Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition

2021 ◽  
Vol 219 ◽  
pp. 113457
Author(s):  
Amany M. Ghanim ◽  
Samar Rezq ◽  
Tarek S. Ibrahim ◽  
Damian G. Romero ◽  
Hend Kothayer
2018 ◽  
Vol 88 (5-6) ◽  
pp. 309-318
Author(s):  
Hae Seong Song ◽  
Jung-Eun Kwon ◽  
Hyun Jin Baek ◽  
Chang Won Kim ◽  
Hyelin Jeon ◽  
...  

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.


Marine Drugs ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 1
Author(s):  
Peeraporn Varinthra ◽  
Shun-Ping Huang ◽  
Supin Chompoopong ◽  
Zhi-Hong Wen ◽  
Ingrid Y. Liu

Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.


2021 ◽  
pp. 153537022110124
Author(s):  
Burak Yazgan ◽  
Filiz Avcı ◽  
Gülsün Memi ◽  
Ebru Tastekin

Chronic kidney disease is a major global public health problem. The peptide hormones adropin and spexin modulate many physiological functions such as energy balance and glucose, lipid and protein metabolism. However, it is unclear whether these peptides may exert effects on renal damage, tissue remodeling, and inflammatory conditions. In view of the limited information, we aimed to investigate the effect of adropin and spexin on matrix metalloproteinase and inflammatory response genes a rat model of adenine-induced chronic kidney failure. Chronic kidney failure was induced in rats by administering adenine hemisulfate. Renal function was determined in an autoanalyzer. Histopathological modifications were assessed by H&E staining. mRNA expression levels of ALOX 15, COX 1, COX 2, IL-1β, IL-10, IL-17A, IL-18 IL-21, IL-33, KIM-1, MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, NGAL, TGFβ1, TIMP-1, and TNFα in kidney tissue were measured by qPCR. Our results showed an increase of 24-h urine volume, serum creatinine, BUN, and urine protein levels in group with adenine-induced CKF. Adropin and spexin treatments decreased urine protein and 24-h urine volume. Renal damage, TIMP-1, IL-33, and MMP-2 increased after CKF induction, while COX 1, MMP-9, and MMP-13 levels were significantly reduced. Furthermore, KIM-1, TIMP-1, IL-33, and MMP-2 were downregulated by spexin treatment. Renal damage, NGAL, TIMP-1 IL-17A, IL-33, MMP-2, and MMP-3 decreased after adropin treatment, while MMP-13 levels were upregulated. Treatment with adropin+spexin decreased KIM-1, NGAL, TIMP-1, IL-1β, IL-17A, IL-18, IL-33, ALOX 15, COX 1, COX 2, TGFβ1, TNFα, MMP-2, MMP-3, and MMP-7, but increased MMP-13 levels. Our findings revealed that inflammatory response and MMP genes were modulated by adropin and spexin. These peptides may have protective effects on inflammation and chronic kidney damage progression.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Xin Cui ◽  
Hao Yan ◽  
Tong-Wen Ou ◽  
Chun-Song Jia ◽  
Qi Wang ◽  
...  

Prostate cancer is a common cancer in men. Genetic variations in inflammatory response genes can potentially influence the risk of prostate cancer. We aimed to examine the association betweenPPARGPro12Ala,NFKB1-94 ins/del,NFKBIA-826C/T,COX-1(50C>T), andCOX-2(-1195G>A) polymorphisms on prostate cancer risk. The genotypes of the polymorphisms were ascertained in 543 prostate cancer patients and 753 controls through PCR-RFLP and the risk association was evaluated statistically using logistic regression analysis. TheNFKB1-94 polymorphism was shown to decrease prostate cancer risk in both heterozygous and homozygous comparison models (odds ratios of 0.74 (95% CI = 0.58–0.96) (P=0.02) and 0.57 (95% CI = 0.42–0.78) (P<0.01), resp.). An opposite finding was observed forCOX-2(-1195) polymorphism (odds ratios of 1.58 (95% CI = 1.15–2.18) (P<0.01) for heterozygous comparison model and 2.08 (95% CI = 1.48–2.92) (P<0.01) for homozygous comparison model). No association was observed for other polymorphisms. In conclusion,NFKB1-94 ins/del andCOX-2(-1195G>A) polymorphisms may be, respectively, associated with decreased and increased prostate cancer risk in the Chinese population.


2018 ◽  
Vol 73 (7-8) ◽  
pp. 273-279 ◽  
Author(s):  
Chang-Suk Kong ◽  
Jung Im Lee ◽  
Fatih Karadeniz ◽  
Hojun Kim ◽  
Youngwan Seo

Abstract The Arctic flora hosts a limited number of species due to its extreme environmental conditions which also yield novel and unique secondary metabolites from withstanding plants. Considering a lack of research on bioactivity potential of Arctic flora, Ranunculus hyperboreus, an Arctic plant, was studied for its anti-inflammatory potential as a part of ongoing research on discovering novel natural bioactive products. Solvent-based fractions (H2O, n-BuOH, 85% aq. MeOH, n-hexane) from R. hyperboreus extract were observed to decrease the elevated nitrate amount during the inflammatory response of lipopolysaccharide-induced mouse macrophage RAW264.7 cells. To some extent, treatment with fractions was able to regulate the expression and protein levels of inflammation-related enzymes, iNOS and COX-2, and pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6. The most active fractions, H2O and 85% aq. MeOH, were suggested to exert their effect through suppressed activation of MAPK pathways, especially JNK. Based on the studies of same species, phenolic glycosides were suggested to be the main active ingredients. To our knowledge, this is the first report of any bioactivity of R. hyperboreus which could be a valuable source of natural bioactive agents against inflammation.


2013 ◽  
Vol 83 (6) ◽  
pp. 1087-1098 ◽  
Author(s):  
Punithavathi V. Ranganathan ◽  
Calpurnia Jayakumar ◽  
Riyaz Mohamed ◽  
Zheng Dong ◽  
Ganesan Ramesh

2010 ◽  
Vol 49 (2) ◽  
pp. 304-311 ◽  
Author(s):  
Qin Shao ◽  
Ling-Hong Shen ◽  
Liu-Hua Hu ◽  
Jun Pu ◽  
Mei-Yan Qi ◽  
...  

2015 ◽  
Vol 33 (11) ◽  
pp. 1724-1731 ◽  
Author(s):  
Bart van Dijk ◽  
Esther Potier ◽  
Maarten van DIjk ◽  
Marloes Langelaan ◽  
Nicole Papen‐Botterhuis ◽  
...  

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