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https://www.readbyqxmd.com/read/28942022/x-11-5-27-a-daidzein-derivative-inhibits-nlrp3-inflammasome-activity-via-promoting-autophagy
#1
Wei Zhou, Xiuting Liu, Kunpeng Cheng, Xin Zhang, Jinrong Lu, Rong Hu
NLRP3 inflammasome is a cytoplasmic multiprotein complex which plays a critical role in response to infection or injury, however, aberrant NLRP3 inflammasome activation is deleterious. In our study, we investigate the inhibitory effect of X-11-5-27, a daidzein derivative, on the NLRP3 inflammasome. The results showed that the activation of NLRP3 inflammasome was inhibited by X-11-5-27 in a dose-dependent manner, followed by a decrease in the cleavage of caspase-1 and maturation of IL-1β. Furthermore, we found that X-11-5-27 significantly restrained the formation of NLRP3 inflammasome...
September 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28940366/lon-protease-a-novel-mitochondrial-matrix-protein-in-the-interconnection-between-drug-induced-mitochondrial-dysfunction-and-er-stress
#2
Miriam Polo, Fernando Alegre, Angela B Moragrega, Lara Gibellini, Alberto Marti-Rodrigo, Ana Blas-Garcia, Juan V Esplugues, Nadezda Apostolova
BACKGROUND AND PURPOSE: Mitochondria-associated membranes (MAMs) are specific ER-domains that enable direct interaction with mitochondria and mediate metabolic flow and Ca(2+) transfer. A growing list of proteins have been identified as MAMs components, but how they are recruited and function during complex cell stress situations is still not understood while the participation of mitochondrial matrix proteins is largely undervalued. EXPERIMENTAL APPROACH: This work compares mitochondrial/ER contact during combined ER stress/mitochondrial dysfunction using a model of human hepatoma cells (Hep3B cell line) treated for 24h with classic pharmacological inducers of ER stress (thapsigargin), mitochondrial dysfunction (CCCP or rotenone) or both (the antiretroviral drug Efavirenz used at clinically relevant concentrations)...
September 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28939292/evolution-of-anti-parkinsonian-activity-of-monoterpenoid-1r-2r-6s-3-methyl-6-prop-1-en-2-yl-cyclohex-3-ene-1-2-diol-in-various-in-vivo-models
#3
Elena Valdman
It has been found recently that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (Diol) demonstrates high antiparkinsonian activity in some animal models. We carried out an extended study of the antiparkinsonian activity of Diol in a set of relevant animal models. Diol (20mg/kg) exhibited an anticataleptogenic effect in the haloperidol-induced catalepsy model and restored motor activity in animals in the reserpine-induced model of oligokinesia. The ability of Diol singly administered before MPTP injection to reduce rigidity comparable to that of activity of L-DOPA (100mg/kg) was found using the model of Parkinsonian syndrome (PS) induced by single injection of MPTP (30mg/kg) to C57BL/6 mice...
September 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28930619/asiatic-acid-nullified-aluminium-toxicity-in-in-vitro-model-of-alzheimer-s-disease
#4
Mashoque Ahmad Rather, Arokiasamy Justin Thenmozhi, Thamilarasan Manivasagam, Jegadeesan Nataraj, Musthafa Mohamed Essa, Saravana Babu Chidambaram
Aluminium (Al) is a ubiquitously distributed environmental toxicant that lacks biological functions; however, its accumulation in the brain has been demonstrated to be linked to several neuropathological conditions particularly Alzheimer's disease (AD). Asiatic acid (AA), a triterpene extracted from Centella asiatica, has been reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. The present study was aimed to explore the neuroprotective effect of AA against aluminium maltolate (Al(mal)3) induced neurotoxicity by assessing cell viability, mitochondrial membrane potential, levels of reactive oxygen species (ROS), DNA damage and apoptosis (Hoechst and dual staining, comet assay; expressions of pro-apoptotic, anti-apoptotic and signaling indices) via AKT/GSK-3β signaling pathway in SH-SY 5Y  neuroblastoma cells...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28930531/isolongifolene-attenuates-rotenone-induced-mitochondrial-dysfunction-oxidative-stress-and-apoptosis
#5
Rengasamy Balakrishnan, Namasivayam Elangovan, Thangavel Mohankumar, Jegadeesan Nataraj, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa, Mohammed Akbar, Mohammed Abdul Sattar Khan
The present study was carried out to investigate the neuroprotective effects of isolongifolene (ILF), a tricyclic sesquiterpene of Murraya koenigii, against rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis in a cellular model. SH-SY5Y human neuroblastoma cells were divided into four experimental groups (control, rotenone (100 nM), ILF (10 microM) + rotenone (100 nanoM), ILF 10 microM alone treated) based on 3-(4, 5-dimethyl 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results of the present study showed that the ILF treatment significantly alleviated rotenone-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in SH-SY5Y cells...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28918840/neuroprotective-effects-of-eexenatide-in-a-rotenone-induced-rat-model-of-parkinson-s-disease
#6
Dürdane Aksoy, Volkan Solmaz, Türker Çavuşoğlu, Ayfer Meral, Utku Ateş, Oytun Erbaş
BACKROUND: Several studies suggest an association between Parkinson's disease (PD) and type 2 diabetes mellitus; these 2 diseases are both known to affect the common molecular pathways. As a synthetic agonist for the glucagon-like peptide 1 receptor, exenatide has been evaluated as a neuroprotective agent in multiple animal models. Rotenone models of PD have great potential for the investigation of PD pathology and motor and nonmotor symptoms, as well as the role of gene-environment interactions in PD causation and pathogenesis...
September 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28917310/screening-of-a-small-well-curated-natural-product-based-library-identifies-two-rotenoids-with-potent-nematocidal-activity-against-haemonchus-contortus
#7
H M P Dilrukshi Herath, Sarah Preston, Andreas Hofmann, Rohan A Davis, Anson V Koehler, Bill C H Chang, Abdul Jabbar, Robin B Gasser
The control of parasitic roundworms (nematodes) is heavily reliant on the use of a limited number of anthelmintic drugs. However, drug resistance is now very widespread and no vaccines are available, such that the discovery of new chemical entities is crucial. Within this context, we screened a library of pure natural products (n=400) against exsheathed third-stage (xL3) larvae of the parasitic nematode Haemonchus contortus using a whole-organism screening method. We identified two plant-derived rotenoids, deguelin and rotenone, with inhibitory activity on xL3 motility...
September 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28903492/editor-s-highlight-nlrp3-is-required-for-inflammatory-changes-and-nigral-cell-loss-resulting-from-chronic-intragastric-rotenone-exposure-in-mice
#8
Eileen M Martinez, Alison L Young, Yash R Patankar, Brent L Berwin, Li Wang, Katharine M von Herrmann, Jaclyn M Weier, Matthew C Havrda
Complex interactions between genetic and environmental factors are widely believed to underlie the incidence and progression of Parkinson's disease (PD). Rotenone is a naturally occurring metabolic toxin employed as an insecticide and piscicide identified as a risk factor for the development of PD in agricultural workers. The Nlrp3 inflammasome is an intracellular mediator that can initiate an inflammatory cascade in response to cellular stress. Reports by others indicating that NLRP3 expression was detectable in tissues obtained from Alzheimer's disease patients and that the PD-associated protein α-synuclein could activate inflammasomes in cultured glial cells, prompted us to test the prediction that Nlrp3 was required for the development of Parkinson's-like changes resulting from rotenone exposure in mice...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28895489/effects-of-mild-running-on-substantia-nigra-during-early-neurodegeneration
#9
Michael F Almeida, Carolliny M Silva, Rodrigo S Chaves, Nathan C R Lima, Renato S Almeida, Karla P Melo, Marilene Demasi, Tiago Fernandes, Edilamar M Oliveira, Luis E S Netto, Sandra M Cardoso, Merari F R Ferrari
Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level...
September 12, 2017: Journal of Sports Sciences
https://www.readbyqxmd.com/read/28885978/in-vitro-evaluation-of-mitochondrial-function-and-estrogen-signaling-in-cell-lines-exposed-to-the-antiseptic-cetylpyridinium-chloride
#10
Sandipan Datta, Guochun He, Alexey Tomilov, Sunil Sahdeo, Michael S Denison, Gino Cortopassi
BACKGROUND: Quaternary ammonium salts (QUATS), such as cetylpyridinium chloride (CPC) and benzalkonium chloride (BAK), are frequently used in antiseptic formulations, including toothpastes, mouthwashes, lozenges, throat and nasal sprays, and as biocides. Although in a recent ruling, the U.S. Food and Drug Administration (FDA) banned CPC from certain products and requested more data on BAK's efficacy and safety profile, QUATS, in general, and CPC and BAK, in particular, continue to be used in personal health care, food, and pharmaceutical and cleaning industries...
August 22, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28881148/protective-effect-of-%C3%AE-bisabolol-on-rotenone-induced-toxicity-in-i-drosophila-melanogaster-i
#11
Gerlânia de Oliveira Leite, Assis Ecker, Rodrigo Lopes Seeger, Bárbara Nunes Krum, Thiago Henrique Lugokenski, Roselei Fachinetto, Jéssie Haigert Sudati, Nilda Vargas Barbosa, Caroline Wagner
(-)-α-Bisabolol (BISA) is a sesquiterpene alcohol, which has with several recognized biological activities, including anti-inflammatory, anti-irritant, and antibacterial properties. In the present study, we investigated the influence of BISA (5, 25, and 250 μM) on rotenone (500 μM)-induced toxicity in <i>Drosophila melanogaster</i> for 7 days. BISA supplementation significantly decreased rotenone-induced mortality and locomotor deficits. The loss of motor function induced by rotenone correlated with a significant change in stress response factors; it decreased thiol levels, inhibited mitochondria complex I, and increased the mRNA expression of antioxidant marker proteins such as superoxide dismutase (SOD), catalase (CAT), and the keap1 gene product...
September 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28871151/time-resolved-pharmacological-studies-using-automated-on-line-monitoring-of-five-parallel-suspension-cultures
#12
Ala A Alhusban, Michael C Breadmore, Nuri Gueven, Rosanne M Guijt
Early stage pharmacological studies rely on in vitro methodologies for screening and testing compounds. Conventional assays based on endpoint measurements provide limited information because the lack in temporal resolution may not determine the pharmacological effect at its maximum. We developed an on-line, automated system for near real-time monitoring of extracellular content from five parallel suspension cultures, combining cell density measurements with a high-resolution separations every 12 minutes for 4 days...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855526/therapeutic-effects-of-baicalein-on-rotenone-induced-parkinson-s-disease-through-protecting-mitochondrial-function-and-biogenesis
#13
Xue Zhang, Lida Du, Wen Zhang, Yulin Yang, Qimeng Zhou, Guanhua Du
Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD) for several decades, and disturbed mitochondrial biogenesis (mitobiogenesis) was recently found to be a common phenomenon in PD. Baicalein, a major bioactive flavone of Scutellaria baicalensis Georgi, exerted neuroprotective effects in several experimental PD models. However, the effects of baicalein in rotenone-induced PD rats and the possible mechanisms remain poorly understood. In this study, we evaluated the therapeutic effects of baicalein and explored its mechanism of action in rotenone-induced PD models...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854218/honokiol-induces-superoxide-production-by-targeting-mitochondrial-respiratory-chain-complex-i-in-candida-albicans
#14
Lingmei Sun, Kai Liao, Dayong Wang
BACKGROUND: Honokiol, a compound extracted from Magnolia officinalis, has antifungal activities by inducing mitochondrial dysfunction and triggering apoptosis in Candida albicans. However, the mechanism of honokiol-induced oxidative stress is poorly understood. The present investigation was designed to determine the specific mitochondrial reactive oxygen species (ROS)-generation component. METHODS/RESULTS: We found that honokiol induced mitochondrial ROS accumulation, mainly superoxide anions (O2•-) measured by fluorescent staining method...
2017: PloS One
https://www.readbyqxmd.com/read/28843595/ginsenosides-rd-and-re-co-treatments-improve-rotenone-induced-oxidative-stress-and-mitochondrial-impairment-in-sh-sy5y-neuroblastoma-cells
#15
E González-Burgos, Carlos Fernández-Moriano, R Lozano, I Iglesias, M P Gómez-Serranillos
Oxidative stress and mitochondrial dysfunction play key roles in Parkinson's disease (PD) initiation and progression. Ginsenosides are major compounds of Ginseng species and they are responsible for pharmacological activity. The aim of this study was to investigate the potential neuroprotective effects and mechanism of the major ginsenosides Rd and Re in rotenone-induced oxidative stress model in human neuroblastoma SH-SY5Y cells. Co-treatments with both ginsenosides inhibited the increased intracellular ROS production and by-products lipid peroxidation accumulation caused by rotenone...
August 23, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28816233/shikonin-induces-glioma-cell-necroptosis-in-vitro-by-ros-overproduction-and-promoting-rip1-rip3-necrosome-formation
#16
Bin Lu, Xu Gong, Zong-Qi Wang, Ye Ding, Chen Wang, Tian-Fei Luo, Mei-Hua Piao, Fan-Kai Meng, Guang-Fan Chi, Yi-Nan Luo, Peng-Fei Ge
Necroptosis is a type of programmed necrosis regulated by receptor interacting protein kinase 1 (RIP1) and RIP3. Necroptosis is found to be accompanied by an overproduction of reactive oxygen species (ROS), but the role of ROS in regulation of necroptosis remains elusive. In this study, we investigated how shikonin, a necroptosis inducer for cancer cells, regulated the signaling leading to necroptosis in glinoma cells in vitro. Treatment with shikonin (2-10 μmol/L) dose-dependently triggered necrosis and induced overproduction of intracellular ROS in rat C6 and human SHG-44, U87 and U251 glioma cell lines...
August 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28813475/evaluation-of-the-adaptogenic-potential-exerted-by-ginsenosides-rb1-and-rg1-against-oxidative-stress-mediated-neurotoxicity-in-an-in-vitro-neuronal-model
#17
Carlos Fernández-Moriano, Elena González-Burgos, Irene Iglesias, Rafael Lozano, M Pilar Gómez-Serranillos
BACKGROUND: Ginseng (Panax sp.) is a drug with multiple pharmacological actions that has been largely used in traditional medicines for the treatment of many health problems. In the therapy of neurodegenerative disorders, it has been employed due to its capacity to strengthen mental processes by enhancing cognitive performance and psychological function. Current work aimed at evaluating the adaptogenic potential of Rb1 and Rg1 against oxidative-stress mediated degeneration in a model of nervous cells...
2017: PloS One
https://www.readbyqxmd.com/read/28806057/rational-design-and-multi-biological-profiling-of-novel-donepezil-trolox-hybrids-against-alzheimer-s-disease-with-cholinergic-antioxidant-neuroprotective-and-cognition-enhancing-properties
#18
Pei Cai, Si-Qiang Fang, Xue-Lian Yang, Jia-Jia Wu, Qiao-Hong Liu, Hao Hong, Xiao-Bing Wang, Lingyi Kong
A novel series of donepezil-trolox hybrids were designed, synthesized and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 μM) and hMAO-B (IC50 = 4.3 μM), significant antioxidant activity (41...
August 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28805762/-a-study-of-combination-treatment-with-nacom-levodopa-carbodope-and-citicoline-in-the-model-of-parkinson-disease-in-rats
#19
V A Kashkin, E V Shekunova, M N Makarova, V G Makarov
AIM: To evaluate the efficacy of the combined use of citicoline (neipilept) and levodopa/carbidopa (nakom) in the rotenone model of Parkinson's disease in rats. MATERIAL AND METHODS: Rotenone was administrated during 14 days in dose 2 mg/kg/day subcutaneously. The duration of treatment was 7 days, intragastrically. Alteration of locomotor behavior components, muscular rigidity in resistance to passive flexion in the ankle joint and signs of extrapyramidal disorders were assessed...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28799615/forsythenethosides-a-and-b-two-new-phenylethanoid-glycosides-with-a-15-membered-ring-from-forsythia-suspensa
#20
Si-Yuan Shao, Zi-Ming Feng, Ya-Nan Yang, Jian-Shuang Jiang, Pei-Cheng Zhang
Forsythenethosides A (1) and B (2), two new phenylethanoid glycosides with an unprecedented 15-membered carbon scaffold ring, were isolated from the fruits of Forsythia suspensa. Their structures, including their geometric configurations, were determined via extensive NMR spectroscopy techniques, especially using 2D NMR data combined with systematic conformational analysis. Forsythenethosides A and B showed strong neuroprotective activities against serum-deprivation-induced PC12 cell damage. Furthermore, they were active on rotenone-induced PC12 cell damage...
August 23, 2017: Organic & Biomolecular Chemistry
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