| Alzheimer’s disease,named after the description of the disease by German doctor Alosi Alzheimer in 1906,is a degenerative disease of the nervous system associated with aging of the organism,and is the most common type of dementia.There is a linear correlation between age and incidence.The incidence is higher in women than in men.Common clinical features of Alzheimer’s disease: abnormal mental behavior,memory loss,confusion,and trouble thinking and communicating.With the improvement of the medical security system and the extension of human life expectancy,the problem of global aging is becoming more and more prominent.Recent epidemiological surveys show that the incidence of AD is increasing year by year,and it has become the fourth biggest killer after cardiovascular and cerebrovascular diseases and tumors.It seriously endangers the mental and physical health of the elderly and has a serious impact on the family and society.AD has become a recognized health problem and one of the most urgent problems in the world.Considering that the pathogenesis of AD is co-involved by multiple factors,oxidative stress and inflammatory responses have been shown to contribute to Aβ42 induced neurotoxicity.Excessive oxidative stress induces inflammatory responses through various signaling pathways,including the nuclear factor κB(NF-κB)pathway,which further exacerbates the damage to the nervous system.Recently,the theory of inflammatory cytokines has attracted more and more attention.Many animal experiments have confirmed that the neurodegeneration in AD patients is the abnormal activation of inflammatory immune response in the brain cell damage and death.In order to further clarify the correlation between AD inflammation and cognitive function,understand the related mechanism of cell damage in the pathogenesis of AD,and further explore the value of Chinese traditional medicine in the treatment of AD.In this study,in the form of clinical combined experiment,related discussions were conducted from the following two aspects.The first part was the correlation study between inflammatory cytokines and cognitive function in Alzheimer’s disease.In the second part,Maackiain prevents amyloid-induced cell damage by activating PKC-Nrf2 pathway to further clarify the mechanism of cell loss.Part One Clinical study on the correlation between inflammatory cyto-kines and AD cognitive functionObjective: To investigate the correlation between inflammatory cytokines and cognitive function in elderly patients with Alzheimer’s disease(AD).Methods: 98 cases of AD patients in our hospital from February 2020 to December 2022 were selected,and the general data of the subjects were collected;According to the Mini-mental state examination MMSE,Clinical dementia rating scale,AD patients were divided into mild cognitive dysfunction group(39 cases),moderate cognitive dysfunction group(32 cases),and severe cognitive dysfunction group(27 cases).Meanwhile,90 healthy volunteers who underwent physical examination during the same period were selected as the control group.Serum collection: Serum Interleukin-1β IL-1β,Interleukin-6 IL-6,and Tumor necrosis factor-α were detected by enzyme-linked immunosorbent assay(ELISA)interferon-γ(IFN-γ)level.The levels of Interleukin-1β,Interleukin-6,Tumor TNF-α and IFN-γ were detected by immunofluorescence method.The levels of four inflammatory cytokines were compared.The correlation of inflammatory cytokines in MMSE score in AD was analyzed with the included patients as the research object.The correlation between inflammatory cytokines level and cognition of AD dementia was analyzed with the AD group as the research object.Results:1.The study on peripheral inflammatory cytokines in 98 patients with AD showed that the expression of inflammatory cytokines in AD patients was significantly higher than that in healthy control group,P<0.05,the difference was statistically significant.These results suggest that inflammatory cytokines may be involved in the development of AD.2.The levels of IL-1β,IL-6,TNF-α and IFN-γ in AD were significantly higher than those in the healthy control group,but there was no correlation with the score of MMSE,considering that inflammatory cytokines were not correlated with the severity of the disease,P>0.05,no statistical significance.3.Peripheral inflammatory cytokines are not appropriate biomarkers for the diagnosis of AD and the severity of dementia.Conclusions: The levels of inflammatory cytokines were higher than those in the healthy control group,and correlated with the cognitive function of the overall population,but had no significant correlation with the severity of dementia in AD patients.Part Two Maackiain Prevents Amyloid-beta Induced Cellular Injuryvia priming PKC-Nrf2 pathwayObjective: Amyloid-beta peptide(Aβ)induces neurotoxicity through oxidative stress and inflammatory response.Brain deposition of a large amount of amyloid beta(Aβ),in particular Aβ42,promotes the development of Alzheimer’s disease(AD).Maackiain is extracted from traditional Chinese medicine Peony Root and possesses anti-oxidative,anti-osteoporosis,antitumor and immunoregulatory effects.Whether Maackiain can reduce neurotoxicity caused by Aβ accumulation remains elusive.Methods: Cell culture,si RNA transfection,Western blot analysis,DCFH-DA assay,mitochondrial membrane potential assay(ΔΨm),SOD activity and MDA level were analyzed.All the measured data were examined by means of mean ± standard deviation.Analysis of variance and q test were used for comparison between groups.Results: Herein,we found that Maackiain down-regulated Aβ42-induced cell injury and apoptosis in PC12 cells.Moreover,Maackiain prevented Aβ42stimulation induced generation of oxidative stress and reduced Aβ42-caused impairment of mitochondrial membrane potential in PC12 cells.Maackiain increased the superoxide dismutase activity and decreased malondialdehyde content that was induced by Aβ42.Mechanistic studies showed that Maackiain increased intranuclear Nrf2 expression.Consistently,Nrf2 silencing by RNA interference weakened the protective role of Maackiain against Aβ exposure.In addition,Calphostin C,a specific antagonist of protein kinase C attenuated the promoting effects of Maackiain on Nrf2 nuclear translocation.Moreover,calphostin C attenuated the anti-oxidant and anti-inflammatory capabilities of Maackiain in PC12 cells.Conclusions: Maackiain promoted Nrf2 activation through the PKC signaling pathway,thus preventing PC12 cells from Aβ-induced oxidative stress and cell injury,suggesting that Maackiain is a potential drug for AD treatment. |
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