Anti-inflammatory agent 1

Colchicine and the heart

Colchicine is a unique, sophisticated anti-inflammatory agent that has been used for decades for the prevention of acute inflammatory flares in gout and familial Mediterranean fever. In recent years, clinical trials have demonstrated its potential in a range of cardiovascular (CV) conditions. Colchicine is avidly taken up by leucocytes, and its ability to bind to tubulin and interfere with microtubular function affects the expression of cytokines and interleukins, and the ability of neutrophils to marginate, ingress, aggregate, express superoxide, release neutrophil extracellular traps, and interact with platelets. In patients with acute and recurrent pericarditis, clinical trials in >1600 patients have consistently shown that colchicine halves the risk of recurrence [relative risk (RR) 0.50, 95% confidence interval (CI) 0.42-0.60]. In patients with acute and chronic coronary syndromes, multicentre randomized controlled trials in >11 000 patients followed for up to 5 years demonstrated that colchicine may reduce the risk of CV death, myocardial infarction, ischaemic stroke and ischaemia-driven revascularization by >30% (RR 0.63, 95% CI 0.49-0.81). The use of colchicine at doses of 0.5-1.0 mg daily in CV trials has proved safe. Early gastrointestinal intolerance limits its use in ?10% of patients; however, ?90% of patients tolerate it well over the long term. Despite isolated case reports, clinically relevant drug interactions with moderate to strong CYP3A4 inhibitors/competitors or P-glycoprotein inhibitors/competitors are rare if this dosage of colchicine is used in the absence of advanced renal or liver disease. The aim of this review is to summarize the contemporary data supporting the efficacy and safety of colchicine in patients with CV disease.

Arzanol, a potent mPGES-1 inhibitor: novel anti-inflammatory agent

Arzanol is a novel phloroglucinol α -pyrone, isolated from a Mediterranean plant Helichrysum italicum (Roth) Don ssp. microphyllum which belongs to the family Asteraceae. Arzanol has been reported to possess a variety of pharmacological activities. However, anti-inflammatory, anti-HIV, and antioxidant activities have been studied in some detail. Arzanol has been reported to inhibit inflammatory transcription factor NF κB activation, HIV replication in T cells, releases of IL-1 β , IL-6, IL-8, and TNF-α , and biosynthesis of PGE? by potentially inhibiting mPGES-1 enzyme. Diversity of mechanisms of actions of arzanol may be useful in treatment of disease involving these inflammatory mediators such as autoimmune diseases and cancer. This review presents comprehensive information on the chemistry, structure-activity relationship, and pharmacological activities of arzanol. In addition this review discusses recent developments and the scope for future research in these aspects.

Anti-inflammatory effects of oral supplementation with curcumin: a systematic review and meta-analysis of randomized controlled trials

Context: Chronic inflammation is a major contributor to the development of noncommunicable diseases. Curcumin, a bioactive polyphenol from turmeric, is a well-known anti-inflammatory agent in preclinical research. Clinical evidence remains inconclusive because of discrepancies regarding optimal dosage, duration, and formulation of curcumin.
Objective: The aim of this systematic review, conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and checklist, was to evaluate the efficacy of curcumin supplementation on systemic inflammatory mediators, comparing dose, duration, and bioavailability status of interventions.
Data sources: The Medline, CINAHL, EMBASE, Scopus, and Cochrane literature databases were searched from 1980 to May-end 2019. Randomized controlled trials investigating effects of dietary curcumin on inflammatory mediators in humans not receiving anti-inflammatory treatment were eligible for inclusion. Two authors independently assessed titles and abstracts of identified articles for potential eligibility and respective, retrieved, full-text articles; disagreements were resolved by a third author. Evidence quality was critically appraised using the Quality Criteria Checklist for Primary Research.
Data extraction: Thirty-two trials (N = 2,038 participants) were included and 28 were meta-analyzed using a random-effects model; effect sizes were expressed as Hedges' g (95%CI).
Data analysis: Pooled data (reported here as weighted mean difference [WMD]; 95%CI) showed a reduction in C-reactive protein (-1.55 mg/L; -1.81 to -1.30), interleukin-6 (-1.69 pg/mL, -2.56 to -0.82), tumor necrosis factor α (-3.13 pg/mL; -4.62 to -1.64), IL-8 (-0.54 pg/mL; -0.82 to -0.28), monocyte chemoattractant protein-1 (-2.48 pg/mL; -3.96 to -1.00), and an increase in IL-10 (0.49 pg/mL; 0.10 to 0.88), with no effect on intracellular adhesion molecule-1.
Conclusion: These findings provide evidence for the anti-inflammatory effects of curcumin and support further investigation to confirm dose, duration, and formulation to optimize anti-inflammatory effects in humans with chronic inflammation.
Systematic review registration: PROSPERO registration no. CRD42019148682.

Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases

Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that this activity of turmeric is due to curcumin (diferuloylmethane). This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various proinflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further.

Glucagon-like peptide-1 receptor agonists as anti-inflammatory agents: A potential mode of cardiovascular benefits