scholarly journals Echinacoside Improves Cognitive Impairment by Inhibiting Aβ Deposition Through the PI3K/AKT/Nrf2/PPARγ Signaling Pathways in APP/PS1 Mice

2021 ◽  
Author(s):  
hui qiu ◽  
min xue liu
Keyword(s):  
Signaling Pathway ◽  
Escape Latency ◽  
Senile Plaques ◽  
Pathological Process ◽  
Tnf Α ◽  
Nrf2 Signaling Pathway ◽  
Ros Formation ◽  
The Times ◽  
The Brain ◽  
Anti Inflammation

Abstract Echinacoside (ECH), a phenylethanoid glycoside, has protective activity in neurodegenerative disease, including anti-inflammation and antioxidation. However, the effects of ECH in Alzheimer’s disease (AD) are not very clear. This present study investigates the role and mechanism of ECH in the pathological process of AD. APP/PS1 mice were treated with ECH in 50 mg/kg/d for 3 months. Morris water maze, nesting test and immunofluorescence staining were used to observe whether ECH could improve AD pathology. Western blot was used to study the mechanism of ECH improving AD pathology. The results showed that ECH alleviated the memory impairment of APP/PS1 mice by reducing the time of escape latency as well as increasing the times of crossing the platform and rescued the impaired ability to construct nests. In addition, ECH significantly reduced the deposition of senile plaques in the brain and decreased the expression of BACE1 in APP/PS1 mice through activating PI3K/AKT/ Nrf2/PPARγ pathway. Furthermore, ECH decreased ROS formation, GP91 and 8-OHdG expression, upregulated the expression of SOD1 and SOD2 as well as activating the PI3K/AKT/Nrf2 signaling pathway. Moreover, ECH inhibited glia cells activation, pro-inflammatory cytokine IL-1β and TNF-α release, NLRP3 inflammasome formation through TXNIP/Trx-1 signaling pathway. In conclusion, this paper reported that ECH improved cognitive function, inhibited oxidative stress and inflammatory response in AD. Therefore, we suggest that ECH may be considered as a potential drug for AD treatment.

scholarly journals Anti-Inflammatory Effects of Neochlorogenic Acid Extract from Mulberry Leaf (Morus alba L.) Against LPS-Stimulated Inflammatory Response through Mediating the AMPK/Nrf2 Signaling Pathway in A549 Cells

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1385 ◽  
Author(s):  
Xiao-han Gao ◽  
Sun-dong Zhang ◽  
Li-tao Wang ◽  
Liang Yu ◽  
Xue-lian Zhao ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
A549 Cells ◽  
Morus Alba ◽  
Mulberry Leaf ◽  
Tnf Α ◽  
Nrf2 Signaling Pathway ◽  
Acute Pneumonia ◽  
Neochlorogenic Acid ◽  
Anti Inflammatory

Neochlorogenic acid (nCGA) is a phenolic compound isolated from mulberry leaf (Morus alba L.), which possesses multiple pharmacological activities containing antioxidant and anti-inflammatory effects. However, the role of nCGA in the treatment of acute pneumonia and the underlying molecular mechanism are still unclear. Hence, the aim of study is to investigate the anti-inflammatory properties of nCGA on LPS-stimulated inflammation in A549 cells. In the present study, results reported that nCGA without cytotoxicity significantly reduced the production of TNF-α, IL-6, and NO, and further suppressed the proteins of iNOS, COX2, TNF-α, IL-6 expression. Furthermore, nCGA also inhibited NF-κB activation and blocked MAPKs signaling pathway phosphorylation. In addition, we found nCGA significantly increased the expression of HO-1 via activating the AMPK/Nrf2 signaling pathway to attenuate the inflammatory response, whereas this protective effect of nCGA was reversed by pre-treatment with compound C (C.C, an AMPK inhibitor). Therefore, all these results indicated that nCGA might act as a natural anti-inflammatory agent for the treatment of acute pneumonia.

The Effects of Naringin on Cigarette Smoke-Induced Dynamic Changes in Oxidation/Antioxidant System in Lung of Mice

2020 ◽  
Vol 15 (8) ◽  
pp. 1934578X2094723
Author(s):  
Pan Chen ◽  
Ziting Xiao ◽  
Hao Wu ◽  
Yonggang Wang ◽  
Weiwei Su ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Cigarette Smoke ◽  
Antioxidant System ◽  
Antioxidant Systems ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dynamic Changes ◽  
Tnf Α ◽  
Nrf2 Signaling Pathway

Naringin possesses strong antioxidative activity and can protect against some respiratory diseases. Oxidative stress is thought to be a major factor in the development of many tobacco-caused diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a critical role in the regulation of oxidative stress. The dynamic changes in the antioxidant system in the lung that are induced by cigarette smoke (CS) are not well investigated, and how naringin affects these changes remains unknown. This study aimed to investigate the dynamic changes between the oxidation and antioxidant systems resulting from CS exposure and the effects of naringin on these changes in mice. Mice were chronically exposed to CS for 30 days. The levels of malondialdehyde (MDA), glutathione (GSH), interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-α); the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px); and the expressions of Nrf2, heme oxygenase-1 (HO-1), and nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1) in lung tissue were measured on days 2, 7, and 30. The levels of MDA, GSH, IL-6, and TNF-α in the lung were found to increase throughout the exposure. SOD and GSH-Px activities showed an increase on day 2 and a decrease on days 7 and 30. The messenger ribonucleic acid expressions of Nrf2, HO-1, and NQO1 were elevated on day 2 and decreased on day 7; Nrf2 and HO-1 expressions were continually decreased, but NQO1 expression was increased again, on day 30. Naringin restored the levels of these biochemical indices to normal throughout the experiment, suggesting that naringin protected against the CS-induced oxidative damage by suppressing the increase of antioxidants resulting from the early stage of CS exposure, as well as inhibiting the depletion of antioxidants due to long-term oxidative stress. Naringin also suppressed lung inflammation by inhibiting IL-6 and TNF-α. These results indicate that naringin possesses a powerful ability to maintain the balance of the oxidation/antioxidant system in the lung when subjected to CS exposure, probably by regulating the Nrf2 signaling pathway.

Effect of acupuncture on neurovascular units after cerebral infarction in rats through PI3K/AKT signaling pathway

2020 ◽  
Vol 75 (4) ◽  
pp. 387-397
Author(s):  
Linlin Wei ◽  
Kexue Zeng ◽  
Juanjuan Gai ◽  
Feixiong Zhou ◽  
Zhenglin Wei ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Signaling Pathway ◽  
Sham Group ◽  
Escape Latency ◽  
Akt Signaling ◽  
Acupuncture Group ◽  
Akt Signaling Pathway ◽  
Model Group ◽  
Protein Expressions ◽  
The Times

OBJECTIVE: To study the effect of acupuncture on neurovascular units after cerebral infarction (CI) in rats through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. METHODS: A total of 36 Sprague-Dawley rats were randomly divided into sham group (n = 12), model group (n = 12) and acupuncture group (n = 12). The external carotid artery was only exposed in model group, while the post-CI ischemia-reperfusion model was established using the suture method in the other 2 groups. After modeling, the rats in sham group and model group were fixed and sampled, while those in acupuncture group were treated with acupuncture intervention for 2 weeks and sampled. The neurological deficits of rats were evaluated using the Zea-Longa score, and the spatial learning and memory of rats were detected via water maze test. Moreover, the expressions of vascular endothelial growth factor (VEGF), growth associated protein-43 (GAP-43) and synuclein (SYN) in brain tissues were detected via immunohistochemistry, and the relative protein expressions of PI3K p85, PI3K p110 and p-AKT were detected via Western blotting. The messenger ribonucleic acid (mRNA) expressions of VEGF, GAP-43 and SYN were detected via quantitative polymerase chain reaction (qPCR). RESULTS: The Zea-Longa score was significantly increased in model group and acupuncture group compared with that in sham group (p < 0.05), while it significantly declined in acupuncture group compared with that in model group (p < 0.05). The escape latency was significantly prolonged and the times of crossing platform were significantly reduced in model group and acupuncture group compared with those in sham group (p < 0.05), while the escape latency was significantly shortened and the times of crossing platform were significantly increased in acupuncture group compared with those in model group (p < 0.05). The positive expressions of VEGF, GAP-43 and SYN were obviously increased in model group and acupuncture group compared with those in sham group (p < 0.05), while they were obviously increased in acupuncture group compared with those in model group (p < 0.05). Besides, model group and acupuncture group had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than sham group (p < 0.05), while acupuncture group also had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than model group (p < 0.05). The relative mRNA expressions of VEGF, GAP-43 and SYN were remarkably increased in model group and acupuncture group compared with those in sham group (p < 0.05), while they were remarkably increased in acupuncture group compared with those in model group (p < 0.05). CONCLUSION: Acupuncture promotes the repair of neurovascular units after CI in rats through activating the PI3K/AKT signaling pathway, thereby exerting a protective effect on neurovascular units.

scholarly journals TNF-α–Induced miR-21-3p Promotes Intestinal Barrier Dysfunction by Inhibiting MTDH Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhifeng Jiang ◽  
Feiyu Yang ◽  
Jingbo Qie ◽  
Chaoyuan Jin ◽  
Feng Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Intestinal Barrier ◽  
Pathological Process ◽  
Dependent Manner ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Potential Biomarker ◽  
Tnf Α ◽  
Cancer Tumor

Intestinal barrier dysfunction is characterized by increased intestinal permeability to lumen endotoxin, showing remarkable predisposition to immune enteropathy, and colorectal cancer tumor necrosis factor (TNF)-α is associated with this pathological process, while the mechanism remains unknown. In this study, different doses of TNF-α were used for Caco-2 cell treatment. We discovered that miR-21-3p expression was obviously increased by TNF-α in a dose-dependent manner. Further study demonstrated that TNF-α could upregulate miR-21-3p expression through the NF-κB signaling pathway. Then, TargetScan and miRWalk miRNA–mRNA interaction prediction online tools were introduced, and metadherin (MTDH) was screened out as a potential target of miR-21-3p. We subsequently found that miR-21-3p could directly target the 3′-untranslated region (UTR) of MTDH mRNA and inhibit its expression. Furthermore, it was demonstrated that miR-21-3p could regulate the Wnt signaling pathway by targeting MTDH mRNA, suggesting the effect of miR-21-3p/MTDH/Wnt axis on intestinal barrier dysfunction. Our findings provide a novel potential biomarker and therapeutic target for intestinal barrier dysfunction and related diseases.

scholarly journals Glycomacropeptide for Management of Insulin Resistance and Liver Metabolic Perturbations

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1140
Author(s):  
Mathilde Foisy Sauvé ◽  
Francis Feldman ◽  
Mireille Koudoufio ◽  
Nour-El-Houda Ould-Chikh ◽  
Lena Ahmarani ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Insulin Signaling ◽  
Systemic Insulin Resistance ◽  
Tnf Α ◽  
Nrf2 Signaling Pathway ◽  
Plasma Insulin Levels

Background and Aims: The increasing prevalence and absence of effective global treatment for metabolic syndrome (MetS) are alarming given the potential progression to severe non-communicable disorders such as type 2 diabetes and nonalcoholic fatty liver disease. The purpose of this study was to investigate the regulatory role of glycomacropeptide (GMP), a powerful milk peptide, in insulin resistance and liver dysmetabolism, two central MetS conditions. Materials and Methods: C57BL/6 male mice were fed a chow (Ctrl), high-fat, high-sucrose (HFHS) diet or HFHS diet along with GMP (200 mg/kg/day) administered by gavage for 12 weeks. Results: GMP lowered plasma insulin levels (in response to oral glucose tolerance test) and HOMA-IR index, indicating a more elevated systemic insulin sensitivity. GMP was also able to decrease oxidative stress and inflammation in the circulation as reflected by the decline of malondialdehyde, F2 isoprostanes and lipopolysaccharide. In the liver, GMP raised the protein expression of the endogenous anti-oxidative enzyme GPx involving the NRF2 signaling pathway. Moreover, the administration of GMP reduced the gene expression of hepatic pro-inflammatory COX-2, TNF-α and IL-6 via inactivation of the TLR4/NF-κB signaling pathway. Finally, GMP improved hepatic insulin sensitization given the modulation of AKT, p38 MAPK and SAPK/JNK activities, thereby restoring liver homeostasis as revealed by enhanced fatty acid β-oxidation, reduced lipogenesis and gluconeogenesis. Conclusions: Our study provides evidence that GMP represents a promising dietary nutraceutical in view of its beneficial regulation of systemic insulin resistance and hepatic insulin signaling pathway, likely via its powerful antioxidant and anti-inflammatory properties.

Schisandrin B ameliorates high-glucose-induced vascular endothelial cells injury by regulating the Noxa/Hsp27/NF-κB signaling pathway

2019 ◽  
Vol 97 (6) ◽  
pp. 681-692 ◽  
Author(s):  
Qiu-Ning Lin ◽  
Yong-Dong Liu ◽  
Si-En Guo ◽  
Rui Zhou ◽  
Qun Huang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Schisandrin B ◽  
Vascular Endothelial ◽  
Inflammatory Cascade ◽  
Tnf Α ◽  
Anti Inflammation

Background: To address the molecular mechanism of the anti-inflammation effects of schisandrin B (Sch B) in atherosclerosis, we examined injured HMEC-1, HBMEC, and HUVEC-12 cells induced by high glucose (HG). Methods: Western blot was performed to detect the levels of the proteins Hsp27, Noxa, TLR5, p-IκBα, and p-p65 in HG-induced cells, while ELISA was used to analyze the inflammatory cytokines TNF-α, IL-6, MCP-1, and IL-1β in cells with Hsp27 or Noxa stable expression. Results: Overexpression of Hsp27 upregulated the inflammatory cytokines and the release of IκBα, promoted transportation of p65 into the nucleus, and lastly, affected the inflammation process, while Sch B counteracted the upregulation. In addition, the effect of Noxa overexpression, which is different from Hsp27 overexpression, was consistent with that of Sch B treatment. Conclusions: Sch B may inhibit the inflammatory cascade and alleviate the injury to HMEC-1, HBMEC, and HUEVC-12 cells caused by HG by regulating the Noxa/Hsp27/NF-κB signaling pathway.

scholarly journals Aerobic Exercise Inhibits Inflammatory Response in Atherosclerosis via Sestrin1 Protein

2021 ◽  
Author(s):  
yunfeng sun ◽  
ke Li ◽  
wei wu ◽  
keping yang
Keyword(s):  
Inflammatory Response ◽  
Aerobic Exercise ◽  
Aerobic Training ◽  
Development Stage ◽  
Pathological Process ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Tnf Α ◽  
Anti Inflammation ◽  
High Expression Level

Abstract Background Aerobic exercise plays an important role in prevention and treatment of atherosclerosis but its role in inflammatory response is not completely clear. Inflammatory response is the main pathological process during occurrence and development stage of atherosclerosis. SESNs are considered as anti-inflammation protein in atherosclerosis. Results In current study, a high expression level of SESN1 is identified under the condition of aerobic exercise, further investigation shows levels of IL-1β/IL-6/TNF-α are significantly suppressed compared to those atherosclerosis mice with no aerobic training. Besides, we find that the activation of NK-κB signaling is impeded. Combine with our previous study, SESN1 is considered as the downstream factor of aerobic exercise which tend to inhibit the activation of inflammatory signaling and result in suppress the expression level of inflammatory factors. Another exciting finding is that MMP9/13 are also suppressed，but the potential mechanism is unclear. Conclusion Overall, present study sheds light on the significance of aerobic exercise for inflammation and stability of plaque through SESN1 may help developing new clinical treatments of atherosclerosis.

TNF-α in Combination with Palmitate Enhances IL-8 Production via TLR4-Dependent Signaling Pathway—Potential Relevance to Metabolic Inflammation

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1730-P
Author(s):  
RASHEED AHMAD ◽  
NADEEM AKHTER ◽  
SHIHAB P. KOCHUMON ◽  
AREEJ ABU ALROUB ◽  
REEBY S. THOMAS ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Metabolic Inflammation ◽  
Tnf Α ◽  
Dependent Signaling Pathway

CLINICAL AND NEUROLOGICAL FEATURES OF TRAUMATIC BRAIN DISEASE DURING THE STAGES OF REHABILITATION

2020 ◽  
Vol 3 (1) ◽  
pp. 51-53
Author(s):  
Rano Azizova ◽  
◽  
Umida Shamsiyeva ◽  
Mirzohid Turabbayev ◽  
Begzod Jorayev ◽  
...  
Keyword(s):  
Mechanical Energy ◽  
Pathological Process ◽  
Brain Disease ◽  
Clinical Forms ◽  
Neurological Features ◽  
Mechanisms Of Development ◽  
The Brain

Traumatic brain disease (TBHD) is a pathological process triggered by the damaging effect of mechanical energy on the brain and is characterized — with a variety of clinical forms — by the unity of etiology, pathogenetic and sanogenetic mechanisms of development and outcomes.

Sign in / Sign up

Export Citation Format

Share Document