Evaluation of the Effect of α-L-Guluronic Acid (G2013) on COX-1, COX-2 Activity and Gene Expression for Introducing this Drug as a Novel NSAID with Immunomodulatory Property

Mirshafiey, Abbas; Mortazavi-Jahromi, Seyed Shahabeddin; Taeb, Mahsa; Cuzzocrea, Salvatore; Esposito, Emanuela

doi:10.2174/1872213x12666180607121809

Cited by 14 publications

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“…Considering the ineffectiveness and wide range of side effects of common treatments, we expect to see a shift away from the NSAIDs with the worst side effect profiles toward those with the lowest side effect profiles. G2013 with immunomodulatory property based on its effects on cyclooxygenase 1 and 2 gene expression and activity under in‐vitro examination has been identified as a new NSAIDs (Mirshafiey et al, 2018). Safety, tolerability, anti‐inflammatory, and immunosuppressive effects of G2013 have been shown on animal models with no observed side effects and toxicity to the kidneys, gastrointestinal, and other tissues (Afraei et al, 2015; Arjomand Fard et al, 2017; Nazeri et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…The present investigation is motivated by two main goals: first to accomplish the study that previously has been done on the effect of G2013 on gene expression of cyclooxygenases enzymes in an in‐vitro model of healthy volunteers PBMCs (Mirshafiey, Mortazavi‐Jahromi, Taeb, Cuzzocrea, & Esposito, 2018) and then to take a step in introducing a new NSAIDs with fewer side effects in the treatment of AS patients in comparison to the conventional NSAIDs. Therefore, this investigation was run using the part of AS patients in phase I/II clinical trial for evaluating the effect of G2013 on gene expression of COX‐1 and COX‐2 enzymes in these patients.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the oral administration of α‐l‐guluronic acid on COX‐1 and COX‐2 gene expression profile in ankylosing spondylitis patients

Sadoughi

Mansouri

Nazeri

et al. 2020

Drug Development Research

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Ankylosing spondylitis (AS) is a chronic autoimmune arthritis disease with a genetic background, affecting the skeletal axis, sacroiliac, and peripheral joints. Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the first‐line treatment for AS to alleviate the inflammation and pain. Despite the beneficial effect, their use is accompanied by a wide variety of possible side effects in the gastrointestinal and kidneys. The α‐l‐guluronic acid (G2013) is a new nonsteroidal anti‐inflammatory patented (PCT/EP2017/067920) drug, which has shown its anti‐inflammatory properties in the previous investigations. The present study revealed the oral administration effect of G2013 on COX‐1 and COX‐2 gene expression in AS patients. The blood samples of twelve 18–45 years old patients suffering AS and BASDAI >4, and BASFI >4, before and after 12 weeks of treatment with G2013 and 12 blood samples of healthy volunteers were collected and the effect of G2013 on the gene expression of COX‐1 and COX‐2 enzymes were assessed by Real‐Time PCR. The results indicate that G2013 is able to reduce the gene expression level of COX‐1 and COX‐2 enzymes in treated AS patients compared to healthy control. Statistically significant differences were not observed between the treatment and the healthy control groups. According to the findings, G2013 might be categorized and introduced as a novel NSAID for the treatment of AS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of the oral administration of α‐l‐guluronic acid on COX‐1 and COX‐2 gene expression profile in ankylosing spondylitis patients

Sadoughi

Mansouri

Nazeri

et al. 2020

Drug Development Research

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“…Aspirin is a Nonsteroidal Anti-Inflammatory Drug (NSAID) used for the treatment of pain, inflammation, fever and arthritis [ 1 - 5 ]. It is also an antiplatelet agent recommended for use in elderly patients in order to prevent various heart diseases and stroke due to blood clotting [ 2 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Aspirin has been found to be efficacious in the treatment of different cancers [ 7 - 11 ]. NSAIDs generally inhibit Cyclooxygenase (COX) enzyme; aspirin specifically and irreversibly inhibits Cyclooxygenase 1 (COX-1) enzyme, unlike other NSAIDs (ibuprofen, indomethacin and naproxen), which reversibly inhibit both COX 1 and COX 2 [ 5 ]. However, the use of aspirin and other NSAIDs generally is limited by severe gastric irritation, and aspirin has been penciled down as a major gastric irritant [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory and Gastroprotective Properties of Aspirin - Entrapped Solid Lipid Microparticles

Chime

Akpa

Ugwuanyi

et al. 2020

IAD

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Background: Aspirin is a nonsteroidal anti-inflammatory drug that is very effective in the treatment of inflammation and other health conditions, however, it causes gastric irritation. Recently, researchers have developed patents (US9757529, 2019) of inhalable aspirin for rapid absorption and circumvention of gastric irritation. Objective: The aim of this work was to formulate aspirin-loaded lipid based formulation in order to enhance oral bioavailability and inhibit gastric irritation. Methods: This solid lipid microparticles loaded with aspirin (SLM) was formulated by a modified cold homogenization-solvent evaporation method. In vitro studies such as in vitro drug release, particle size, Encapsulation Efficiency (EE), micromeritic properties and loading capacity were carried out. Pharmacodynamics studies such as anti-inflammatory and ulcerative properties of the SLM were also carried out in Wistar rats. Results: The results showed that aspirin entrapped SLM exhibited the highest EE of 72% and particle size range of 7.60 + 0.141µm to 20.25 + 0.070µm. Formulations had about 55% drug release at 6h in simulated intestinal fluid pH 6.8. The formulations had good flowability that could facilitate filling into hard gelatin capsule shells. The SLM exhibited 100% gastroprotection against aspirin-induced ulcers (p < 0.05). The percentage of anti-inflammatory activities also showed that aspirin-entrapped SLM had 78% oedema inhibition at 7h, while the reference had 68% inhibition at 7h. Conclusion: Aspirin-entrapped SLM showed good sustained-release properties, enhanced antiinflammatory properties and total gastric protection from aspirin-induced ulcers and could be used as once-daily oral aspirin.

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“…There are mainly two important isoforms of the COX enzyme. The first one is the COX-1 isoform, which represents the constitute isoform that is distributed normally in certain tissues of the body such as the kidney and the gastrointestinal tract (GIT), this isoform carries out physiological functions such as gastric protection and maintenance of renal homeostasis [4,5,6]. The other isoform is the COX-2, which is the inducible isoform that is only expressed during exposure to certain substances such as cytokines, which are produced during injury.…”

Section: Introductionmentioning

confidence: 99%

Novel Series of Methyl 3-(Substituted Benzoyl)-7-Substituted-2-Phenylindolizine-1-Carboxylates as Promising Anti-Inflammatory Agents: Molecular Modeling Studies

et al. 2019

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The cyclooxygenase-2 (COX-2) enzyme is considered to be an important target for developing novel anti-inflammatory agents. Selective COX-2 inhibitors offer the advantage of lower adverse effects that are commonly associated with non-selective COX inhibitors. In this work, a novel series of methyl 3-(substituted benzoyl)-7-substituted-2-phenylindolizine-1-carboxylates was synthesized and evaluated for COX-2 inhibitory activity. Compound 4e was identified as the most active compound of the series with an IC50 of 6.71 μM, which is comparable to the IC50 of indomethacin, a marketed non-steroidal anti-inflammatory drug (NSAID). Molecular modeling and crystallographic studies were conducted to further characterize the compounds and gain better understanding of the binding interactions between the compounds and the residues at the active site of the COX-2 enzyme. The pharmacokinetic properties and potential toxic effects were predicted for all the synthesized compounds, which indicated good drug-like properties. Thus, these synthesized compounds can be considered as potential lead compounds for developing effective anti-inflammatory therapeutic agents.

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Evaluation of the Effect of α-L-Guluronic Acid (G2013) on COX-1, COX-2 Activity and Gene Expression for Introducing this Drug as a Novel NSAID with Immunomodulatory Property

Cited by 14 publications

References 0 publications

Evaluation of the oral administration of α‐l‐guluronic acid on COX‐1 and COX‐2 gene expression profile in ankylosing spondylitis patients

Evaluation of the oral administration of α‐l‐guluronic acid on COX‐1 and COX‐2 gene expression profile in ankylosing spondylitis patients

Anti-Inflammatory and Gastroprotective Properties of Aspirin - Entrapped Solid Lipid Microparticles

Novel Series of Methyl 3-(Substituted Benzoyl)-7-Substituted-2-Phenylindolizine-1-Carboxylates as Promising Anti-Inflammatory Agents: Molecular Modeling Studies

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