Anti-inflammatory effects and molecular mechanisms of 8-prenyl quercetin

• Published in: Molecular nutrition & food research Vol. 60; no. 5; pp. 1020 - 1032
• Main Authors: Hisanaga, Ayami, Mukai, Rie, Sakao, Kozue, Terao, Junji, Hou, De-Xing
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.05.2016
• Subjects: animal models; Animals; anti-inflammatory activity; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Cellular signaling; Cyclooxygenase 2 - metabolism; cytokines; Cytokines - metabolism; Dinoprostone - metabolism; Direct binding; Disease Models, Animal; edema; Edema - drug therapy; Edema - etiology; enzyme-linked immunosorbent assay; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; foods; inducible nitric oxide synthase; Inflammatory mediators; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; mitogen-activated protein kinase; Models, Molecular; Molecular targets; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Prenyl quercetin; prostaglandin synthase; prostaglandins; Protein Conformation; quercetin; Quercetin - analogs & derivatives; Quercetin - chemistry; Quercetin - pharmacology; RAW 264.7 Cells; Toll-like receptor 4; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Western blotting; Molecular targets; Prenyl quercetin; Inflammatory mediators; Cellular signaling; Direct binding
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.201500871

Scope 8‐prenyl quercetin (PQ) is a typical prenylflavonoid distributed in plant foods. It shows higher potential bioactivity than its parent quercetin (Q) although the mechanisms are not fully understood. This study aims to clarify the anti‐inflammatory effects and molecular mechanisms of PQ in cell and animal models, compared to Q. Methods and results RAW264.7 cells were treated with PQ or Q to investigate the influence on the production of inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), and protein kinases by Western blotting. Nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by the Griess method and ELISA, respectively. Cytokines were assayed by the multiplex technology. Mouse paw edema was induced by LPS. The results revealed that PQ had stronger inhibition on the production of iNOS, COX‐2, NO, PGE2, and 12 kinds of cytokines, than Q. PQ also showed in vivo anti‐inflammatory effect by attenuating mouse paw edema. Molecular data revealed that PQ had no competitive binding to Toll‐like receptor 4 with LPS, but directly targeted SEK1‐JNK1/2 (where SEK is stress‐activated protein kinase and JNK1/2 is Jun‐N‐terminal kinase 1/2) and MEK1‐ERK1/2 (where ERK is extracellular signal regulated kinase). Conclusion PQ as a potential inhibitor revealed anti‐inflammatory effect in both cell and animal models at least by targeting SEK1‐JNK1/2 and MEK1‐ERK1/2. 8‐prenyl quercetin (PQ) shows a higher bioactivity than the parent quercetin. This study clarified the anti‐inflammatory effects and molecular mechanisms of PQ. PQ revealed stronger anti‐inflammatory effects in both cell and rat models than quercetin. Molecular data demonstrated that PQ had no competitive binding to Toll‐like receptor 4 with LPS, but might directly bind to SEK1‐JNK1/2 (where SEK is stress‐activated protein kinase and JNK1/2 is Jun‐N‐terminal kinase 1/2) and MEK1‐ERK1/2 (where ERK is extracellular signal regulated kinase) kinases to attenuate inflammatory signaling.