ABSTRACT
BACKGROUND: Severe neurological condition like Alzheimer's disease (AD) has a significantly negative impact on families and society, wherein there is no proven cure. As one of the principal active constituents of Achyranthes bidentata Blume, ecdysterone (ECR) has demonstrated antioxidant and cognitive dysfunction improvement effects. Nonetheless, the mechanism underlying the improvement of cognitive dysfunction by ECR remains unclear. This study sought to ascertain whether ECR may allebviate cognitive impairment by reducing oxidative stress via activation of the nuclear factor erythroid-2-related factor-2 (Nrf2) antioxidant system through Akt/GSK3ß pathway. METHODS: In terms of the experimental procedure, we determined the neuroprotective benefits of ECR in vivo via a cognitive impairment model of senescence-accelerated mouse prone 8 (SAMP8), we performed procedures such as behavioral testing, biochemical assaying, Nissl and TUNEL stainings, as well as flow cytometry, immunohistochemistry and western blotting. Furthermore, we investigated the underlying mechanistic action of ECR by activating PC12 cells with ß-amyloid peptide fragment 25-35 (Aß25-35). RESULTS: In vivo studies showed that ECR effectively improved cognitive impairment in SAMP8 via enhancement of learning and memory capabilities, but decreased oxidative stress, apoptosis and neuronal damage in the hippocampus. During the in vitro study, we observed that ECR dose-dependently reduced the oxidative stress and apoptosis that were induced in PC12 cells by Aß25-35. Additionally, the use of Akt inhibitors further established the potential of ECR to control Nrf2 through activation of the Akt/GSK3ß pathway and protect the PC12 cells from Aß25-35 induced damage. CONCLUSIONS: These findings offer proof that ECR reduces cognitive impairment by triggering the Nrf2 antioxidant system via the Akt/GSK3ß pathway and offer fresh information on ECR's potential as a promising therapeutic development candidate for AD.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Neuroprotective Agents , Humans , Rats , Mice , Animals , Glycogen Synthase Kinase 3 beta/metabolism , Antioxidants/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , NF-E2-Related Factor 2/metabolism , Ecdysterone/pharmacology , Ecdysterone/therapeutic use , Oxidative Stress , Signal Transduction , Amyloid beta-Peptides/toxicity , Amyloid beta-Peptides/metabolism , Alzheimer Disease/drug therapy , Cognitive Dysfunction/drug therapy , Cognition , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic useABSTRACT
OBJECTIVE: To probe into the relevance between the parameters of mild moxibustion (persistent time, interval time, treatment session) and the efficacy, as well as the optimum treatment program of mild moxibustion in hypercholesterolemia. METHODS: The patients with hypercholesterolemia were selected as the observation objects. Mild moxibustion was applied to Shenque (CV 8) and Zusanli (ST 36). The total cholesterol (TC) was taken as the index. The orthogonal experimental design was adopted for paired combination of 3 factors (persistent time, interval time and treatment session) that affected TC reducing in mild moxibustion. Moreover, the changes in blood lipid were observed to choose the optimum treatment program. RESULTS: The importance of the factors of mild moxibustion that induced TC reducing in the patients with hypercholesterolemia was interval time > treatment session > persistent time. The effect of 10 min moxibustion on each point was better than that of 5 min moxibustion. The effect of once moxibustion every other day was better than that of once every day; and the effect of 6-week treatment was better than that of 12-week treatment. CONCLUSION: The interval time of mild moxibustion is the chief factor of the efficacy on hypercholesterolemia. The optimum treatment program is mild moxibustion, 10 min on each point, once every other day and lasting 6 weeks.
