Diosmin protects against cerebral ischemia/reperfusion injury through activating JAK2/STAT3 signal pathway in mice

Liu, X.; Zhang, X.; Zhang, J.; Kang, Ning; Zhang, N.; Wang, H.; Xue, Jing; Yu, Jingying; Yang, Yi; Cui, Haiying; Cui, Lili; Wang, L.; Wang, X.

doi:10.1016/j.neuroscience.2014.03.032

Cited by 81 publications

(70 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We were able to discover the involvement of the JAK2/STAT3 pathway in the proliferation, differentiation, oxidative stress, or apoptosis in central nervous system . Particularly, the activation of JAK2/STAT3 signaling pathway could protect mouse from cerebral I/R injury, as evident by Liu X et al miR‐337‐3p could target JAK2 which has been validated in our experiments, as similar as in hepatic carcinoma cells . In our CoCl 2 ‐treated PC12 cell models, miR‐337‐3p inhibitors could upregulate mRNA and phosphorylation of JAK2 and STAT3.…”

Section: Discussionsupporting

confidence: 74%

Inhibition of miR‐337‐3p involved in the protection of CoCl₂‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway

Wang

Jiang

2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

Objective To investigate the possibility of microRNA (miR)‐337‐3p in the protection of hypoxia‐induced injury in PC12 cells via modulating the JAK2/STAT3 signaling pathway. Methods Dual‐luciferase reporter assay analyzed the relationship between the miR‐337‐3p and JAK2. PC12 cells were divided into normal, CoCl2, CoCl2 + NC, CoCl2 + inhibitors, CoCl2 + JAK2, and CoCl2 + mimics + JAK2 groups. Then, PC12 cell viability and apoptosis were measured by the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) and Annexin‐V‐fluorescein isothiocyanate/propidium iodide methods. Quantitative real‐time polymerase chain reaction and Western blot analysis were used to determine expressions. Besides, the intracellular reactive oxygen species (ROS) was examined by dichloro‐dihydro‐fluorescein diacetate (DCFH‐DA) while the mitochondrial membrane potential (MMP) by using JC‐1. Results The negative targeting relationship between miR‐337‐3p and JAK2 was confirmed. When compared with the normal group, miR‐337‐3p was increased while JAK2 and STAT3 were decreased in CoCl2‐induced PC12 cells, with decreased cell viability. Moreover, either miR‐337‐3p inhibitor or JAK2 overexpression could partially reverse CoCl2‐induced decrease in PC12 cell viability. Besides, CoCl2 could also trigger PC12 cell apoptosis by increasing cleaved caspase 3 and Bax but decreasing Bcl‐2 and Bcl‐XL, which, however, were abolished with the transfection of miR‐337‐3p inhibitors or lentivirus transfection to activate JAK2. Compared with the CoCl2 group, the average of fluorescent signals of ROS in the CoCl2 + inhibitors group and the CoCl2 + JAK2 group was lower, while the activities of superoxide dismutase, catalase, glutathione peroxidase, and total anti‐oxidative capacity were higher, together with an increase in MMP. Conclusion Inhibiting miR‐337‐3p could activate the JAK2/STAT3 signaling pathway to suppress CoCl 2‐induced cytotoxicity and apoptosis and ameliorate oxidative stress and MMP in PC12 cells.

show abstract

Section: Discussionsupporting

confidence: 74%

Inhibition of miR‐337‐3p involved in the protection of CoCl₂‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway

Wang

Jiang

2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…(Jelenkovic et al, 2014) Likewise, the immune modulating effects of green tea component EGCG (epigallocatechin 3-gallate) can sensitize effects of temozolomide in models of intracranially implanted human U87 or U251 glioblastoma and enhance GBM to ionizing radiation (Chen et al, 2011, McLaughlin et al, 2006). Similar effects are often reported for turmeric root ( Curcuma Longa )/curcumin both in attenuation of CNS injuries (Li et al, 2015a, Li et al, 2015b, Zhu et al, 2014) as well as comprising anti-cancer modulators in general and particularly for glioblastoma. (Dhandapani et al, 2007, Karmakar et al, 2007, Perry et al, 2010)…”

Section: Discussionsupporting

confidence: 70%

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

Mazzio

Bauer

Mendonca

et al. 2017

Journal of Neuroimmunology

View full text Add to dashboard Cite

Chronic or acute central nervous system (CNS) inflammation is carried out by glial cells, which can contribute to neurological injuries associated with head trauma, stroke, and infection, Parkinson’s or Alzheimer ’s disease. The process of aging combined with inflammation are also risk factors for developing glioblastoma multiforme (GBM) as well as perpetuating its malignant aggression. With growing public curiosity in complementary and alternative medicines (CAMs), in this work we conduct a high throughput (HTP) screening of >1400 natural herbs, plants and over the counter (OTC) products for anti-inflammatory effects on lipopolysaccharide (LPS)/interferon gamma (IFNγ) activated C6 glioma cells. Validation studies suggest a pro-inflammatory profile mediated by LPS [3μg/ml/IFNγ 3ng/ml] is consistent with elevation [> 8.5 fold] of MCP-1 and cytokine-induced neutrophil chemo-attractants (CINC) 1, CINC 2a and CINC3. The data show no evidence of changes to the following, IL-13, TNF-a, fracktaline, leptin, LIX, GM-CSF, ICAM1, L-Selectin, activin A, agrin, IL-1α, MIP-3a, B72/CD86, NGF, IL-1b, MMP-8, IL-1 R6, PDGF-AA, IL-2, IL-4, prolactin R, RAGE, IL-6, Thymus Chemokine-1, CNTF,IL-10 or TIMP-1. The data also show a LPS/IFNγ mediated rise in iNOS and NO2− as often reported. A HTP screening was conducted, where we employ an in vitro efficacy index (iEI) defined as the ratio of toxicity (LC50)/anti-inflammatory potency (IC50) to ensure biological effects were occurring in fully viable cells (ratio > 3.8). Using NO2− as a guideline molecule, the data show that 1.77 % (25 of 1410 tested) (at <250μg/ml) had anti-inflammatory effects with an iEI ratio >3.8. These include reference drugs (hydrocortisone, dexamethasone N6-(1-iminoethyl)-L-lysine and NSAIDS : diclofenac, tolfenamic acid), a histone deacetylase inhibitor (apicidin) and the following natural products; Ashwaganda (Withania somnifera), Elecampagne Root (Inula helenium), Feverfew (Tanacetum parthenium), Green Tea (Camellia sinensis), Turmeric Root (Curcuma Longa) Ganthoda (Valeriana wallichii), Tansy (Tanacetum vulgare), Maddar Root (Rubia tinctoria), Red Sandle wood (Pterocarpus santalinus), Bay Leaf (Laurus nobilis, Lauraceae), quercetin, cardamonin, fisetin, EGCG, biochanin A, galangin, apigenin and curcumin. The herb with the largest iEI was Ashwaganda where the IC50/LC50 was 11.1/>1750.0 μg/mL, and the compound with the greatest iEI was quercetin where the IC50/LC50 was 10.0/>363.6 ug/mL. These substances also downregulate the production of iNOS expression and attenuate CINC-3 release. In summary, this HTP screening provides guideline information as to efficacy of natural products that in the long term, could prevent inflammatory processes associated with neurodegenerative disease and aggressive glioma tumor growth.

show abstract

“…The JAK2–STAT3 signal pathway is a central component of organ protection, and it is involved in many organs such as the heart, brain, kidney and liver (Das et al, 2012; Grozovsky et al, 2015; Kim et al, 2016; Li, Li & Li, 2015; Si et al, 2014). JAK2–STAT3 signal pathways play key roles in ischemic preconditioning, particularly by protecting the myocardium at a late stage of preconditioning and by upregulating protection proteins, such as LOS and COX-2, and the proportions of anti-apoptosis proteins (Gross, Hsu & Gross, 2006).…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway

Xie

et al. 2017

PeerJ

View full text Add to dashboard Cite

BackgroundSevoflurane postconditioning (S-post) has similar cardioprotective effects as ischemic preconditioning. However, the underlying mechanism of S-post has not been fully elucidated. Janus kinase signaling transduction/transcription activator (JAK2–STAT3) plays an important role in cardioprotection. The purpose of this study was to determine whether the cardioprotective effects of S-post are associated with activation of the JAK2–STAT3 signal pathway.MethodsAn adult male Sprague–Dawley (SD) rat model of myocardial ischemia/reperfusion (I/R) injury was established using the Langendorff isolated heart perfusion apparatus. At the beginning of reperfusion, 2.4% sevoflurane alone or in combination with AG490 (a JAK2 selective inhibitor) was used as a postconditioning treatment. The cardiac function indicators, myocardial infarct size, lactic dehydrogenase (LDH) release, mitochondrial ultrastructure, mitochondrial reactive oxygen species (ROS) generation rates, ATP content, protein expression of p-JAK, p-STAT3, Bcl-2 and Bax were measured.ResultsCompared with the I/R group, S-post significantly increased the expression of p-JAK, p-STAT3 and Bcl-2 and reduced the protein expression of Bax, which markedly decreased the myocardial infarction areas, improved the cardiac function indicators and the mitochondrial ultrastructure, decreased the mitochondrial ROS and increased the ATP content. However, the cardioprotective effects of S-post were abolished by treatment with a JAK2 selective inhibitor (p < 0.05).ConclusionThis study demonstrates that the cardioprotective effects of S-post are associated with the activation of JAK2–STAT3. The mechanism may be related to an increased expression of p-JAK2 and p-STAT3 after S-post, which reduced mitochondrial ROS generation and increased mitochondrial ATP content, thereby reducing apoptosis and myocardial infarct size.

show abstract

Diosmin protects against cerebral ischemia/reperfusion injury through activating JAK2/STAT3 signal pathway in mice

Cited by 81 publications

References 61 publications

Inhibition of miR‐337‐3p involved in the protection of CoCl₂‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway

Inhibition of miR‐337‐3p involved in the protection of CoCl₂‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway

Contact Info

Product

Resources

About

Diosmin protects against cerebral ischemia/reperfusion injury through activating JAK2/STAT3 signal pathway in mice

Cited by 81 publications

References 61 publications

Inhibition of miR‐337‐3p involved in the protection of CoCl2‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway

Inhibition of miR‐337‐3p involved in the protection of CoCl2‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

Sevoflurane postconditioning protects the myocardium against ischemia/reperfusion injury via activation of the JAK2–STAT3 pathway

Contact Info

Product

Resources

About

Inhibition of miR‐337‐3p involved in the protection of CoCl₂‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway

Inhibition of miR‐337‐3p involved in the protection of CoCl₂‐induced injury in PC12 cells via activating JAK2/STAT3 signaling pathway