Inhibitory effect inflammatory edema

Inhibitory Effects on TPA, HHPA, and Croton Oil-Induced Inflammatory Edema... 

The inhibitory effects of the sterols and triterpenoids on TPA-induced inflammatory ear edema in mice are shown in Table 2. The inhibitory effects of three reference compounds, quercetin (4), a known inhibitor of TPA-induced inflammation in mice, and of two commercially available anti-inflammatory drugs, indomethacin (5) and hydrocortisone (6), were included for comparison. As is evident from Table 2, most of the compounds examined exhibited activity almost equivalent to or higher than quercetin (4). Inhibitory effects on the other experimental models were also included in Table 2. 

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]. 

Yasukawa et al. [84] demonstrated the anti-inflammatory activity of some sterols and triterpenes on the TPA-induced ear edema test in mouse. Among them, karounidiol 3-O-benzoate, a D C-friedooleanane triterpene, showed an interesting inhibitory effect (95%) of the edema formation at a dose of 2 mg/ear its ID50 was 0.4 pmol/ear. 

Documented effects Preparation from this species are used as a hemostatic (Zemlinsky 1958) and to treat chronic bronchitis (Nosal and Nosal 1959). Compounds in the herb showed inhibitory effects on mouse ear edema (Murai et al. 1995). Results of experimental research confirmed anti-inflammatory, antispasmodic, and immunostimulatory actions (Wegener and Kraft 1999). 

Shibata, S., H. Inoue, S. Iwata, R.-D. Ma, L.-J. Yu, H. Ueyama, J. Takayasu, T. Hasegawa, H. Tokuda, A. Nishino, H. Nishino, and A. Iwashima Inhibitory Effects of Licochalcone A Isolated from Glycyrrhiza inflata Root on Inflammatory Ear Edema and Tumour Promotion in Mice. Planta Med., 57, 221 (1991). 

Besides neuropeptides, nitric oxide is an inflammatory mediator in the airways, which is also a vasodilator and a neurotransmitter. Nitric oxide is produced by the enzymatic action of nitric oxide synthetase on L-arginine. Airways contain this enzyme in three different forms, two of which termed neuronal and endothelial nitric oxide synthetase are constitutive whereas the third form called inducible nitric oxide synthetase is inducible. The inflammatory cytokines including IL-1 and TNF-a augment the expression of inducible nitric oxide synthetase in human airway epithelial cells. Nitric oxide causes bronchodilation as a result of the relaxation of bronchial smooth muscles. It has also been suggested that nitric oxide is the neurotransmitter of the inhibitory NANC bronchodilation. The detrimental effects of nitric oxide include airway inflammation and vasodilation. It causes airway edema by increasing the erudition of plasma due to increased blood flow to postcapillary venules. The increased blood flow may also contribute to an increased mucus secretion. The role of nitric oxide in inflammatory responses has not yet been established. 

At present, BP 2.94 (36) is under clinical development in Phase II trials for the treatment of asthma, pneumoallergic diseases, and others. Preclinical studies in rodents clearly displayed anti-inflammatory as well as antinociceptive activity of BP 2.94 (36) given orally at low doses. These effects are mediated by inhibitory H3 receptors located on sensory C-fibres in several different tissues. In particular, capsaicin-induced plasma protein extravasation was dose-dependently inhibited in airways, digestive tract, skin, conjunctiva, urinaiy bladder, nasal mucosa, and dura mater of the rat. In the p-phenylbenzoquinone-induced writhing test in mice, BP 2.94 (36) had a pronounced antinociceptive activity similar to that of acetylsalicylic acid. This effect was significantly abolished by the H3 receptor antagonist thioperamide but not by naloxone. Furthermore, BP 2.94 (36) reduced zymosan-induced edema. This antiinflammatory effect was also abolished by thioperamide [6]. 

Numerous monoterpenes were identified in the essential oil of the rhizomes of Z. cassumunar [279]. From the hexane extract of the rhizomes of Z. cassumunar, thirteen aromatic compounds 309,310, 312, 317-324, 326 and 327 were isolated [280-282]. The structures of these compounds were determined on the basis of their spectroscopic data and by syntheses. The crystal structures of cyclohexene derivative 312 and quinone 324 were determined by X-ray diffraction analysis [280]. Evaluation of the biological activity of these compounds revealed that compound 317 possessed smooth muscle relaxant activity ( guinea-pig ileum and tracheal chain) [283].The mechanism of bronchodilator activity of 317 was found to be similar to those of aminophylline and papaverine [284]. Compound 317 also exhibited uterine relaxant effect and shared a similar mechanism of action with papaverine [285]. Anti-inflammatory activity of 309, 312, 317-319, 326 and 327 was evaluated using the carragenin-induced rat paw edema model and compound 317 was reported to possess the strongest inhibitory activity on the edema formation [286]. Compounds 322 and 323 exhibited insecticidal activity towards neonate larvae ofSpodoptera littoral is [266]. 

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