Antiarthritic effect of bee venom: Inhibition of inflammation mediator generation by suppression of NF‐κB through interaction with the p50 subunit

Abstract

Objective. To investigate the molecular mechanisms of the antiarthritic effects of bee venom (BV) and melittin (a major component of BV) in a murine macrophage cell line (Raw 264.7) and in synoviocytes obtained from patients with rheumatoid arthritis.Methods. We evaluated the antiarthritic effects of BV in a rat model of carrageenan-induced acute edema in the paw and in a rat model of chronic adjuvantinduced arthritis. The inhibitory effects of BV and melittin on inflammatory gene expression were measured by Western blotting, and the generation of prostaglandin E 2 (PGE 2 ) and nitric oxide (NO) and the intracellular calcium level were assayed. NF-B DNA binding and transcriptional activity were determined by gel mobility shift assay or by luciferase assay. Direct binding of BV and melittin to the p50 subunit of NF-B was determined with a surface plasmon resonance analyzer.Results. BV (0.8 and 1.6 g/kg) reduced the effects of carrageenan-and adjuvant-induced arthritis. This reducing effect was consistent with the inhibitory effects of BV (0.5, 1, and 5 g/ml) and melittin (5 and Conclusion. Target inactivation of NF-B by directly binding to the p50 subunit is an important mechanism of the antiarthritic effects of BV.

Inflexinol inhibits colon cancer cell growth through inhibition of nuclear factor-κB activity via direct interaction with p50

“…Very similar to our findings, kamebakaurin and kamebanin were found to be able to interact with both the p50 and p65 subunits of NF-κB (41). Similar inhibition mechanisms have been shown by other agents, such as N-ethylmaleimide, cyclopentenone prostaglandin, 2-hydroxycinnamaldehyde, snake venom toxin, and melittin, which showed anti-inflammatory and anticancer properties (24,26,38,42). Cysteine residues in IκB kinases (IKK) have also been modified by same mechanism with several compounds such as arsenite (43), auranofin (44), and cyclopentenone prostanoids prostaglandin A 1 and 15d-prostaglandin J 2 and their derivatives (45).…”

“…We also included on each plate a negative control (without inflexinol) and a positive control (with labeled antibodies and p50 protein). We also analyzed the p50 and inflexinol binding using plasmon resonance analysis, as described elsewhere (26), using Biacore system and CM5 sensor chip (both supplied by Biacore AB).…”

Co-administration of Water Containing Magnesium Ion Prevents Loxoprofen-Induced Lesions in Gastric Mucosa of Adjuvant-Induced Arthritis Rat

“…Rheumatoid arthritis (RA) is a complex chronic inflammatory disease dependent on multiple interacting environmental and genetic factors, such as T cells, 1) neutrophils, 2) activated T lymphocytes, 3) macrophages, 4) eicosanoids 5) and cytokines, 6,7) making it difficult to understand its pathogenesis and thereby to find effective therapies. 8) In treatments for RA, the focus is on the reduction of pain, inflammation and joint damage.…”

Apitherapy Have a Role in Treatment of Multiple Sclerosis

“…The therapeutic benefits of honeybee venom have been known for a long time to relieve pain and to treat inflammatory diseases particularly for treatment of arthritic and rheumatic conditions in humans [21,22] and in animals [23][24][25]. Specific immunotherapy with bee venom can result in an almost complete protection against adverse (or allergic) reactions from stings in the great majority of cases [26].…”