Trilobatin, a Component from Lithocarpus polystachyrus Rehd., Increases Longevity in C. elegans Through Activating SKN1/SIRT3/DAF16 Signaling Pathway

Trilobatin (TLB) is an effective component from Lithocarpus polystachyrus Rehd. Our previous study revealed that TLB protected against oxidative injury in neuronal cells by AMPK/Nrf2/SIRT3 signaling pathway. However, whether TLB can delay aging remains still a mystery. Therefore, the present study was designed to investigate the possible longevity-enhancing effect of TLB, and further to explore its underlying mechanism in Caenorhabditis elegans (C. elegans). The results showed that TLB exerted beneficial effects on C. elegans, as evidenced by survival rate, body movement assay and pharynx-pumping assay. Furthermore, TLB not only significantly decreased ROS and MDA levels, but also increased anti-oxidant enzyme activities including CAT and SOD, as well as its subtypes SOD2 andSOD3, but not affect SOD1 activity, as evidenced by heat and oxidative stress resistance assays. Whereas, the anti-oxidative effects of TLB were almost abolished in SKN1, Sir2.3, and DAF16 mutant C. elegans. Moreover, TLB augmented the fluorescence intensity of DAF16: GFP, SKN1:GFP, GST4:GFP mutants, indicating that TLB increased the contents of SKN1, SIRT3 and DAF16 due to fluorescence intensity of these mutants, which were indicative of these proteins. In addition, TLB markedly increased the protein expressions of SKN1, SIRT3 and DAF16 as evidenced by ELISA assay. However, its longevity-enhancing effect were abolished in DAF16, Sir2.3, SKN1, SOD2, SOD3, and GST4 mutant C. elegans than those of non-TLB treated controls. In conclusion, TLB effectively prolongs lifespan of C. elegans, through regulating redox homeostasis, which is, at least partially, mediated by SKN1/SIRT3/DAF16 signaling pathway.

Download Full-text

Ferulic Acid Supplementation Increases Lifespan and Stress Resistance via Insulin/IGF-1 Signaling Pathway in C. elegans

International Journal of Molecular Sciences ◽

10.3390/ijms22084279 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4279

Author(s):

Hui Li ◽

Xiaoxuan Yu ◽

Fanwei Meng ◽

Zhenyu Zhao ◽

Shuwen Guan ◽

...

Keyword(s):

Ferulic Acid ◽

Signaling Pathway ◽

Underlying Mechanism ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Lifespan Extension ◽

Rna Seq ◽

E Coli ◽

C Elegans ◽

Mitochondrial Signaling

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 in Caenorhabditis elegans (C. elegans). Results suggested that FA increased the lifespan of C. elegans, rather than altering the growth of E. coli OP50. Meanwhile, FA promoted the healthspan of C. elegans by 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 the hlh-30, skn-1, and hsf-1 were involved in the FA-mediated lifespan extension. Furthermore, FA treatment had no impact on the lifespan of daf-2, hlh-30, skn-1, and hsf-1 mutants, 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 in C. elegans.

Download Full-text

Faculty Opinions recommendation of The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1020955.240571 ◽

2004 ◽

Author(s):

Michael Hall

Keyword(s):

Life Span ◽

Larval Development ◽

Signaling Pathway ◽

Insulin Signaling ◽

Insulin Signaling Pathway ◽

Tor Pathway ◽

C Elegans

Download Full-text

Dietary Quercetin Alleviated DSS-induced Colitis in Mice Through Several Possible Pathways by Transcriptome Analysis

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200711152726 ◽

2020 ◽

Vol 21 (15) ◽

pp. 1666-1673 ◽

Cited By ~ 1

Author(s):

Yuanyang Dong ◽

Jiaqi Lei ◽

Bingkun Zhang

Keyword(s):

Antioxidant Capacity ◽

Underlying Mechanism ◽

Control Group ◽

Sequencing Analysis ◽

Colon Tissue ◽

Beneficial Effects ◽

Intestinal Integrity ◽

Inflammatory Bowel ◽

Vegetables And Fruits ◽

Key Pathways

Background: The prevalence of inflammatory bowel disease is rapidly increasing around the world. Quercetin is a flavonoid commonly found in vegetables and fruits and has been reported to exert numerous pharmacological activities such as enhancing antioxidant capacity or suppressing inflammation. Objective: We aimed to explore whether quercetin was effective for IBD and the underlying mechanism of quercetin for the ameliorative effects on the DSS-induced colitis in mice. Methods: Thirty-six mice were randomly assigned to three treatments, including the control group (Ctr), DSS-induced colitis group (DSS) and DSS-induced colitis supplemented with 500 ppm quercetin (DQ500). Colitis was induced by DSS intake, and body weight was recorded every day. After six days administration of DSS, intestinal permeability was measured, and the liver was taken for antioxidant enzyme tests. Colonic tissue was taken for the histopathlogical score and RNA-sequencing analysis. Results: In this experiment, dietary quercetin for 500ppm alleviated the DSS-induced colitis, possibly by strengthening intestinal integrity, liver antioxidant capacity. Based on the results of the transcriptome of colon tissue, several key genes were modulated by quercetin. ERK1/2-FKBP pathway and RXR-STAT3 pathway were involved in the development of IBD, furthermore, in the down-regulation of S100a8/9, FBN2 contributed to lowering the risk of colongenesis. Conclusion: We demonstrated that dietary quercetin alleviated the DSS-induced colitis in mice. This is most likely due to its beneficial effects on intestinal integrity and modulation of several key pathways. Based on our research, quercetin was a promising candidate for IBD and its pharmaceutical effects on both IBD and colongenesis need further research.

Download Full-text

Treatment effect of oil-based contrast is related to experienced pain at HSG: a post-hoc analysis of the randomised H2Oil study

Human Reproduction ◽

10.1093/humrep/dez206 ◽

2019 ◽

Vol 34 (12) ◽

pp. 2391-2398 ◽

Cited By ~ 6

Author(s):

N van Welie ◽

K Dreyer ◽

J van Rijswijk ◽

H R Verhoeve ◽

M Goddijn ◽

...

Keyword(s):

Underlying Mechanism ◽

Pregnancy Rates ◽

P Value ◽

Ongoing Pregnancy ◽

Research Grants ◽

Enhancing Effect ◽

Post Hoc Analysis ◽

Infertile Women ◽

Water Based ◽

Post Hoc

Abstract STUDY QUESTION Does pain or volume of used contrast medium impact the effectiveness of oil-based contrast during hysterosalpingography (HSG)? SUMMARY ANSWER In women who report moderate to severe pain during HSG, the use of oil-based contrast resulted in more ongoing pregnancies compared to the use of water-based contrast, whereas in women who reported mild or no pain, no difference in ongoing pregnancies was found. WHAT IS KNOWN ALREADY We recently showed that in infertile women undergoing HSG, the use of oil-based contrast results in more ongoing pregnancies within 6 months as compared to the use of water-based contrast. However, the underlying mechanism of this fertility-enhancing effect remains unclear. STUDY DESIGN, SIZE, DURATION We performed a post-hoc analysis of the H2Oil study, a multicentre randomised controlled trial (RCT) evaluating the therapeutic effect of oil- and water-based contrast at HSG. Here, we evaluated the impact of pain experienced at HSG and volume of used contrast media during HSG on ongoing pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS In a subset of 400 participating women, pain during HSG by means of the Visual Analogue Scale (VAS) (range: 0.0–10.0 cm) was reported, while in 512 women, we registered the volume of used contrast (in millilitres). We used logistic regression analyses to assess whether pain and volume of used contrast media modified the effect of oil-based contrast on ongoing pregnancy rates. Data were analysed according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE In 400 women in whom pain scores were reported, the overall median pain score was 5.0 (Interquartile range (IQR) 3.0–6.8) (oil group (n = 199) 4.8 (IQR 3.0–6.4); water group (n = 201) 5.0 (IQR 3.0–6.7); P-value 0.28). There was a significant interaction between pain (VAS ≤5 versus VAS ≥6) and the primary outcome ongoing pregnancy (P-value 0.047). In women experiencing pain (VAS ≥6), HSG with oil-based contrast resulted in better 6-month ongoing pregnancy rates compared to HSG with water-based contrast (49.4% versus 29.6%; RR 1.7; 95% CI, 1.1–2.5), while in women with a pain score ≤5, 6-month ongoing pregnancy rates were not significantly different between the use of oil- (28.8%) versus water-based contrast (29.2%) (RR 0.99; 95% CI, 0.66–1.5). In the 512 women in whom we recorded contrast, median volume was 9.0 ml (IQR 5.7–15.0) in the oil group versus 8.0 ml (IQR 5.9–13.0) in the water group, respectively (P-value 0.72). Volume of used contrast was not found to modify the effect of oil-based contrast on ongoing pregnancy (P-value for interaction 0.23). LIMITATIONS, REASONS FOR CAUTION This was a post-hoc analysis that should be considered as hypothesis generating. The RCT was restricted to infertile ovulatory women, younger than 39 years of age and with a low risk for tubal pathology. Therefore, our results should not be generalised to infertile women who do not share these features. WIDER IMPLICATIONS OF THE FINDINGS The underlying mechanism of the fertility-enhancing effect induced by HSG with the use of oil-based contrast remains unclear. However, these findings suggest a possible mechanistic pathway, that is increasing intrauterine pressure occurring prior to dislodging pregnancy hindering debris or mucus plugs from the proximal part of otherwise normal fallopian tubes. This information might help in the search of the underlying fertility-enhancing mechanism found by using oil-based contrast during HSG. STUDY FUNDING/COMPETING INTEREST(S) The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports consultancy for Guerbet. H.V. reports consultancy fees from Ferring. C.B.L. reports speakers’ fees from Ferring and research grants from Ferring, Merck and Guerbet. V.M. reports receiving travel and speakers fees as well as research grants from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. The other authors do not report conflict of interests. TRIAL REGISTRATION NUMBER The H2Oil study was registered at the Netherlands Trial Registry (NTR 3270). TRIAL REGISTRATION DATE 1 February 2012. DATE OF FIRST PATIENT’S ENROLMENT 3 February 2012.

Download Full-text

Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation

Antioxidants ◽

10.3390/antiox10030357 ◽

2021 ◽

Vol 10 (3) ◽

pp. 357

Author(s):

Mojca Trstenjak Prebanda ◽

Petra Matjan-Štefin ◽

Boris Turk ◽

Nataša Kopitar-Jerala

Keyword(s):

Mouse Model ◽

Redox Homeostasis ◽

Underlying Mechanism ◽

Loss Of Function ◽

Altered Expression ◽

Lps Challenge ◽

Progressive Myoclonus Epilepsy ◽

Myoclonus Epilepsy ◽

The Brain ◽

Deficient Mice

Stefin B (cystatin B) is an inhibitor of endo-lysosomal cysteine cathepsin, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht–Lundborg disease (EPM1), a form of progressive myoclonus epilepsy. Stefin B-deficient mice, a mouse model of the disease, display key features of EPM1, including myoclonic seizures. Although the underlying mechanism is not yet completely clear, it was reported that the impaired redox homeostasis and inflammation in the brain contribute to the progression of the disease. In the present study, we investigated if lipopolysaccharide (LPS)-triggered neuroinflammation affected the protein levels of redox-sensitive proteins: thioredoxin (Trx1), thioredoxin reductase (TrxR), peroxiredoxins (Prxs) in brain and cerebella of stefin B-deficient mice. LPS challenge was found to result in a marked elevation of Trx1 and TrxR in the brain and cerebella of stefin B deficient mice, while Prx1 was upregulated only in cerebella after LPS challenge. Mitochondrial peroxiredoxin 3 (Prx3), was upregulated also in the cerebellar tissue lysates prepared from unchallenged stefin B deficient mice, while after LPS challenge Prx3 was upregulated in stefin B deficient brain and cerebella. Our results imply the role of oxidative stress in the progression of the disease.

Download Full-text

Anti–Na+/K+-ATPase immunotherapy ameliorates α-synuclein pathology through activation of Na+/K+-ATPase α1–dependent autophagy

Science Advances ◽

10.1126/sciadv.abc5062 ◽

2021 ◽

Vol 7 (5) ◽

pp. eabc5062

Author(s):

Lei Cao ◽

Siping Xiong ◽

Zhiyuan Wu ◽

Lei Ding ◽

Yebo Zhou ◽

...

Keyword(s):

Monoclonal Antibody ◽

Tyrosine Hydroxylase ◽

Neurodegenerative Diseases ◽

Motor Function ◽

Therapeutic Strategy ◽

Underlying Mechanism ◽

Behavioral Tests ◽

Behavioral Deficits ◽

Cellular Homeostasis ◽

Beneficial Effects

Na+/K+-ATPase (NKA) plays important roles in maintaining cellular homeostasis. Conversely, reduced NKA activity has been reported in aging and neurodegenerative diseases. However, little is known about the function of NKA in the pathogenesis of Parkinson’s disease (PD). Here, we report that reduction of NKA activity in NKAα1+/− mice aggravates α-synuclein–induced pathology, including a reduction in tyrosine hydroxylase (TH) and deficits in behavioral tests for memory, learning, and motor function. To reverse this effect, we generated an NKA-stabilizing monoclonal antibody, DR5-12D, against the DR region (897DVEDSYGQQWTYEQR911) of the NKAα1 subunit. We demonstrate that DR5-12D can ameliorate α-synuclein–induced TH loss and behavioral deficits by accelerating α-synuclein degradation in neurons. The underlying mechanism for the beneficial effects of DR5-12D involves activation of NKAα1-dependent autophagy via increased AMPK/mTOR/ULK1 pathway signaling. Cumulatively, this work demonstrates that NKA activity is neuroprotective and that pharmacological activation of this pathway represents a new therapeutic strategy for PD.

Download Full-text

Effects of subjective successful aging on emotional and coping responses to the COVID-19 pandemic

BMC Geriatrics ◽

10.1186/s12877-021-02076-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dannii Y. Yeung ◽

Edwin K. H. Chung ◽

Alfred H. K. Lam ◽

Alvin K. K. Ho

Keyword(s):

Older Adults ◽

Adult Development ◽

Successful Aging ◽

Underlying Mechanism ◽

Middle Aged ◽

Coping Responses ◽

Beneficial Effects ◽

Longitudinal Effects ◽

Development And Aging ◽

And Coping

Abstract Background Middle-aged and older adults are more vulnerable to hospitalization and mortality if they are infected with the COVID-19 virus. The present study investigates the longitudinal effects of subjective successful aging on middle-aged and older adults’ emotional and coping responses to the COVID-19 pandemic, and explores an underlying mechanism through perceived time limitation during the pandemic. Methods A sample of 311 Hong Kong Chinese middle-aged and older adults (Mage = 64.58, SD = 10.14, Range = 45–90 years) were recruited from an Adult Development and Aging Project and participated in a questionnaire study via an online platform or phone interview. Their levels of subjective successful aging, perceived time limitation, and emotional and coping responses to the pandemic were measured. Results The respondents who perceived themselves as more successful in aging process reported more positive and fewer negative emotions compared with their counterparts with lower levels of subjective successful aging. The mediation analysis showed that perceived time limitation could partially account for the effects of subjective successful aging on emotional and coping responses. Conclusions Findings of this study unveil the beneficial effects of subjective views of successful aging on emotional and coping responses to the pandemic through alleviating their perception of time limitation.

Download Full-text

Gabapentin Reduces Alcohol Intake in Rats by Regulating NF-κB Signaling Pathway Via PPAR γ

Alcohol and Alcoholism ◽

10.1093/alcalc/agab065 ◽

2021 ◽

Author(s):

Jing Li ◽

Kewei Xu ◽

Hao Ding ◽

Qiaozhen Xi

Keyword(s):

Locomotor Activity ◽

Signaling Pathway ◽

Specific Inhibitor ◽

Underlying Mechanism ◽

Ethanol Consumption ◽

Diglycidyl Ether ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Ppar Γ ◽

Tnf Α

Abstract Aims Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism. Methods The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20 days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot. Results GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ. Conclusions Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.

Download Full-text

Modulation of gut microbiota and intestinal barrier function during alleviation of antibiotic-associated diarrhea with Rhizoma Zingiber officinale (Ginger) extract

Food & Function ◽

10.1039/d0fo01536a ◽

2020 ◽

Vol 11 (12) ◽

pp. 10839-10851

Author(s):

Zhi-jie Ma ◽

Huan-jun Wang ◽

Xiao-jing Ma ◽

Yue Li ◽

Hong-jun Yang ◽

...

Keyword(s):

Gut Microbiota ◽

Barrier Function ◽

Intestinal Barrier ◽

Zingiber Officinale ◽

Underlying Mechanism ◽

Intestinal Barrier Function ◽

Ginger Extract ◽

Beneficial Effects ◽

Antibiotic Associated Diarrhea

Ginger extract showed beneficial effects on rats with antibiotic-associated diarrhea, and the underlying mechanism might be associated with the recovery of gut microbiota and intestinal barrier function.

Download Full-text