Bee venom and melittin reduce proinflammatory mediators in lipopolysaccharide-stimulated BV2 microglia

• Published in: International immunopharmacology 2007-08, Vol.7 (8), p.1092-1101
• Main Authors: Moon, Dong-Oh, Park, Sung-Yong, Lee, Kyeong-Jun, Heo, Moon-Soo, Kim, Ki-Cheon, Kim, Mun-Ock, Lee, Jae-Dong, Choi, Yung Hyun, Kim, Gi-Young
• Format: Article
• Language: English
• Subjects: Akt; Animals; Antioxidants - pharmacology; Bee venom; Bee Venoms - chemistry; Bee Venoms - pharmacology; Biological and medical sciences; c-Jun N-terminal kinase; Cell Line, Transformed; Cell Survival - drug effects; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Dinoprostone - metabolism; Dose-Response Relationship, Drug; Down-Regulation - drug effects; I-kappa B Kinase - metabolism; Immunoblotting; Inflammation Mediators - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; JNK Mitogen-Activated Protein Kinases - metabolism; Lipopolysaccharides - pharmacology; Medical sciences; Melitten - chemistry; Melitten - pharmacology; Melittin; Microglia - cytology; Microglia - drug effects; Microglia - metabolism; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide - secretion; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nuclear factor kappa B; Pharmacology. Drug treatments; Proline - analogs & derivatives; Proline - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Thiocarbamates - pharmacology
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2007.04.005

Bee venom (BV), well known as a traditional Oriental medicine, has been shown to exhibit anti-arthritic and anti-carcinogenic effects. However, the molecular mechanisms responsible for the anti-inflammatory activity of BV have not been elucidated in microglia. In the present study, we investigated the anti-inflammatory effect of BV and its major component, melittin (MEL), on lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results indicate that BV and MEL suppress LPS-induced nitric oxide (NO) and inducible NO synthase (iNOS) expression in a dose-dependent manner, without causing cytotoxicity in BV2 microglia. Moreover, BV and MEL suppressed LPS-induced activation of nuclear factor kappa B (NF-κB) by blocking degradation of IκBα and phosphorylation of c-Jun N-terminal kinase (JNK) and Akt, which resulted in inhibition of iNOS expression. Our data also indicate that BV and MEL exert anti-inflammatory effects by suppressing the transcription of cyclooxygenase (COX)-2 genes and proinflammatory cytokines, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. BV and MEL also attenuated the production of prostaglandin E 2 (PGE 2). These results demonstrate that BV and MEL possess a potent suppressive effect on proinflammatory responses of BV2 microglia and suggest that these compounds may offer substantial therapeutic potential for treatment of neurodegenerative diseases that are accompanied by microglial activation.