Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator‐activated receptor‐γ by flavonoids in mouse macrophages

Abstract

Peroxisome proliferator-activated receptor (PPAR)Q Q transcription factor has been implicated in anti-inflammatory response. Of the compounds tested, apigenin, chrysin, and kaempferol significantly stimulated PPARQ Q transcriptional activity in a transient reporter assay. In addition, these three flavonoids strongly enhanced the inhibition of inducible cyclooxygenase and inducible nitric oxide synthase promoter activities in lipopolysaccharide-activated macrophages which contain the PPARQ Q expression plasmids. However, these three flavonoids exhibited weak PPARQ Q agonist activities in an in vitro competitive binding assay. Limited protease digestion of PPARQ Q suggested these three flavonoids produced a conformational change in PPARQ Q and the conformation differs in the receptor bound to BRL49653 versus these three flavonoids. These results suggested that these three flavonoids might act as allosteric effectors and were able to bind to PPARQ Q and activate it, but its binding site might be different from the natural ligand BRL49653. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Taiwanofungus camphoratusActivates Peroxisome Proliferator-Activated Receptors and Induces Hypotriglyceride in Hypercholesterolemic Rats

“…28) Our previous study has also demonstrated that several flavonoids were able to activate PPAR and result in decreased inflammation by a transient transfection assay on mouse macrophages. 24) Several studies 31) have further found that a compound of Momordica charantia, 9c, 11t, 13t-conjugated linolenic acid, was the active compound in wild bitter gourd and acted as a PPAR agonist. In the first 6 weeks of our study, the rats were provided with food and water ad libitum.…”

“…After 48 h of incubation, the cells were treated with various extracts of the wild fruiting body of T. camphoratus for 18 h. A total cell lysate was used to determine the luciferase activity with the Dual-Luciferase Reporter Assay kit (Promega) as described previously. 24) Animals and treatments. Male Sprague-Dawley (SD) rats (6 weeks old) were purchased from the National Laboratory Animal Center (Taipei, Taiwan), housed in stainless steel wire-bottomed cages, and acclimatized under laboratory conditions (19-23 C, 60% humidity, 12-h light/dark cycle) throughout the experimental period.…”

The role of herbs and spices in cancer prevention

“…Liang et al found that a higher concentration (IC 50 was 50 μM) was needed to bind to a Gst-PPARγ in an in vitro competitive binding assay, indicating flavonoids might not bind directly to PPARγ (82). Liang et al also found a cytotoxic effect at 20 μM of apigenin in RAW264.7 cells and a corresponding decrease in PPARγ activation (82). Quercetin, a known LOX inhibitor, was found to block keratinocyte differentiation and directly inhibit PPARs and the expression of PPAR-regulated genes (83).…”

“…One PPAR sub-family, PPARγ, is thought to be involved with immune response, specifically by activating arachidonic acid metabolites (82). PPARs serve as a link between pro-inflammatory cytokines and gene transcription factors and can influence cellular differentiation, apoptosis, and inflammation (66).…”

“…PPARs serve as a link between pro-inflammatory cytokines and gene transcription factors and can influence cellular differentiation, apoptosis, and inflammation (66). Liang et al (82) examined flavonoids, and found that flavones, flavonols, and isoflavones, but not flavanones and flavan-3-ols, were able to activate PPARγ, possibly because of the number and position of hydroxyl residues. Apigenin (a flavone) and kaempferol (a flavanol) in basil, coriander/ cilantro, cumin, rosemary, and thyme activate PPARγ to inhibit COX-2 expression in a dosedependent with an EC 50 of approximately 5 μM and 10 μM respectively (82).…”