Paw edema test

Ring-constrained analogues 37 of the anti-inflammatory drug, diclofenac, have been prepared by acid-catalyzed condensation of aldehydes (or ethylene ketals of ketones) with 36 (Equation 4) <1998MI201>. This reaction presumably proceeds via intramolecular nucleophilic attack by the carboxylic acid group on an iminium ion intermediate from condensation of the secondary amine. Interestingly, the compounds 37 showed comparable activities to diclofenac in the formalin-induced rat paw edema test. 

Bouchea Jlummensis Stimulating. Regulator of digestive Lamiide Anti-infla mmatory Active (p o.) in carrageenin-induccd paw edema test Cancer chemopreventlve [128]... 

A further study was carried out on the anti-inflammatory effect of the EO of Iranian black cumin seeds (BCS) (N. sativa L. Ranunculaceae) by Hajhashemi et al. (2004). p-Cymene (37.3%) and thymoquinone (13.7%) were found to be the main compounds. For the detection of the anti-inflammatory activity, carrageenan-induced paw edema test in rats was used and also the croton oil-induced ear edema in mice. After oral administration of this EO at various doses no significant anti-inflammatory effect could be observed in the carrageenan test, whereas i.p. injection of the same doses significantly reduced carrageenan-induced paw edema. At doses of 10 and 20 pL/ear, BCS-EO also caused a reduction of a CTOton oil-induced edema. An anti-inflanunatory effect could be observed after both systanic and local administration and thymoquinone seemed to play an important role in this pharmacological effect. 

Anti-inflammatory and antiarthritic activities have been established in vitro and in the carrageenan-induced paw edema test, in arthritic rats and in dogs with inflammatory joint and spinal disease. The anti-inflammatory activity is apparently mediated through inhibition of TNF-a, IL-ip, NO, MAPK, and 5-LO, as well as P-selectin-mediated recruitment of inflammatory cells. Earlier clinical trials in India have been conducted on arthritis patients with positive results, and boswellic acid and other related pentacycUc triterpene acids are marketed as antiarthritic drugs in India. More recent trials have demonstrated the efficacy of olibanum prepara-... 

Primary screening data correlated with the in vivo results. Four selected hits, when tested on a carrageenan induced rat paw edema model of acute inflammation and were bioavailable and pharmacologically active, reducing swelling of the paw (data not shown here). The efficacies of the extracts were measured by calculating the reduction in swelling as compared to the vehicle-treated control. Aspirin was used as a positive control for anti-inflammatory activity. These observations validated the potential use of the hits discovered in the RT-PCR assay for the in vivo anti-inflammatory applications. 

The in vivo assays for the Cox-2 inhibitors are essentially those used historically for NSAIDs to evaluate both their desired effects on inflammation, pain, and fever and their undesired effects, mainly on GI lesions. The primary in vivo assay for anti-inflammatory efficacy is the carrageenan-induced rat paw edema assay, and 51 Cr fecal excretion is used to test for damage to the intestinal mucosa in rats and in squirrel monkeys. Additional tests for efficacy are the endotoxin-induced pyresis in rats and squirrel monkeys for control of fever and the carrageenan-induced rat paw hyperalgesia assay for analgesic efficacy. These in vivo assays have been described (Chan et al., 1995 Chan et al., 1997). The rat... 

The ED50 values for the rat paw edema assay, described in the text, to test the in vivo anti-inflammatory potency of the compounds. 

The pharmacologic screening must be performed by a battery of tests, which will prove its efficacy by various methods (e.g., antiinflammatory). These tests are necessary to ascertain the activity of rat paw edema, adjuvant arthritis, granuloma pouch, ascitis, and others. 

Two commonly used models to detect anti-inflammatory activity are carrageenan-induced paw edema and adjuvant-induced polyarthritis in rats. The former represents an acute and the latter a chronic inflammatory process. Non-steroidal anti-inflammatory agents inhibit the formation of carrageenan-induced paw edema. However, to detect activity in the developing and established phases of chronic inflammation, the polyarthritis model is well accepted. In both tests the measured endpoint is volume of the hind paw. This is done by immersing the hind paw in the well of a mercury displacement... 

A number of alkaloids producing a pronounced enhancement of phagocytosis were isolated by Wagner et al. (20) As a part of our continuing search for new biologically active metabolites from U. tomentosa we preceded to a bioassay-directed fractionation of the extracts from V. tomentosa. The extracts and fractions have been bioassayed by the carrageenan induced edema test on rat paw. This allowed us to identify a quinovic acid derivative with a C-3,27 glycosidation pattern, 21. as one of the active anti-inflammatory principles of U. tomentosa. (11). 

Jatrorrhizine was found to possess anti-inflammatory activity as measured in the cobra venom factor-induced (CVF) rat paw edema. CVF edema was used to examine jatrorrhizine and other substances in order to detect novel compounds, since it has been shown that joint cyclooxygenase and lipoxygenase inhibitors, as well as immunoreactive drugs, exhibit more pronounced inhibitory effects on CVF in comparison to carrageenin-induced edema. CVF edema is dependent on activation of the complement system which plays an important role in acute and chronic inflammatory reactions, mediating the activity of immune complexes. This test system represents a functionally new type of acute inflammation via activation of the alternative complement pathway [290]. 

Documented effects An extract of the root had anti-inflammatory effects on induced rat paw edema and analgesic effects in tests with rats (Farsam et al. 2000). In parenteral toxicity tests in mice, an extract of the total alkaloids was classified as a moderately toxic agent. Dermal acute toxicity tests showed no sign of toxicity (Ostad et al. 2003). 

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