Design of balanced COX inhibitors based on anti-inflammatory and/or COX-2 inhibitory ascidian metabolites

Zhang, Ju; Hong, Jongki; Kim, Eun La; Moon, Hyung Ryong; Chung, Hae Young; Kim, Suhkmann; Jung, Jee H.

doi:10.1016/j.ejmech.2019.07.016

Cited by 40 publications

(25 citation statements)

References 36 publications

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“…Enhanced expression of Cox-2 resulting in proinflammatory eicosanoids synthesis has been proposed as the main contributor of alcohol-induced liver injury. The ability of NSAIDs to exert their anti-inflammatory effects has been proposed via inhibiting the Cox-2 pathway to decrease prostanoid [23,27]. In this study, as the Cox-2 inhibitor, PR also could effectively suppress the Cox-2 and TNF-α expression in the chronic alcohol-induced liver injury rat model.…”

Section: Discussionmentioning

confidence: 84%

“…The inducible form of cyclooxygenase, Cox-2, has been regarded as a pro-inflammatory emergency enzyme, for it can induce production of prostanoids, participate in inflammatory diseases and carcinogenesis, and be characterized by recruitment of inflammatory cells and injury of tissue [23, 24]. Under the normal condition, Cox-2 is at a low expression level in the tissues of the liver.…”

Section: Discussionmentioning

confidence: 99%

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Puerarin Exerts the Hepatoprotection from Chronic Alcohol-Induced Liver Injury via Inhibiting the Cyclooxygenase-2 and the 5-Lipoxygenase Pathway in Rats

et al. 2020

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Background: Puerarin (PR) as one of the main ingredients of the root of the traditional herb Kudzu has been suggested to improve chronic alcohol-induced liver injury. We explore the specific mechanisms of PR on hepatocellular changes after administration of alcohol. Methods: Sprague-Dawley rats were treated with 55% alcohol for 12 weeks to induce a chronic alcoholic liver damage model. Then the rats in each group were administered by oral gavage with zileuton, celecoxib, and PR for 2 weeks, respectively. Results: In the PR group, the weight loss was markedly improved and the abnormal serum alanine aminotransferase and aspartate aminotransferase were significantly lowered after PR treatment when compared to the alcoholic liver injured model group. Pathological examination indicated that alcohol-induced hepatocellular injury was improved by the PR treatment. The 5-lipoxygenase (5-Lox) and cyclooxygenase-2 (Cox-2) at the protein level and the mRNA level were obviously downregulated accompanied with the PR treatment. Meanwhile, the peroxisome proliferator-activated receptor γ (PPAR-γ) at the protein and mRNA level was notably elevated and the tumor necrosis factor α at the protein and mRNA level was markedly decreased following the PR treatment. Conclusion: The possible cytoprotective mechanisms of PR may be involved inhibition of the Cox-2 pathway and the 5-Lox pathway to suppress inflammatory response and regulate the protective factor PPAR-γ expression.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Puerarin Exerts the Hepatoprotection from Chronic Alcohol-Induced Liver Injury via Inhibiting the Cyclooxygenase-2 and the 5-Lipoxygenase Pathway in Rats

et al. 2020

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“…The inhibition of NO production by compound 4d may be correlated with its suppressive effect on LPS-induced iNOS. Thus, the inhibitory effects of compound 4d on LPS-mediated expressions of iNOS were analyzed by western blotting [30,31]. Nitric oxide synthase (iNOS) protein levels were analyzed after exposure to LPS for 24 h in the presence or absence of compound 4d (5, 10, 20 μM).…”

Section: Resultsmentioning

confidence: 99%

“…The RAW264.7 cell line was purchased from Cell Bank of Chinese Academy of Sciences (Shanghai, China). The cells were cultured in DMEM (Hyclone, Logan, UT, USA), supplemented with 10% fetal bovine serum (Biological industries) and antibiotics (100 U/mL penicillin A and 100 U/mL streptomycin), and maintained at 37 °C in a humidified atmosphere containing 5% CO 2 [31].…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis and Investigation of the Potential Anti-Inflammatory Activity of 7-O-Amide Hesperetin Derivatives

et al. 2019

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To develop new anti-inflammatory agents, a series of 7-O-amide hesperetin derivatives was designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. All compounds showed inhibitory effect on LPS-induced NO production. Among them, 7-O-(2-(Propylamino)-2-oxoethyl)hesperetin (4d) and 7-O-(2-(Cyclopentylamino)-2-oxoethyl)hesperetin (4k) with hydrophobic side chains exhibited the most potent NO inhibitory activity (IC50 = 19.32 and 16.63 μM, respectively), showing stronger inhibitory effect on the production of pro- inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) than indomethacin and celecoxib at 10 μM. The structure-activity relationships (SARs) suggested that the 7-O-amide unit was buried in a medium-sized hydrophobic cavity of the bound receptor. Furthermore, compound 4d could also significantly suppress the expression of inducible nitric oxide synthase enzymes (iNOS) and cyclooxygenase-2 (COX-2), through the nuclear factor-kappa B (NF-κB) signaling pathway.

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“…A lot of work has been conducted in designing new COX inhibitors [ 68 ]. QSAR modeling is the most used and powerful approach that allows correlating chemical modifications in a molecule with its biological activity [ 69 ].…”

Section: Nonsteroidal Anti-inflammatory Drugs (Nsaids)mentioning

confidence: 99%

The Role of Organic Small Molecules in Pain Management

Cuesta

Meneses

2021

Molecules

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In this review, a timeline starting at the willow bark and ending in the latest discoveries of analgesic and anti-inflammatory drugs will be discussed. Furthermore, the chemical features of the different small organic molecules that have been used in pain management will be studied. Then, the mechanism of different types of pain will be assessed, including neuropathic pain, inflammatory pain, and the relationship found between oxidative stress and pain. This will include obtaining insights into the cyclooxygenase action mechanism of nonsteroidal anti-inflammatory drugs (NSAID) such as ibuprofen and etoricoxib and the structural difference between the two cyclooxygenase isoforms leading to a selective inhibition, the action mechanism of pregabalin and its use in chronic neuropathic pain, new theories and studies on the analgesic action mechanism of paracetamol and how changes in its structure can lead to better characteristics of this drug, and cannabinoid action mechanism in managing pain through a cannabinoid receptor mechanism. Finally, an overview of the different approaches science is taking to develop more efficient molecules for pain treatment will be presented.

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Design of balanced COX inhibitors based on anti-inflammatory and/or COX-2 inhibitory ascidian metabolites

Cited by 40 publications

References 36 publications

Puerarin Exerts the Hepatoprotection from Chronic Alcohol-Induced Liver Injury via Inhibiting the Cyclooxygenase-2 and the 5-Lipoxygenase Pathway in Rats

Puerarin Exerts the Hepatoprotection from Chronic Alcohol-Induced Liver Injury via Inhibiting the Cyclooxygenase-2 and the 5-Lipoxygenase Pathway in Rats

Design, Synthesis and Investigation of the Potential Anti-Inflammatory Activity of 7-O-Amide Hesperetin Derivatives

The Role of Organic Small Molecules in Pain Management

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