更新于：2024-11-01

LTB4R x COX-2

更新于：2024-11-01

基本信息

关联

项与 LTB4R x COX-2 相关的药物

RP-66364

靶点

COX-2 x LTB4R

作用机制

COX-2抑制剂 [+1]

在研机构-

原研机构

Rhone-Poulenc SA

在研适应症-

非在研适应症

炎症

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

LY-210073

靶点

COX-2 x LTB4R

作用机制

COX-2抑制剂 [+1]

在研机构-

原研机构

Eli Lilly & Co.

在研适应症-

非在研适应症

关节炎 [+2]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

LY-264086

靶点

COX-2 x LTB4R

作用机制

COX-2抑制剂 [+1]

在研机构-

原研机构

Eli Lilly & Co.

在研适应症-

非在研适应症

哮喘 [+2]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 LTB4R x COX-2 相关的临床结果

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100 项与 LTB4R x COX-2 相关的转化医学

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0 项与 LTB4R x COX-2 相关的专利（医药）

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项与 LTB4R x COX-2 相关的文献（医药）

2024-08-01·Prostaglandins & Other Lipid Mediators

Zerumbone exhibits anti-inflammatory effects by suppressing eicosanoid signaling: Evidence from LPS-induced peripheral blood leukocytes

Article

作者: Nair, Devika ; Acharya, Pooja ; Zarei, Mehrdad ; Uppin, Vinayak ; Talahalli, Ramaprasad ; Kempaiah, Bettadaiah

Zerumbone, a sesquiterpene isolated from Zingiber zerumbet, has many bioactivities, exhibiting anti-inflammatory properties. However, the effect of zerumbone on the eicosanoid signaling pathway has yet to be examined. Here, we deciphered the anti-eicosanoid properties of zerumbone isolated from ginger. The molecular interaction between zerumbone and eicosanoid metabolizing enzymes (COX-2, 5-LOX, FLAP, and LTA₄-hydrolase) and receptors (EP-4, BLT-1, and ICAM-1) along with NOS-2 were assessed using Auto-Dock 4.2 and visualized by chimera and Liggplot⁺ software. Further, the leukocytes were treated with zerumbone (1-20 μM) and activated using bacterial lipopolysaccharide (LPS-10 nM). The oxidative stress (OS) markers, antioxidant enzymes, and the eicosanoid pathway mediators such as COX-2, 5-LOX, BLT-1, and EP-4 were assessed. The molecular interaction of zerumbone with eicosanoids showed a higher binding affinity with mPGES-1, followed by NOS-2, FLAP, COX-2, LTA-4-hydrolase, and BLT-1. The concentration of 5 μM zerumbone effectively prevented the generation of reactive oxygen species (ROS) and nitric oxide (NO). Likewise, zerumbone significantly (p<0.05) inhibited COX-2, 5-LOX, NOS-2, EP-4, BLT-1, and ICAM-1 expression in LPS-induced peripheral blood leukocytes from rats. Further, the zerumbone treatment on the human PBMCs activated with LPS showed significant inhibition in the expression of ICAM1, COX-2, 5-LOX, and the generation of inflammatory cytokines compared to the control. Overall, the data presented infers that zerumbone positively modulates critical enzymes and receptors of eicosanoids in leukocytes activated with lipopolysaccharides. Thus, zerumbone can be a potential anti-eicosanoid drug in managing inflammation.

2023-04-04·International journal of molecular sciences

Dysregulation of Resolvin E1 Metabolism and Signaling in a Light-Damage Model of Age-Related Macular Degeneration.

Article

作者: Leuti, Alessandro ; Maccarrone, Mauro ; Maccarone, Rita ; Tisi, Annamaria ; Carozza, Giulia

Resolvin E1 (RvE1) is an eicosapentaenoic acid-derived lipid mediator involved in the resolution of inflammation. Here, we investigated whether RvE1 alterations may occur in an animal model of age-related macular degeneration (AMD). To this end, Sprague Dawley albino rats underwent light damage (LD), and retinas and serum were analyzed immediately or seven days after treatment. Western blot of retinas showed that the RvE1 receptor ChemR23 and the RvE1 metabolic enzymes 5-LOX and COX-2 were unchanged immediately after LD, but they were significantly up-regulated seven days later. Instead, the RvE1 receptor BLT1 was not modulated by LD, and neither was the RvE1 degradative enzyme 15-PGDH. Moreover, ChemR23, 5-LOX, COX-2 and BLT1 were found to be more expressed in the inner retina under all experimental conditions, as observed through ImageJ plot profile analysis. Of note, amacrine cells highly expressed BLT1, while ChemR23 was highly expressed in the activated microglia of the outer retina. ELISA assays also showed that LD rats displayed significantly higher circulating levels and reduced retinal levels of RvE1 compared to controls. Altogether, our data indicate that RvE1 metabolism and signaling are modulated in the LD model, suggesting a potentially relevant role of this pathway in AMD.

2021-01-01·Life Sciences3区 · 医学

Ginger and turmeric lipid-solubles attenuate heated oil-induced hepatic inflammation via the downregulation of NF-kB in rats

3区 · 医学

Article

作者: Zarei, Mehrdad ; Talahalli, Ramaprasad Ravichandra ; Acharya, Pooja

PURPOSEReusing deep-fried vegetable oils multiple times is a common practice to save costs, and their chronic consumption may cause hepatic dysfunction. In this investigation, we assessed the modulatory effects of ginger and turmeric lipid-solubles that may migrate to oils during heating on the hepatic inflammatory response in rats.METHODSMale Wistar rats were fed with; 1) control {native canola (N-CNO) or native sunflower (N-SFO)} oil, 2) heated (heated canola {(H-CNO) or heated sunflower (H-SFO)} oil, and 3) heated oil with ginger or turmeric {heated canola with ginger (H-CNO + GI) or heated canola oil with turmeric (H-CNO + TU), heated sunflower oil with ginger (H-SFO + GI) or heated sunflower oil with turmeric (H-SFO + TU)} for 120 days. Hepatic inflammatory response comprising eicosanoids, cytokines, and NF-kB were assessed.RESULTSCompared to respective controls, feeding heated oils significantly (p < 0.05); 1) increased eicosanoids (PGE₂, LTB₄, and LTC₄) and cytokines (TNF-α, MCP-1, IL-1β, and IL-6), 2) increased nuclear translocation of NF-kB in the liver, and 3) increased the hepatic expression of 5-LOX, COX-2, BLT-1, and EP-4. However, feeding oils heated with ginger or turmeric positively countered the changes induced by consumption of heated oils.CONCLUSIONSConsumption of repeatedly heated oil may cause hepatic dysfunction by inducing inflammatory stress through NF-kB upregulation. Lipid-solubles from ginger and turmeric that may migrate to oil during heating prevent the hepatic inflammatory response triggered by heated oils in rats.