Parkinson's disease (PD), a chronic and progressive neurodegenerative disease, can reduce the population of dopaminergic neurons in the substantia nigra. The cause of this neuronal death remains unclear. 1-Methyl-4-phenylpyridinium ion (MPP+) is a potent neurotoxin that can destroy dopaminergic (DA) neurons and promote PD. Garcinol, a polyisoprenylated benzophenone derivative, was extracted from Garcinia indica and is an important active compound it has been used as an anticancer, antioxidant, and anti-inflammatory, agent and it can suppress reactive oxygen species (ROS) mediated cell death in a PD model. Human neuroblastoma (SH-SY5Y) cells (1 × 105 cells) were treated with MPP+ (1 mM) for 24 h to induce cellular ROS production. The formation of ROS was suppressed by pretreatment with different concentrations of garcinol (0.5 and 1.0 μM) for 3 h in SH-SY5Y cells. The present study found that MPP+ treatment increased the formation of reactive oxygen species (ROS), and the increased ROS began to promote cell death in SH-SY5Y cells. However, our natural compound garcinol effectively blocked MPP+-mediated ROS formation by activating the DJ-1/SIRT1 and PGC-1α mediated antioxidant pathway. Further findings indicate that the activated SIRT1 can also regulate p-AMPK-mediated autophagy to protect the neurons from the damage it concludes that garcinol sub-sequential regulates intracellular autophagy in this model, and the productive efficacy of garcinol was confirmed by western blot analysis and MitoSOX DCFDA and MTT assays. The results showed garcinol increased protection due to the prevention of MPP+-induced ROS and the promotion of cell survival.
Abstract Habitual chewing of areca nut increases the risk of cardiovascular disease mortality, but less report demonstrate the toxic mechanism of areca nut on heart. To investigate toxicity of areca nut on cardiomyocytes, we induced the heart injury with arecoline to evaluate the acute damage of areca nut on heart. Different concentrations of are coline (lowdosage: 5 mg/kg/day and high dosage 50 mg/kg/day) were injected into Sprague‐Dawley rat via intra‐peritoneal method for 21 days to create negative effects of arecoline on cardiomyocyte. Themyocardial architecture of the rat heart was observed. The arecoline‐induced apoptotic proteins were analysed via western blotting. The myocardialarchitecture of heart was injured with arecoline and TUNEL stain was also shown are coline‐induced cardiac apoptosis. Arecoline promoted the protein expression of both Fas dependent snd mitochondrial dependent apoptosis. In summary, arecoline induces cardiac toxicity and apoptosis by inducing both death receptor and mitochondria‐dependent apoptotic pathways on heart.
Taxol modulates local inflammatory conditions in peripheral nerves, which may impair their regeneration and recovery when injured. This study aimed to determine the effects of rosmarinic acid (RA, a polyphenol constituent of many culinary herbs) on the regeneration of the sciatic nerves in the bridging conduits.
Some clinical studies have indicated the patients with Alzheimer's disease (AD) display an increased risk of cardiovascular disease (CVD). Here, to examine the relationship between AD and CVDs, we investigated the changes in heart function in triple-transgenic late-stage AD model mice (3× Tg-AD; APPSwe, PS1M146V, and tauP301L). We fed the AD mice folic acid (FA) or folinic acid (FN) and analyzed the protective effects of the compounds on the heart; specifically, 20-month-old triple-transgenic AD mice, weighing 34-55 g, were randomly allocated into three groups-the AD, AD + FA, and AD + FN groups-and subject to gastric feeding with FA or FN once daily at 12 mg/kg body weight (BW) for 3 months. Mouse BWs were assessed throughout the trial, at the end of which the animals were sacrificed using carbon dioxide suffocation. We found that BW, whole-heart weight, and left-ventricle weight were reduced in the AD + FA and AD + FN groups as compared with the measurements in the AD group. Furthermore, western blotting of excised heart tissue revealed that the levels of the hypertrophy-related protein markers phospho(p)-p38 and p-c-Jun were markedly decreased in the AD + FA group, whereas p-GATA4, and ANP were strongly reduced in the AD + FN group. Moreover, the fibrosis-related proteins uPA, MMP-2, MEK1/2 and SP-1 were decreased in the heart in both AD + FN group. In summary, our results indicate that FA and FN can exert anti-cardiac hypertrophy and fibrosis effects to protect the heart in aged triple-transgenic AD model mice, particular in FN.
Abstract Background Cardiomyocytes undergoing apoptosis have been found in a variety of pathological conditions. Evidence suggests that Alzheimer’s disease (AD) and cardiovascular disease share some risk factors, and persons with AD have a higher risk of incident ischemic heart disease. Objectives This study sought to assess the anti-apoptotic effect and survival enhancement in aged AD mice heart in response to folic acid (FA) and folinic acid (FN). Methods In this study, 16-month-old triple-transgenic (3xTg-AD; PS1M146V, APPS we and tauP301L) late-stage AD mice, were randomly allocated into three groups; AD, AD plus FA, and AD plus FN. Mice were orally fed FA or FN once daily at a dose corresponding to 1.2 mg/kg body weight (BW). After sacrifice, the excised heart tissues were processed, and morphological analyses and TUNEL assays were carried out. Further, Western blot assays were performed to quantify the amount of apoptosis and survival protein expression in the AD group compared to the FA and FS groups. Results Results indicated reduced intercellular space and well-maintained cardiac cell morphology in both FA- and FN-treated mouse heart tissue. These were even more pronounced in the FN-treated mice. Moreover, the AD groups had a greater number of TUNEL-positive cardiac cells than the other groups. The Western blotting results showed a greater reduction of FAS/L and C-Caspase-3 in FA-treated mice, but FADD and Caspase-8 were strongly reduced in FN-treated mice. Conclusion Collectively, our results suggest that FA or FN could inhibit heart damage by promoting cardiac cell survival and preventing apoptosis in triple-transgenic late-stage AD aging mice.
Alpha-synuclein (α-syn) and amyloid-beta peptide (Aβ) accumulation cause neurodegenerative diseases. The accumulation of neurotoxins, like Aβ, tau, and α-syn is related to aging therefore studying aging mediated neurodegenerative disease is important. In this study, we used A53T tg mice in this mice behavioral and motor abnormalities could be promoted by Aβ and α-syn interaction, and we decided to prevent this interaction and their associated accumulation in the SN brain region in the A53T tg mice by Hericium erinaceus treatment. Three-month-old A53T mice were separated into three groups A53T, A53T+ low dose alcohol extracted mycelium (3.2 mg/30 g BW/day), and A53T+ high dose alcohol extracted mycelium (6.4 mg/30 g BW/day). Age-matched normal mice were used as a control. Our results confirmed that Hericium erinaceus mycelia extract prevented the formation of Aβ-mediated α-syn accumulation in the SN brain region of A53T tg mice by activating SIRT-1/ERK-1/2 mediated autophagy. We confirmed that SIRT-1/ERK-1/2 mediated autophagy via Hericium erinaceus treatment prevents Aβ and α-syn accumulation and regulates dopamine neuron survival. Our study makes significant contribution because we reported for the first time that Hericium erinaceus mycelia prevents the formation and accumulation of Aβ and α-syn in A53T tg mice by regulating SIRT-1/ERK-1/2 mediated autophagy.
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