Review of Scientific Literature

Honey Bee Venom

Here are some articles on bee venom therapy from the scientific literature.

Allergy

Patopllo, E.A.  Epidemiological and clinical study on bee venom allergy among beekeepers.  Boll-Ist-Sieroter-Milan. 1988. 67(5-6), p. 386-92.  A randomized population of 222 beekeepers from Lombardy (203 males, 19 females, of mean age 42.5 years) was studied to determine the frequency of allergic reactions to bee sting.  The results suggest that practice of beekeeping induces a relatively high incidence of allergic reactions, but with a trend to the spontaneous improvement of symptoms and a low incidence of severe reactions.

Reisman, R.E.  Livingston, A.  Late-onset allergic reactions, including serum sickness, after insect stings.  J. Allergy Clin. Immunol. 1989 Sep. 84(3), p. 331-7.  Allergic reactions after insect stings may have a delayed onset, differing from the usual immediate anaphylactic pattern.  The observations suggest that after an insect sting, patients may develop delayed onset allergic symptoms that range from typical anaphylaxis to serum sickness and are mediated by venom-specific IgE.

Glaucoma

Kam-J. Waron-M.  Intraocular pressure in cats is lowered by drops of hornet venom.  Comp-Biocben-Physiol [C].  1989. 92(2), p. 329-31.  Nine cats were given an intravenous injection of the Oriental hornet (Vespa orientalis, Vespinae; Hymenoptera) venom sacextract (VSE) and seven cats had the same VSE administered as eye drops.  This study shows that the active components of the hornet venom which caused a decrease in the intraocular pressure can cross the cornea and exert a hypotensive effect in the eye.

Alzheimer’s Disease

Ikeda-M. Dewar-D. McCulloch-J.Tl   Selective reduction of [1251] apamin binding sites in Alzheimer hippocampus:  a Quantitative autoradiographic study.  Brain-Res. 1991 Dec 13. S67(l). P Sl-6.JT-[l251]  Apamin binding sites were examined using quantitative autoradiography in the hippocampus of 9 patients with Alzheimer’s disease and 8 age-matched controls.

Within the hippocampal formation from control subjects, [1251] apamin binding sites were highly concentrated in the subiculum and CAl.  In Alzheimer’s disease there was a marked and discrete loss of [1251]apamin binding sites in the subiculum.  This reduction of [12SI]aparru'n binding sites in the subiculum correlated with cell density but not neuritic plaque density.  These results indicate that an anatomically discrete loss of Ca(2+)-dependent K+ channels within the hippocampal formation occurs in Alzheimer's disease.

Cancer

Ginsberg-N-J. Dauer-M. Slotta-K-H.T1  Melittin used as a protective agent against x-irradiation.  Nature. 1968 Dec 28. 220(174), p. 1334.  Hait-W-N. Grais-L. Benz-C. Cadman-E-C.TI  Inhibition of growth of leukemic cells by inhibitors of calmodulin: phenothiazines and melittin, Cancer-Chemother-Pharmacol. 1985. 14(3). P 202-5.AB Calmodulin, a ubiquitous calciumbinding protein, has recently been shown to play an important role in cellular proliferation.  The calmodulin inhibitors melittin, trifluoperazine, and chlorpromazine inhibited the growth and clonogenicity of human and murine leukemic cells, and their potency reflected their activity as inhibitors of calmodulin.  Melittin, which is a far more potent inhibitor of calmodulin activity, was also a more potent inhibitor of cell growth and clonogenicity.  The less active phenothiazine metabolite, chlorpromazine sulfoxide, had much less potent cytotoxic activity.

Killion, JJ. Dunn-J-D.Tl.  Differential cytolysis of murine spleen, bone-marrow, and leukemia cells by melittin reveals differences in membrane topography.  Biocbem-Biophys Res-Commun. 1986 Aug 29. 139(l), p. 222-7.  AB L1210 leukemia cells are 2-4 fold more sensitive to the cytolytic effects of melittin, the membrane-active toxin of bee venom, than normal DBA/2 mouse spleen and bone-marrow cells.

Gerst, J.E., Salomon-Y.TI.  Inhibition by Melittin and fluphenazine of melanotropin receptor function and adeylate cyclase in M2R melanoma cell membranes.  Endocrinology.  1987 Nov.121(5), p. 1766-72.

Multiple Sclerosis

Habermann-E.Tl.  Intrathecal apamin selectively facilitates activity in ascending axons of rat spinal cord evoked by stimulation of afferent C fibers in dural nerve.  Brain-Res 1983 Nov 28. 280(l), p. 186-9.  The results indicate that apamin facilitates synaptic transmission from high-threshold afferent C fibers to secondary neurons.

Renaud-J-F. Desnuelle-C. Serratrice-G. Lazdunski -M. TI. Expression of apamin receptor in muscles of patients with myotonic dystrophy.  Nature 1986 Feb 20-26. 319(600S), p. 678-80.  Myotonic muscular dystrophy, or Steinert disease, is a dominantly inherited disease of muscle which occurs with a frequency of between 1 in 18,000 and 1 in 7,500 people (refs 1, 2).  One of the prominent clinical manifestations is muscle stiffness and difficulty in relaxation of muscles after voluntary contractions.  We show here for the first time that muscle membranes of patients with myotonic muscular dystrophy contain the receptor for apamin, a bee venom toxin known to be a specific and high-affinity blocker of one class of Ca2+ activated K+ channels in mammalian muscle.  The apamin receptor is completely absent in normal human muscle as well as in muscles of patients with spinal anterior horn disorders.

Somerfield-S-D. Stach-J-L. Mraz-C. Gervais-F. Skamene-E.T.  Bee venom melittin blocks neutrophil O2- production.  Inflammation.  1986 Jun. 10(2), p. 175-82.  Bee venom (BV) is used in folk medicine to treat arthritis.  It has anti-inflammatory effects in animal models of rheumatic disease.  We have studied the effects of BV on human neutrophil production of superoxide (02-) and hydrogen peroxide, finding potent, nontoxic, dose-dependent production inhibition.  Melittin, the major fraction of BV (SO-70%) shows high affinity calmodulin binding (Kd 3 nM).  Drugs which bind calmodulin, such as trifluoperazine, inhibit O2-production by human neutrophils.  For these reasons, we have investigated the effect of melittin and other BV peptides on O2-production by human peripheral blood leukocytes.  We show that melittin inhibited O2- production both pre- and post-stimulation in contrast to other BV fractions which were without effect.  Oxygen radicals and their derivatives from inflammatory cells are implicated in the tissue damage occurring during inflammation.  The inhibition is due to a direct effect on cells, and not indicator medium, dismutation, toxic or scavenging effects.  We propose that melittin may sere as a prototype small (mol wt 1280), cationic, amphipathic, calmodulin-binding, membrane-active, super oxide-production-inhibiting peptide, providing a model for peptides which could have a role in vivo regulation of radical production.

Serkedjieva-J.  Anti-influenza virus effect of some propolis constituents and their analogues (esters of substituted cinnamic acids).  J-Nat-Prod. 1992 Mar. 55(3), p. 294-302.  The anti-viral activity of six synthetic substances, esters of substituted cinnamc acids, identical with or analogous to some of the constituents of the Et2O fraction of propolis was studied in vitro.  One of them isopentyl ferulate, inhibited significantly the infectious activity of influenza virus A/Hong Kong (H3N2) in vitro and the production of hemagglutinins in ovo.

Steketee-J-D. Kalivas-P-W.T.  Effect of microinjections of apamin into the A10 dopamine region of rats:  a behavioral and neurochemical analysis.  J-Pharmacol-Exp-Ther. 1990 Aug. 254(2), p. 711-9.  Hyperpolarization of dopamine neurons by activation of D2 and gamma-aminobutyric acid B receptors involves an increased conductance of K, ions.  Apamin, a blocker of Ca2(+)-activated K+ channels, has been reported to increase activity of dopamine neurons.  Increased activity of the mesolimbic dopamine system is associated with increased motor activity.  Thus, we investigated the behavioral and neurochemical effects of acute and daily microinjections of apamin into the A10 region of the rat. Apamin increased motor activity in a dose-dependent manner, and this effect was blocked by pretreatment with 0.1 mg/kg haloperidol.  In postmortem analysis, 6.0 pmol of apamin significantly increased the levels of dihydroxyphenylacetic acid in the A10 region and of dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens, and 2.0 pmol of apamin significantly increased the level of dopamine in the prefrontal cortex. In vivo dialysis in the nucleus accumbens of freely moving rats revealed that apamin elevated extracellular dopamine metabolites.  Rats receiving daily microinjections of apamin into the A10 region did not exhibit an augmentation in motor activity, suggesting that rats did not become sensitized to chronic treatment.  These data are discussed in terms of the role of apamin-sensitive dopamine mechanisms in motor behavior and sensitization of these motor behaviors.

Dermatology

Grange-J-M. Reply:  Honey and propolis as possible promoters of the healing of in leprosy [letter; comment]. Lep,-Rev. 1990 Jun. 61(2), p. 195.

Grange-J-M. Davey-R-W. Antibacterial properties of propolis (bee glue). J-R-Soc-Med. 1990 Mar. 83(3). P 159-60.  Propolis (bee glue) was found to have antibacterial activity against a range of commonly encountered cocci and Gram-positive rods, including the human tubercle bacillus, but only limited activity against Gram-negative bacilli.  These findings confirm previous reports of antimicrobial properties of this material, possibly attributable to its high flavonoid content.

Dobrowolski-J-W.  Antibacterial, antifungal, antiamoebic, anti-inflammatory and antipyretic studies on propolis bee products.  J-Ethnopbarmacol. 1991 Oct. 35(l), p. 77-82.

Anti-inflammatory

Krol-W. Scheller-S.  Anti-oxidant property of ethanolic extract of propolis (EEP) as evaluated by inhibiting the chemiluminescence oxidation of luminol.  Biochem-Int. 1990. 21(4), p. 593-7.  Ethanolic extract of propolis (EEP) has remarkable medical properties, including protection of mice against gamma-irradiation.  Its anti-oxidative effect has been attributed to its radical scavenging ability.  This manuscript demonstrates the ability of increasing amounts of EEP to inhibit luminol-H202 chemiluminescence in vitro and suggests that its anti-oxidative capacity is partly due to its high content of flavonoids.

Scheller-S.  Free radical scavenging by ethanol extract of propolis.  Int-J-Radiat-Biol.  1990 Mar. 57(3), p. 461-5.

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