EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Ying Wang,Qiong Cheng,Qina Su,Xuesong Yu,Tianqi Shen,Xiaoling Yang,Weizhang Jia
Aesculin , a coumarin compound, is one of the major active ingredients of traditional Chinese herbal medicine Qinpi (Cortex Fraxini), which has been reported to exhibit antioxidative, anti-inflammatory and neuroprotective properties against oxidative stress and cellular apoptosis . However, the regulatory mechanisms remain poorly characterized in vivo . This research was performed to explore the underlying molecular mechanisms behind aesculin response conferring oxidative stress resistance, and the protective effects on amyloid-β (Aβ)-mediated neurotoxicity in Caenorhabditis elegans . Study indicated that aesculin plays the protective roles for C. elegans against oxidative stress and Aβ-mediated neurotoxicity and reduces the elevated ROS and MDA contents through enhancement of antioxidant defenses. The KEGG pathway analysis suggested that the differentially expressed genes are mainly involved in longevity regulating pathway, and the nuclear translocation of DAF-16 and the RNAi of daf-16 and hsf-1 indicated that DAF-16 and HSF-1 play critical roles in integrating upstream signals and inducing the expressions of stress resistance-related genes. Furthermore, the up-regulated expressions of their target genes such as sod-3 and hsp-16.2 were confirmed in transgenic GFP reporter strains CF1553 and CL2070, respectively. These results indicated that the regulators DAF-16 and HSF-1 elevate the stress resistance of C. elegans by modulating stress-responsive genes. Further experiments revealed that aesculin is capable of suppressing Aβ-induced oxidative stress and apoptosis and improves chemosensory behavior dysfunction in Aβ-transgenic nematodes. In summary, this study suggested that aesculin offers increased resistance against oxidative stress and protective effects against Aβ-induced neurotoxicity through activation of stress regulators DAF-16 and HSF-1 in nematodes .
研究领域:
分子生物学
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神经科学
·
药理学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 21
·10538-10549
·
IF 5.396
Jiali Zhang,Lu Zhang,Zhengzhang Wu,Peng Zhang,Ruijie Liu,Ming Chang,Xingguo Wang
Phytosterols are important bioactive compounds in rice bran and rice bran oil, and the compositions of different phytosterols in rice bran and rice bran oil were investigated in our previous research. In this study, the dopaminergic neuroprotective effects and the underlying mechanisms of sitosterol, cycloartenyl ferulate, 24-methylenecycloartanyl ferulate and campesteryl ferulate identified in rice bran and rice bran oil were investigated in a rotenone-treated C. elegans model. The results indicated that the increased oxidative stress resistance induced by the activation of the DAF-16/FOXO pathway and the inhibition of the apoptotic protein CED-3 overexpression might play an important role in protecting the dopaminergic neurons. The results of this research reveal a new bioactivity of different phytosterols and are helpful for the further nutritional evaluation of rice bran and rice bran oil.
研究领域:
神经科学
·
营养学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Aging Neuroscience
·
2021
·
IF 5.75
Bai Shuju,Wang Wenbo,Zhang Zhiwei,Li Mengyao,Chen Zehan,Wang Jiuqiao,Zhao Yanlin,An Lu,Wang Yuxiang,Xing Shu,Fu Xueqi,Ma Junfeng
Amyloid-β, a hallmark of Alzheimer’s disease, forms toxic intracellular oligomers and extracellular senile plaques resulting in neuronal toxicity. Ethanol is widely consumed worldwide. Moderate ethanol consumption has numerous benefits in humans. We found that ethanol could significantly extend the lifespan of Caenorhabiditis elegans in a previous study. Based on that study, we tested the effect of ethanol on Alzheimer’s disease transgenic Caenorhabiditis elegans strain CL4176, which expresses amyloid-β1-42 peptide in body wall muscle cells. Ethanol delayed paralysis and reduced amyloid-β oligomers in Caenorhabiditis elegans worms of the CL4176 strain. Moreover, ethanol could induce the nuclear translocation of DAF-16 in the nematodes. However, in worms that were fed daf-16 RNAi bacteria, ethanol no longer delayed the paralysis. The qPCR assays showed that ethanol increases the expression of daf-16, hsf-1 and their common target genes- small heat shock protein genes. In addition, we also found that ethanol could increase lysosome mass in the CL4176 worms. In summary, our study indicated that ethanol attenuated amyloid-β toxicity in the Alzheimer’s disease model of Caenorhabiditis elegans via increasing the level of lysosomes to promote amyloid-β degradation and upregulating the levels of small heat shock protein genes to reduce amyloid-β aggregation.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2022
·Vol. 59
·期 9
·5612-5629
·
IF 5.682
Cao Shu-qin,Aman Yahyah,Fang Evandro F.,Tencomnao Tewin
Alzheimer’s disease (AD) is a common and devastating disease characterized by pathological aggregations of beta-amyloid (Aβ) plaques extracellularly, and Tau tangles intracellularly. While our understandings of the aetiologies of AD have greatly expanded over the decades, there is no drug available to stop disease progression. Here, we demonstrate the potential of Passiflora edulis ( P. edulis ) pericarp extract in protecting against Aβ-mediated neurotoxicity in mammalian cells and Caenorhabditis elegans ( C. elegans ) models of AD. We show P. edulis pericarp protects against memory deficit and neuronal loss, and promotes longevity in the Aβ model of AD via stimulation of mitophagy, a selective cellular clearance of damaged and dysfunctional mitochondria. P. edulis pericarp also restores memory and increases neuronal resilience in a C. elegans Tau model of AD. While defective mitophagy-induced accumulation of damaged mitochondria contributes to AD progression, P. edulis pericarp improves mitochondrial quality and homeostasis through BNIP3/DCT1-dependent mitophagy and SOD-3-dependent mitochondrial resilience, both via increased nuclear translocation of the upstream transcriptional regulator FOXO3/DAF-16. Further studies to identify active molecules in P. edulis pericarp that could maintain neuronal mitochondrial homeostasis may enable the development of potential drug candidates for AD.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2020
·
IF 9.038
Qiang Chu,Wen Chen,Ruoyi Jia,Xiang Ye,Yonglu Li,Yangyang Liu,Yong Jiang,Xiaodong Zheng
Acrylamide (ACR), as a raw material of polyacrylamide that used in water purification, was verified to possess various toxicity. Tetrastigma hemsleyanum (TH) is a medicinal plant widely used to anti-inflammation and anti-tumor in Chinese folks. However, more researches focused on the biological activities in tubers and the leaves were ignored. Thus, the protective effect of Tetrastigma hemsleyanum leaves extract (THLE) against ACR-induced toxicity in HepG2 cells and Caenorhabditis elegans ( C. elegans ) was explored in this study. In vitro , we observed that THLE attenuated ACR-induced toxicity in HepG2 cell via regulating Akt/mTOR/FOXO1/MAPK signaling pathway. Further research proved that 5-caffeoylquinic acid (5-CA) plays a major role in THLE’s amelioration effect of ACR toxicity. In vivo , it was found that THLE possesses the same protective effect in ACR-treated wild-type N2 C. elegans and daf-2 (-) (deficit in DAF-2) mutants. However, the anti-ACR toxicity effect of THLE in daf-16 (-) mutants (deficit in DAF-16 that homologous to FOXO family in human) was weakened. Our results indicated that THLE exhibited protective effects against ACR-induced toxicity both in HepG2 cells and C. elegans , while DAF-16/FOXO gene is involved in THLE’ protective effect via regulating the expression levels of downstream antioxidant genes.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 7
·859
·
IF 6
Ruifeng Wang,Anping Ding,Jiaye Wang,Jiaxue Wang,Yujie Zhou,Miao Chen,Shuang Ju,Mingpu Tan,Zengxu Xiang
Astragalin (AG), a typical flavonoid found inThesium chinenseTurcz (T. chinense), is abundant in various edible plants and possesses high nutritional value, as well as antioxidant and antibacterial effects. In this study, we initially predicted the mechanism of action of AG with two anti-aging and antioxidant-related protein targets (CD38 and IGFR) by molecular docking and molecular dynamics simulation techniques. Subsequently, we examined the anti-aging effects of AG inCaenorhabditis elegans(C. elegans), the antioxidant effects in zebrafish, and verified the related molecular mechanisms. InC. elegans, AG synergistically extended the lifespan ofC. elegansby up-regulating the expression ofdaf-16through inhibiting the expression ofdaf-2/IGFRand also activating the AMPK and MAPK pathways to up-regulate the expression ofsir-2.1,sir-2.4, andskn-1. In oxidatively damaged zebrafish embryos, AG demonstrated a synergistic effect in augmenting the resistance of zebrafish embryos to oxidative stress by up-regulating the expression levels ofSIRT1andSIRT6within the zebrafish embryos system via the suppression of CD38 enzymatic activity and then inhibiting the expression ofIGFRthrough high levels ofSIRT6. These findings highlight the antioxidant and anti-aging properties of AG and indicate its potential application as a supplementary ingredient in aquaculture for enhancing fish health and growth.
研究领域:
分子生物学
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老年医学
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营养科学
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水产养殖
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 6
·3313-3320
·
IF 3.289
Yue Zhou,Qinggang Xu,Xinghua Zhou,Shuang Song,Beiwei Zhu
Bioactive peptides derived from mussels have multiple healthcare functions. Herein, we aimed to examine the effects of mussel peptide preparation on lifespan, stress resistance, apoptosis and aging in Caenorhabditis elegans. Lifespan was determined by counting the number of surviving nematodes daily. ROS level and lipofuscin were measured using a fluorescent microscope. The mussel protein was prepared and hydrolyzed, and then fractionated by ultrafiltration. The fraction (<3 kDa) was purified by gel filtration to obtain the bioactive peptides, and the peptide sequences included in the fractions were identified, which were mostly composed of peptides with <20 amino acid residues. Mussel peptides treatment was found to significantly increase oxidative stress resistance and extend the lifespan of C. elegans. Moreover, this treatment also reduced endogenous ROS level and aging pigments accumulation in C. elegans as well as apoptosis. Collectively, these findings demonstrated that mussel peptides could contribute to healthspan extension of C. elegans through regulating mRNA expression of daf-2 and daf-16. These results highlighted the important role of mussel peptides for food and pharmaceutical industries to develop new nutraceuticals and functional foods.
研究领域:
分子生物学
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老年学
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营养保健品
·
功能性食品
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 5
·
IF 5.6
Tong Chen,Jing Zhang,Shaoqin Jian,Bocen Chen,Yingjie Ma,Wenguang Wang,Tianpeng Ma,Jiran Shi,Jin Yang,Man Xiao
Paederia scandens(Lour.)Merris a substance exhibiting medicine–food homology (MFH), commonly used in China. However, the antioxidant and anti-aging effects ofpaederoside(PSG) have not been thoroughly investigated; therefore, in this study,Caenorhabditis elegans(C. elegans) was treated with PSG to investigate these effects. We found that 50, 80, and 100 μg/mL of PSG could prolong the lifespan ofC. elegans, and administration of 100 μg/mL PSG significantly reduced the accumulation of lipofuscin. Under conditions of oxidative stress, RT-qPCR analysis revealed that PSG treatment significantly up-regulated the expression of key antioxidant geneskn-1and longevity-associated genedaf-16. In addition, PSG increased the activity of the antioxidant enzymes SOD and CAT and reduced the level of MDA. When DAF-2 activity is reduced or inhibited inC. elegans, DAF-16 and SKN-1 are activated and translocate to the nucleus to promote stress resistance and prolong lifespan. Finally, by utilizing HeLa cell models, we demonstrated that the core component ofPaederia scandens, PSG, promotes targeted degradation of IGF1R through the ubiquitin–proteasome system. Our results suggest that feedingC. elegansPSG is effective in extending this organism’s lifespan by improving oxidative stress resistance; thus, PSG has significant potential for development as an anti-aging food product and drug.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Aging Neuroscience
·
2024
·
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
·
药理学
·
老年学
·
分子生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2021
·Vol. 10
·期 11
·1697
·
IF 6.313
Shiling Feng,Chunyan Zhang,Tao Chen,Lijun Zhou,Yan Huang,Ming Yuan,Tian Li,Chunbang Ding
Oleuropein (OLE) is a secoiridoid glycoside that mainly exists in olives with multifaceted health benefits. The present study aimed to investigate the stress resistance and lifespan extension effects of OLE inCaenorhabditis elegans. The results showed that OLE could significantly prolong the lifespan ofC. elegansby 22.29%. Treatment with OLE also significantly increased the survival rates of worms against lethal heat shock and oxidative stress. Meanwhile, OLE supplementation increased the expression and activity of antioxidant enzymes and suppressed the generation of malondialdehyde in nematodes. In addition, the results from mutants implied that OLE might mediate longevity and stress resistance via DAF-16/FoxO, which played a vital role in the insulin/IGF-1 signaling (IIS) pathway. To further identify the molecular targets of OLE, mRNA level and loss-of-function mutants of IIS-associated genes were investigated. The data revealed that OLE activated IIS by down-regulating the upstream components,daf-2andage-1. Furthermore, another stress response and longevity pathway in parallel to DAF-16, SKN-1/Nrf2, was also shown to involve in OLE-induced beneficial effects. Collectively, these results provide the theoretical basis that OLE could enhance the stress resistance and increase the lifespan ofC. elegansthrough the IIS and SKN-1/Nrf2 signaling pathways.Keywords:oleuropein;Caenorhabditis elegans;longevity;stress resistance
研究领域:
分子生物学
·
老年学
·
药理学
·
遗传学
✓ 已验证
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
·
毒理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 23
·12127-12141
·
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
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
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