scholarly journals Unmet needs in Chronic Pain Management: The potential use of Curcumin

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2891-2895
Author(s):  
Rizaldy Taslim Pinzon ◽  
Angela ◽  
Andryawan Wahyu Pradana ◽  
Vanessa Veronica
Keyword(s):  
Pain Management ◽  
Side Effects ◽  
Large Scale ◽  
Unmet Needs ◽  
Synergistic Effects ◽  
Cartilage Degradation ◽  
Therapeutic Interventions ◽  
Direct Role ◽  
Cox 2 ◽  
Cox 1

The ultimate goal of treatment for osteoarthritis can be achieved by modifying disease progression and also symptom reduction. Non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors are inflammation and pain management medications that are widely used in osteoarthritis. However, this agent has been linked to have several side effects such as cardiovascular, gastrointestinal, and kidney. These side effects represent the unmet needs in the safety of existing treatment of osteoarthritis. Such results can be caused by the overlapping functions of COX-1 and COX-2 in physiological and pathophysiological systems. The overlapping functions of COX-1 and COX-2 can be the source of these side effects. The extensive history of the use of curcuminoids and boswellia in pain relief coupled with recent findings shows that this phytochemical can play a direct role in several inflammatory processes and offers strong evidence that this product can slow down cartilage degradation and reduce pain in patients with knee osteoarthritis. Our study indicated that by reducing pain and improving function, while lowering the risk of side effects, curcuminoid formulations might become a useful addition to osteoarthritis patients for pharmacological therapeutic interventions. However, further research is needed with high-quality and large-scale RCT research probably to investigates the synergistic effects of these products with other osteoarthritis treatments.

scholarly journals Synthesis, Characterization and Acute Anti-inflammatory Evaluation of New Mefenamic Acid Derivatives Having 4-Thiazolidinone Nucleus

2019 ◽  
Vol 28 (1) ◽  
pp. 138-146
Author(s):  
Mustafa H. Ali Alsafi ◽  
Muthanna S. Farhan
Keyword(s):  
Side Effects ◽  
Mefenamic Acid ◽  
Paw Edema ◽  
Compound I ◽  
Reference Drug ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Derivatives Of ◽  
Cox 1 ◽  
Inflammatory Effect

Mefenamic acid (MA) is one of the non-steroidal anti-inflammatory drugs, it is widely used probably due to having both anti-inflammatory and analgesic activity, the main side effects of mefenamic acid include gastrointestinal tract (GIT) disturbance mainly diarrhea, peptic ulceration, and gastric bleeding. The analgesic effects of NSAIDs are probably linked to COX-2 inhibition, while COX-1 inhibition is the major cause of this classic adverse effects. Introduction of thiazolidinone may lead to the increase in the bulkiness leads to the preferential inhibition of COX-2 rather than COX-1 enzyme. The study aimed to synthesize derivatives of mefenamic acid with more potency and to decrease the drug's potential side effects, new series of 4-thiazolidinone derivatives of mefenamic acid were synthesized IVa-g. The synthetic procedures for target compounds and their intermediates are designed to be as follows: acylation of secondary amine of mefenamic acid by chloroacetylchloride to produce compound (I), then reaction between compound (I) and hydrazine hydrate to form hydrazine derivative of mefenamic acid (compound II). After that, Schiff base formation by addition of seven benzaldehyde derivatives and finally, cyclization in presence of thioglycolic acid to form 4-thiazolidinone heterocyclic ring. The characterization of the titled compounds has been established on the basis of their spectral FTIR, 1HNMR data, and by measurements of their physical properties. In vivo acute anti-inflammatory effect of the synthesized compounds was evaluated in rats using egg-white induced edema model of inflammation. The tested compounds and the reference drug produced significant reduction of paw edema with respect to the effect of dimethyl sulfoxide 10%v/v (control group). Compound IVe showed more potent effect than mefenamic acid at 240-300 min, while at time 300 min, compounds IVa and IVd exhibit more potent anti-inflammatory effect than mefenamic acid (50mg/kg, i.p.) as they reduced paw edema significantly more than mefenamic acid at mentioned intervals (p<0.05) . On the other hand compound IVc exhibited lower anti-inflammatory effect.

2-Substituted Benzoxazoles as Potent Anti-Inflammatory Agents: Synthesis, Molecular Docking and In Vivo Anti-Ulcerogenic Studies

2021 ◽  
Vol 18 ◽  
Author(s):  
Iqra Hamid ◽  
Humaira Nadeem ◽  
Sameen Fatima Ansari ◽  
Sonia Khiljee ◽  
Inzamam Abbasi ◽  
...  
Keyword(s):  
Side Effects ◽  
Therapeutic Interventions ◽  
Binding Potential ◽  
Spectroscopic Techniques ◽  
Standard Drug ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Protein Pocket

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are the commonly used therapeutic interventions of inflammation and pain that competitively inhibit the cyclooxygenase (COX) enzymes. Several side effects like gastrointestinal and renal toxicities are associated with the use of these drugs. The therapeutic anti-inflammatory benefits of NSAIDs are produced by the inhibition of COX-2 enzymes, while undesirable side effects arise from the inhibition of COX-1 enzymes. Objectives: In the present study, a new series of 2-substituted benzoxazole derivatives 2(a-f) and 3(a-e) were synthesized in our lab as potent anti-inflammatory agents with outstanding gastro-protective potential. The new analogs 2(a-f) and 3(a-e) were designed depending upon the literature review to serve as ligands for the development of selective COX-2 inhibitors. Methods: The synthesized analogs were characterized using different spectroscopic techniques (FTIR, 1HNMR, 13CNMR) and elemental analysis. All synthesized compounds were screened for their binding potential in the protein pocket of COX-2 and evaluated for their anti-inflammatory potential in animals using the carrageenan-induced paw edema method. Further 5 compounds were selected to assess the in vivo anti-ulcerogenic activity in an ethanol-induced anti-ulcer rat model. Results: Five compounds (2a, 2b, 3a, 3b and 3c) exhibited potent anti-inflammatory activity and significant binding potential in the COX-2 protein pocket. Similarly, these five compounds demonstrated a significant gastro-protective effect (p<0.01) in comparison to the standard drug, Omeprazole. Conclusion: Depending upon our results, we hypothesize that 2-substituted benzoxazole derivatives have excellent potential to serve as candidates for the development of selective anti-inflammatory agents (COX-2 inhibitors). However, further assessments are required to delineate their underlying mechanisms.

scholarly journals Comparative Analysis of Pharmacologic and/or Genetic Disruption of Cyclooxygenase-1 and Cyclooxygenase-2 Function in Female Reproduction in Mice*

Endocrinology ◽  
2001 ◽  
Vol 142 (7) ◽  
pp. 3198-3206 ◽  
Author(s):  
Jeff Reese ◽  
Xuemei Zhao ◽  
Wen-Ge Ma ◽  
Naoko Brown ◽  
Timothy J. Maziasz ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Synergistic Effects ◽  
Female Reproduction ◽  
Cox Inhibitors ◽  
Cyclooxygenase 1 ◽  
Simultaneous Inhibition ◽  
Cox 2 ◽  
Alternative Sources ◽  
First Time ◽  
Cox 1

Abstract Cyclooxygenase (COX)-derived prostaglandins are critical in female reproduction. Gene targeting studies show that ovulation, fertilization, implantation, and decidualization are defective in COX-2 deficient mice. We used genetic and pharmacologic approaches to perturb COX function and examine the differential and synergistic effects of inhibition of COX-1, COX-2, or of both isoforms on reproductive outcomes during early pregnancy in mice. The results demonstrate that simultaneous inhibition of COX-1 and COX-2 produces more severe effects on early pregnancy events than inhibition of either isoform alone. The effects of pharmacological inhibition of COX-2 on female reproductive functions were less severe than the null mutation of the COX-2 gene. A combined approach showed that COX-2 inhibition in COX-1−/− mice induced complete reproductive failure, suggesting a lack of alternative sources of prostaglandin synthesis. This investigation raises caution regarding the indiscriminate use of COX inhibitors and shows for the first time the distinct and overlapping pathways of the cyclooxygenase systems in female reproduction.

Renal side effects of NSAIDs: role of COX-1 and COX-2

1998 ◽  
pp. 87-98 ◽  
Author(s):  
J. C. Frölich ◽  
D. O. Stichtenoth
Keyword(s):  
Side Effects ◽  
Cox 2 ◽  
Cox 1

Features of NSAIDs' use in pandemic. Gastroenterologist's view

2021 ◽  
Vol 1 (6) ◽  
pp. 32-34
Author(s):  
E. I. Sas
Keyword(s):  
Chronic Pain ◽  
Gastrointestinal Tract ◽  
Side Effects ◽  
Viral Infection ◽  
Mechanism Of Action ◽  
Clinical Course ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Inflammatory Changes ◽  
Cox 1

Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs used to treat acute and chronic pain associated primarily with inflammatory changes. This group of drugs is widely used in neurology, rheumatology, traumatology, etc. The main mechanism of action of the drugs is associated with the effect on cyclooxygenase-2 (COX-2) and blockade of the synthesis of pro-inflammatory prostaglandins (PG), as well as the effect on COX-1 and suppression of the synthesis of cytoprotective PG, which determines the possibility of side effects from the gastrointestinal tract. In the pandemic, the use of this group of drugs has increased many times over. Features of the clinical course of both the viral infection itself and the use of other drugs leads to a significant change in the pharmacodynamics and pharmacokinetics of NSAIDs, which may lead to the development of undesirable side effects.

Flavocoxid (Limbrel ®) manages osteoarthritis through modification of multiple inflammatory pathways: a review

2012 ◽  
Vol 2 (11) ◽  
pp. 379 ◽  
Author(s):  
Bruce P. Burnett ◽  
Robert M. Levy
Keyword(s):  
Side Effects ◽  
Joint Inflammation ◽  
International Normalized Ratio ◽  
Cartilage Degradation ◽  
Necrosis Factor Alpha ◽  
Inflammatory Pathways ◽  
Equivalent Efficacy ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Medical Foods

Limbrel (flavocoxid) is marketed as an FDA-regulated medical food for the clinical dietary management of osteoarthritis (OA) to be used under physician supervision. Flavocoxid is composed of a >90% mixture of baicalin and catechin and represents a non-targeted anti-inflammatory which works differently than non-steroidal anti-inflammatory drugs (NSAIDs) that bind to and only inhibit the cyclooxygenase moieties of COX-1 and COX-2. Flavocoxid binds to and weakly modulates the peroxidase activity of the COX enzymes permitting low level expression of prostaglandins (PGs), prostacyclin (PGI2) and thromboxane (TxA2). In addition, flavocoxid weakly inhibits phospholipase A2 (PLA2) and 5-lipoxygenase (5-LOX) as well as increases IϰBα and prevents nuclear factor kappa B (NFϰB) activation/induction of inflammatory genes such as tumor necrosis factor-alpha (TNFα), interleukin-1β (IL-1 β), IL-6, COX-2, inducible nitric oxide synthase (iNOS) and 5-LOX. In clinical studies, flavocoxid shows equivalent efficacy to naproxen with statistically fewer renal (edema) and upper gastrointestinal (GI) side effects, does not affect platelet function and bleeding times, does not change international normalized ratio (INR) in warfarinized patients, is well-tolerated in patients with previous NSAID-induced GI side effects, and decreases or eliminates the use of gastroprotective medications in patients who previously required them to tolerate NSAIDs. With its broad, non-targeted and multiple weak activities which result in fewer side effects compared to NSAIDs, flavocoxid represents a different way managing OA by working on the underlying and multiple causes of cartilage degradation as well as joint inflammation.  Keywords: Flavocoxid, Limbrel, osteoarthritis, inflammatory pathways, and medical foods

Cyclooxygenase isoforms and atherosclerosis

2003 ◽  
Vol 5 (9) ◽  
pp. 1-18 ◽  
Author(s):  
Orina Belton ◽  
Desmond J. Fitzgerald
Keyword(s):  
Side Effects ◽  
Chronic Administration ◽  
Selective Inhibition ◽  
Gastric Ulcers ◽  
Analgesic Effects ◽  
Vascular Regulation ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Effective Use ◽  
Cox 1

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of arthritis and pain. However, their long-term use is limited by gastrointestinal (GI) side effects such as gastric ulcers. NSAIDs act by inhibiting an enzyme called cyclooxygenase. Cyclooxygenase (COX) catalyses the generation of prostaglandins from arachidonic acid. Two isoforms of the enzyme exist – COX-1 and COX-2 – both of which are targets for NSAIDs. Although they are associated with GI toxicity, NSAIDs have important antithrombotic and anti-inflammatory effects. The GI injury has been attributed to COX-1 inhibition and the anti-inflammatory effects to COX-2 inhibition. As COX-2 is traditionally viewed as an inducible enzyme, selective inhibition of COX-2 by ‘coxibs’ (selective COX-2 inhibitors) has been employed to achieve anti-inflammatory and analgesic effects without GI side effects. However, recently there have been suggestions that chronic administration of coxibs might increase the risk of cardiovascular events, such as atherosclerosis, compared with traditional NSAIDs. In vascular disease, there is increased expression of both COX-1 and COX-2, resulting in enhanced prostaglandin generation. The specific role of COX-1 and COX-2 in vascular regulation is still unknown but such knowledge is essential for the effective use of coxibs. Although more evidence is pointing to selective COX-1 inhibition as a therapeutic measure in inflammatory atherosclerosis, there are some studies that suggest that inhibition of COX-2 might have a potential benefit on atherosclerosis.

Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse

2000 ◽  
Vol 278 (6) ◽  
pp. R1415-R1423 ◽  
Author(s):  
Gil Gross ◽  
Takuji Imamura ◽  
Sherri K. Vogt ◽  
David F. Wozniak ◽  
D. Michael Nelson ◽  
...  
Keyword(s):  
Side Effects ◽  
Preterm Delivery ◽  
Preterm Labor ◽  
Selective Inhibitor ◽  
Specific Inhibition ◽  
Threefold Increase ◽  
Cox 2 ◽  
Deficient Mice ◽  
Term Labor ◽  
Cox 1

Prostaglandins (PGs) have proven important during parturition, but inhibition of PG production treating preterm labor (PTL) results in significant maternal and fetal side effects. We hypothesize that specific inhibition of either cyclooxygenase (COX)-1 or -2 may result in separation of therapeutic and toxic effects. We demonstrate that COX-2, but not COX-1, is induced during inflammation-mediated PTL caused by lipopolysaccharide (LPS) administration. A two- to threefold increase in uterine and ovarian PG concentrations coincides with this induction of COX-2. The COX-2-selective inhibitor SC-236 proved effective in stopping preterm delivery and the increases in PGs. The COX-1-selective inhibitor SC-560 also attenuated uterine and ovarian PG production after LPS but did not inhibit PTL as efficiently as SC-236. COX-1-deficient mice, which show delay in the onset of term labor, exhibited no delay in onset of PTL after LPS. These findings suggest that the mechanisms for initiation of inflammation-mediated PTL and term labor differ and that selective COX-2 inhibition may provide a means of stopping inflammation-induced PTL in humans.

scholarly journals Novel NSAIDs

2020 ◽  
pp. S45-S48
Author(s):  
NY Fening
Keyword(s):  
Side Effects ◽  
Careful Consideration ◽  
The Body ◽  
Ulcer Disease ◽  
Novel Technology ◽  
The Face ◽  
Liver And Kidney ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most commonly used drugs to relieve a multitude of pain symptoms.F They are readily available and used extensively. There is a lot of concern about their adverse side effects namely cardiovascular (CV) and gastrointestinal (GI) side effects. It is important to have a good grasp of the pharmacology of these drugs in order to use them safely and effectively. NSAIDs work by inhibiting the cyclooxygenase (COX) enzyme system responsible for production of prostaglandins. Prostaglandins mediate pain inflammation and temperature regulation in the body. NSAIDS can be divided into selective and non-selective types. Three isoforms of COX have been identified COX-1, COX-2 and COX-3. Selective NSAIDs act on these isoforms. COX-1 is anti-inflammatory, COX-2 pro-inflammatory and COX-3, a variant of COX-1, does not produce prostaglandins. The CV side effects of these drugs can be wide ranging and include a rise in blood pressure (BP) and a higher risk of thromboembolic events. Patients also suffer from peptic ulcer disease or bleeding in the stomach as a result of their use. NSAIDs can cause liver and kidney toxicity and should be used with caution in patients with bleeding tendencies. New NSAIDs on the market include; lornoxicam (xefo®), meloxicam (coxflam®), celecoxib (celebrex®), parecoxib (rayzon®) and etoricoxib (arcoxia®). New ways of delivering NSAIDs to the body with minimal or no side effects are being researched. Novel technology in this field includes nano formulated NSAIDs; indomethacin (tivorbex®) and dicofenac (zorvolex), prodrugs and multi action drugs; cyclooxygenase inhibiting nitric oxide donors and hydrogen sulphide releasing drugs. Further exciting innovations are in the pipeline that could change the face of how we use these drugs. Until then they must be used with careful consideration and only if the benefits of use outweigh the risks.

scholarly journals Synthesis of an Adamantyl Derivative and their Theoretical Interaction with both COX-1 and COX-2 Enzymes

2021 ◽  
Vol 12 (5) ◽  
pp. 5884-5892
Keyword(s):  
Side Effects ◽  
Pain Treatment ◽  
Theoretical Models ◽  
Theoretical Evaluation ◽  
Docking Model ◽  
Cox 2 ◽  
Therapeutic Alternatives ◽  
Chemical Strategies ◽  
Cox 1

Various drugs have been used to treat pain; nevertheless, several drugs can produce side effects such as bronchospasm, thinning, and angioedema. In the search for new therapeutic alternatives, some drugs have been elaborated using different reagents that are difficult to handle and require special conditions such as different pH and higher temperatures. Therefore, this research aimed to prepare an adamantyl derivative (compound 4) from 1-Adamantyl bromomethyl ketone using some chemical strategies. Besides, a theoretical evaluation of the interaction of compound 4 with both cyclooxygenase enzymes (COX-1 and COX-2) was evaluated using either 4cox or 5jw1 proteins as theoretical models. In addition, both indomethacin and celecoxib drugs were used as controls in a docking model. The results showed that compound 4 has a higher affinity by both 4cox and 5jw1 proteins surface compared with either indomethacin or celecoxib drugs. In conclusion, these data suggest that 4 could be a good candidate for pain treatment.

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