| Objective:Alzheimer’s disease(AD)is a type of dementia that is marked by a progressive decline in cognitive functions and an increased vulnerability to illnesses and mortality.This neurodegenerative condition is a source of significant distress for individuals and their families.Despite significant advances in treatment options,there are still limitations in clinical efficacy,with non-curative and drug-resistant forms of the disease being treatable.Thus,there is a great need for effective therapies for AD.Methods:This study primarily aimed to examine the impact of Alpinia oxyphylla Miquel(AOM)formula granules on cognitive impairment in Alzheimer’s disease mouse,genetically modified to carry three copies of the Alzheimer’s gene.The study used the 3xTg Alzheimer’s mice model and examined memory using a Y maze,an open field,followed by Morris’s water maze to better understand the effect of AOM.In order to assess the histological alterations and apoptotic features,HE staining and TUNEL staining techniques were utilized in this study.Moreover,the levels of cleaved-caspase3,cleaved-caspase8,and cleaved-caspase9 were measured through western blot(WB)analysis.Additionally,changes in the mRNA expression levels of caspase3,caspase8,and caspase9 were determined using quantitative polymerase chain reaction(qPCR).By utilizing these methods,this study aimed to identify any potential molecular mechanisms underlying the effects of the AOM formula granules on cognitive deficit in the mice model.This study also involved the use of western blot to examine the concentrations of different pro-inflammatory and pro-apoptotic factors,such as p53,p65,IKK-α,and Iκ B-α.By assessing the expression levels of these factors,the study aimed to determine their potential contribution to the cognitive decline observed in the triple-transgenic mice model,as well as to evaluate any potential therapeutic effects of the AOM formula granules.The results of this analysis could provide insight into the molecular mechanisms underlying Alzheimer’s disease and suggest possible targets for future treatment options.Results:Relative to the control group,group receiving AOM formula granules demonstrated significant improvements in cognitive function.Specifically,the mice receiving AOM formula granules displayed a greater spontaneous alteration ratio in the Y maze,indicating better working memory performance.Moreover,the treated mice exhibited increased quadrant dwell time and platform crossings in the water maze,demonstrating enhanced spatial cognition.Additionally,the treated mice showed a decrease in escape latency,indicating improved performance in water maze task.The observation made indicates that the AOM formula granules may have potential therapeutic effects for treating cognitive impairment associated with the condition.The NF-κB with apoptosis-related pathways was significantly inhibited in the hippocampus and to varying degrees in the cortex by the drug-treated groups.These observations imply,AOM has the potential to be an effective treatment for cognitive and behavioral deficiencies in triple-transgenic Alzheimer’s mice.The results of this study suggest that AOM possesses anti-inflammatory and anti-apoptotic properties that could be linked to its ability to treat AD.This study found that the AOM formula granules exhibit a distinct anti-Alzheimer’s disease activity that is attributed to its anti-inflammatory and anti-cell death properties.The AOM formula granules demonstrated significant ameliorative effects on cognitive dysfunction in the mice model,indicating that it may be a promising option for the development of treatments for AD.By targeting the underlying molecular mechanisms of AD,such as inflammation and apoptosis,AOM formula granules might present a fresh approach to management and prevention of cognitive decline associated with AD.The inhibition of NF-κB by AOM is particularly noteworthy because this pathway associated with the development of Alzheimer’s disease.Empirical evidence indicates that this factor exerts regulatory control over the expression of inflammatory cytokines and chemotactic factors,both of which are key contributors to the neuro-inflammatory response that occurs in Alzheimer’s disease.The inhibition of this pathway by AOM implies that it may be a potentially valuable therapeutic target for the treatment of AD.Additionally,AOM may be effective in treating AD by targeting the apoptotic pathway.Caspase3 is an effector molecule that contributes significantly to apoptotic pathway,and its disclosure is directly proportional to the amount of apoptosis.AOM was found to directly activate caspase3 via caspase9,suggesting that it may be able to start the process of apoptosis by activating either the mitochondrial pathway or the membrane receptor pathway.Conclusion:The study also revealed that the AOM formula granules possess anti-apoptotic effects that are independent of caspase8,a protein that has been linked to the genesis and escalation of Alzheimer’s disease.This finding is significant as caspase8 inhibition has been demonstrated to have therapeutic potential in preclinical models of AD.Therefore,the ability of AOM to exert its anti-apoptotic activity via a caspase8-independent mechanism could provide a novel approach to treating AD.In summary,the outcomes of this research propose that AOM formula granules have promising therapeutic potential for the treatment of AD. |
PDF Full Text Request