Relative Anti-inflammatory Potency Research Articles

Mechanistic Differences in the Inhibition of NF-κB by Turmeric and Its Curcuminoid Constituents.

Turmeric extract, a mixture of curcumin and its demethoxy (DMC) and bisdemethoxy (BDMC) isomers, is used as an anti-inflammatory preparation in traditional Asian medicine. Curcumin is considered to be the major bioactive compound in turmeric but less is known about the relative anti-inflammatory potency and mechanism of the other components, their mixture, or the reduced in vivo metabolites. We quantified inhibition of the NF-κB pathway in cells, adduction to a peptide mimicking IκB kinase β, and the role of cellular glutathione as a scavenger of electrophilic curcuminoid oxidation products, suggested to be the active metabolites. Turmeric extracts (IC50 14.5 ± 2.9 μM), DMC (IC50 12.1 ± 7.2 μM), and BDMC (IC50 8.3 ± 1.6 μM), but not reduced curcumin, inhibited NF-κB similar to curcumin (IC50 18.2 ± 3.9 μM). Peptide adduction was formed with turmeric and DMC but not with BDMC, and this correlated with their oxidative degradation. Inhibition of glutathione biosynthesis enhanced the activity of DMC but not BDMC in the cellular assay. These findings suggest that NF-κB inhibition by curcumin and DMC involves their oxidation to reactive electrophiles, whereas BDMC does not require oxidation. Because it has not been established whether curcumin undergoes oxidative transformation in vivo, oxidation-independent BDMC may be a promising alternative to test in clinical trials.

2-Substituted-3-(4-bromo-2-carboxyphenyl)-5-methyl-4-thiazolidinones as potential anti-inflammatory agents

New anthranilic acid derivatives, 2-substituted-3-(4-bromo-2-carboxyphenyl)-5-methyl-4-thiazolidinone, were synthesized and evaluated for their anti-inflammatory activity against carrageenan-induced oedema in albino rats. The most active member of the series, 3-(4-bromo-2-carboxyphenyl)-2-(2-fluorophenyl)-5-methyl-4-thiazolidinone 6 was compared with phenylbutazone for its relative anti-inflammatory potency and ulcerogenic liability. ED 50, cardiovascular and central nervous system effects of 6 were also studied.

Comparison of the efficacy of diclofenac and betamethasone following strabismus surgery

AIMSTo compare the relative anti-inflammatory potency and safety of topical diclofenac–gentamicin with beta methasone–neomycin following strabismus surgery.METHODSA single centre, single observer, prospective, randomised, and double masked clinical trial of 25...

Flexible classification for the clinical potency of topical corticosteroid proprietaries.

A flexible system of classifying topical corticosteroid proprietaries is proposed to help the clinician understand the relative antiinflammatory potency of these products. This system has the advantage of indicating not only the relative potency of a specific proprietary preparation but also noting the number of divisions in the classification. It allows for new product development and keeps the clinician informed of the change by the number of divisions being used. The system also has the potential for the classification of relative severity of both local and systemic side effects of corticosteroids.

Anti-inflammatory activity of amino acyl benzoates

Nineteen new piperazino or morpholino amino acyl benzoates were synthesized and screened against carrageenin induced oedema in albino rats. Several compounds of the series showed potent anti-inflammatory activity. Compound 10 was found to be the most potent. This compound was further evaluated in detail and compared with phenylbutazone for its relative anti-inflammatory potency and ulcerogenic liability. The compound, in addition, was compared with acetyl salicylic acid for its analgesic activity. This compound showed potent anti-inflammatory activity with minimal ulcerogenic liability.

A new potent anti-inflammatory quinazolone

Summary Nineteen new 3-aryl quinazolones substituted with piperazine or piperidine were synthesized and screened against carrageenin induced oedema in albino rats. Several compounds of the series showed potent anti-inflammatory activity. Compound number 16 (2-homopiperidino methyl-3-(o-tolyl)-4-(3H)-6-iodoquinazolone) was found to be most potent. This compound (16) was further evaluated in detail and compared with phenylbutazone for its relative anti-inflammatory potency, ulcerogenic liability and acute toxicity. It was found to be almost equipotent to phenylbutazone as regards anti-inflammatory activity was concerned but had minimal ulcerogenic liability, cardiovascular and CNS effects. Therefore, it seems promising as an anti-inflammatory agent in our preliminary studies.

Differential and Integral Corticosteroid Feedback Effects on ACTH Secretion in Hypoadrenocorticism

Recent work suggests the existence of a dual corticosteroid feedback mechanism of stress-induced ACTH secretion in the rat. This possibility led us to study the kinetics of suppression of ACTH levels by corticosteroid administration in patients with nonstress ACTH hypersecretion secondary to hypoadrenocorticism. Cortisol was administered according to different protocols, which were chosen to provide extreme variations of the input signal. By this means, two phases of suppression of ACTH levels could be differentiated. A first decrease occurred without latency whenever, and as long as, plasma cortisol levels were rising. There was a linear regression between the logarithm of the increments in cortisol concentrations and the decrease in ACTH levels per minute (r = 0.951) (differential or rate-sensitive feedback mechanism). Neither the absolute doses of cortisol, nor plasma cortisol concentrations were closely correlated with the degree of suppression of ACTH by this rapid mechanism. A second decrease in ACTH levels began congruent with30 min after corticosteroid administration. In this case there was a significant linear regression between the degree of inhibition of ACTH levels and the cortisol doses (r = 0.997) (integral or dose-sensitive feedback mechanism). The dose-sensitive feedback effects of dexamethasone were less than might have been predicted from its relative anti-inflammatory potency. No rate-sensitive effects were seen with dexamethasone doses of 1.0 or 1.25 mg.

Partial purification of rabbit aorta contracting substance-releasing factor and inhibition of its activity by anti-inflammatory steroids.

Rabbit aorta contracting substance-releasing factor (RCS-RF) is found in perfusates from guinea pig lungs during anaphylaxis. It has been identified as a small peptide which releases arachidonic acid from lung tissue, thus generating prostaglandin endoperoxides and tbromboxanes and causing bronchocconstriction. Anti-inflammatory steroids block the release of arachidonate by RCS-RF. In this activity their relative potency is very similar to their relative anti-inflammatory potency, suggesting that the two actions may be related.

The effect of large doses of prednisone on acute rheumatic fever; observations on the treatment of seventeen patients with carditis with a two-year follow-up.

The introduction of steroids has presented a new therapeutic approach to the treatment of rheumatic fever. This problem has been the subject of extensive studies over the past few years. The detailed observations made in an effort to evaluate the effect of hormone therapy have resulted in a renewed interest in many aspects of this disease. In 1955, when a newly synthesized steroid, prednisone, became available, a study was undertaken to test its effectiveness in children with rheumatic fever. The objectives of this study were (1) to determine the relative anti-inflammatory potency of this new steroid in rheumatic fever; (2) to determine what proportion of children with rheumatic carditis treated early in their first attack with large amounts of prednisone for a prolonged period would escape permanent cardiac damage; (3) to determine whether extension of steroid therapy to 14 weeks, in contrast to the conventional 6 weeks, would reduce the