排序方式: 共有22条查询结果,搜索用时 31 毫秒
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Xueyang Xiao Zhou Tong Yuexing Zhang Hui Zhou Mengying Luo Tianhui Hu Ping Hu Luqi Kong Zeqin Liu Chan Yu Zhiyong Huang Linzhen Hu 《Marine drugs》2022,20(3)
Oxidative stress has been implicated in the etiology of Parkinson’s disease (PD). Molecules non-covalently binding to the Keap1–Nrf2 complex could be a promising therapeutic approach for PD. Herein, two novel prenylated indole alkaloids asperpenazine (1), and asperpendoline (2) with a scarce skeleton of pyrimido[1,6-a]indole were discovered from the co-cultivated fungi of Aspergillus ochraceus MCCC 3A00521 and Penicillium sp. HUBU 0120. Compound 2 exhibited potential neuroprotective activity on SH-SY5Y cells against oxidative stress. Molecular mechanism research demonstrated that 2 inhibited Keap1 expression, resulting in the translocation of Nrf2 from the cytoplasm to the nucleus, activating the downstream genes expression of HO-1 and NQO1, leading to the reduction in reactive oxygen species (ROS) and the augment of glutathione. Molecular docking and dynamic simulation analyses manifested that 2 interacted with Keap1 (PDB ID: 1X2R) via forming typical hydrogen and hydrophobic bonds with residues and presented less fluctuation of RMSD and RMSF during a natural physiological condition. 相似文献
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Peroxisome proliferator-activated receptor (PPAR) expression has been implicated in pathological states such as cancer, inflammation, diabetes, and neurodegeneration. We isolated natural PPAR agonists—eight 2,5-diketopiperazines—from the jellyfish-derived fungus Aspergillus flavus. Cyclo-(L-Pro-L-Phe) was the most potent PPAR-γ activator among the eight 2,5-DKPs identified. Cyclo-(L-Pro-L-Phe) activated PPAR-γ in Ac2F rat liver cells and SH-SY5Y human neuroblastoma cells. The neuroprotective effect of this partial PPAR-γ agonist was examined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase release, and the Hoechst 33342 staining assay in SH-SY5Y cells. Our findings revealed that cyclo-(L-Pro-L-Phe) reduced hydrogen peroxide-induced apoptosis as well as the generation of reactive oxygen species. Rhodamine 123 staining and western blotting revealed that cyclo-(L-Pro-L-Phe) prevented the loss of mitochondrial membrane potential and inhibited the activation of mitochondria-related apoptotic proteins, such as caspase 3 and poly (ADP-ribose) polymerase. Moreover, cyclo-(L-Pro-L-Phe) inhibited the activation and translocation of nuclear factor-kappa B. Thus, the partial PPAR-γ agonist cyclo-(L-Pro-L-Phe) demonstrated potential neuroprotective activity against oxidative stress-induced neurodegeneration in SH-SY5Y cells. 相似文献
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Joon Ha Park Tae-Kyeong Lee Dae Won Kim Ji Hyeon Ahn Choong-Hyun Lee Jong-Dai Kim Myoung Cheol Shin Jun Hwi Cho Jae-Chul Lee Moo-Ho Won Soo Young Choi 《Marine drugs》2022,20(4)
Astaxanthin is a powerful biological antioxidant and is naturally generated in a great variety of living organisms. Some studies have demonstrated the neuroprotective effects of ATX against ischemic brain injury in experimental animals. However, it is still unknown whether astaxanthin displays neuroprotective effects against severe ischemic brain injury induced by longer (severe) transient ischemia in the forebrain. The purpose of this study was to evaluate the neuroprotective effects of astaxanthin and its antioxidant activity in the hippocampus of gerbils subjected to 15-min transient forebrain ischemia, which led to the massive loss (death) of pyramidal cells located in hippocampal cornu Ammonis 1-3 (CA1-3) subfields. Astaxanthin (100 mg/kg) was administered once daily for three days before the induction of transient ischemia. Treatment with astaxanthin significantly attenuated the ischemia-induced loss of pyramidal cells in CA1-3. In addition, treatment with astaxanthin significantly reduced ischemia-induced oxidative DNA damage and lipid peroxidation in CA1-3 pyramidal cells. Moreover, the expression of the antioxidant enzymes superoxide dismutase (SOD1 and SOD2) in CA1-3 pyramidal cells were gradually and significantly reduced after ischemia. However, in astaxanthin-treated gerbils, the expression of SOD1 and SOD2 was significantly high compared to in-vehicle-treated gerbils before and after ischemia induction. Collectively, these findings indicate that pretreatment with astaxanthin could attenuate severe ischemic brain injury induced by 15-min transient forebrain ischemia, which may be closely associated with the decrease in oxidative stress due to astaxanthin pretreatment. 相似文献
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William A. Beltran 《Veterinary ophthalmology》2009,12(3):192-204
Inherited retinal degenerations (RDs) are a common cause of blindness in dogs and in humans. Over the past two decades numerous genes causally associated with these diseases have been identified and several canine models have been used to improve our understanding of the molecular mechanisms of RDs, as well as to test the proof of principle and safety of novel therapies. This review briefly summarizes the drug delivery approaches and therapeutic strategies that have been and are currently tested in dogs, with a particular emphasis on corrective gene therapy, and retinal neuroprotection. 相似文献
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Sajad Fakhri Akram Yarmohammadi Mostafa Yarmohammadi Mohammad Hosein Farzaei Javier Echeverria 《Marine drugs》2021,19(3)
In recent decades, several neuroprotective agents have been provided in combating neuronal dysfunctions; however, no effective treatment has been found towards the complete eradication of neurodegenerative diseases. From the pathophysiological point of view, growing studies are indicating a bidirectional relationship between gut and brain termed gut-brain axis in the context of health/disease. Revealing the gut-brain axis has survived new hopes in the prevention, management, and treatment of neurodegenerative diseases. Accordingly, introducing novel alternative therapies in regulating the gut-brain axis seems to be an emerging concept to pave the road in fighting neurodegenerative diseases. Growing studies have developed marine-derived natural products as hopeful candidates in a simultaneous targeting of gut-brain dysregulated mediators towards neuroprotection. Of marine natural products, carotenoids (e.g., fucoxanthin, and astaxanthin), phytosterols (e.g., fucosterol), polysaccharides (e.g., fucoidan, chitosan, alginate, and laminarin), macrolactins (e.g., macrolactin A), diterpenes (e.g., lobocrasol, excavatolide B, and crassumol E) and sesquiterpenes (e.g., zonarol) have shown to be promising candidates in modulating gut-brain axis. The aforementioned marine natural products are potential regulators of inflammatory, apoptotic, and oxidative stress mediators towards a bidirectional regulation of the gut-brain axis. The present study aims at describing the gut-brain axis, the importance of gut microbiota in neurological diseases, as well as the modulatory role of marine natural products towards neuroprotection. 相似文献
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Chien-Wei Feng Han-Chun Hung Shi-Ying Huang Chun-Hong Chen Yun-Ru Chen Chun-Yu Chen San-Nan Yang Hui-Min David Wang Ping-Jyun Sung Jyh-Horng Sheu Kuan-Hao Tsui Wu-Fu Chen Zhi-Hong Wen 《Marine drugs》2016,14(10)
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways. Additionally, we found that 11-de could reverse the 6-OHDA-induced downregulation of total swimming distance in a zebrafish model of PD. Using a rat model of PD, we showed that a 6-OHDA-induced increase in the number of turns, and increased time spent by rats on the beam, could be reversed by 11-de treatment. Lastly, we showed that 6-OHDA-induced attenuation in tyrosine hydroxylase (TH), a dopaminergic neuronal marker, in zebrafish and rat models of PD could also be reversed by treatment with 11-de. Moreover, the patterns of DJ-1 expression observed in this study in the zebrafish and rat models of PD corroborated the trend noted in previous in vitro studies. 相似文献
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木奶果醇提物的抗氧化活性及其对Aβ25-35致PC12细胞损伤的神经保护作用 总被引:1,自引:0,他引:1
为了探明木奶果不同部位的总酚含量和抗氧化活性及其对Aβ25-35致PC12细胞损伤的神经保护作用的差异,以期为木奶果高价值产品开发提供理论依据。以木奶果果皮、果肉、果核3个部位醇提物为研究对象,采用Folin-Ciocalteu法、DPPH、ABTS、羟基自由基清除能力测定体外抗氧化活性,并采用Aβ25-35诱导PC12细胞成阿尔兹海默病细胞模型测定醇提物对不同浓度Aβ25-35所致PC12细胞损伤的神经保护作用。结果显示:木奶果果皮、果肉、果核3个部位的总酚含量分别为(101.03±5.99)、(16.03±1.13)、(51.27±4.02)mg GAE/g干物质;抗氧化活性与样品浓度存在剂量关系,其中果皮的抗氧化活性最强,果核次之,果肉最差;果皮醇提物对Aβ25-35所致PC12细胞损伤的神经保护作用最佳,当木奶果果皮醇提物浓度为1 mg/m L时,能将Aβ25-35诱导的PC12细胞致死率从(41.6±1.36)%降为(11.95±1.98)%;PC12细胞的凋亡率从(84.69±5.78)%降至(25.26±3.18)%。可见,木奶果醇提物对Aβ25-35所致PC12细胞氧化损伤具有很好的保护作用。 相似文献
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过氧化物酶体增殖剂激活受体γ(PPARγ)是核激素受体超家族转录因子成员之一,在机体能量代谢、细胞分化、神经损伤、炎性反应及心脑血管疾病中发挥重要的调控作用。本文就PPARγ及其配体的结构特征和生物学功能作了简要介绍。 相似文献