- |||||||||| Review, Journal: Gut Microbiota in NSAID Enteropathy: New Insights From Inside. (Pubmed Central) - Jul 28, 2021
In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.
- |||||||||| indomethacin / Generic mfg.
[VIRTUAL] GASTROPROTECTIVE ACTION OF APELIN/AJP SYSTEM AGAINST ISCHEMIA-REPERFUSION INJURY. ROLE OF OXIDATIVE STRESS, NITRIC OXIDE AND SENSORY NEUROPEPTIDES (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_4172;
Rats were pretreated with L-NAME (5 mg/kg i.g.), 2) indomethacin (2 mg/kg i.g.), and 3) capsaicin (125 mg/kg s.c.) to induce functional ablation of sensory nerves.by qPCR... 1) apelin/APJ signaling inhibits gastric I/R damage by enhancing gastric microcirculation, down-regulating pro-inflammatory cytokines and biomarkers, and by inhibiting lipid peroxidation and I/R-induced oxidative stress, and 2) apelin-induced gastric protection is likely mediated by NO and sensory neuropeptides, but appears to be independent of the PG / COX biosynthetic pathway.
- |||||||||| indomethacin / Generic mfg.
[VIRTUAL] GASTROPROTECTIVE ACTION OF APELIN/AJP SYSTEM AGAINST ISCHEMIA-REPERFUSION INJURY. ROLE OF OXIDATIVE STRESS, NITRIC OXIDE AND SENSORY NEUROPEPTIDES (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_1992;
Rats were pretreated with L-NAME (5 mg/kg i.g.), 2) indomethacin (2 mg/kg i.g.), and 3) capsaicin (125 mg/kg s.c.) to induce functional ablation of sensory nerves.by qPCR... 1) apelin/APJ signaling inhibits gastric I/R damage by enhancing gastric microcirculation, down-regulating pro-inflammatory cytokines and biomarkers, and by inhibiting lipid peroxidation and I/R-induced oxidative stress, and 2) apelin-induced gastric protection is likely mediated by NO and sensory neuropeptides, but appears to be independent of the PG / COX biosynthetic pathway.
- |||||||||| indomethacin / Generic mfg.
[VIRTUAL] GASTROPROTECTIVE ACTION OF APELIN/AJP SYSTEM AGAINST ISCHEMIA-REPERFUSION INJURY. ROLE OF OXIDATIVE STRESS, NITRIC OXIDE AND SENSORY NEUROPEPTIDES (Poster Exhibition) - Jul 20, 2021 - Abstract #UEGW2021UEGW_161;
Rats were pretreated with L-NAME (5 mg/kg i.g.), 2) indomethacin (2 mg/kg i.g.), and 3) capsaicin (125 mg/kg s.c.) to induce functional ablation of sensory nerves.by qPCR... 1) apelin/APJ signaling inhibits gastric I/R damage by enhancing gastric microcirculation, down-regulating pro-inflammatory cytokines and biomarkers, and by inhibiting lipid peroxidation and I/R-induced oxidative stress, and 2) apelin-induced gastric protection is likely mediated by NO and sensory neuropeptides, but appears to be independent of the PG / COX biosynthetic pathway.
- |||||||||| temozolomide / Generic mfg.
Preclinical, Journal: In Vitro Effects of Selective COX and LOX Inhibitors and Their Combinations with Antineoplastic Drugs in the Mouse Melanoma Cell Line B16F10. (Pubmed Central) - Jul 18, 2021
We also explore their combinatorial pharmacological space with dacarbazine and temozolomide (median effect method)...When the selected inhibitors are combined with the antineoplastic drugs, only meloxicam provides clear synergy, with LOX inhibitors mostly antagonizing. These apparent contradictions between single and combination treatments, together with some paradoxical effects observed in the biosynthesis of eicosanoids after FLAP inhibition in short term incubations, warrant further mechanistical in vitro and in vivo scrutiny.
- |||||||||| metformin / Generic mfg.
Journal: Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2. (Pubmed Central) - Jul 15, 2021
Clinically, high expression levels of COX-2 and p-4E-BP1 in tissues of patients with breast cancer were significantly associated with enhanced lymphatic metastasis and distant metastasis. Thus, the current data suggested that metformin may have potential value as a synergistic therapy targeting both the COX-2 and mTOR signaling pathways.
- |||||||||| indomethacin / Generic mfg.
Journal: Crystallography, Molecular Modeling, and COX-2 Inhibition Studies on Indolizine Derivatives. (Pubmed Central) - Jul 15, 2021
In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a-e) were carried out and evaluated for COX-2 enzyme inhibition...The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 2/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, β = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)Å. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy.
- |||||||||| indomethacin / Generic mfg.
Journal: TRP Channel Agonists Activate Different Afferent Neuromodulatory Mechanisms in Guinea Pig Urinary Bladder. (Pubmed Central) - Jul 13, 2021
AITC (100 μM) increased (231%) area of spontaneous bladder contractions (SBCs) an effect reduced by a TRPA1 antagonist (HC3-03001, HC3, 10 μM) and reversed to inhibition by indomethacin (INDO, 500 nM) a cyclooxygenase inhibitor...OA-NO also induced excitation in 23% of bladder strips. These observations raise the possibility that guinea pig bladder is innervated by at least two types of afferent nerves: [1] Type A express TRPA1 receptors that induce the release of prostaglandins and excite the detrusor, [2] Type B express TRPV1, TRPA1 and TRPC receptors and release CGRP that inhibits the detrusor.
- |||||||||| SB202190 / Amgen
Preclinical, Journal: Acute P38-Mediated Enhancement of P2X3 Receptor Currents by TNF-α in Rat Dorsal Root Ganglion Neurons. (Pubmed Central) - Jul 9, 2021
TNF-α-induced mechanical allodynia was also alleviated after local P2X3 receptors were blocked. These results suggested that TNF-α rapidly sensitized P2X3 receptors in primary sensory neurons via a p38 MAPK dependent pathway, which revealed a novel peripheral mechanism underlying acute mechanical hypersensitivity by peripheral administration of TNF-α.
- |||||||||| aspirin / Generic mfg.
Review, Journal: The Expanding Role of the COX Inhibitor/Opioid Receptor Agonist Combination in the Management of Pain. (Pubmed Central) - Jul 9, 2021
It should be tailored to the patients' analgesic necessities, and his/her gastrointestinal and cardiovascular risk, and potential concurrent aspirin use...This invited narrative review deals with the literature evidence covering the components of multimodal opioid-sparing analgesic regimens. Also, it provides insights into the clinically relevant choice criteria to ensure a patient-tailored analgesia.
- |||||||||| glibenclamide / Generic mfg., celecoxib oral / Generic mfg.
[VIRTUAL] L-DOPA+celecoxib Reduces Hyperalgesia Via NO/GMPc/K+ATP in Parkinsonian Rat () - Jun 29, 2021 - Abstract #IASP2021IASP_752;
The findings do not support a protective role of aspirin on HNC outcomes. Taken together, this data suggests that L-DOPA + celecoxib combination produces an antihyperalgesic synergistic interaction at the systemic level, and these effects are mediated, at the central level, through activation of the NO–cGMP–ATP-sensitive K+ channel pathway
- |||||||||| glibenclamide / Generic mfg.
Preclinical, Journal: Gastroprotective effects of irsogladine maleate on ethanol/hydrochloric acid induced gastric ulcers in mice. (Pubmed Central) - Jun 26, 2021
IM also decreased the level of thiobarbituric acid reactive substances. We concluded that IM exhibited significant gastroprotective effects in an ethanol/HCl-induced ulcer model, which appear to be mediated, at least in part, by NO, cAMP, endogenous prostaglandins, KATP channel opening, activation of TRPV1 channels, and antioxidant properties.
- |||||||||| aspirin / Generic mfg.
Journal: Low Dose Aspirin and COX Inhibition in Human Skeletal Muscle. (Pubmed Central) - Jun 24, 2021
Aerobic exercise does not appear to alter the inhibitory efficacy of aspirin. These findings may have implications for the tens of millions of individuals that chronically consume low dose aspirin.
- |||||||||| Xenical (orlistat) / Roche, GSK
Preclinical, Journal: Phytochemical Profile and In Vitro Antioxidant, Antimicrobial, Vital Physiological Enzymes Inhibitory and Cytotoxic Effects of Artemisia jordanica Leaves Essential Oil from Palestine. (Pubmed Central) - Jun 24, 2021
In addition, the tested EO displayed a potent α-amylase suppressing effect compared with the positive control acarbose...The (AJ) EO has strong antioxidant, antibacterial, antifungal, anti-α-amylase, anti-α-glucosidase, and COX inhibitory effects which could be a favorite candidate for the treatment of various neurodegenerative diseases caused by harmful free radicals, microbial resistance, diabetes, and inflammations. Further in-depth investigations are urgently crucial to explore the importance of such medicinal plants in pharmaceutical production.
- |||||||||| Journal: Natural COX-2 inhibitors as promising anti-inflammatory agents: an update. (Pubmed Central) - Jun 23, 2021
The utilization of these natural remedies in future cancer prevention was also discussed. In all, the survey on the characterized COX-2 inhibitors from natural sources paths the further development of more potent and selective COX-2 inhibitors in the future.
- |||||||||| otenaproxesul (ATB-346) / Antibe
Clinical, P2 data, Journal: A Proof-of-Concept, Phase 2 Clinical Trial of the Gastrointestinal Safety of a Hydrogen Sulfide-Releasing Anti-Inflammatory Drug. (Pubmed Central) - Jun 22, 2021
In all, the survey on the characterized COX-2 inhibitors from natural sources paths the further development of more potent and selective COX-2 inhibitors in the future. This phase 2B study provides unequivocal evidence for a marked reduction of GI toxicity of the H S-releasing analgesic/anti-inflammatory drug, ATB-346, as compared to the conventional dose of naproxen which produced equivalent suppression of cyclooxygenase.
- |||||||||| grapiprant (RQ-00000007) / AskAt, Ikena Oncology, Maruishi Pharma
Journal: Determination of grapiprant plasma and urine concentrations in horses. (Pubmed Central) - Jun 22, 2021
Oral administration of grapiprant (2 mg kg) in horses did not achieve those concentrations. The dose was well tolerated; therefore, studies with larger doses could be conducted.
- |||||||||| indomethacin / Generic mfg.
Preclinical, Journal: Relaxant effect of diallyl sulfide on nonpregnant rat uterus: Involvement of voltage-dependent calcium channels. (Pubmed Central) - Jun 22, 2021
EEMec shown a great photoprotective property to prevent keratinocytes damage induced by UV radiation and, thus a candidate potential to application as an adjuvant in sunscreen formulations as a strategy to reduce risk of sunburn and prevent skin diseases associated with UV-induced inflammation and cancer. Diallyl sulfide has a relaxing effect on KCl-contracted rat uterus strips and an inhibitory effect on spontaneous uterine activity, possibly by decreasing the calcium influx into the cytoplasm of uterine smooth muscle cells.
- |||||||||| ibuprofen / Generic mfg.
Journal: In silico characterisation of olive phenolic compounds as potential cyclooxygenase modulators. Part 1. (Pubmed Central) - Jun 22, 2021
It has previously been found that oleocanthal, a phenolic compound derived from the olive, had similar effects to ibuprofen, a commonly used NSAID...The residue contributions to binding free energy were computed using Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) methods, revealing that residues Leu93, Val116, Leu352, and Ala527 in COX-1 and COX-2 were key determinants of potential inhibition. Along with part 2 of this study, this work aims to identify and characterise novel phenolic compounds which may possess COX inhibitory properties.
- |||||||||| Journal: In silico characterisation of olive phenolic compounds as potential cyclooxygenase modulators. Part 2. (Pubmed Central) - Jun 22, 2021
It is proposed that inter-residue network metrics provide additional measures of the potential bioactivity of ligands, which may form a useful adjunct to conventional direct predictions of binding affinity, in determining the efficacy of potential small-molecule inhibitors. Overall, this two-part study characterises anti-inflammatory effects of low dosage dietary COX inhibitors, and provides a possible avenue for the development of therapeutics in inflammatory diseases.
- |||||||||| indomethacin / Generic mfg.
Preclinical, Journal: Mechanisms of vascular dysfunction in the interleukin-10-deficient murine model of preeclampsia indicate nitric oxide dysregulation. (Pubmed Central) - Jun 22, 2021
Treatment of isolated aortas with indomethacin, a cyclooxygenase inhibitor, improved, but failed to normalize contraction to phenylephrine to that of wild type normotensive mice, suggesting the additional contribution from nitric oxide downregulation and effects of indomethacin-resistant vasoconstricting factors...Thus, our results identify the role of IL-10 deficiency in dysregulation of the cyclooxygenase pathway and vascular dysfunction in the IL-10-/-sPE murine model of preeclampsia, and point towards a possible contribution of nitric oxide dysregulation. These compounds and related mechanisms may serve both as diagnostic markers and therapeutic targets for preventive and treatment strategies in preeclampsia.
- |||||||||| Journal: Symmetrical and un-symmetrical curcumin analogues as selective COX-1 and COX-2 inhibitor. (Pubmed Central) - Jun 22, 2021
We report here that most of the curcumin analogues display selective inhibition of COX-2, whereas a few suppress COX-1 activity. Further, we examined the binding of these inhibitors by molecular docking and observed that the compound with pronounced selectivity for COX-2 displayed better binding to COX-2 compared to curcumin.
- |||||||||| meloxicam / Generic mfg.
Retrospective data, Journal: Non-steroidal anti-inflammatory drugs at embryo transfer on pregnancy rates in cows: A meta-analysis. (Pubmed Central) - Jun 22, 2021
The results also highlight that the use of NSAIDs at the time of ET was particularly effective in cows with difficulty in passing the catheter from the cervix during ET, with 71% more likely P/ET (RR = 1.71, 95% CI = 1.07 to 2.74) with the use of NSAIDs for these cows compared to other cows. The data were too limited to analyse the influence of NSAID molecules (flunixin meglumine [FM] and meloxicam), cyclooxygenase (COX) inhibitor type (non-selective COX inhibitor [both COX-1 and COX-2] and selective COX inhibitor [only COX-2]), embryo processing (embryo production, embryo conservation and embryo quality), stress, synchronization, breed and parity on the relationship between NSAIDs and P/ET.
- |||||||||| naproxen / Generic mfg.
Journal: A combination of Omega-3 PUFAs and COX inhibitors: A novel strategy to manage obesity-linked dyslipidemia and adipose tissue inflammation. (Pubmed Central) - Jun 16, 2021
Here, we sought to determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in combination with naproxen (NX), a COX inhibitor, on dyslipidemia and gene expression in adipose tissue (AT) in humans...The plasma level of glycine-conjugated hyodeoxycholic acid, a secondary bile acid with hypolipidemic property, increased significantly in ω-3 PUFAs + NX-treated group. Our data suggest that combining NX with ω-3 PUFAs increases their effectiveness in reducing serum TG and favorably altering AT gene expression and plasma bile acid profile.
- |||||||||| Review, Journal: Anti-inflammatory and anti-virus potential of poxytrins, especially protectin DX. (Pubmed Central) - Jun 11, 2021
Because of their E,Z,E conjugated triene, poxytrins may inhibit inflammation associated with cyclooxygenase (COX) activities, and reactive oxygen species (ROS) formation. In addition of inhibiting COX activities, at least one poxytrin, namely protectin DX (PDX) from docosahexaenoic acid (DHA), has also been reported as able to inhibit influenza virus replication by targeting its RNA metabolism.
- |||||||||| metamizole / Generic mfg., paracetamol / Generic mfg.
Journal: Non-opioid Analgesics and the Endocannabinoid System. (Pubmed Central) - Jun 10, 2021
In addition, several mechanisms are implicated in the elevation of endocannabinoid levels following administration of non-opioid analgesics. Of these, reduction of endocannabinoid degradation via FAAH and/or COX-2 inhibition, accumulation of arachidonic acid to endocannabinoid biosynthesis following COX inhibition, inhibition of cellular uptake of endocannabinoids directly or following inhibition of nitric oxide synthase production, and induction of endocannabinoid release are among the proposed mechanisms.
- |||||||||| Journal: Selective inhibition of the K efflux sensitive NLRP3 pathway by Cl channel modulation. (Pubmed Central) - Jun 8, 2021
Through iterative screening and rational chemical design, we established a collection of chloride channel inhibiting active lead molecules with potent activity at the canonical NLRP3 inflammasome and no activity at COX enzymes, but only in response to stimuli that activated NLRP3 by a K efflux-dependent mechanism. This study identifies a model for the isolation and removal of unwanted off-target effects, with the enhancement of desired activity, and establishes a new chemical motif for the further development of NLRP3 inflammasome inhibitors.
- |||||||||| Review, Journal: Prostaglandins as potential targets for the treatment of polycystic kidney disease. (Pubmed Central) - Jun 3, 2021
In an orthologous model of the main form of PKD, PGD and PGI were the two PG highest in kidneys and most affected by a COX2 inhibitor. Future studies are needed to determine whether specific blockage of PGD and/or PGI activity would lead to more targeted and effective treatments with fewer undesirable side-effects.
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