSE)scale,Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-Cog),and Activity of Daily Living(ADL)scale were evaluated before and after treatment.Pattern and Element of Syndrome of Alzheimer's Disease(AD-PES-11)scale and clinical efficacy of TCM syndromes were assessed.Spearman correlation analysis was used to analyze the correlation between the score of AD-PES-11 scale and neuropsychological test scales.Serum levels of IL-1βand NF-κB were detected using enzyme linked immunosorbent assay(ELISA).The level of miR-146a was detected by fluorescence quantitative PCR.Besides,adverse reactions were observed during the treatment.Results Compared with before treatment in the same group,the score of MMSE significantly increased after treatment(P<0.01),and the scores of ADAS-Cog and ADL significantly decreased in the two groups after treatment(P<0.01).Compared with before treatment,the scores of AD-PES-11 scale,scores of Shen deficiency,Pi deficiency,medullary decrease,phlegm turbidity,and blood stasis significantly decreased after treatment in the treatment group(P<0.05,P<0.01).In the control group,the score of Pi deficiency increased significantly after treatment(P<0.05).Compared with the control group,the scores of AD-PES-11 scale,Shen deficiency,Pi deficiency,phlegm turbidity,and blood stasis decreased significantly in the treatment group after treatment(P<0.01).The total effective rate was 69.23%(18/26 cases)in the treatment group,with statistical difference as compared with that of the control group[7.69%(2/26 cases)].Statistical difference existed in clinical efficacy between the two groups(P<0.01).Correlation analysis showed that there was a negative correlation between MMSE score and Pi deficiency score/total scores(P<0.05,P<0.01).There was a positive correlation between ADAS-Cog score/ADL score and Pi deficiency/medullary decrease/total scores(P<0.05,P<0.01).Compared with before treatment,the levels of IL-1βand NF-κB decreased in both groups after treatment(P<0.05,P<0.01).The treatment group was superior to the control group in reducing IL-1βand NF-κB content(P<0.05).Compared with before treatment,the level of miR-146a decreased after treatment in the two groups(P<0.05,P<0.01).No obvious adverse reactions were observed during the treatment.Conclusion MYP can effectively improve the cognitive function and ADL of mild and moderate AD patients,improve their TCM symptoms and signs,and its mechanism may be related to inhibiting the expressions of IL-1β/NF-κB/miR-146a in peripheral blood and blocking inflammatory reactions.