Down regulation of COX-2, IL-1β, TNF-α in cynoviocyte by essential oil of Fraxinus excelsior

2018 ◽  
Vol 9 (03) ◽  
pp. 20192-20203
Author(s):  
Dr Maghsoudi, Hossein ◽  
Samaneh Haj-allahyari
Keyword(s):  
Liver Toxicity ◽  
Rna Extraction ◽  
Current Treatment ◽  
Fraxinus Excelsior ◽  
Peptic Ulcers ◽  
Down Regulation ◽  
Bovine Articular Cartilage ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Cox 2

Osteoarthritis (arthritis) is biomechanical, biochemical and cellular phenomenon, and is not known as a degenerative disease. Arthritis is one of the common chronic diseases and the most important reason of physical disability in the world. According to its side effect such as peptic ulcers, gastrointestinal bleeding, liver toxicity and renal complications dueofprescribing current treatment contain corticosteroid and non-steroidal, we decided to evaluate possible effect of anti-inflammatory Esential oil of Fraxinus excelsior (EOFE) on biomarkers involved in disease. EOFE were prepared of genetic resources center. Bovine  articular cartilage derived from the metacarpophalangeal joints of 14–18-month-old animals (without any sign of inflammation and bleeding) sent to laboratory in sterile bags at 4ºC. Cells were cultured in appropriate condition and counted by hemocytometer, viability assessed by trypan blue. After LPS treatment, cytokine levels were assayed. Cells cultures again and were kept in 37C, 90% humidity in CO2 incubator and after RNA extraction, RT-PCR and PCR done. Also by Real-time PCR, gene expression was evaluated. E.E.F.E level cause down regulation of COX-2, IL-1β, TNF-α in LPS-stimulated cells.

Venlafaxine demonstrated anti-arthritic activity possibly through down regulation of TNF-α, IL-6, IL-1β, and COX-2

2021 ◽  
Author(s):  
Mater Hussen Mahnashi ◽  
Zeeshan Jabbar ◽  
Alamgeer ◽  
Hafiz Muhammad Irfan ◽  
Mulazim Hussain Asim ◽  
...  
Keyword(s):  
Down Regulation ◽  
Tnf Α ◽  
Cox 2

scholarly journals Down-regulation of protease-activated receptor 2 ameliorated osteoarthritis in rats through regulation of MAPK/NF-κB signaling pathway in vivo and in vitro

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Shichang Yan ◽  
Huimin Ding ◽  
Junyang Peng ◽  
Xinqiang Wang ◽  
Chenglong Pang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pathological Condition ◽  
Inflammatory Factors ◽  
Potential Candidate ◽  
Down Regulation ◽  
Tnf Α ◽  
Cox 2 ◽  
Protease Activated Receptor 2

Abstract Recently, protease-activated receptor 2 (PAR2) has been proved to be involved in the inflammatory response including osteoarthritis (OA). In the present study, we found that PAR2 antagonist could remarkably improve the pathological condition of OA rats in vivo. In addition, we also found that PAR2 antagonist could suppress the production of inflammatory factors (TNF-α and Cox-2), decrease the levels of MMP-1 and MMP-13, and restrain the levels of P62 proteins and aggravate the expression of LC3-II both in vivo and in vitro. Besides, in vitro, PAR2 antagonist could increase the proliferation and colony formation of chondrocytes induced with IL-1β. Moreover, PAR2 antagonist could decrease the expression of expressions of p-p38, p-IκBα and p-NF-κB in vitro. However, PAR2 agonist exhibited the opposite effects. Furthermore, SB203580, a p38 MAPK inhibitor, could remarkably promote the proliferation of chondrocytes induced with IL-1β, could alleviate the production of TNF-α and Cox-2, could down-regulate the protein expressions of MMP-1 and MMP-13, and could decrease the expression of P62 and increase the expressions of LC3-II of chondrocytes induced with IL-1β. Importantly, SB203580 could reverse the effects of PAR2 agonist on the functions of chondrocytes induced with IL-1β. Taken together, the present data suggest that down-regulation of PAR2 can ameliorate OA through inducing autophagy via regulation of MAPK/NF-κB signaling pathway in vivo and in vitro, and PAR2 can be considered as a potential candidate to treat OA.

scholarly journals Synthesis, Molecular Docking, Biological Potentials and Structure Activity Relationship of New Quinazoline and Quinazoline-4-one Derivatives

2021 ◽  
Vol 33 (2) ◽  
pp. 423-438
Author(s):  
Rita M. Borik ◽  
Mohammed A. Hussein
Keyword(s):  
Molecular Docking ◽  
Active Sites ◽  
Liver Toxicity ◽  
Albino Rats ◽  
Oxidative Stress Biomarkers ◽  
Tnf Α ◽  
Dpph Method ◽  
Ic50 Values ◽  
Cox 2 ◽  
Anti Inflammatory

In this work, a new derivative of ethyl 5-chloro-2-(3-(4-hydroxyphenyl)propanamido)benzoate (1) was synthesized by reacting the amino group of 3-(4-hydroxyphenyl)propanoic acid (0.01 mol) and methyl 2-amino-5-chlorobenzoate in presence of PCl3. Cyclcondensation of 1 with hydrazine hydrate afforded the corresponding 2-(4-hydroxyphenethyl)-3-amino-6-chloroquinazolin-4(3H)-one (2). Also, new Schiff base 3 was prepared via reaction of 2-(4-hydroxyphenethyl)-3-amino-6-chloroquinazolin- 4(3H)-one (2) with 4-hydroxy-3-methoxybenzaldehyde. The synthesized compounds were characterized by elemental analysis, IR, 1H NMR and mass spectral data. Also, the median lethal doses (LD50s) of compounds 1-3 in rats were 1125, 835 and 1785 mg/kg b.w., respectively. IC50 values of compounds (1, 3) as measured by DPPH• method was 136.47 and 73.54 μg/mL, respectively. IC50 values of compounds (1-3) as measured by ABTS•+ radical method was 0.8, 0.92 and 0.08 mg/mL, respectively. Antiulcerogenic activity at dose 1/20 LD50 in albino rats was 47.94, 24.60 and 56.45%, respectively. However, the anti-inflammatory effect at dose 1/20 LD50 of compounds (1-3) induced edema model after 120 min were 74.19, 69.93 and 59.03%, respectively. The synthesized compounds also possess hepatocytes and gastric mucosa protective activity against ibuprofen induced ulceration and LPS-induced liver toxicity, respectively in rats via normalization of oxidative stress biomarkers and inflammatory mediators (Na+/K+-ATPase, ALT, AST, LDH, TNF-α, NO, TBARS, GPx, CAT and SOD). Also, TNF-α, NO, PGE2 and COX-2 were inhibited in peritoneal macrophage cells at a concentration of 100 μg/L. Molecular docking suggested that the most active compounds 1 and 2 can be positioned within the active sites of COX-2 at Arg121 & Tyr356 similarly to ibuprofen (Arg-120, Glu-524 and Tyr-355). The compound 3–COX-2 complex generated by docking, revealed intricate interactions with a COX-2 channel, including hydrogen bonds with key residues Arg121 and phe519. These findings suggest that compounds 1-3 exhibited good antioxidant, antiulcer, anti-inflammatory activity and safe on liver enzymes in rats.

Sorghum Fermented by Aspergillus oryzae NK Enhances Inhibition of Vascular Inflammation in TNF-α-stimulated Human Aortic Smooth Muscle Cells

2018 ◽  
Vol 88 (5-6) ◽  
pp. 309-318
Author(s):  
Hae Seong Song ◽  
Jung-Eun Kwon ◽  
Hyun Jin Baek ◽  
Chang Won Kim ◽  
Hyelin Jeon ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Response ◽  
Smooth Muscle Cells ◽  
Adhesion Molecule ◽  
Vascular Inflammation ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Tnf Α ◽  
Cox 2

Abstract. Sorghum bicolor L. Moench is widely grown all over the world for food and feed. The effects of sorghum extracts on general inflammation have been previously studied, but its anti-vascular inflammatory effects are unknown. Therefore, this study investigated the anti-vascular inflammation effects of sorghum extract (SBE) and fermented extract of sorghum (fSBE) on human aortic smooth muscle cells (HASMCs). After the cytotoxicity test of the sorghum extract, a series of experiments were conducted. The inhibition effects of SBE and fSBE on the inflammatory response and adhesion molecule expression were measured using treatment with tumor necrosis factor-α (TNF-α), a crucial promoter for the development of atherosclerotic lesions, on HASMCs. After TNF-α (10 ng/mL) treatment for 2 h, then SBE and fSBE (100 and 200 μg/mL) were applied for 12h. Western blotting analysis showed that the expression of vascular cell adhesion molecule-1 (VCAM-1) (2.4-fold) and cyclooxygenase-2 (COX-2) (6.7-fold) decreased, and heme oxygenase-1 (HO-1) (3.5-fold) increased compared to the TNF-α control when treated with 200 μg/mL fSBE (P<0.05). In addition, the fSBE significantly increased the expression of HO-1 and significantly decreased the expression of VCAM-1 and COX-2 compared to the TNF-α control in mRNA level (P<0.05). These reasons of results might be due to the increased concentrations of procyanidin B1 (about 6-fold) and C1 (about 30-fold) produced through fermentation with Aspergillus oryzae NK for 48 h, at 37 °C. Overall, the results demonstrated that fSBE enhanced the inhibition of the inflammatory response and adherent molecule expression in HASMCs.

Hepatoprotective Role of Berberine on Doxorubicin Induced Hepatotoxicity - Involvement of Cyp

2020 ◽  
Vol 21 (7) ◽  
pp. 541-547
Author(s):  
Bao Sun ◽  
Yue Yang ◽  
Mengzi He ◽  
Yanan Jin ◽  
Xiaoyu Cao ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Cardiac Tissue ◽  
Liver Toxicity ◽  
Elevated Serum ◽  
Similar Response ◽  
Wide Range ◽  
Cytokine Levels ◽  
Major Organ ◽  
Anti Oxidant

Background: The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs, although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue. Objective: The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion. Methodology: In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in DOX induced liver toxicity and its possible reversal by berberine was ascertained. Results: DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels. Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6, and 3A1 although showed a decline, but it did not revert the expression back to control levels. Conclusion: It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It possesses low to moderate cytochrome modulatory potentials.

The Effect of Antiretroviral Therapy on IL-6, IL-1β, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients

2020 ◽  
Vol 18 (5) ◽  
pp. 354-361
Author(s):  
Gülay Okay ◽  
Meliha Meric Koc ◽  
Eray Metin Guler ◽  
Ayşegül Yabaci ◽  
Abdürrahim Kocyigit ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Cell Count ◽  
Cd4 T Cell ◽  
Positive Correlation ◽  
Hiv Rna ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Cd4 T Cell Count

Background: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). Objectives: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. Methods: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. Results: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). Conclusions: Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

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.

Sign in / Sign up

Export Citation Format

Share Document