Frontiers in Aging Neuroscience
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2024
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IF 4.1
Yu Xingzhi,Tao Jie,Xiao Tian,Duan Xiaohua
Introduction: Gastrodia elata Blume is a widely used medicinal and edible herb with a rich chemical composition. Moreover, prescriptions containing Gastrodia elata are commonly used for the prevention and treatment of cardiovascular, cerebrovascular, and aging-related diseases. Recent pharmacological studies have confirmed the antioxidant and neuroprotective effects of Gastrodia elata, and, in recent years, this herb has also been used in the treatment of Alzheimer’s disease (AD) and other neurodegenerative disorders. We have previously shown that 4,4′-methylenediphenol, a key active ingredient of Gastrodia elata, can mitigate amyloid-β (Aβ)-induced paralysis in AD model worms as well as prolong the lifespan of the animals, thus displaying potential as a treatment of AD.Methods: We investigated the effects of 4,4′-methylenediphenol on AD and aging through paralysis, lifespan, and behavioral assays. In addition, we determined the anti-AD effects of 4,4′-methylenediphenol by reactive oxygen species (ROS) assay, lipofuscin analysis, thioflavin S staining, metabolomics analysis, GFP reporter gene worm assay, and RNA interference assay and conducted in-depth studies on its mechanism of action.Results: 4,4′-Methylenediphenol not only delayed paralysis onset and senescence in the AD model worms but also enhanced their motility and stress tolerance. Meanwhile, 4,4′-methylenediphenol treatment also reduced the contents of reactive oxygen species (ROS) and lipofuscin, and decreased Aβ protein deposition in the worms. Broad-spectrum targeted metabolomic analysis showed that 4,4′-methylenediphenol administration had a positive effect on the metabolite profile of the worms. In addition, 4,4′-methylenediphenol promoted the nuclear translocation of DAF-16 and upregulated the expression of SKN-1, SOD-3, and GST-4 in the respective GFP reporter lines, accompanied by an enhancement of antioxidant activity and a reduction in Aβ toxicity; importantly, our results suggested that these effects of 4,4′-methylenediphenol were mediated, at least partly, via the activation of DAF-16.Conclusion: We have demonstrated that 4,4′-methylenediphenol can reduce Aβ-induced toxicity in AD model worms, suggesting that it has potential for development as an anti-AD drug. Our findings provide ideas and references for further research into the anti-AD effects of Gastrodia elata and its active ingredients.
研究领域:
神经科学
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药理学
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老年学
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分子生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2022
·
IF 8.943
Man Qu,He Chen,Hanpeng Lai,Xing Liu,Dayong Wang,Xing Zhang
Nanoplastics represented by nanopolystyrene (NPS) and its chemically modified derivatives are environmentally ecotoxicological hotpots in recent years, but their toxicity and underlying mechanisms have not been fully identified. Here we employed Caenorhabditis elegans as an animal model to systematically compare the toxicity between nanopolystyrene and its 4 chemically modified derivatives (PS-PEG, PS-COOH, PS-SOOOH and PS-NH 2 ) at predicted environmental concentrations. Our study demonstrated that compared with PS exposed group, PS-NH 2 exposure (15 μg/L) caused a significant decline in lifespan by suppressed DAF-16/insulin signaling and shortened body length by inhibiting DBL-1/TGF β signaling. Different from PS-NH 2 exposed group, PS-SOOOH exposure (15 μg/L) could not cause changes in lifespan, but shortened body length by inhibiting DBL-1/TGF β signaling. In addition, PS-COOH, PS-SOOOH or PS-NH 2 exposure (1 μg/L or 15 μg/L) caused more serious toxicity in reducing locomotion behavior and causing gut barrier deficit. Hence the rank order in toxicity of PS-NH 2 ＞PS-SOOOH＞PS-COOH＞PS＞PS-PEG was identified. Furthermore, we also presented evidence to support the contention that the observed toxic effects on nematodes were linked to oxide stress and activation of anti-oxidative molecules for reversing the adverse effects induced by nanopolystyrene and its 4 chemically modified derivatives. Our data highlighted nanoplastics may be charge-dependently toxic to environmental organisms, and the screened low toxic modification may support polystyrene nanoparticles continued application for daily consumer goods and biomedicine.
研究领域:
环境科学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 23
·12127-12141
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IF 5.396
Yue Ge,Huibin Chen,Jilite Wang,Guishan Liu,Steve W. Cui,Ji Kang,Yumei Jiang,Hao Wang
Naringenin (NN) is one of the most abundant flavonoids in citrus and grapefruits and has been shown to have antioxidant properties in vitro. The purpose of the study is to examine the antioxidant and anti-aging activities of NN in C. elegans, and to further explore the molecular mechanism. The results showed that NN enhanced the lifespan under normal and oxidative stress induced by H2O2. After treatment with NN, locomotion capability was improved and aging pigment accumulation was suppressed. NN also delayed the paralysis and reversed the defective chemotaxis behavior induced by Aβ protein. Meanwhile, the treatment with NN enhanced the activities of antioxidant enzymes and reduced the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) content. The possible targets and pathways interacting with NN were predicted by network pharmacology. Real-time PCR analysis indicated that NN upregulated the expression levels of daf-16, sek-1 and skn-1, downregulated the expression levels of daf-2, age-1 and akt-1, and further activated sod-3, ctl-1, ctl-2, gst-4 and mtl-1. Moreover, the selected mutant strains were used and molecular docking was conducted to further suggest that IIS and MAPK pathways could be involved in the NN-mediated longevity-promoting effect.
研究领域:
老年学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Functional Foods
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2018
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IF 3.47
Sixu Zhao,Qiong Cheng,Qiong Peng,Xuesong Yu,Xiquan Yin,Ming Liang,Chung Wah Ma,Zebo Huang,Weizhang Jia
The papain hydrolyzate prepared from purple sea urchin ( Strongylocentrotus nudus ) gonad exerts significant antioxidant activity. Through ultrafiltration, gel filtration and high performance liquid chromatography, the active fractions from the hydrolyzate were screened by alleviating paraquat-induced oxidative stress in Caenorhabditis elegans , and the peptide components were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two antioxidant peptides SnP7 (AAVPSGASTGIYEALELR, 1805.03 Da) and SnP10 (NPLLEAFGNAK, 1173.34 Da) exhibit significant antioxidant capacity, which reduce reactive oxygen species (ROS) level and the expression of superoxide dismutase-3 (SOD-3) and heat shock protein-16.2 (HSP-16.2) in oxidation-damaged nematodes. Further studies indicated that SnP7 and SnP10 induce DAF-16 nuclear translocation and the expression of stress-related genes such as sod-3 . RNA interference (RNAi) suggested that peptide-induced enhancement of resistance is dependent on DAF-16. Taken together, S. nudus antioxidant peptides might act through activate DAF-16 signaling pathway, and induce the expression of DAF-16 target genes that enhance antioxidant potential of organisms.
研究领域:
生物化学
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分子生物学
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药理学
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毒理学
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产品关联
DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-13
·
IF 14.7
Wang Zihao,Zhang Qian,Jiang Yayun,Zhou Jun,Tian Ye
Morphogens play a critical role in coordinating stress adaptation and aging across tissues, yet their involvement in neuronal mitochondrial stress responses and systemic effects remains unclear. In this study, we reveal that the transforming growth factor beta (TGF-β) DAF-7 is pivotal in mediating the intestinal mitochondrial unfolded protein response (UPR mt ) in Caenorhabditis elegans under neuronal mitochondrial stress. Two ASI sensory neurons produce DAF-7, which targets DAF-1/TGF-β receptors on RIM interneurons to orchestrate a systemic UPR mt response. Remarkably, inducing mitochondrial stress specifically in ASI neurons activates intestinal UPR mt , extends lifespan, enhances pathogen resistance, and reduces both brood size and body fat levels. Furthermore, dopamine positively regulates this UPR mt activation, while GABA acts as a systemic suppressor. This study uncovers the intricate mechanisms of systemic mitochondrial stress regulation, emphasizing the vital role of TGF-β in metabolic adaptations that are crucial for organismal fitness and aging during neuronal mitochondrial stress.
研究领域:
神经科学
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分子生物学
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衰老研究
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细胞应激反应
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 4
·607-624
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IF 6.331
Andy Wijaya,Yi Wang,Dan Tang,Yuan Zhong,Boyan Liu,Meng Yan,Quhui Jiu,Wei Wu,Guixue Wang
Nitric oxide (NO) is an exceptional endogenous biological gas that mediates and regulates physiological and pathological processes in the human body. However, its synthesis process is impaired during athero-progression and formation. Hence, a strategy to boost NO production and target endothelial nitric oxide synthase (eNOS) is crucial and intriguing in atherosclerosis (AS) management. Herein, we prepare L-arginine (LA) and lovastatin (LV) co-loaded PLGA nanomedicine to achieve sustainable release for enhancing NO production. The utilization of LA reveals that LA has dual contributions, acting as a NO donor and enhancing the solubility of LV by stabilizing PLGA NPs. PLGA-LA/LV demonstrated its potential to boost NO in vitro and in vivo confirmed using DAF-FM DA, augment eNOS and p-eNOS mRNA and protein levels, and suppress the ki67 proliferation marker in VSMCs; in addition, it lowers the total cholesterol level of blood plasma in C57BL/6 mice. Moreover, PLGA can protect the compound delivered and enhance the bioavailability to reach and get released in the blood circulation after oral administration. Collectively, our results endow a safe and efficient nanomedicine outcome, specifically with potential for AS management.
研究领域:
药学
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心血管疾病
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Bu-Da Su,Xiao-Meng Li,Zhi-Wei Huang,Yue Wang,Jia Shao,Yan-Yan Xu,Le-Xin Shu,Yu-Bo Li
Ochratoxin A (OTA) is a common fungal toxin frequently detected in food and human plasma samples. Currently, the physiologically based toxicokinetic (PBTK) model plays an active role in dose translation and can improve and enhance the risk assessment of toxins. In this study, the PBTK model of OTA in rats and humans was established based on knowledge of OTA-specific absorption, distribution, metabolism, and excretion (ADME) in order to better explain the disposition of OTA in humans and the discrepancies with other species. The models were calibrated and optimized using the available kinetic and toxicokinetic (TK) data, and independent test datasets were used for model evaluation. Subsequently, sensitivity analyses and population simulations were performed to characterize the extent to which variations in physiological and specific chemical parameters affected the model output. Finally, the constructed models were used for dose extrapolation of OTA, including the rat-to-human dose adjustment factor (DAF) and the human exposure conversion factor (ECF). The results showed that the unbound fraction (F up ) of OTA in plasma of rat and human was 0.02–0.04% and 0.13–4.21%, respectively. In vitro experiments, the maximum enzyme velocity (V max ) and Michaelis–Menten constant (K m ) of OTA in rat and human liver microsomes were 3.86 and 78.17 μg/g min −1 , 0.46 and 4.108 μg/mL, respectively. The predicted results of the model were in good agreement with the observed data, and the models in rats and humans were verified. The PBTK model derived a DAF of 0.1081 between rats and humans, whereas the ECF was 2.03. The established PBTK model can be used to estimate short- or long-term OTA exposure levels in rats and humans, with the capacity for dose translation of OTA to provide the underlying data for risk assessment of OTA.
研究领域:
毒理学
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药代动力学
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食品安全
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）