FOREST PATHOLOGY
·
2019
·Vol. 49
·期 2
·e12467
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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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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
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生物化学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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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
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
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分子生物学
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细胞生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
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IF 8.7
Yuxin Liao,Hongliang Li,Qiong Liu,Jia Zhang,Jiajie Lin,Qiaohui Du,Wanqiao He,Yongyin Li,Zhaoyang Dong,Xuanbin Wang,Lei Gao
Aging is characterized by a progressive decline in muscle strength and mass, posing a significant threat to global quality of life in the absence of effective therapeutic interventions. The edible herb Polygonatum sibiricum and its polysaccharide (PSP) have been shown to delay aging in animal models, although the underlying mechanisms remain poorly understood. In this study, we investigated the anti-aging effects of PSP in Caenorhabditis elegans ( C. elegans ). Our results demonstrate that PSP reduces oxidative stress, stabilizes mitochondrial function, and preserves sarcomere integrity during aging. Notably, the beneficial effects of PSP were abolished upon silencing of daf-2 , confirming their dependence on the insulin/IGF-1 signaling (IIS) pathway. Furthermore, daf-2 silencing eliminated any additional protective effects of PSP, indicating that this pathway is essential for its activity. These findings underscore the potential of PSP-based nutraceuticals in delaying sarcopenia and extending human healthspan.
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PubMed
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 106
·期 6
·e70214
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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
EUROPEAN JOURNAL OF PHARMACOLOGY
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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
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药理学
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遗传学
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DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
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2022
·Vol. 59
·期 9
·5612-5629
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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
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DOI
PubMed
高影响因子
Food & Function
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2021
·Vol. 12
·期 21
·10538-10549
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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
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营养学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Aging Neuroscience
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2021
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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
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2020
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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
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PubMed
高影响因子
CATALYSIS LETTERS
·
2025
·Vol. 155
·期 8
·1-7
·
IF 2.4
He Huichao,Fu Xiaoxue,Guo Yujie,Ke Gaili
Since the traditional approaches for 3,3’-diamino-4,4’-azofurazan (DAAF) synthesis are not environment-friendly and economical enough, the development of green and low-cost approaches for the synthesis of DAAF is valuable and significant. Herein, the electrochemical synthesis of DAAF from the oxidation of 3 4-diaminofurazan (DAF) was studied in different electrode and electrolyte systems. It was found that the pH of alkaline aqueous electrolyte, the solvent of electrolyte and electrode play important role in DAF oxidation into DAAF. In an electrochemical cell with graphite sheet anode, Pt wire cathode and DAF/ n Bu 4 NBF 4 /acetonitrile electrolyte, the optimal DAAF yield of 63% and faradic efficiency above 60% (at 1.80 V vs. Ag/AgCl) were achieved. Mechanism investigations revealed that the electrochemical synthesis of DAAF in such an electrochemical cell is originated from the direct oxidation of DAF on graphite anode, not involving radical pathway. Graphical
研究领域:
电化学
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有机合成
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绿色化学
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材料科学
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化学工程
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高影响因子
危险品化学品经营许可证（带存储）