INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2021
·Vol. 22
·期 8
·4279
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IF 5.924
Hui Li,Xiaoxuan Yu,Fanwei Meng,Zhenyu Zhao,Shuwen Guan,Liping Wang
Ferulic acid (FA) is a naturally-occurring well-known potent antioxidant and free radical scavenger. FA supplementation is an effective strategy to delay aging, but the underlying mechanism remains unknown. In the present study, we examined the effects of FA on lifespan extension and its mechanism of FA inCaenorhabditis elegans(C. elegans). Results suggested that FA increased the lifespan ofC. elegans, rather than altering the growth ofE. coliOP50. Meanwhile, FA promoted the healthspan ofC. elegansby improving locomotion and reducing fat accumulation and polyQ aggregation. FA increased the resistance to heat and oxidative stress through reducing ROS. The upregulating of the expression of thehlh-30,skn-1, andhsf-1were involved in the FA-mediated lifespan extension. Furthermore, FA treatment had no impact on the lifespan ofdaf-2,hlh-30,skn-1, andhsf-1mutants, confirming that insulin/IGF-1 signaling pathway and multiple longevity mechanisms were associated with the longevity mechanism of FA. We further found that mitochondrial signaling pathway was modulation involved in FA-mediated lifespan extension. With the results from RNA-seq results and mutants lifespan assay. These findings contribute to our knowledge of the lifespan extension and underlying mechanism of action of FA inC. elegans.Keywords:ferulic acid;lifespan;stress resistant;insulin/IGF-1;Caenorhabditis elegans
研究领域:
生物化学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Tao Long,Qian Wu,Jing Wei,Yong Tang,Yan-Ni He,Chang-Long He,Xue Chen,Lu Yu,Chong-Lin Yu,Betty Yuen-Kwan Law,Jian-Ming Wu,Da-Lian Qin,An-Guo Wu,Xiao-Gang Zhou
Parkinson’s disease (PD) is a complex neurological disorder characterized by motor and nonmotor features. Although some drugs have been developed for the therapy of PD in a clinical setting, they only alleviate the clinical symptoms and have yet to show a cure. In this study, by employing the C. elegans model of PD, we found that ferulic acid (FA) significantly inhibited α-synuclein accumulation and improved dyskinesia in NL5901 worms. Meanwhile, FA remarkably decreased the degeneration of dopaminergic (DA) neurons, improved the food-sensing behavior, and reduced the level of reactive oxygen species (ROS) in 6-OHDA-induced BZ555 worms. The mechanistic study discovered that FA could activate autophagy in C. elegans, while the knockdown of 3 key autophagy-related genes significantly revoked the neuroprotective effects of FA in α-synuclein- and 6-OHDA-induced C. elegans models of PD, demonstrating that FA exerts an anti-PD effect via autophagy induction in C. elegans. Furthermore, we found that FA could reduce 6-OHDA- or H2O2-induced cell death and apoptosis in PC-12 cells. Moreover, FA was able to induce autophagy in stable GFP-RFP-LC3 U87 cells and PC-12 cells, while bafilomycin A1 (Baf, an autophagy inhibitor) partly eliminated the protective effects of FA against 6-OHDA- and H2O2-induced cell death and ROS production in PC-12 cells, further confirming that FA exerts an anti-PD effect via autophagy induction in vitro. Collectively, our study provides novel insights for FA as a potent autophagy enhancer to effectively prevent neurodegenerative diseases such as PD in the future.
研究领域:
神经科学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2021
·Vol. 22
·期 18
·9668
·
IF 5.924
Xiaoxuan Yu,Hui Li,Dongfa Lin,Weizhuo Guo,Zhihao Xu,Liping Wang,Shuwen Guan
Panax ginsengis a valuable traditional Chinese medicine in Northeast China. Ginsenoside, the active component of ginseng, has not been investigated much for its effects on aging and its underlying mechanism(s) of action. Here, we investigated the effects of total ginsenoside (TG), a mixture of the primary active ginsenosides fromPanax ginseng, on the lifespan ofCaenorhabditis elegans(C. elegans). We found that TG extended the lifespan ofC. elegansand reduced lipofuscin accumulation. Moreover, TG increased the survival ofC. elegansin response to heat and oxidative stress via the reduction of ROS. Next, we used RNA-seq to fully define the antiaging mechanism(s) of TG. The KEGG pathway analysis showed that TG can prolong the lifespan and is involved in the longevity regulating pathway. qPCR showed that TG upregulated the expression ofnrh-80,daf-12,daf-16,hsf-1and their downstream genes. TG also reduced the fat accumulation and promoted lipid metabolism. Moreover, TG failed to extend the lifespan ofdaf-16andhsf-1mutants, highlighting their role in the antiaging effects of TG inC. elegans. The four main constitution of TG were then confirmed by HPLC and included ginsenoside Re, Rg1, Rg2and Rd. Of the ginsenosides, only ginsenoside Rd prolonged the lifespan ofC. elegansto levels comparable to TG. These findings provided mechanistic insight into the antiaging effects of ginsenoside inC. elegans.Keywords:Panax ginseng;lifespan;lipid metabolism;stress-resistant;Caenorhabditis elegans
研究领域:
药理学
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衰老研究
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分子生物学
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DOI
PubMed
高影响因子
STAR Protocols
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2023
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IF 0
Shu-qin Cao,He-Ling Wang,Konstantinos Palikaras,Nektarios Tavernarakis,Evandro Fei Fang
Summary Here, we present an olfactory-dependent chemotaxis assay for evaluating changes in memory-like behavior in both wild-type and Alzheimer’s-disease-like C. elegans models. We describe steps for synchronizing and preparing C. elegans populations and for performing isoamyl alcohol conditioning during starvation and chemotaxis assaying. We then detail counting and quantification procedures. This protocol is applicable to mechanistic exploration and drug screening in neurodegenerative diseases and brain aging.
研究领域:
神经生物学
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药理学
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衰老研究
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DOI
PubMed
STAR Protocols
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2024
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IF 1.3
Ruipeng Wang,Jingxuan Guo,Hanlu Yao,Xuekai Luo,Yixiang Deng,Yuhang Tian,Yan Zhang,Shangbang Gao
Summary In deep tissue, optogenetics faces limitations with visible light. Here, we present a protocol for near-infrared (NIR) optogenetics manipulation of neurons and motor behavior in Caenorhabditis elegans using emissive upconversion nanoparticles (UCNPs). We describe steps for synthesizing and modifying UCNPs. We then detail procedures for regulating neurons using these UCNPs in the model organism C. elegans . Using NIR light allows for superior tissue penetration to manipulate neuronal activities and locomotion behavior. For complete details on the use and execution of this protocol, please refer to Guo et al., 1 Ao et al., 2 and Zhang et al. 3
研究领域:
神经科学
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生物技术
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2019
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IF 3.579
Mohan Zhang,Xin Yang,Wan Xu,Xiaobo Cai,Mingxiang Wang,Yuying Xu,Peilin Yu,Jun Zhang,Yifan Zheng,Jiang Chen,Jun Yang,Xinqiang Zhu
High sugar content in beverage or food can affect the aging process, and thus natural/artificial sweeteners are widely used as substitutes. However, whether sweeteners have such adverse effects as sugar remains to be clarified. Therefore, in the current study, three sulfa sweeteners, namely, saccharin sodium salt hydrate (SAC 2 ), sodium cyclamate (CYC 3 ) and acesulfame potassium (AceK 4 ) were evaluated for their effects on the lifespan, deposition of lipofuscin, exercise activity, food intake, and intestinal fat deposition (IFD 5 ) of Caenorhabditis elegans ( C. elegans 6 ). It was shown that SAC at 0.3 and 10 mg/mL shortened the lifespan of C. elegans and impaired the exercise capacity, while at other concentrations no significant effects were observed. In contrast, CYC at 0.1, 1 and 10 mg/mL prolonged the lifespan of C. elegans. On the other hand, AceK at 1 mg/mL increased the lifespan of C. elegans , and could decrease both lipofuscin deposition and IFD in a dose-dependent manner. Taken together, these results indicated that although SAC, CYC, and AceK all belong to the sulfa sweeteners, each has distinct effects on different physiological activities associated with aging, at least in C. elegans .
研究领域:
生物化学
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衰老研究
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营养学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Xiao Man,Chen Bocen,Niu Kun,Long Ziyu,Yang Fan,Xie Yiqiang
Background: Alpiniae Oxyphylla Fructus (AOF) is Traditional Chinese medicine and a dietary supplements for centuries, which posseses cardiotonic, neuroprotective, antioxidant, warming the kidney and nourish the spleen, these biological fuction is related to potential anti-aging properties. However, little is known about their effects on aging. This work aimed to investigate the effects of extracts of AOF on longevity and stress resistance in Caenorhabditis elegans (C. elegans) and the mechanisms that underlie its effects.Methods: Wild-type (WT) strand of C.elegans (N2)worms were cultured in growth medium with or without AOF. First, we examined the effects of AOF on lifespan, reproduction and healthspan assay, stress resistance and oxidative analysis, lipofuscin levels. Second, The levels of ROS and MDA, the antioxidant enzyme activities were examined to explore the underlying mechanism of AOF. Finally, the expression of the longevity-related genes were investigated to further understand the AOF’s underlying mechanism.Results: The lifespan of C. elegans was prolonged by 23.44% after treatment with high-dose AOF (100 ug/ml). AOF alleviated aging-related declines in C. elegans health and enhanced resistance to heat shock. Furthermore, AOF decreased reactive oxygen species and malondialdehyde, increased the activities of superoxide dismutase and catalase, and reduced accumulation of fat. AOF upregulated the expression of sod-3, gst-4, daf-16, and skn-1 but downregulated the expression of daf-2 and age-1 and accelerated the translocation of DAF-16 into the nucleus. The extended lifespan induced by AOF was reversed in daf-16(mu86) and skn-1(zu135) mutants, indicating that this gene is involved in AOF-regulated longevity.Conclusion: Our findings demonstrated that AOF extends lifespan and healthspan and enhances stress via boosting the activity of the antioxidant enzyme and controlling the expression of genes associated with insulin/IGF signaling and SKN-1 pathways. As a result, this work suggested AOF as a possible candidate to reduce the signs of aging by activating and inhibiting target genes.
研究领域:
老年学
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分子生物学
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中医药学
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遗传学
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产品关联
DOI
PubMed
高影响因子
Micromachines
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2023
·Vol. 14
·期 8
·1576
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IF 3.4
Jinchi Zhu,Yu Wang,Shuting Tang,Huiying Su,Xixian Wang,Wei Du,Yun Wang,Bi-Feng Liu
Associative learning is a critical survival trait that promotes behavioral plasticity in response to changing environments. Chemosensation and mechanosensation are important sensory modalities that enable animals to gather information about their internal state and external environment. However, there is a limited amount of research on these two modalities. In this paper, a novel PDMS–agar hybrid microfluidic device is proposed for training and analyzing chemical–mechanical associative learning behavior in the nematodeCaenorhabditis elegans. The microfluidic device consisted of a bottom agar gel layer and an upper PDMS layer. A chemical concentration gradient was generated on the agar gel layer, and the PDMS layer served to mimic mechanical stimuli. Based on this platform,C. eleganscan perform chemical–mechanical associative learning behavior after training. Our findings indicated that the aversive component of training is the primary driver of the observed associative learning behavior. In addition, the results indicated that the neurotransmitter octopamine is involved in regulating this associative learning behavior via the SER-6 receptor. Thus, the microfluidic device provides a highly efficient platform for studying the associative learning behavior ofC. elegans, and it may be applied in mutant screening and drug testing.Keywords:associative learning behavior;microfluidic device;Caenorhabditis elegans;octopamine
研究领域:
神经科学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Kexin Shi,Bentian Jing,Yifan Feng,Yong Yu
Ethnopharmacological relevance Within Anemarrhena asphodeloides Bunge (AAB), the pivotal bioactive constituents are identified as Anemarrhena asphodeloides Bunge total saponins (ABS). In traditional pharmacology, ABS has exhibited notable anti-inflammatory, hypoglycemic, and cardioprotective properties. Despite these observed effects, the specific protective mechanisms of ABS against metabolic diseases and improving the endocrine system remain largely uncharted. Aim to study This work intends to shed light on the effects and intrinsic mechanisms of ABS on metabolic diseases. Materials and methods The characterization of ABS components was achieved through High-Performance Liquid Chromatography/Mass Spectrometry (HPLC/MS). To evaluate ABS's anti-inflammatory efficacy, mouse macrophages underwent analysis using the Griess method. Induced differentiation of mouse fibroblasts was assessed through Oil Red O staining. In an obesity model with C57BL/6 N mice, ABS administration prompted measurements of glucose and insulin tolerance. Western blot analysis quantified lipolysis and anti-inflammatory protein expression. Nile red staining gauged body fat content in C. elegans post-ABS treatment. The mechanism of ABS action was elucidated through mRNA sequencing, further validated using RNA interference technology, and nematode mutants. Results ABS showcased the ability to diminish Nitric Oxide (NO) production in inflammatory macrophages and shrink adipocyte lipid droplets. In mice experiments, ABS was effective in alleviating fat accumulation and affecting serum lipid metabolism in diabetic mice. It enhanced oral glucose tolerance and insulin tolerance while increasing lipolysis-associated protein expression. ABS notably reduced fat content in C. elegans . Mechanistically, ABS downregulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and monoamine oxidase A (MAOA) expression while enhancing UGT, ilys-2 , and ilys-3 . Lipolysis emerged as a pivotal pathway for ABS in the therapeutic intervention of metabolic diseases. Conclusions Our investigation has revealed that ABS exert a role in combating metabolic diseases by enhancing the body's defense mechanisms. ABS activate the NLRP3-neurotransmitter-visceral adipose pathway in mice, thereby bolstering resistance and diminishing fat accumulation. In C. elegans , ABS downregulated the expression of MAOA, bolstered resistance, and augmented glucuronidase activity, consequently leading to a reduction in fat content.
研究领域:
药理学
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代谢学
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分子生物学
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生物化学
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民族药理学
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DOI
PubMed
高影响因子
Cell Reports
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2022
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IF 9.995
Xinyu Li,Jiasheng Li,Di Zhu,Ning Zhang,Xusheng Hao,Wenfeng Zhang,Qian Zhang,Yangli Liu,Xueying Wu,Ye Tian
Summary Coordination of inter-tissue stress signaling is essential for organismal fitness. Neuronal mitochondrial perturbations activate the mitochondrial unfolded-protein response (UPR mt ) in the intestine via the mitokine Wnt signaling in Caenorhabditis elegans . Here, we found that the protein disulfide isomerase PDI-6 coordinates inter-tissue UPR mt signaling via regulating the Wnt ligand EGL-20. PDI-6 is expressed in the endoplasmic reticulum (ER) and interacts with EGL-20 through disulfide bonds that are essential for EGL-20 stability and secretion. pdi-6 deficiency results in misfolded EGL-20, which leads to its degradation via ER-associated protein degradation (ERAD) machinery. Expression of PDI-6 declines drastically with aging, and animals with pdi-6 deficiency have decreased lifespan. Overexpression of PDI-6 is sufficient to maintain Wnt/EGL-20 protein levels during aging, activating the UPR mt , and significantly extending lifespan in a Wnt- and UPR mt -dependent manner. Our study reveals that protein disulfide isomerase facilitates Wnt secretion to coordinate the inter-tissue UPR mt signaling and organismal aging.
研究领域:
分子生物学
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衰老研究
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细胞信号传导
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发育生物学
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DOI
PubMed
高影响因子
Antioxidants
·
2025
·Vol. 14
·期 6
·689
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IF 6.6
Jun Liu,Yansheng Zhao,Fei Leng,Xiang Xiao,Weibo Jiang,Shuntang Guo
Soy protein isolate (SPI) is a high-purity protein from defatted soybeans, providing emulsifying and gelling functions for plant-based foods and supplements. Hydrolysis can facilitate the production of bioactive small-molecule proteins or peptides with potential functional applications. In this study, 20% hydrolyzed soy protein (20% HSP) was prepared from SPI, and the effects of 20% HSP and SPI on alleviating oxidative stress inCaenorhabditis elegans(C. elegans) and regulating immune–gut microbiota in cyclophosphamide (CTX)-induced immunocompromised BALB/c mice were investigated. InC. elegans, both SPI and 20% HSP (300 μg/mL) enhanced locomotive activities, including body bending and head thrashing, and improved oxidative stress resistance under high glucose conditions. This improvement was mediated by increased antioxidant enzyme activities (SOD, CAT, and GSH-Px), while malondialdehyde (MDA) content was reduced by 60.15% and 82.28%, respectively. Both of them can also significantly extend the lifespan of normalC. elegansand paraquat-induced oxidative stress models by inhibiting lipofuscin accumulation. This effect was mediated through upregulation ofdaf-16and suppression ofdaf-2andakt-1expression. In immunocompromised mice, 20% HSP alleviated CTX-induced immune dysfunction by increasing peripheral white blood cells and lymphocytes, attenuating thymic atrophy, and reducing hepatic oxidative stress via MDA inhibition. Gut microbiota analysis revealed that 20% HSP restored microbial balance by suppressingEscherichia-Shigellaand enriching beneficial genera, likePsychrobacter. These findings highlight 20% HSP and SPI’s conserved anti-aging mechanisms viadaf-16activation inC. elegansand immune–gut modulation in mice, positioning them as plant-derived nutraceuticals targeting oxidative stress and immune dysregulation.
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
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2025
·
IF 4.3
Chen Xue,Zhou Xing-Yue,Lan Cai,Fu Hai-Jun,Li Zhi-Chao,Chen Meng-Yi,Wen Yong-Ping,Yu Lu,Qin Da-Lian,Wu An-Guo,Wu Jian-Ming,Zhou Xiao-Gang
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by pathological protein aggregation and oxidative stress, leading to progressive neurodegeneration. Enhancing autophagy, the primary intracellular pathway for clearing misfolded proteins, represents a promising therapeutic strategy. In this study, we identify Araloside A (ARA), a triterpenoid saponin derived from Aralia elata , as a potent autophagy inducer that alleviates AD- and PD-related pathology. In neuronal cell models, ARA promotes autophagosome formation, increases LC3-II and Beclin-1 levels, and decreases P62, indicating enhanced autophagic activity. Mechanistic investigations reveal that ARA directly binds to Raf, MEK, and ERK proteins and activates autophagy in a Raf/MEK/ERK-dependent manner. This activation facilitates the clearance of APP, total Tau, phosphorylated Tau, and α-synuclein, thereby reducing cytotoxicity. Furthermore, in transgenic Caenorhabditis elegans models of AD and PD, ARA treatment alleviates protein aggregation and behavioral deficits via ERK-dependent autophagy. Together, these findings identify ARA as a natural compound that enhances autophagic clearance of neurotoxic aggregates via Raf/MEK/ERK pathway activation, offering promising therapeutic insights for neurodegenerative proteinopathies.
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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神经退行性疾病
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细胞生物学
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天然产物化学
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产品关联
DOI
PubMed
高影响因子
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