β-Sitosterol Attenuates the Intracranial Aneurysm Growth by Suppressing TNF-α-Mediated Mechanism

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 303-311 ◽  
Author(s):  
Qian Yang ◽  
Delin Yu ◽  
Yi Zhang
Keyword(s):  
Inflammatory Cytokines ◽  
Cerebral Aneurysms ◽  
Gelatin Zymography ◽  
Suppressive Effect ◽  
Male Rats ◽  
Lipid Lowering ◽  
Protective Effects ◽  
Inflammatory Reactions ◽  
Vascular Walls ◽  
Tnf Α

Background: Onset of inflammation associated with increased extracellular matrix degradation of vascular walls in the neuronal area is the pathophysiology of cerebral aneurysms. It has been documented well that β-sitosterol has protective effects on various brain-related diseases independent of their lipid-lowering effects; the current work was framed to examine the effect of β-sitosterol on CA progression. Materials and Methods: To study whether β-sitosterol has a suppressive effect on the growth of CA, β-sitosterol administration started prior to aneurysm induction. CA was induced in Wistar male rats with or without oral administration of β-sitosterol. The expression of chemokines and inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-8, IL-1β, IL-17, IL-6, matrix metalloproteinases (MMP)-2 and -9, was elucidated by ELISA and RT-PCR. Results: Rats treated with β-sitosterol exhibited a significant reduction in aneurysmal size compared with control rats. In addition, β-sitosterol administration reduced the expression of chemokines and inflammatory cytokines, while gelatin zymography data revealed declined activity of MMP-2 and -9 in aneurismal walls. Furthermore, the levels of cytokines were significantly reduced in β-sitosterol-administered rats compared to CA rats. Conclusions: Treatment with β-sitosterol suppresses the development of CA by inhibiting inflammatory reactions including TNF-α and thus β-sitosterol can be a suggestive candidate for the prevention of CA treatment and progression.

scholarly journals MiR-24-3p Attenuates IL-1β-Induced Chondrocyte Injury Associated With Osteoarthritis by Targeting BCL2L12

2020 ◽  
Author(s):  
Jin Xu ◽  
Xiaozhong Qian ◽  
Ren Ding
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract Background: Osteoarthritis (OA) is a chronic and degenerative joint disease prevalent in the elderly. MiR-24-3p has been reported to be involved in an OA-resembling environment. However, the functional role and underlying mechanism of miR-24-3p in chondrocyte injury associated with OA remains unknown. Methods: The expression of miR-24-3p was determined in OA cases and control patients, as well as IL-1β-stimulated chondrocyte cell line CHON-001 using reverse transcription quantitative PCR analysis. Cell viability was analyzed by CCK-8 assay. Apoptosis status was assessed by caspase-3 activity detection. The pro-inflammatory cytokines (TNF-α and IL-18) were determined using ELISA assay. The association between miR-24-3p and BCL2L12 was confirmed by luciferase reporter assay.Results: We first observed that miR-24-3p expression level was lower in the OA cases than in the control patients and IL-1β decreased the expression of miR-24-3p in the chondrocyte CHON-001. Functionally, overexpression of miR-24-3p significantly attenuated IL-1β-induced chondrocyte injury, as reflected by increased cell viability, decreased caspase-3 activity, pro-inflammatory cytokines (TNF-α and IL-18). Western blot analysis showed that overexpression of miR-24-3p weakened IL-1β-induced cartilage degradation, as reflected by reduction of MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-5) protein expression, as well as markedly elevation of COL2A1 (collagen type II). Importantly, BCL2L12 was demonstrated to be a target of miR-24-3p. BCL2L12 knockdown imitated, while overexpression significantly abrogated the protective effects of miR-24-3p against IL-1β-induced chondrocyte injury.Conclusions: In conclusion, our work provides important insight into targeting miR-24-3p/BCL2L12 axis in OA therapy.

scholarly journals Induction of analgesia using atorvastatin in experimental diabetic neuropathy through NMDA receptor and inflammatory cytokines inhibition

2020 ◽  
Keyword(s):  
Nmda Receptor ◽  
Diabetic Neuropathy ◽  
Inflammatory Cytokines ◽  
Interleukin 1 ◽  
Male Rats ◽  
Control Group ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Tnf Α ◽  
Study Results

Background: Diabetic neuropathy is a complication of diabetes causing damage to the nerves. Objectives: Considering the neuroprotective anti-inflammatory antioxidant characteristics of statins, the current study aimed at determining the effects of atorvastatin on diabetic neuropathy through assessing the involvement of N-methyl-D-aspartic acid (NMDA) receptor, factors of oxidative stress, and inflammatory cytokines in rats with diabetes. Methods: Male rats were randomly assigned into six groups of the saline- and atorvastatin-treated controls, and streptozotocin (STZ)-induced diabetic animals treated with vehicle, diabetic animals treated with morphine (5 mg/kg), and rats treated with atorvastatin (10 mg/kg/day for 10 weeks) alone or in combination with NMDA receptor agonist. The hot plate and formalin tests were carried out on the rats. Moreover, malondialdehyde level, catalase and superoxide dismutase activities, levels of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the dorsal root ganglia (DRG) of the animals were measured. Finally, the expression of the NMDA receptor in DRG was investigated in the current study. Results: Diabetes resulted in analgesia in all tests, and pretreatment with atorvastatin exacerbated diabetes-induced analgesic effects in the hot plate and early phase of the formalin test (P≤0.01 and P≤0.05 in comparison to those reported for the diabetic vehicle-treated group, respectively). The injection of NMDA could reverse the atorvastatin-induced analgesia in the hot plate test (P≤0.05). Diabetes caused to increase the levels of IL-1β, IL-6, and TNF-α in DRG in comparison to those reported for the control group (P≤0.05). Furthermore, the pretreatment of rats using atorvastatin could significantly reverse the increase in TNF-α level (P≤0.05). Conclusions: Atorvastatin showed analgesic properties, which might be acting through NMDA receptors and reduction of inflammatory cytokines.

scholarly journals Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats

Marine Drugs ◽  
2021 ◽  
Vol 19 (9) ◽  
pp. 525
Author(s):  
Shimaa M. Abou-Zeid ◽  
Samira H. Aljuaydi ◽  
Huda O. AbuBakr ◽  
Enas A. Tahoun ◽  
Alessandro Di Cerbo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
High Mobility ◽  
Suppressive Effect ◽  
Male Rats ◽  
Cell Mediated Immunity ◽  
Protective Effects ◽  
Human Beings ◽  
Hepatotoxic Effect ◽  
Neonicotinoid Insecticide ◽  
Toxic Hazard

Thiacloprid (TCP) is a widely used neonicotinoid insecticide with a probable toxic hazard to animals and human beings. This hazard has intensified the demand for natural compounds to alleviate the expected toxic insults. This study aimed at determining whether astaxanthin (ASX) could mitigate the hepatotoxic effect of TCP and diminish its suppressive effect on immune responses in rats. Animals received TCP by gavage at 62.1 mg/kg (1/10th LD50) with or without ASX at 40 mg/kg for 60 days. Intoxicated rats showed modulation of serum transaminases and protein profiles. The hemagglutination antibody titer to sheep red blood cells (SRBC) and the number of plaque-forming cells in the spleen were reduced. The cell-mediated immunity and phagocytosis were suppressed, while serum interleukins IL-1β, IL-6, and IL-10 were elevated. Additionally, malondialdehyde, nitric oxide, and 8-hydroxy-2′-deoxyguanosine levels were increased in the liver, spleen, and thymus, with depletion of glutathione and suppression of superoxide dismutase and catalase activities. The expressions of inducible nitric oxide synthase and the high mobility group box protein 1 genes were upregulated with histomorphological alterations in the aforementioned organs. Cotreatment with ASX markedly ameliorated the toxic effects of TCP, and all markers showed a regression trend towards control values. Collectively, our data suggest that the protective effects of ASX on the liver and immune system of TCP-treated animals depend upon improving the antioxidant status and relieving the inflammatory response, and thus it may be used as a promising therapeutic agent to provide superior hepato- and immunoprotection.

scholarly journals Effect of caraway on gentamicin-induced oxidative stress, inflammation and nephrotoxicity in rats

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Hoda Erjaee ◽  
Fatemeh Azma ◽  
Saeed Nazifi
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Group Treatment ◽  
Structural Damage ◽  
Seed Oil ◽  
Treated Group ◽  
Control Group ◽  
Protective Effects ◽  
Simultaneous Treatment ◽  
Tnf Α

Different potentially therapeutic approaches to prevent or attenuate gentamicin (GEM) induced nephrotoxicity have been proposed. The aim of the present study was to investigate the possible protective effects of caraway seed oil against GEM-induced nephrotoxicity in rats. Rats (24) were randomly assigned into four equal groups: i) normal control group, ii) treated with GEM, iii) pretreated with orally caraway seed oil 10 (mg kg−1) plus GEM and iv) treated with GEM and caraway seed oil 10 mg kg−1. Biochemical examinations were utilized for evaluation of the oxidative stress and renal nephrotoxicity. Creatinine, blood urea nitrogen (BUN), plasma malondialdehyde (MDA) levels, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined. Administration of gentamicin to rats induced a marked renal failure, characterized by a significant increase in plasma creatinine and BUN concentrations. The animals treated with gentamicin alone showed a significantly higher plasma MDA level andlower SOD, GSH-Px and CAT activities when compared with the control group. Treatment and simultaneous treatment with caraway seed oil produced amelioration in MDA and increased the activity of antioxidant enzymes SOD, GSH-Px and CAT when compared with the gentamicin treated group. In addition, GEM nephrotoxicity increased renal inflammatory cytokines (TNF-α, IL-6 and IFN-γ). Pro-inflammatory cytokines were significantly decreased (P<0.05) in the test groups administered caraway seed oil. These findings suggest that caraway seed oil treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress and inflammation in rats.

scholarly journals Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jeonghyeon Moon ◽  
Seon-yeong Lee ◽  
Jeong Won Choi ◽  
A Ram Lee ◽  
Jin Hee Yoo ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Th17 Cells ◽  
Skin Fibroblasts ◽  
Inflammatory Factors ◽  
Metformin Treatment ◽  
Protective Effects ◽  
Stat3 Signaling ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

AbstractScleroderma is an autoimmune disease that causes dermal fibrosis. It occurs when collagen accumulates in tissue as a result of persistent inflammation. Th17 cells and pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, and TNF-α play important roles in the pathogenesis of scleroderma. Because metformin, a medication used to treat diabetes, has effective immunoregulatory functions, we investigated its therapeutic function in scleroderma. Mice in a model of bleomycin-induced scleroderma were treated with metformin for 2 weeks. Histological assessment demonstrated protective effects of metformin against scleroderma. Metformin decreased the expression of pro-inflammatory factors in dermal tissue and lymphocytes. It also decreased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α) and fibrosis-inducing molecules both in vivo and in vitro. These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1β, IL-6, and TNF-α. To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that phosphorylated mTOR and phosphorylated STAT3 protein expression were decreased by metformin treatment. These results suggest that metformin has potential to treat scleroderma by inhibiting pro-inflammatory cytokines and anti-inflammatory activity mediated by mTOR-STAT3 signaling.

Antiglaucoma Potential of β-Glucogallin Is Mediated by Modulating Mitochondrial Responses in Experimentally Induced Glaucoma

2021 ◽  
pp. 1-10
Author(s):  
Tingting Cao ◽  
Jun Wang ◽  
Yuanyuan Wu ◽  
Lianfeng Wang ◽  
Huiqin Zhang
Keyword(s):  
Hydrostatic Pressure ◽  
Inflammatory Cytokines ◽  
Antioxidant Status ◽  
Cultured Cells ◽  
Mitochondrial Enzymes ◽  
Oxygen Species ◽  
Protective Effects ◽  
Caveolin 1 ◽  
Tnf Α

<b><i>Background:</i></b> The use of phytochemicals for the treatment of various bodily ailments has been in practice since ancient days. Even though in practice, scientific studies on the protective effect of β-glucogallin (BG) against glaucoma is limited. <b><i>Objectives:</i></b> In the present study, the in vitro glaucoma model (hydrostatic pressure) using PC12 neuronal cells exposed to BG were used to elucidate its protective effects. <b><i>Method:</i></b> The cultured cells were analyzed for the mitochondrial responses, oxidant-antioxidant status, and expression of <i>caveolin-1</i>, <i>ANGPTL7</i>, the glaucoma markers, and cytokines. <b><i>Results:</i></b> We demonstrated a significant increase in the expression of glial fibrillary acidic protein, ANGPTL7, with altered mitochondrial enzymes in glaucoma cells compared to the control. Moreover, cells predisposed to hydrostatic pressure demonstrated an increase in oxidative stress with augmented (<i>p</i> &#x3c; 0.01) inflammatory cytokines such as IL-2, CXCR4, IL-6, IL-8, MCP-1, and TNF-α. On the other hand, cells pretreated with BG attenuated the reactive oxygen species levels with improved antioxidant enzymes. Simultaneously, the levels of inflammatory cytokines and ANGPTL7 proteins were found attenuated with restored mitochondrial responses in BG pretreated cells. <b><i>Conclusion:</i></b> Thus, the results of the present study demonstrate that the use of BG on retinal cells against relieving the intraocular pressure may be a promising therapeutic for controlling the disease progression.

scholarly journals Immunomodulatory effect of melatonin supplementation in experimental diabetes

Pharmacia ◽  
2020 ◽  
Vol 67 (4) ◽  
pp. 223-228
Author(s):  
Yana I. Ivankiv ◽  
Oleksandra M. Oleshchuk
Keyword(s):  
Inflammatory Responses ◽  
Suppressive Effect ◽  
Male Rats ◽  
Immune Reactivity ◽  
Standard Diet ◽  
Tnf Α ◽  
Experimental Type ◽  
Necrosis Factor

Aim: To investigate the effect of melatonin on the immunomodulatory response in experimental type 1 and 2 diabetes mellitus. Methods: Experiments were performed on male rats (180–200 g), purchased from the Experimental Animal Holding,. Animals were maintained in standard diet conditions. Two pathological states were simulated on male rats: experimental type 1 and type 2 diabetes. Melatonin was introduced from 14 to 23 days of experiment intraperitoneally. Levels of immunoglobulin classes A, M and G (Ig A, M, G), circulating immune complexes (CIC), interleukin 1β (EE), interleukin 6 (IL-6), and tumor necrosis factor (TNF-a) were measured. Results: We demonstrated that melatonin in case of immune hyperactivity, can, provide a suppressive effect and is able to enhance immune reactivity under conditions of its limitation, indicating the immunostimulating activity. Furthermore, we found that administration of melatonin decreased inflammatory responses by mediating the levels of immunomodulatory factors, including TNF-α, IL-1β and IL-6. Conclusion: Melatonin is a positive regulator of immune system, may be a potential therapeutic agent, it has no reported side effects.

Protective effects of baicalin on LPS-induced injury in intestinal epithelial cells and intercellular tight junctions

2015 ◽  
Vol 93 (4) ◽  
pp. 233-237 ◽  
Author(s):  
Jian Chen ◽  
Ren Zhang ◽  
Jian Wang ◽  
Peng Yu ◽  
Quan Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Protein Expression ◽  
Tight Junctions ◽  
Inflammatory Cytokines ◽  
Intestinal Epithelial Cells ◽  
Expression Level ◽  
Protective Effects ◽  
Intestinal Epithelial ◽  
Tnf Α ◽  
Mrna And Protein Expression

Aims: To investigate the protective effects and mechanisms of baicalin on lipopolysaccharide (LPS)-induced injury in intestinal epithelial cells and intercellular tight junctions. Methods: IEC-6 cells were stimulated with LPS (1.0 μg/mL), with or without baicalin, for 24 h. The levels of the inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were determined using ELISA. Quantitative real-time PCR was used for determining the mRNA expression level of claudin-3, occludin, and ZO-1; Western blot and immunofluorescence analysis were used for analyzing the expression level and the distribution patterns of ZO-1 protein. Results: Pretreatment with baicalin (10.0 μg/mL) improved LPS-stimulated cell viability and repressed IL-6 and TNF-α levels. In addition, pretreatment with baicalin up-regulated mRNA and protein expression levels of ZO-1 and kept the protein intact in IEC-6 cells injured with LPS. Conclusion: Baicalin has the capacity to protect IEC-6 cells and the intercellular tight junctions from LPS-induced injury. The mechanisms may be associated with inhibiting the production of inflammatory cytokines, and up-regulating the mRNA and protein expression of ZO-1.

scholarly journals The Protective Effect of Dapsone Against Ethanol, Stress, and Indomethacin-Induced Gastric Erosion in Rats

2021 ◽  
Author(s):  
Mohammad Sheibani ◽  
Sadaf Nezamoleslami ◽  
Nastaran Rahimi ◽  
Ata Abbasi ◽  
Ahmad Reza Dehpour
Keyword(s):  
Inflammatory Cytokines ◽  
Experimental Models ◽  
Gastric Damage ◽  
Male Rats ◽  
Ethanol Stress ◽  
Control Group ◽  
Gastric Erosion ◽  
Protective Effects ◽  
Gastric Erosions ◽  
Anti Inflammatory

Several factors contribute to the development of gastric erosions, including corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, and stress. These factors can cause or worsen gastrointestinal ulcers by activating inflammatory pathways or by altering gastric mucosal blood flow. Dapsone is an antimicrobial compound with anti-inflammatory properties. The aim of this study was to evaluate the protective effects of dapsone against gastric erosions induced by alcohol, stress, or indomethacin. Gastric damage was induced in male rats in three different experimental models: ethanol (5 ml/kg, p.o.)-, water-immersion stress-, and indomethacin (30 mg/kg, p.o.)- induced ulcer. Rats in each of these three experimental models were divided into five groups: Normal group, 2. Control group (gastric damage+vehicle), 3. Gastric damage+dapsone 1 mg/kg, 4. Gastric damage+dapsone 3 mg/kg, 5. Gastric damage+dapsone 10 mg/kg. In this study, the J- score ulcer index and histopathological assessment were performed. In addition, inflammatory cytokines levels, NF-κB expression, and MPO activity were determined. Dapsone reduced the tissue injuries and erosion area in all three experimental groups compared to the control group. In addition, serum levels of inflammatory cytokines, TNF-alpha, and IL-1β were reduced in the dapsone treatment groups. The expression of NF-κB and tissue concentration of myeloperoxidase (a marker of neutrophil activation) was also reduced in rats given dapsone. To conclude, dapsone exhibits significant protective effects against the development of experimental gastric erosions in rats, and these effects seem to be related to its anti-inflammatory and antioxidant properties.

scholarly journals Irbesartan ameliorate inflammatory responses, and apoptosis induced by myocardial ischemia/reperfusion in male rats

2019 ◽  
Vol 7 (2) ◽  
pp. 138-150
Author(s):  
Najah R. Hadi ◽  
Fadhil G. Al-Amran
Keyword(s):  
Myocardial Ischemia ◽  
Troponin I ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Male Rats ◽  
Control Group ◽  
Inflammatory Reactions ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia–reperfusion (I-R) represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. This study was undertaken to investigate the potential role of Irbesartan in amelioration of myocardial I/R injury induced by ligation of coronary artery (LAD) in a rat model. We are pretreated the animals with Irbesartan 3mg/kg i.p. 30 minutes before ligation of LAD. At the end of experiment (2 h of reperfusion), blood samples were collected from the heart for measurement of plasma level of cardiac troponin I (cTn-I). Compared with the sham group, levels of myocardial TNF-α, IL-1β, IL-6, MCP-1, MIP-1 alpha, and plasma cTn-I were increased (P<0.05). Histologically, all rats in control group showed significant cardiac injury after I-R. Furthermore, rats in control group showed significant apoptosis. Irbesartan significantly counteract the increased in myocardium level of TNF-α, IL-1B, IL-6, MCP-1, MIP-1 alpha, plasma cTn-I and apoptotosis (P<0.05). Histological analysis revealed that Irbesartan markedly reduced the severity of heart injury in the rats underwent LAD ligation procedure. We concluded that Irbesartan may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions and apoptosis which induced by I/R injury.

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