Ibuprofen-based advanced therapeutics: breaking the inflammatory link in cancer, neurodegeneration, and diseases.
TL;DR: Ibuprofen is a classical nonsteroidal anti-inflammatory drug (NSAID) highly prescribed to reduce acute pain and inflammation under an array of conditions, including rheumatoid arthritis, osteoarthritis, dysmenorrhea, and gout.
Abstract: Ibuprofen is a classical nonsteroidal anti-inflammatory drug (NSAID) highly prescribed to reduce acute pain and inflammation under an array of conditions, including rheumatoid arthritis, osteoarthritis, dysmenorrhea, and gout. Ibuprofen acts as a potential inhibitor for cyclooxygenase enzymes (COX-1 and COX-2). In the past few decades, research on this small molecule has led to identifying other possible therapeutic benefits. Anti-tumorigenic and neuroprotective functions of Ibuprofen are majorly recognized in recent literature and need further consideration. Additionally, several other roles of this anti-inflammatory molecule have been discovered and subjected to experimental assessment in various diseases. However, the major challenge faced by Ibuprofen and other drugs of similar classes is their side effects, and tendency to cause gastrointestinal injury, generate cardiovascular risks, modulate hepatic and acute kidney diseases. Future research should also be conducted to deduce new methods and approaches of suppressing the unwanted toxic changes mediated by these drugs and develop new therapeutic avenues so that these small molecules continue to serve the purposes. This article primarily aims to develop a comprehensive and better understanding of Ibuprofen, its pharmacological features, therapeutic benefits, and possible but less understood medicinal properties apart from major challenges in its future application.KEY POINTSIbuprofen, an NSAID, is a classical anti-inflammatory therapeutic agent.Pro-apoptotic roles of NSAIDs have been explored in detail in the past, holding the key in anti-cancer therapies.Excessive and continuous use of NSAIDs may have several side effects and multiple organ damage.Hyperactivated Inflammation initiates multifold detrimental changes in multiple pathological conditions.Targeting inflammatory pathways hold the key to several therapeutic strategies against many diseases, including cancer, microbial infections, multiple sclerosis, and many other brain diseases.
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TL;DR: In this article, a review of the emerging evidence enlightening the neuroprotective outcomes of PPAR agonists in in vivo and in vitro models experiencing Parkinson's disease is presented.
Abstract: One of the utmost frequently emerging neurodegenerative diseases, Parkinson’s disease (PD) must be comprehended through the forfeit of dopamine (DA)-generating nerve cells in the substantia nigra pars compacta (SN-PC). The etiology and pathogenesis underlying the emergence of PD is still obscure. However, expanding corroboration encourages the involvement of genetic and environmental factors in the etiology of PD. The destruction of numerous cellular components, namely oxidative stress, ubiquitin-proteasome system (UPS) dysfunction, autophagy-lysosome system dysfunction, neuroinflammation and programmed cell death, and mitochondrial dysfunction partake in the pathogenesis of PD. Present-day pharmacotherapy can alleviate the manifestations, but no therapy has been demonstrated to cease disease progression. Peroxisome proliferator-activated receptors (PPARs) are ligand-directed transcription factors pertaining to the class of nuclear hormone receptors (NHR), and are implicated in the modulation of mitochondrial operation, inflammation, wound healing, redox equilibrium, and metabolism of blood sugar and lipids. Numerous PPAR agonists have been recognized to safeguard nerve cells from oxidative destruction, inflammation, and programmed cell death in PD and other neurodegenerative diseases. Additionally, various investigations suggest that regular administration of PPAR-activating non-steroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, indomethacin), and leukotriene receptor antagonists (montelukast) were related to the de-escalated evolution of neurodegenerative diseases. The present review elucidates the emerging evidence enlightening the neuroprotective outcomes of PPAR agonists in in vivo and in vitro models experiencing PD. Existing articles up to the present were procured through PubMed, MEDLINE, etc., utilizing specific keywords spotlighted in this review. Furthermore, the authors aim to provide insight into the neuroprotective actions of PPAR agonists by outlining the pharmacological mechanism. As a conclusion, PPAR agonists exhibit neuroprotection through modulating the expression of a group of genes implicated in cellular survival pathways, and may be a propitious target in the therapy of incapacitating neurodegenerative diseases like PD.
9 citations
TL;DR: In this article , a series of novel 1-aryl-3-(4-methylsulfonylphenyl) pyrazole derivatives were synthesized, characterized by several spectroscopic techniques, and investigated as potential anti-inflammatory and anticancer agents.
2 citations
TL;DR: In this paper , the authors focused on the enzymatic esterification of glycerol and ibuprofen at high concentrations in two triphasic systems composed of toluene+ibuprofene (apolar) liquid phases, and a solid phase with the industrial immobilized lipase B from Candida antarctica named Novozym®435 (N435) acting as the biocatalyst.
Abstract: This work was focused on the enzymatic esterification of glycerol and ibuprofen at high concentrations in two triphasic systems composed of toluene+ibuprofene (apolar) and glycerol or glycerol–water (polar) liquid phases, and a solid phase with the industrial immobilized lipase B from Candida antarctica named Novozym®435 (N435) acting as the biocatalyst. Based on a preliminary study, the concentration of the enzyme was set at 30 g·L−1 and the stirring speed at 720 r.p.m to reduce external mass transfer limitations. To obtain more information on the reaction system, it was conducted at a wide range of temperatures (50 to 80 °C) and initial concentrations of ibuprofen (20–100 g·L−1, that is, 97 to 483 mM). Under these experimental conditions, the external mass transfer, according to the Mears criterion (Me = 1.47–3.33·10−4 << 0.15), was fast, presenting no limitation to the system productivity, regardless of the presence of water and from 50 to 80 °C. Considering that the enzyme is immobilized in a porous ion-exchange resin, limitations due to internal mass transfer can exist, depending on the values of the effectiveness factor (η). It varied from 0.14 to 0.23 at 50 to 80 °C and 0.32–1 mm particle diameter range in the absence of water, and in the same ranges, from 0.40 to 0.66 in the presence of 7.4% w/w water in the glycerol phase. Thus, it is evident that some limitation occurs due to mass transfer inside the pores, while the presence of water in the polar phase increases the productivity 3–4 fold. During the kinetic study, several kinetic models were proposed for both triphasic reacting systems, with and without first-order biocatalyst deactivation, and their fit to all relevant experimental data led to the observation that the best kinetic model was a reversible hyperbolic model with first-order deactivation in the anhydrous reaction system and a similar model, but without deactivation, for the system with added water at zero time. This fact is in sharp contrast to the use of N435 in a water-glycerol monophasic system, where progressive dissolution of ibuprofen in the reacting media, together with a notable enzyme deactivation, is observed.
1 citations
TL;DR: In this article , the effect of 3,6′-dimethoxychalcone on melanogenesis and lipopolysaccharides (LPS)-induced inflammation in mouse B16F10 and RAW 264.7 cells was investigated.
Abstract: In this study, we demonstrated that 2′-hydroxy-3,6′-dimethoxychalcone (3,6′-DMC) alleviated α-MSH-induced melanogenesis and lipopolysaccharides (LPS)-induced inflammation in mouse B16F10 and RAW 264.7 cells. In vitro analysis results showed that the melanin content and intracellular tyrosinase activity were significantly decreased by 3,6′-DMC, without cytotoxicity, via decreases in tyrosinase and the tyrosinase-related protein 1 (TRP-1) and TRP-2 melanogenic proteins, as well as the downregulation of microphthalmia-associated transcription factor (MITF) expression through the upregulation of the phosphorylation of extracellular-signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K)/Akt, and glycogen synthase kinase-3β (GSK-3β)/catenin, and downregulation of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and protein kinase A (PKA). Furthermore, we investigated the effect of 3,6′-DMC on macrophage RAW264.7 cells with LPS stimulation. 3,6′-DMC significantly inhibited LPS-stimulated nitric oxide production. 3,6′-DMC also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 on the protein level. In addition, 3,6′-DMC decreased the production of the tumor necrosis factor-α and interleukin-6. Successively, our mechanistic studies revealed that 3,6′-DMC also suppressed the LPS-induced phosphorylation of the inhibitor of IκBα, p38MAPK, ERK, and JNK. The Western blot assay results showed that 3,6′-DMC suppresses LPS-induced p65 translocation from cytosol to the nucleus. Finally, the topical applicability of 3,6′-DMC was tested through primary skin irritation, and it was found that 3,6′-DMC, at 5 and 10 μM concentrations, did not cause any adverse effects. Therefore, 3,6′-DMC may provide a potential candidate for preventing and treating melanogenic and inflammatory skin diseases.
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TL;DR: The action of these two anti-inflammatory agents provides further support for the suggestion that some of their therapeutic effects depend on the inhibition of the production of prostaglandin.
Abstract: The action of these two anti-inflammatory agents provides further support for the suggestion that some of their therapeutic effects depend on the inhibition of the production of prostaglandin.
894 citations
TL;DR: Rofecoxib use increases the risk of serious coronary heart disease compared with celecoxib use, and naproxen use does not protect against serious coronaryHeart disease.
890 citations
TL;DR: The coxibs are a subclass of nonsteroidal antiinflammatory drugs (NSAIDs) designed to inhibit selectively cyclooxygenase-2 (COX-2), which is the source of prostaglandins E2 and I2, which mediate inflammation.
Abstract: The coxibs are a subclass of nonsteroidal antiinflammatory drugs (NSAIDs) designed to inhibit selectively cyclooxygenase-2 (COX-2).1 Their development was based on the hypothesis that COX-2 was the source of prostaglandins E2 and I2, which mediate inflammation, and that cyclooxygenase-1 (COX-1) was the source of the same prostaglandins in gastric epithelium, where they afford cytoprotection. Three coxibs — celecoxib, rofecoxib, and valdecoxib — have been approved for use by the Food and Drug Administration (FDA); a fourth, etoricoxib, has been approved by the European regulatory authority, and it and a fifth, lumiracoxib, are currently under consideration for FDA . . .
885 citations
TL;DR: The efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs and the presence of fewer than five erosions at each site and not more than mild dyspepsia was compared.
Abstract: Background Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs. Methods In a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 μg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 μg of misoprostol twice daily, or placebo for six months. Re...
831 citations
TL;DR: The American College of Cardiology Foundation (ACCF) Task Force on Clinical Expert Consensus Documents (ECDs) as mentioned in this paper developed by the ACCF and other cosponsors are intended to inform practitioners, payers, and other interested parties of the opinion of the ACC and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community.
Abstract: This document has been developed by the American College of Cardiology Foundation (ACCF) Task Force on Clinical Expert Consensus Documents, the American College of Gastroenterology (ACG), and the American Heart Association (AHA). Expert consensus documents (ECDs) are intended to inform practitioners, payers, and other interested parties of the opinion of the ACCF and document cosponsors concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice community. Topics chosen for coverage by ECDs are so designed because the evidence base, the experience with technology, and/or the clinical practice are not considered sufficiently well developed to be evaluated by the formal American College of Cardiology/American Heart Association (ACC/AHA) practice guidelines process. Often the topic is the subject of ongoing investigation. Thus, the reader should view ECDs as the best attempt of the ACCF and other cosponsors to inform and guide clinical practice in areas where rigorous evidence may not be available or the evidence to date is not widely accepted. When feasible, ECDs include indications or contraindications. Topics covered by ECDs may be addressed subsequently by the ACC/AHA Practice Guidelines Committee as new evidence evolves and is evaluated.
The Task Force on ECDs makes every …
824 citations