INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Ruoyi Jia,Wen Chen,Yangyang Liu,Yonglu Li,Xiang Ye,Yong Jiang,Xiaodong Zheng
Ethyl Carbamate (EC), as a carcinogen widely found in fermented foods, was verified that its cytotoxicity was associated with oxidative stress. Polysaccharides from natural sources due to their antioxidative capacity have attracted great attention in the past time. In this study, purified polysaccharide from Tetrastigma hemsleyanum vines (TVP) with 64.89 kDA was extracted and conducted multiple analysis to identify its structural information. It could be discovered that TVP was composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro , TVP could inhibit cytotoxicity and genotoxicity, attenuate oxidative damage and mitochondrial dysfunction induced by EC in Caco-2 cells. Meanwhile, TVP could suppress apoptosis by mTOR and Bcl-2 signaling pathways, ameliorate oxidative via Sirt1-FoxO1 and Nrf2-Keap1 signaling pathways. In vivo , EC as well triggered the decline of survival and athletic ability in Caenorhabditis elegans ( C. elegans ) and TVP could reverse the decline. In the meantime, TVP could ameliorate oxidative damage in N2 and daf-2 (-) mutant but fail in daf-16 (-) mutant, which suggested that DAF-16 (FOXO) might affect the antioxidative protection of TVP in C. elegans . In brief, our results manifested that TVP could attenuate EC-induced cytotoxicity both in vitro and in vivo .
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
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DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 3
·1219-1231
·
IF 5.396
Hui Li,Xiaoxuan Yu,Chenxi Li,Lei Ma,Zhenyu Zhao,Shuwen Guan,Liping Wang
Caffeic acid (CA), a derivative of cinnamic acid, exists in various vegetables and fruits. Natural compounds as beneficial antioxidants play an important role in the research of Alzheimer's disease (AD). In this study, we evaluated the effects of CA against AD using the C. elegans models of AD. We found that CA significantly alleviated Aβ-induced toxicity, increased lifespan, decreased body paralysis, and improved reproductive defects. Also, CA treatment increased resistance to heat and oxidative stress in N2 and CL4176. Moreover, reactive oxygen species (ROS) levels and polyglutamine (polyQ40) aggregate formation were reduced. Furthermore, the mechanistic studies revealed that CA activated transcription factor DAF-16 and its downstream targets SOD-3 and GST-4 to protect against Aβ toxicity. Also, the heat shock proteins hsf-1 and hsp-16.2 mRNA were up-regulated in CL4176. Moreover, CA activated the mRNA expression of lgg-1. Lastly, the KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of RNA-seq data revealed that there was a significant change in the metabolism-related pathways. Overall, these results suggested an underlying mechanism of action of CA in treating AD at an organism level.
研究领域:
神经科学
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分子生物学
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药理学
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PubMed
高影响因子
Journal of Functional Foods
·
2018
·
IF 3.47
Shiling Feng,Haoran Cheng,Zhou Xu,Ming Yuan,Yan Huang,Jinqiu Liao,Ruiwu Yang,Lijun Zhou,Chunbang Ding
Panax notoginseng is Traditional Chinese medicine and also a China Food and Drug Administration (CFDA) approved food additive. In present study, we used Caenorhabditis elegans model to illustrate stress resistance and lifespan extension effect of a polysaccharide fraction form P. notoginseng (MRP5). Our data showed that MRP5 could significantly increase survival rate and markedly decreased ROS level of C. elegans under oxidative stress . Moreover, MRP5 could reduce the level of carbonyl protein and malondialdehyde of BA17 strain and extend lifespan of wild-type worms. The mechanism study revealed that MRP5 was able to promote the nuclear localization of DAF-16 resulting in the activation of antioxidant enzymatic systems. We also observed that MRP5 increased lifespan of daf-16 loss-of function mutant, suggesting MRP5-prolonged lifespan partially required daf-16 gene. Overall, our results illustrated the potential utilization of MRP5 as a functional food ingredient to delay aging.
研究领域:
分子生物学
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药理学
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衰老研究
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DOI
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Chen Haiyan,Li Rongji,Zhao Feng,Luan Li,Han Tiantian,Li Zhong
Numerous studies reported that betulinic acid (BA), a natural product extracted from birch bark, exhibited various beneficial effects in vitro. However, its pharmacological activities in aging are rarely understood. In this study, Caenorhabditis elegans was deployed as a whole animal model to investigate the impacts of BA on lifespan and stress resistance. Wild-type C. elegans were fed in the presence or absence of BA and tested for a series of phenotypes, including longevity, mobility, reproductive capacity, pharyngeal pumping, heat stress, and oxidative stress. BA at the optimal dose (50 μg/mL) extended the lifespan, improved the healthspan, and significantly evoked the increased oxidative stress resistance in C. elegans. Incorporating the genetic analysis with different types of longevity mutants, DAF-16, the downstream effector of the Insulin/IGF-1 receptor signaling, was revealed to mediate the protective effects of BA on lifespan and antioxidant activity. Together, these data showcased the potential of BA in promoting healthy aging, which shall facilitate its further development in the food and pharmaceutical industries.
研究领域:
衰老研究
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Antioxidants
·
2026
·Vol. 15
·期 10
·1230
·
IF 8.2
Lijun Yang,Jiuyi Li,Yihan Zhou,Huaying Xu,Yu Wang,Jiayuan Zhao,Yanan Wang
Background: Aging involves progressive functional decline driven by oxidative stress and mitochondrial dysfunction, and dietary flavonoids are promising aging interventions due to their multi-target regulatory pathways. Methods: This study systematically evaluated the anti-aging activity of myricitrin (MYR) and its underlying mechanisms usingCaenorhabditis elegans, testing MYR at 0.25 mg/mL, employing a rotenone-induced model of mitochondrial oxidative stress, and performing reporter strain analyses, qRT-PCR, and molecular docking analysis with acetylcholinesterases (ACE-1/2). Results: MYR at 0.25 mg/mL significantly extended lifespan and improved locomotor performance without detectable toxicity regarding growth, feeding, or reproduction; reduced reactive oxygen species accumulation and restored antioxidant enzyme activities in the rotenone-induced model; was accompanied by the nuclear translocation of DAF-16 and the upregulation of associated downstream antioxidant genes (sod-3,gst-4); enhanced mitochondrial quality control by upregulatingsir-2.1and modulating genes associated with the mitochondrial unfolded protein response (atfs-1,hsp-6) and mitochondrial dynamics (fzo-1,drp-1); and indicated a favorable interaction between MYR and acetylcholinesterases (ACE-1/2). Conclusions: MYR represents a promising candidate compound for mitigating aging-related phenotypes, with its beneficial effects linked to a DAF-16-associated antioxidant response and SIR-2.1-correlated mitochondrial quality control network.
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高影响因子
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
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2016
·Vol. 72
·期 4
·464-472
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IF 5.476
Zheng Shan-Qing,Huang Xiao-Bing,Xing Ti-Kun,Ding Ai-Jun,Wu Gui-Sheng,Luo Huai-Rong
Coffee and tea, two of the most popular drinks around the world, share many in common from chemical components to beneficial effects on human health. One of their shared components, the polyphenols, most notably chlorogenic acid (CGA), was supposed to account for many of the beneficial effects on ameliorating diseases occurred accompanying people aging, such as the antioxidant effect and against diabetes and cardiovascular disease. CGA is also present in many traditional Chinese medicines. However, the mechanism of these effects was vague. The aging signaling pathways were conservative from yeast and worms to mammals. So, we tested if CGA had an effect on aging in Caenorhabditis elegans. We found that CGA could extend the lifespan of C. elegans by up to 20.1%, delay the age-related decline of body movement, and improve stress resistance. We conducted genetic analysis with a series of worm mutants and found that CGA could extend the lifespan of the mutants of eat-2, glp-1, and isp-1, but not of daf-2, pdk-1, akt-1, akt-2, sgk-1, and clk-1. CGA could activate the FOXO transcription factors DAF-16, HSF-1, SKN-1, and HIF-1, but not SIR-2.1. Taken together, CGA might extend the lifespan of C. elegans mainly via DAF-16 in insulin/IGF-1 signaling pathway.
研究领域:
生物化学
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分子生物学
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衰老研究
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DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Yinyin Gao,Cheng Li,Junfei Li,Mengyao Duan,Xuan Li,Lina Zhao,Ying Wu,Shaobin Gu
Introduction: Hyperuricemia (HUA) refers to the presence of excess uric acid (UA) in the blood, which increases the risk of chronic kidney disease and gout. Probiotics have the potential to alleviate HUA.Methods: This study established a hyperuricemia model using Caenorhabditis elegans (C. elegans), and studied the anti-hyperuricemia activity and potential mechanisms of Weizmannella coagulans BC99 (W. coagulans) at different concentrations (107 CFU/mL BC99, 108 CFU/mL BC99). Subsequently, we utilized UPLC-Q-TOF/MS to investigate the impact of BC99 on endogenous metabolites in C. elegans and identified pathways and biomarkers through differential metabolomics analysis.Results: The results of this study showed that BC99 treatment significantly reduced the expression of P151.2 and T22F3.3 (p < 0.05), reduced the levels of UA and xanthine oxidase (XOD) in nematodes (p < 0.05), while extending their lifespan and movement ability (p < 0.05). Mechanistically, BC99 activates the transcription factors DAF-16 and SKN-1, thereby inducing the expression of stress response genes, enhancing the activity of antioxidant enzymes and tolerance to heat stress in the body, and reducing the production of ROS (p < 0.001). This effect was most significant in the H-BC99 group. Furthermore, non-targeted metabolomics indicated that BC99 predominantly regulated pathways associated with amino acid metabolism (Carnosine), glycerophospholipid metabolism, and purine metabolism.Discussion: These results underscore BC99 as an effective and economical adjunct therapeutic agent for hyperuricemia, providing a scientific basis for further development and application.
研究领域:
医学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
FOREST PATHOLOGY
·
2019
·Vol. 49
·期 2
·e12467
·
IF 1.434
Buyong Wang,Rongrong Wen,Ling Ma,Yan Ma,T. Hua Zhou
The Forkhead box O transcription factor DAF-16 is an important downstream transcription factor in the well-conserved insulin signalling (IIS) pathway in Caenorhabditis elegans . The nuclear localization of DAF-16 can activate a series of genes that mediate oxidative stress, heat shock, xenobiotic responses, innate immunity, metabolism and autophagy. In this study, a Bxdaf-16-2b gene encoding 510 amino acids was cloned from Bursaphelenchus xylophilus . Sequence analysis showed that the BxDAF-16-2b protein shared the highest similarity value (92%) with the DAF16-2 (accession no. ADD84716.1 ) of B. xylophilus . Using in situ hybridization, Bxdaf-16-2b was shown to be constitutively expressed in the circum-pharyngeal nerve rings and intestines of males, and in the head neurons and the ovaries of females. Quantitative RT-PCR showed that the highest gene expression was found in females, followed by juveniles, males and eggs. Bxdaf-16-2b expression was up-regulated after treatment with the botanical pesticides rotenone and matrine. RNA interference showed that the expression of Bxdaf-16-2b gene was reduced by dsRNA, and the silencing of Bxdaf-16-2b suppressed the expression of several IIS pathway genes. Bursaphelenchus xylophilus showed increased mortality at sublethal doses of rotenone and matrine when subjected to Bxdaf-16-2b gene silencing. Thus, Bxdaf-16-2b may participate in the stress response of B. xylophilus and play important roles in the immune system. This study paves the way towards design of new drug targets for non-polluting control of nematodes.
研究领域:
分子生物学
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遗传学
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植物保护
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DOI
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2022
·Vol. 102
·期 15
·7017-7029
·
IF 4.125
Wenhan Yang,Wen Xia,Bisheng Zheng,Tong Li,Rui Hai Liu
BACKGROUND Ferulic acid (FA) is a dietary polyphenol widely found in plant tissues. It has long been considered to have health-promoting qualities. However, the biological properties of dietary polyphenols depend largely on their absorption during digestion, and the effects of their intestinal metabolites on human health have attracted the interest of researchers. This study evaluated the effects of three main colonic metabolites of FA – 3-(3,4-dihydroxyphenyl)propionic acid (3,4diOHPPA), 3-(3-hydroxyphenyl)propionic acid (3OHPPA) and 3-phenylpropionic acid (3PPA) – on longevity and stress resistance in Caenorhabditis elegans . RESULTS Our results showed that 3,4diOHPPA, 3OHPPA and 3PPA extended the lifespan under normal conditions in C. elegans whereas FA did not. High doses of 3,4diOHPPA (0.5 mmol L −1 ), 3OHPPA (2.5 mmol L −1 ) and 3PPA (2.5 mmol L −1 ) prolonged the mean lifespan by 11.2%, 13.0% and 10.6%, respectively. Moreover, 3,4diOHPPA, 3OHPPA and 3PPA treatments promoted stress tolerance against heat, UV irradiation and paraquat. Furthermore, three metabolites ameliorated physical functions, including reactive oxygen species and malondialdehyde levels, motility and pharyngeal pumping rate. The anti-aging activities mediated by 3,4diOHPPA, 3OHPPA and 3PPA depend on the HSF-1 and JNK-1 linked insulin/IGF-1 signaling pathway, which converge onto DAF-16. CONCLUSION The current findings suggest that colonic metabolites of FA have the potential for use as anti-aging bioactivate compounds. © 2022 Society of Chemical Industry.
研究领域:
药理学
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老年学
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分子生物学
·
生物化学
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DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Lu-Yao Zheng,Yan-Xin Da,Xiu Luo,Xiao Zhang,Zhi-Jie Sun,De-Li Dong
Sorafenib is a targeted anticancer drug in clinic. Low-dose sorafenib has been reported to activate AMPK through inducing mitochondrial uncoupling without detectable toxicities. AMPK activation has been the approach for extending lifespan, therefore, we investigated the effect of sorafenib on lifespan and physical activity of C. elegans and the underlying mechanisms. In the present study, we found that the effect of sorafenib on C. elegans lifespan was typically hermetic. Sorafenib treatment at higher concentrations (100 μM) was toxic but at lower concentrations (1, 2.5, 5 μM) was beneficial to C. elegans . Sorafenib (1 μM) treatment for whole-life period extended C. elegans lifespan and improved C. elegans physical activity as manifested by increasing pharyngeal pumping and body movement, preserving intestinal barrier integrity, muscle fibers organization and mitochondrial morphology. In addition, sorafenib (1 μM) treatment enhanced C. elegans stress resistance. Sorafenib activated AMPK through inducing mitochondrial uncoupling in C. elegans . Sorafenib treatment activated DAF-16, SKN-1, and increased SOD-3, HSP-16.2, GST-4 expression in C. elegans . Sorafenib treatment induced AMPK-dependent autophagy in C. elegans . We conclude that low-dose sorafenib protects C. elegans against aging through activating AMPK/DAF-16 dependent anti-oxidant pathways and stimulating autophagy responses. Low-dose sorafenib could be a strategy for treating aging and aging-related diseases.
研究领域:
药理学
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老年学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Fu-Yi Shi,Chun Li,Xi-Yang Zhang,Li-Lan Ou,Gui-Sheng Wu,Huai-Rong Luo
Ethnopharmacological relevance Corylin is a natural flavonoid isolated from the seeds of Psoralea corylifolia L., a traditional medicinal herb historically used to treat bone-related disorders such as osteoporosis. However, its role in organismal aging and the underlying molecular mechanisms remain largely unexplored. Aim of the study This study aimed to evaluate the anti-aging efficacy of corylin and elucidate the molecular basis of its action. Materials and methods Using Caenorhabditis elegans ( C. elegans ) as a model organism, we systematically assessed the impact of corylin on lifespan and multiple aging-associated phenotypes, including locomotor capacity, muscle integrity, lipofuscin accumulation, and resistance to thermal, pathogenic, and oxidative stress. Neuroprotective potential was evaluated using transgenic models of Parkinson's and Huntington's diseases. To uncover the mechanisms involved, we analyzed the DAF-16/SKN-1 signaling axis and autophagy-related processes using transgenic reporter strains, RNA interference, and RT-qPCR. Results Corylin treatment significantly extended lifespan, improved locomotor performance, and reduced lipofuscin accumulation. Furthermore, it enhanced resistance to environmental stresses and conferred neuroprotection in models of neurodegeneration. Mechanistically, corylin promoted nuclear translocation of DAF-16 and upregulated the expression of DAF-16/SKN-1 target genes. This transcriptional activation was associated with enhanced autophagic flux and improved mitochondrial quality. Crucially, the beneficial effects of corylin were abolished in daf-16 and skn-1 mutants, as well as under autophagy-deficient conditions. Conclusion Corylin exerts multifaceted anti-aging effects in C. elegans by coordinately activating the DAF-16/SKN-1 signaling axis, thereby enhancing autophagic flux and maintaining mitochondrial homeostasis. These findings identify corylin as a promising natural candidate for aging intervention.
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PubMed
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 106
·期 6
·e70214
·
IF 3.3
Guihua Jia,Jiayi Li,Abbas Khan,Aman Chandra Kaushik,Diyi Wu,Hongyu Chen,Rongpei Li,Jian Wang,Chen Zhang,Adil Farooq,Xueying Mao,Aamir Mehmood,Weidong Zhang,Heng Wang,Dong-Qing Wei
WGX-50, a previously reported drug candidate for Alzheimer's disease, is derived from Zanthoxylum bungeanum Maxim commonly called Sichuan pepper. Its pharmacological actions for the long run benefit of human health have been extensively investigated. However, in terms of its anti-aging effect, it totally remains unexplored. In this work, WGX-50 was first reported to promote healthy aging in Caenorhabditis elegans with insights from drug target prediction and molecular dynamics simulations. Further investigations have experimentally demonstrated that: Firstly, both daf-16 and skn-1 genes are causative to WGX-50 mediated longevity. WGX-50 failed to extend lifespan upon depletion of these genes in transgenic worms. Their orthologs Foxo1 and Nrf2 were also activated even in D-galactose (D-gal) induced aging and Zmpste24 −/− progeria mice intestines. Secondly, WGX-50 inhibits IIS signaling via downregulating daf-2 , and activating daf-16 and skn-1 genes, which thus enable downstream pro-longevity effectors increasing stress resistance and promoting healthier aging. WGX-50 increased expression levels of sod-3 , ctl-1 , gst-7/8/12/33 , gsto-1 , and heat shock protein genes such as hsp-12.2 , hsp-90 , F44E5.4/0.5 , T05E11.9 and their inducer hsf-1 . In addition, the accumulation of lipofuscin, fat, and reactive oxygen species levels with age was decreased significantly upon WGX-50 supplementation without physiological impairments. Thirdly, in progeria, D-gal and naturally aged mice, WGX-50 is incapable of inducing aging. Senescent genes and SASP factors were not produced at higher levels in livers and small intensities. No impact was observed on key organ indices, blood biochemistry parameters, and bone histomorphometry. WGX-50 perhaps prolongs lifespan through other mechanisms such as reducing fertility, inducing dietary restriction, and improving proteostasis with lowered levels of polyQ35 aggregates. Our findings thus provide primary insights for the potential medical use of WGX-50 in anti-aging and long-term healthcare.
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PubMed
高影响因子
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