RESUMO
Objective: The objective of the study is to investigate whether quercetin ameliorates Alzheimer's disease (AD)-like pathology in APP/PS1 double transgenic mice and its hypothesized mechanism, contributing to the comprehension of AD pathogenesis. Methods: A total of 30 APP/PS1 transgenic mice were randomized into model group (APP/PS1), quercetin group (APP/PS1+Q), and donepezil hydrochloride group (APP/PS1+DON). Simultaneously, there were 10 C57 mice of the same age served as a control group. Three months posttreatment, the effects of quercetin on AD mice were evaluated using the Morris water maze (MWM) test, Y maze experiment, immunohistochemistry, immunofluorescence, and western blotting. Results: Results from the water maze and Y maze indicated that quercetin significantly improved cognitive impairment in APP/PS1 transgenic AD mice. Additionally, serum enzyme-linked immunosorbent assay (ELISA) results demonstrated that quercetin elevated MDA, superoxide dismutase (SOD), CAT, GSH, acetylcholine (ACh), and acetylcholinesterase (AChE) levels in AD mice. Hematoxylin-eosin (HE) staining, Nissl staining, and hippocampal tissue thioflavine staining revealed that quercetin reduced neuronal damage and Aß protein accumulation in AD mice. Western blot validated protein expression in the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 pathway associated with oxidative stress and apoptosis, confirming quercetin's potential molecular mechanism of enhancing AD mouse cognition. Furthermore, western blot findings indicate that quercetin significantly alters protein expression in the Keap1/Nrf2/HO-1 pathway. Moreover, molecular docking analysis suggests that Keap1, NQO1, HO-1, caspase-3, Bcl-2, and Bax proteins in the Keap1/Nrf2/HO-1 pathway may be potential regulatory targets of quercetin. These findings will provide a molecular basis for quercetin's clinical application in AD treatment. Conclusion: Quercetin can improve cognitive impairment and AD-like pathology in APP/PS1 double transgenic mice, potentially related to quercetin's activation of the Keap1/Nrf2/HO-1 pathway and reduction of cell apoptosis.
Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Apoptose , Encéfalo , Disfunção Cognitiva , Modelos Animais de Doenças , Heme Oxigenase-1 , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Quercetina , Animais , Quercetina/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Heme Oxigenase-1/metabolismo , Apoptose/efeitos dos fármacos , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Transdução de Sinais/efeitos dos fármacos , Presenilina-1/genética , Presenilina-1/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Antioxidantes/farmacologia , Antioxidantes/metabolismoRESUMO
BACKGROUND: To evaluate the efficacy and pharmacological mechanisms of resveratrol in Alzheimer's disease (AD) patients. METHODS: We conducted a thorough exploration of existing randomized controlled trials concerning the treatment of Alzheimer's disease patients using resveratrol, utilizing accessible open databases. Quantitative variables were represented as a standardized mean difference (SMD), accompanied by a 95% confidence interval (CI). Additionally, we examined the potential targets and plausible pathways associated with the impact of resveratrol on Alzheimer's disease using network pharmacology techniques. RESULTS: Our meta-analysis comprised five trials involving 271 AD patients, of whom 139 received resveratrol treatment and 132 received placebo treatment. Compared with placebo therapy, resveratrol treatment resulted in a significant improvement in Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADAS-ADL) scores (SMD=0.51; 95% CI, 0.24 to 0.78) and cerebrospinal fluid (CSF) Aß40 (SMD=0.84; 95% CI, 0.21 to 1.47) and plasma Aß40 levels (SMD=0.43; 95% CI, 0.07 to 0.79). However, the improvement in the resveratrol-treated group compared with the placebo treatment group on the Mini-Mental State Examination (MMSE) score, CSF Aß42 and plasma Aß42 levels, and brain volume was not significant. There were no noteworthy statistical variances in the occurrence of adverse effects noted between the two groups. The outcomes of network pharmacology divulged that the principal enriched interaction pathway between resveratrol and Alzheimer's disease is primarily concentrated within the PI3K signaling pathways. Resveratrol's potential key targets for the treatment of AD include MAKP1, HRAS, EGFR, and MAPK2K1. CONCLUSION: While having a high safety profile, resveratrol has efficacy in AD patients to a certain extent, and more data are required to validate the efficacy of resveratrol for the treatment of AD in the future. Suppression of the PI3K signaling pathways could hold significant importance in the treatment of AD patients using resveratrol.
Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Resveratrol/uso terapêutico , Atividades Cotidianas , Fosfatidilinositol 3-Quinases , Resultado do TratamentoRESUMO
BACKGROUND: Knee osteoarthritis (KOA) is more common in middle-aged and elderly people, and seriously affects the quality of life of those affected. Traditional Chinese medicine (TCM) treatment of KOA has been widely recognized. In recent years, warm needling acupuncture (WNA) has been used to treat KOA and has achieved good results. However, there is a lack of comparison of the efficacy of WNA and other TCM treatments for KOA. METHODS: We conducted a search for reports of WNA and/or TCM treatment of KOA in English- and Chinese-language databases. The data was retrieved from inception of the database until October 2021. The Cochrane risk of bias tool was used to evaluate the quality of the included studies, and the network meta-analysis was performed using the software RevMan 5.20. RESULTS: A total of 8 articles met the inclusion criteria, including 399 patients treated with WNA (WNA group), and 396 patients treated with other TCM (TCM group). The results of meta-analysis showed that compared with patients in the TCM group, the effective rate [relative risk (RR)] was 1.18, 95% confidence interval (CI): 1.06 to 1.33, the last follow-up osteoarthritis index [mean difference (MD)] was -6.93, 95% CI: -12.14 to -1.72, and the last follow-up knee pain visual analogue scale (VAS) MD was -1.06, 95% CI: -1.61 to -0.51, which were all statistically significant. However, the difference in daily activities (MD: -4.31, 95% CI: -10.90 to 2.28) was not statistically significant. DISCUSSION: Compared with other TCM treatments for KOA, WNA has better overall patient efficacy. However, further randomized controlled studies are needed to compare WNA and other TCM treatments individually to confirm the efficacy of WNA.