In Vitro and In Vivo Anti-Allergic and Anti-Inflammatory Effects of eBV, a Newly Developed Derivative of Bee Venom, through Modulation of IRF3 Signaling Pathway in a Carrageenan-Induced Edema Model

• Published in: PloS one Vol. 11; no. 12; p. e0168120
• Main Authors: Chung, Hwa-Jin, Lee, Jinho, Shin, Joon-Shik, Kim, Me-Riong, Koh, Wonil, Kim, Min-Jeong, Lee, Jae-Woong, Kim, Eun Jee, Lee, In-Hee, Kim, Won Kyung, Lee, Yoon Jae, Lee, Sang Kook, Ha, In-Hyuk
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.12.2016; Public Library of Science (PLoS)
• Subjects: Acupuncture; Allergies; Alternative medicine; Analgesics; Animals; Antigens; Apis mellifera; Arthritis; Back pain; Bee venoms; Bee Venoms - therapeutic use; Biology and Life Sciences; Blotting, Western; Carrageenan; Carrageenan - pharmacology; Chromatography, High Pressure Liquid; Compound 48/80; Cytokines; Dinoprostone - metabolism; Disease Models, Animal; Edema; Edema - chemically induced; Edema - drug therapy; Epstein-Barr virus; Gene expression; Histamine; Histamine - metabolism; Hypersensitivity; Hypersensitivity - drug therapy; IL-1β; Immune system; Immunology; In vivo methods and tests; Inflammation; Inflammation - drug therapy; Inflammatory diseases; Inflammatory response; Interferon; Interferon regulatory factor; Interferon regulatory factor 3; Interferon Regulatory Factor-3 - antagonists & inhibitors; Interleukin; Interleukin-4 - metabolism; Interleukins; Kinases; Lipopolysaccharides; Macrophages; Male; Medicine and Health Sciences; Mice; Natural products; Nitric oxide; Pharmacy; Phospholipase; Phospholipase A2; Phospholipases; Phosphorylation; Physical Sciences; Prostaglandin E2; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells - drug effects; Real-Time Polymerase Chain Reaction; Research and Analysis Methods; Serum levels; Signal transduction; Signal Transduction - drug effects; Signaling; Skin; Stat1 protein; STAT1 Transcription Factor - drug effects; Transducers; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Venom; Asia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0168120

Bee venom (BV), a type of toxin extracted from honeybees (Apis mellifera), has been empirically and widely used to treat inflammatory diseases throughout Asia. Essential BV (eBV) was developed by removing phospholipase A2 (PLA2) and histamine to lower occurrence of allergic reaction. This study investigated the anti-allergic and anti-inflammatory activities of eBV in vitro and in vivo and its underlying mechanism of action. The anti-inflammatory potential of eBV was assessed in vivo using a carrageenan-induced paw edema model. To further investigate the mechanism by which eBV exerts anti-allergic and anti-inflammatory effects, compound 48/80-stimulated RBL-2H3 cells and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells were studied in vitro. Release of β-hexosaminidase and histamine was increased by eBV in a dose-dependent manner, but these levels were lower in eBV compared to original BV at the same concentration. In addition, eBV suppressed compound 48/80-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in RBL-2H3 cells. eBV was also shown to suppress nitric oxide (NO) production by down-regulating mRNA expression and subsequent protein expression of inflammatory mediators in LPS-induced RAW 264.7 cells. Phosphorylation of activators and signal transducers of transcription 1/interferon regulatory factor 3 (STAT1/IRF3) was attenuated by eBV treatment. eBV significantly inhibited carrageenan-induced acute edema in vivo. Serum levels of prostaglandin E2 (PGE2), TNF-α, and IL-1β were also down-regulated by eBV. These results demonstrate that eBV inhibits allergic and inflammatory response by reducing inflammatory mediator production via regulation of the STAT1/IRF3 signaling pathway, suggesting that eBV is a feasible candidate for regulation of allergic-inflammatory response in complementary and alternative medicine.