Altered synaptic currents,mitophagy,mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with alterations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,transmission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assessment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

Efficacy and safety of oral Chinese patent medicine combined with sacubitril/valsartan in the treatment of chronic heart failure:A Metaanalysis

Objective:To systematically evaluate the clinical efficacy of oral Chinese patent medicine combined with sacubitril/valsartan in treating chronic heart failure(CHF).Methods:CNKI,CSPD,CCD,CBM,PubMed,Web of Science,Cochrane Library and EMbase were retrieved to screen out randomized controlled trials Chinese patent medicine and Western medicine in treating CHF.Manual retrieval was also applied as a supplement.The Cochrane Reviewers Handbook 5.1.0 was used to evaluate the bias risk of the included studies and RevMan 5.4 software was used for Meta-analysis.Results:A total of 1301 patients enrolled in the 13 RCTs were included.According to the results of Meta-analysis,a combination of oral Chinese patent medicine and sacubitril/valsartan could further improve total effectiveness rate(RR=1.23,95%CI[1.16,1.30],P<0.001),increase 6 minutes’walk distance(MD=53.04,95%CI[33.43,72.64],P<0.001),improve left ventricular ejection fraction(MD=6.67,95%CI[5.15,8.19],P<0.001)and stroke volume(MD=7.56,95%CI[3.94,11.18],P<0.001),reduce left ventricular end-diastolic dimension(MD=-3.68,95%CI[-4.57,-2.78],P<0.001)and N terminal pro B type natriuretic peptide(MD=-434.08,95%CI[-518.95,-349.22],P<0.001)and no statistically significant difference in drug safety was found between the sacubitril/valsartan-only group and the combined treatment group(RR=0.73,95%CI[0.32,1.65],P=0.45).Conclusion:It’s indicated that a combination of traditional Chinese patent medicine and sacubitril/valsartan had a good clinical efficacy in the treatment of CHF,which had certain guiding significance for clinical practice.