Pterostilbene Suppressed Lipopolysaccharide-Induced Up-Expression of iNOS and COX-2 in Murine Macrophages

Abstract

Pterostilbene, an active constituent of blueberries, is known to possess anti-inflammatory activity and also to induce apoptosis in various types of cancer cells. Here, we investigated the inhibitory effects of pterostilbene on the induction of NO synthase (NOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Western blotting and real-time polymerase chain reaction (PCR) analyses demonstrated that pterostilbene significantly blocked the protein and mRNA expression of iNOS and COX-2 in LPS-induced macrophages. Treatment with pterostilbene resulted in the reduction of LPS-induced nuclear translocation of the nuclear factor-kappaB (NFkappaB) subunit and the dependent transcriptional activity of NFkappaB by blocking phosphorylation of inhibitor kappaB (IkappaB)alpha and p65 and subsequent degradation of IkappaB alpha. Transient transfection experiments using NFkappaB reporter constructs indicated that pterostilbene inhibits the transcriptional activity of NFkappaB in LPS-stimulated mouse macrophages. We found that pterostilbene also inhibited LPS-induced activation of PI3K/Akt, extracellular signal-regulated kinase 1/2 and p38 MAPK. Taken together, these results show that pterostilbene down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFkappaB by interfering with the activation of PI3K/Akt/IKK and MAPK. These results have an important implication for using pterostilbene toward the development of an effective anti-inflammatory agent.

Pterostilbene protects against acute renal ischemia reperfusion injury and inhibits oxidative stress, inducible nitric oxide synthase expression and inflammation in rats via the Toll‑like receptor 4/nuclear factor‑κB signaling pathway

“…In the present study, administration of Pter significantly suppressed MPO levels and iNOS protein expression levels following renal IRI in rats. A previous study reported that Pter attenuated inflammation via suppression of MPO levels and the TLR4/NF-κB signaling pathway in rat hearts following ischemia-reperfusion (17). In addition, Pan et al (17) demonstrated that Pter inhibited lipopolysaccharide-induced iNOS expression in murine macrophages.…”

“…A previous study reported that Pter attenuated inflammation via suppression of MPO levels and the TLR4/NF-κB signaling pathway in rat hearts following ischemia-reperfusion (17). In addition, Pan et al (17) demonstrated that Pter inhibited lipopolysaccharide-induced iNOS expression in murine macrophages. A previous study demonstrated that IL-10 exhibits protective effects against IRI (18).…”

Some Phytochemicals and Anti-inflammation Effect of Juice from <i>Tiliacora triandra</i> Leaves

“…The cells were incubated in medium composing of LPS (100 ng/mL) and the sample in DMSO at various concentration was added. Cells treated with 0.1% DMSO were set as vehicle control [20].…”

“…The supernatant (100 μL) were mixed with Griess reagent (1% of sulfanilamide in 5% of phosphoric acid and 0.1% of naphthylethylenediamine dihydrochloride in water) and the absorbance of the mixture was measured at 550 nm in an enzyme-linked immunosorbent assay (ELISA) plate reader (Dynatech MR-7000; Dynatech Labs, Chantilly, VA, USA) [20].…”

Pterostilbene Reduced Post-Antibiotic Effect Time of Linezolid against Methicillin-Resistant Staphylococcus aureus

“…A high content of these phenylpropanoid compounds, notably resveratrol and its analogue pterostilbene, identified in Vitis vinifera leaves [15] , heartwood of sandalwood Pterocarpus marsupium [16] and in some species of Vaccinium berries [17] are known to have diverse pharmacological activities [18] . Pterostilbene possesses potent antioxidant activity [19] , anticancer property [20] , anti-antiinflammatory [21] , antifungal [22] and to date, possess antibacterial activity against MRSA [23] .…”