scholarly journals The impact of Keap1/Nrf2, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 signaling pathways in the protective effects of berberine against methotrexate-induced nephrotoxicity

2019 ◽  
Vol 109 ◽  
pp. 47-56 ◽  
Author(s):  
Emad H.M. Hassanein ◽  
Abdel-Gawad S. Shalkami ◽  
Marwa M. Khalaf ◽  
Wafaa R. Mohamed ◽  
Ramadan A.M. Hemeida
Keyword(s):  
Signaling Pathways ◽  
Caspase 3 ◽  
Protective Effects ◽  
The Impact

Role of gambogenic acid in regulating PI3K/Akt/NF-kβ signaling pathways in rat model of acute hepatotoxicity

2021 ◽  
Vol 85 (3) ◽  
pp. 520-527
Author(s):  
Zhongyang Ding ◽  
Ying Li ◽  
Zhangfeng Tang ◽  
Xiaoyi Song ◽  
Fa Jing ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Caspase 3 ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Histopathological Changes ◽  
Phosphatidylinositol 3 Kinase ◽  
Tnf Α ◽  
Protein Expressions ◽  
Apoptosis Markers

ABSTRACT The purpose of this study is to investigate the protective effect of gambogenic acid (GA) in acetaminophen (APAP)-induced hepatotoxicity in rat models. GA (10 mg/kg) was administered intraperitoneal (i.p.) to rats for 7 consecutive days followed by APAP (500 mg/kg) single dose (i.p.) on the final day after GA administration. The levels of MDA, GSH, SOD, CAT, GPx, GST, ALP, AST, ALT, proinflammatory cytokines (TNF-α, IL-1β, IL-6), apoptosis markers (caspase-3 and -9, Bax, Bcl-2), 4-hydroxynonenal (4-HNE), and prostaglandin E2 (PGE2) were evaluated. Results exhibited protective effects of GA by inhibiting inflammation, preventing oxidative stress and apoptosis in APAP-induced liver. Histopathological changes caused by APAP were attenuated, protein expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) were upregulated, and nuclear factor–kappa β (NF-kβ) was downregulated by GA. In summary, GA significantly exerted anti-inflammatory and antiapoptotic effects against APAP-induced hepatotoxicity potentially through regulation of PI3K/Akt and NF-kβ signaling pathways.

scholarly journals Antiepileptic Effects of Protein-Rich Extract from Bombyx batryticatus on Mice and Its Protective Effects against H2O2-Induced Oxidative Damage in PC12 Cells via Regulating PI3K/Akt Signaling Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Meibian Hu ◽  
Yujie Liu ◽  
Liying He ◽  
Xing Yuan ◽  
Wei Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Signaling Pathways ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Maximal Electroshock ◽  
Protective Effects ◽  
Caspase 9 ◽  
Protein Rich

Bombyx batryticatus is a known traditional Chinese medicine (TCM) utilized to treat convulsions, epilepsy, cough, asthma, headaches, and purpura in China for thousands of years. This study is aimed at investigating the antiepileptic effects of protein-rich extracts from Bombyx batryticatus (BBPs) on seizure in mice and exploring the protective effects of BBPs against H2O2-induced oxidative stress in PC12 cells and their underlying mechanisms. Maximal electroshock-induced seizure (MES) and pentylenetetrazole- (PTZ-) induced seizure in mice and the histological analysis were carried out to evaluate the antiepileptic effects of BBPs. The cell viability of PC12 cells stimulated by H2O2 was determined by MTT assay. The apoptosis and ROS levels of H2O2-stimulated PC12 cells were determined by flow cytometry analysis. Furthermore, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), lactate dehydrogenase (LDH), and glutathione (GSH) in PC12 cells were assayed by ELISA and expressions of caspase-3, caspase-9, Bax, Bcl-2, PI3K, Akt, and p-Akt were evaluated by Western blotting and quantitative real-time polymerase chain reaction (RT-qPCR) assays. The results revealed that BBPs exerted significant antiepileptic effects on mice. In addition, BBPs increased the cell viability of H2O2-stimulated PC12 cells and reduced apoptotic cells and ROS levels in H2O2-stimulated PC12 cells. By BBPs treatments, the levels of MDA and LDH were reduced and the levels of SOD and GSH-Px were increased in H2O2-stimulated PC12 cells. Moreover, BBPs upregulated the expressions of PI3K, Akt, p-Akt, and Bcl-2, whereas they downregulated the expressions of caspase-9, caspase-3, and Bax in H2O2-stimulated PC12 cells. These findings suggested that BBPs possessed potential antiepileptic effects on MES and PTZ-induced seizure in mice and protective effects on H2O2-induced oxidative stress in PC12 cells by exerting antioxidative and antiapoptotic effects via PI3K/Akt signaling pathways.

scholarly journals Liraglutide Protects Nucleus Pulposus Cells Against High-Glucose Induced Apoptosis by Activating PI3K/Akt/ mTOR/Caspase-3 and PI3K/Akt/GSK3β/Caspase-3 Signaling Pathways

2021 ◽  
Vol 8 ◽  
Author(s):  
Mingyan Yao ◽  
Jing Zhang ◽  
Zhihong Li ◽  
Xiaoliang Bai ◽  
Jinhui Ma ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Nucleus Pulposus ◽  
High Glucose ◽  
Caspase 3 ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Protective Effects ◽  
Nucleus Pulposus Cells ◽  
Gene And Protein Expression ◽  
Induced Apoptosis

Background and Objective: Diabetes mellitus (DM) is reportedly a significant risk factor for intervertebral disc degeneration (IDD). Incretin system and particularly glucagon-like peptide 1 (GLP-1) because of its glucose-lowering effects has become an important target in therapeutic strategies of type 2 diabetes (T2D). Liraglutide is a GLP-1 receptor (GLP-1R) agonist with glucoregulatory and insulinotropic functions as well as regulatory functions on cell proliferation, differentiation, and apoptosis. However, little is known on the roles and signaling pathways of apoptosis protecting effects of liraglutide in IDD. This study aimed to investigate the potential protective effects of liraglutide against high glucose-induced apoptosis of nucleus pulposus cells (NPCs) and the possible involved signaling pathways.Methods: The human NPCs were incubated with 100 nM liraglutide alone or in combination with LY294002 (PI3K inhibitor), rapamycin (mTOR inhibitor), and SB216763 (GSK3β inhibitor) in a high glucose culture for 48 h. The four groups were assessed further for apoptosis and genes expressions. The apoptotic effect was evaluated by flow cytometry and further confirmed by cell death detection enzyme-linked immunoassay plus (ELISAPLUS). The gene and protein expression levels were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting techniques. The results were comparatively assessed between the four groups.Results: The results confirmed the presence of GLP-1R in the NPCs indicating that liraglutide inhibited the high glucose-induced apoptosis, which was blocked by silencing GLP-1R with siRNA. Moreover, liraglutide stimulated the phosphorylation of Akt, mTOR and GSK3β. Treatment with LY294002 significantly increased the apoptosis of NPCs and reduced the levels of their downstream substrates (p-AKT, p-mTOR, and p-GSK3β). Further assessments revealed that activation of mTOR and GSK3β was almost completely inhibited by rapamycin and SB216763, respectively, which significantly increased the caspase-3 levels.Conclusion: Liraglutide could protect NPCs against high glucose-induced apoptosis by activating the PI3K/AKT/mTOR/caspase-3 and PI3K/AKT/GSK3β/caspase-3 signaling pathways.

The Impact of Ultraviolet Radiation on Barrier Function in Human Skin: Molecular Mechanisms and Topical Therapeutics

2019 ◽  
Vol 25 (40) ◽  
pp. 5503-5511 ◽  
Author(s):  
Abdulaziz Alhasaniah ◽  
Michael J. Sherratt ◽  
Catherine A. O'Neill
Keyword(s):  
Ultraviolet Radiation ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Transepidermal Water Loss ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Positive Effects ◽  
Terrestrial Mammals ◽  
The Impact

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However, studies in mice and more limited work in humans suggest that the epidermal barrier becomes more permeable, as measured by increased transepidermal water loss, in response UVR, at doses sufficiently high to induce erythema. The mechanisms may include disturbance in the organisation of lipids in the stratum corneum (the outermost layer of the epidermis) and reduction in tight junction function in the granular layer (the first living layer of the skin). By contrast, suberythemal doses of UVR appear to have positive effects on epidermal barrier function. Topical sunscreens have direct and indirect protective effects on the barrier through their ability to block UV and also due to their moisturising or occlusive effects, which trap water in the skin, respectively. Some topical agents such as specific botanical extracts have been shown to prevent the loss of water associated with high doses of UVR. In this review, we discuss the current literature and suggest that the biology of UVR-induced barrier dysfunction, and the use of topical products to protect the barrier, are areas worthy of further investigation.

The Protective Effects of Green Tea Catechins in the Management of Neurodegenerative Diseases: A Review

2019 ◽  
Vol 16 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Tahereh Farkhondeh ◽  
Hanieh Shaterzadeh Yazdi ◽  
Saeed Samarghandian
Keyword(s):  
Neurodegenerative Diseases ◽  
Signaling Pathways ◽  
Green Tea ◽  
Molecular Mechanisms ◽  
Main Role ◽  
Related Factor ◽  
Protective Effects ◽  
Tea Catechins ◽  
Green Tea Catechins ◽  
And Control

Background: The therapeutic strategies to manage neurodegenerative diseases remain limited and it is necessary to discover new agents for their prevention and control. Oxidative stress and inflammation play a main role in the pathogenesis of neurodegenerative diseases. The aim of this study is to review the effects of green tea catechins against the Neurodegenerative Diseases. Methods: In this study, we extensively reviewed all articles on the terms of Green tea, catechins, CNS disorders, and different diseases in PubMed, Science Direct, Scopus, and Google Scholar databases between the years 1990 and 2017. Results: The present study found that catechins, the major flavonoids in green tea, are powerful antioxidants and radical scavengers which possess the potential roles in the management of neurodegenerative diseases. Catechins modulate the cellular and molecular mechanisms through the inflammation-related NF-&amp;#954;B and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Conclusion: The findings of the present review shows catechins could be effective against neurodegenerative diseases due to their antioxidation and anti-inflammation effects and the involved biochemical pathways including Nrf2 and NF-kB signaling pathways.<P&gt;

The Impact of Royal Jelly against Hepatic Ischemia/Reperfusion-Induced Hepatocyte Damage in Rats: The Role of Cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-α Signaling Pathways

2020 ◽  
Vol 14 (1) ◽  
pp. 88-100
Author(s):  
Fares E.M. Ali ◽  
Heba M. Saad Eldien ◽  
Nashwa A.M. Mostafa ◽  
Abdulrahman H. Almaeen ◽  
Mohamed R.A. Marzouk ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
P38 Mapk ◽  
Royal Jelly ◽  
Ischemia Reperfusion ◽  
Histopathological Changes ◽  
Down Regulation ◽  
Hepatic Ischemia ◽  
Tnf Α ◽  
Hepatic Ischemia Reperfusion ◽  
The Impact

Objective: The present study was conducted to elucidate the underlying molecular mechanism as well as the potential hepatoprotective effects of royal jelly (RJ) against hepatic ischemia/reperfusion (IR) injury. Methods: Rats were assigned into four groups; sham (received vehicle), IR (30 minutes ischemia and 45 minutes reperfusion), sham pretreated with RJ (200 mg/kg P.O.), and IR pretreated with RJ (200 mg/kg P.O.). The experiment has lasted for 28 days. Results: Hepatic IR significantly induced hepatic dysfunctions, as manifested by elevation of serum transaminases, ALP and LDH levels. Moreover, hepatic IR caused a significant up-regulation of P38-MAPK, NF-κB-p65, TNF-α and MDA levels along with marked down-regulation of Nrf-2, HO-1, COX-4, cytoglobin, IκBa, IL-10, GSH, GST and SOD levels. Additionally, marked histopathological changes were observed after hepatic IR injury. On the contrary, pretreatment with RJ significantly improved hepatic functions along with the alleviation of histopathological changes. Moreover, RJ restored oxidant/antioxidant balance as well as hepatic expressions of Nrf-2, HO-1, COX-4, and cytoglobin. Simultaneously, RJ significantly mitigated the inflammatory response by down-regulation of P38-MAPK, NF-κB-p65, TNF-α expression. Conclusion: The present results revealed that RJ has successfully protected the liver against hepatic IR injury through modulation of cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF-α signaling pathways.

scholarly journals Comparison of Phenolic Contents and Scavenging Activities of Miang Extracts Derived from Filamentous and Non-Filamentous Fungi-Based Fermentation Processes

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1144
Author(s):  
Aliyu Dantani Abdullahi ◽  
Pratthana Kodchasee ◽  
Kridsada Unban ◽  
Thanawat Pattananandecha ◽  
Chalermpong Saenjum ◽  
...  
Keyword(s):  
Filamentous Fungi ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Protective Effects ◽  
Tea Leaves ◽  
Antioxidant Power ◽  
Phenolic Contents ◽  
Ic50 Values ◽  
Ferric Reducing Antioxidant Power ◽  
The Impact

The study investigated the impact of the fermentation process on the phenolic contents and antioxidant and anti-inflammatory activities in extracts of Miang, an ethnic fermented tea product of northern Thailand. The acetone (80%) extraction of Miang samples fermented by a non-filamentous fungi-based process (NFP) and filamentous fungi-based process (FFP) had elevated levels of total polyphenols, total tannins, and condensed tannins compared to young and mature tea leaves. The antioxidant studies also showed better the half-maximal inhibitory concentration (IC50) values for fermented leaves in both 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity assays as well as improved ferric reducing antioxidant power (FRAP) compared to young and mature tea leaves. Extracts of NFP and FFP samples at concentrations of 50 and 100 ppm showed better protective effects against hydrogen peroxide (H2O2)-induced intracellular reactive oxygen species (ROS) production in HT-29 colorectal cells without exerting cytotoxicity. Additionally, lipopolysaccharide (LPS)-induced production of nitric oxide (a proinflammatory mediator as well as a reactive nitrogen species) was also inhibited by these fermented Miang extracts with an IC50 values of 17.15 μg/mL (NFP), 20.17 μg/mL (FFP), 33.96 μg/mL (young tea leaves), and 31.33 μg/mL (mature tea leaves). Therefore, both NFP-Miang and FFP-Miang showed the potential to be targeted as natural bioactive functional ingredients with preventive properties against free radical and inflammatory-mediated diseases.

scholarly journals Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Camille Ternet ◽  
Christina Kiel
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathways ◽  
Intestinal Microbiota ◽  
Critical Role ◽  
Neuroendocrine Cells ◽  
Cell Junction ◽  
Intestinal Cell ◽  
Intestinal Homeostasis ◽  
Cell Functions ◽  
The Impact

AbstractThe intestinal epithelium acts as a physical barrier that separates the intestinal microbiota from the host and is critical for preserving intestinal homeostasis. The barrier is formed by tightly linked intestinal epithelial cells (IECs) (i.e. enterocytes, goblet cells, neuroendocrine cells, tuft cells, Paneth cells, and M cells), which constantly self-renew and shed. IECs also communicate with microbiota, coordinate innate and adaptive effector cell functions. In this review, we summarize the signaling pathways contributing to intestinal cell fates and homeostasis functions. We focus especially on intestinal stem cell proliferation, cell junction formation, remodelling, hypoxia, the impact of intestinal microbiota, the immune system, inflammation, and metabolism. Recognizing the critical role of KRAS mutants in colorectal cancer, we highlight the connections of KRAS signaling pathways in coordinating these functions. Furthermore, we review the impact of KRAS colorectal cancer mutants on pathway rewiring associated with disruption and dysfunction of the normal intestinal homeostasis. Given that KRAS is still considered undruggable and the development of treatments that directly target KRAS are unlikely, we discuss the suitability of targeting pathways downstream of KRAS as well as alterations of cell extrinsic/microenvironmental factors as possible targets for modulating signaling pathways in colorectal cancer.

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