Nitric-oxide synthases anti-inflammatory

Figure 6. Comparative gene expression ratios in ARF kidneys of MSC- and vehicle-treated animals. Data were generated by referencing each gene to p-actin as internal control. A MSC treatment cansed significant (P < 0.05) suppression (> 10 fold) of proinflammatory IL-ip, TNF a, and IFN-y (above bars actnal valnes). Anti-inflammatory lL-10 was robustly expressed in MSC-and not in vehicle treated animals. Filled bars on all panels depict gene expression ratio of 1, i.e., a value obtained when gene expression ratios between MSC- and vehicle-treated animals are "equal. B MSC treatment cansed increased gene expression of bFGF and TGF-a, whereas that of HGF was suppressed. C antiapoptotic Bcl-2 expression was robnstly indnced, whereas that of inducible nitric oxide synthase (iNOS) was snppressed in MSC- vs. vehicle-treated animals. eNOS, endothelial NOS.

Andrographolide, thus, has different mechanisms of anti-inflammatory activity. It can inhibit the activation of NF-kB, suppress inducible nitric oxide synthase (iNOS) expression, inhibit COX-2 expression in human fibroblast cells and also prevent oxygen radical production by human. The compound is also able to modulate T-cell activation both in vitro as well as in vivo, it is evident that it could prevent initial T-cell priming by interfering with DC maturation and antigen presentation capacity. Therefore, andrographolide may have utility as a therapeutic agent for the treatment of autoimmune diseases, such as multiple sclerosis. " ... 

In addition to the inhibition of COX, lornoxicam shows weak inhibition of LPS-induced inducible nitric oxide synthase (iNOS IC50 65 pM) and LPS-induced interleukin-6 (IC50 54 pM), both of which could contribute to its potent anti-inflammatory and analgesic action (Berg et al., 1999). 

Garcia-Mediavilla V, Crespo I, Collado PS, Esteller A, Sanchez-Campos S, Tunon MJ, Gonzalez-Gallego J. 2007. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive... 

In addition to direct effects on genes regulating inflammation, glucocorticoids also inhibit the transcription factors that initiate synthesis of pro-inflammatory cytokines (e.g., interleukin-1, tumor necrosis factor), enzymes (e.g., COX-2, nitric oxide synthase), and receptor proteins (e.g., natural killer receptors).17,87,89 Glucocorticoids may also exert some of their effects via a membrane-bound receptor that regulates activity of macrophages, eosinophils, T lymphocytes, and several other types of cells involved in the inflammatory response.89 Consequently, glucocorticoids affect many aspects of inflammation, and their powerful anti-inflammatory effects in rheumatoid arthritis result from their ability to blunt various cellular and chemical components of the inflammatory response. 

Anti-inflammatory effects Prevents downregulation of endothelial nitric oxide synthase Decreased synthesis of endothelin-1 Reduced endothelial and soluble adhesion molecules... 

Maggi, L. B.Jr., Sadeghi, H., Weigand, C., Scarim, A. L., Heitmeier, M. R., and Corbett, J. A. (2000). Anti-inflammatory actions of 15-deoxy-delta 12,14-prostaglandin J2 and troglitazone Evidence for heat shock-dependent and -independent inhibition of cytokine-induced inducible nitric oxide synthase expression. Diabetes 49, 346-355. 

Prostaglandins (PG) and nitric oxide (NO) produced by inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the processes of inflammation and carcinogenesis. Potential COX-2 and iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents [25]. 

Bisphosphonates (particularly clodronate) have been shown to have anti-inflammatory effects in animal models of rheumatoid arthritis (RA), as well as in arthritis in humans. In adjuvant- and antigen-induced arthritis in rats, clodronate suppresses the inflammatory articular lesions in the inflamed joints [29], whilst in human RA, clodronate decreases the levels of interleukin (ILJ-1, tumor necrosis factor-alpha (TNFaand /1-microglobulin in the circulation [30]. In vitro, clodronate inhibits cytokine and nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in macrophage-like cells. 

Aminoalkyl-3, 4-dihydroquinoline derivatives, (VII), prepared by Jaroch (8) were effective as nitric oxide synthase inhibitors and used as anti-inflammatory agents. 

Kim WK, Jang PG, Woo MS, Han lO, Piao HZ, Lee K, Lee H, Joh TH, Kim HS (2004) A new anti-inflammatory agent KL-1037 represses proinflammatory cytokine and inducible nitric oxide synthase (iNOS) gene expression in activated microglia. Neuro-pharmacology 47 243—252. 

Knowles, R.G., Salter, M., Brooks, S.L. and Moncada, S. (1990). Anti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat. Biochem. Biophys. Res. Comm. 172, 1042-1048. 

Some bisbibenzyls exhibited anti-inflammatory activity through the inhibition of LPS-induced nitric oxide synthase (NOS) in RAW 264.7 macrophages. Of the 19 bisbibenzyls tested, marchantin A (812) was the most potent (ICso 1.44 //M), which might involve in the inhibition of LPS-induced iNOS mRNA expression. The presence of phenolic hydroxyls and saturation at C-7, C-8 and/or C-7VC-8 are required for the inhibition of NO production [490]. 

Exhaled nitric oxide was used as the marker of airway inflammation after patients who had asthma were found to have increased levels of exhaled nitric oxide and nitric oxide synthase expression [17]. Exhaled nitric oxide correlated with a response to steroid, defined as change in pulmonary function testing, asthma symptoms, and BHR [18]. Patients who have symptoms of asthma who respond to steroids have higher exhaled nitric oxide than those who do not, implying inadequate anti-inflammatory treatment. The cutoff of exhaled nitric oxide for steroid response was determined to be approximately 48 parts per billion in one study [18], but no standards are widely used. 

Attur MG, Patel R, Thakker G, Vyas P, Levartovsky D, Patel P, Naqvi S, Raza R, Patel K, Abramson D, Bruno G, Abramson SB, Amin AR. Differential anti-inflammatory effects of immunosuppressive drugs cyclosporin, rapamycin and FK-506 on inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and PGE2 production. Inflamm Res 2000 49 20-26. 

Tanacetum parthenium (Asteraceae), commonly known as feverfew, is a popular herbal remedy used a prophylactic in the treatment of migraine [88]. Studies have revealed that the action of feverfew is probably mediated by the sesquiterpene lactone parthenolide. Indeed, feverfew and parthenolide produce anti-inflammatory and antinociceptive effects in experimental animals [89]. Parthenolide is a potent inhibitor of the transcription factor NF-kB activation, a key regulator of pro-inflammatory protein production, such as cytokines, COX-2 and inducible nitric oxide synthase [90]. However, a clinical study revealed that feverfew did not provide any benefit in the treatment of rheumatoid arthritis [91]. Additional clinical studies must be carried out to explore the feverfew efficacy as an analgesic. 

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