Luteolin and luteolin-7-O-glucoside inhibit lipopolysaccharide-induced inflammatory responses through modulation of NF- κ B/AP-1/PI3K-Akt signaling cascades in RAW 264.7 cells

Luteolin is a flavonoid found in abundance in celery, green pepper, and dandelions. Previous studies have shown that luteolin is an anti-inflammatory and anti-oxidative agent. In this study, the anti-inflammatory capacity of luteolin and one of its glycosidic forms, luteolin-7-O-glucoside, were compared and their molecular mechanisms of action were analyzed. In lipopolysaccharide (LPS)-activated RAW 264.7 cells, luteolin more potently inhibited the production of nitric oxide (NO) and prostaglandin E-2 as well as the expression of their corresponding enzymes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) than luteolin-7-O-glucoside. The molecular mechanisms underlying these effects were investigated to determine whethet the inflammatory response was related to the transcription factors, nuclear factor (NF)-kappa B and activator protein (AP)-1, or their upstream signaling molecules, mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K). Luteolin attenuated the activation of both transcription factors, NF-kappa B and AP-1, while luteolin-7-O-glucoside only impeded NF-kappa B activation. However, both flavonoids inhibited Akt phosphorylation in a dose-dependent manner. Consequently, luteolin more potently ameliorated LPS-induced inflammation than luteolin-7-O-glucoside, which might be attributed to the differentially activated NF-kappa B/AP-1/PI3K-Akt pathway in RAW 264.7 cells.