Antiarthritic effect of bee venom: Inhibition of inflammation mediator generation by suppression of NF-?B through interaction with the p50 subunit

College of Pharmacy, Chungbuk National University, 48 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.
Arthritis & Rheumatology (Impact Factor: 7.76). 11/2004; 50(11):3504-15. DOI: 10.1002/art.20626
Source: PubMed


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.
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 adjuvant-induced 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-kappaB 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-kappaB was determined with a surface plasmon resonance analyzer.
BV (0.8 and 1.6 mug/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 mug/ml) and melittin (5 and 10 mug/ml) on lipopolysaccharide (LPS; 1 mug/ml)-induced expression of cyclooxygenase 2, cytosolic phospholipase A(2), inducible NO synthase, generation of PGE(2) and NO, and the intracellular calcium level. BV and melittin prevented LPS-induced transcriptional and DNA binding activity of NF-kappaB via the inhibition of IkappaB release and p50 translocation. BV (affinity [K(d)] = 4.6 x 10(-6)M) and melittin (K(d) = 1.2 x 10(-8)M) bound directly to p50.
Target inactivation of NF-kappaB by directly binding to the p50 subunit is an important mechanism of the antiarthritic effects of BV.

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Available from: Dong Ju Son, Sep 01, 2014
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    • "Bee venom therapy, also acupuncture (apipuncture), is used by some as a treatment for rheumatism and joint diseases , due to its anticoagulant and anti-inflammatory properties [6, 9–12]. BV also has an antiarthritic effect in patients with rheumatoid arthritis [4]. Anti-inflammatory and analgesic effect of BV may be explained by process of counterirritation , which increases pain thresholds sensitivity and "
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    ABSTRACT: The aim of the study was the evaluation of myorelaxant action of bee venom (BV) ointment compared to placebo. Parallel group, randomized double blinded trial was performed. Experimental group patients were applying BV for 14 days, locally over masseter muscles, during 3-minute massage. Placebo group patients used vaseline for massage. Muscle tension was measured twice (TON1 and TON2) in rest muscle tonus (RMT) and maximal muscle contraction (MMC) on both sides, right and left, with Easy Train Myo EMG (Schwa-medico, Version 3.1). Reduction of muscle tonus was statistically relevant in BV group and irrelevant in placebo group. VAS scale reduction was statistically relevant in both groups: BV and placebo. Physiotherapy is an effective method for myofascial pain treatment, but 0,0005% BV ointment gets better relief in muscle tension reduction and analgesic effect. This trial is registered with NCT02101632 .
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    • "Honeybee (Apis mellifera) venom (BV) tops the list of the newly introduced natural anticancer agents [5]. The radioprotective , antimutagenic, pain-relieving, anti-inflammatory, antiarthritic, antihyperalgesic, and antinociceptive effects of BV have been documented [6] [7] [8]. BV is a highly complex blend of at least 18 active components , including active peptides, enzymes, and amines that contain histamine, catecholamines, polyamines, melittin, and phospholipase A 2 [9]. "
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    • "It is a small linear peptide composed of 26 amino acids with a hydrophobic N-terminal region and a hydrophilic C-terminal region [21]. Many studies have shown that melittin has an anti-viral, anti-arthritic, and anti-inflammatory effect [22, 23, 24]. Recent studies have shown that melittin induced apoptosis in hepatic and vascular smooth muscle cells through nuclear factor kappa B (NF-κB) inhibition and alpha serine/threonine-protein kinase 1 (AKT) activation [25]. "
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