1: In Vivo. 2005 Jul-Aug;19(4):801-5.

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Inhibitory effect of whole bee venom in adjuvant-induced arthritis.

Lee JY, Kang SS, Kim JH, Bae CS, Choi SH.

College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Republic of Korea.

The aim of this study was to assess the inhibitory effect of whole bee venom (BV) on adjuvant-induced arthritis in the rat. Rats were divided into pre-apitherapy, post-apitherapy and control experimental groups. The pre-apitherapy group was subcutaneously stung with a honeybee (Apis mellifera L.) and the control group was subcutaneously injected with 0.1 ml of physiological saline solution one day prior to complete Freund's adjuvant (CFA) injection. The post-apitherapy group was subcutaneously stung with a honeybee on day 14 after CFA injection. When arthritis had developed in the rat, the post-apitherapy group was subcutaneously administered whole BV every other day for a further 14 days. Clinical signs, hematological values and radioglogical features were observed during the entire experimental period. In the pre-apitherapy group, the development of inflammatory edema and polyarthritis was inhibited. Significant differences in lameness score, hind paw edema volume and radiological features were observed between control and pre-apitherapy rats. White blood cell counts indicated that the degree of leucocytosis was significantly different between the pre-apitherapy and control groups (p < 0.01). Inflammatory edema, polyarthritis and bone change into the right hind paw were effectively inhibited in pre-apitherapy rats during the two-week period post-CFA injection. In conclusion, whole BV was found to inhibit arthritic inflammation and bone changes in the rat. This may be an alternative treatment for arthritis in humans.

PMID: 15999553 [PubMed - indexed for MEDLINE]

2: Toxicon. 2005 Jul;46(1):39-45.

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Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patients with rheumatoid arthritis.

Hong SJ, Rim GS, Yang HI, Yin CS, Koh HG, Jang MH, Kim CJ, Choe BK, Chung JH.

Department of Internal Medicine, College of Medicine, Pochon CHA University, 351 Yatap-dong, Bundang-gu, Sungnam-si, Kyonggi-do 463-712, South Korea.

Bee venom (BV) has been used traditionally for the control of pain and inflammation in various chronic inflammatory diseases, including rheumatoid arthritis (RA) in Oriental medicine. However, it is still unclear how BV exerts its beneficial effects on the clinical course of RA patients. To investigate the effect of BV on the treatment of rheumatoid synovitis, we examined the inhibition of cell growth and induction of apoptosis in human rheumatoid synovial fibroblasts. Rheumatoid synovial fibroblasts were surgically obtained from patients with RA. Cell proliferation and viability were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis of synovial cells treated with 10 microg/ml BV for 24 h was identified by 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, DNA fragmentation assay, RT-PCR, and Western blot analysis. It was demonstrated that rheumatoid synovial cells treated with 10 microg/ml BV for 24 h exhibited apoptotic features and fragmentation of DNA. In addition, BV induces apoptosis in rheumatoid synovial cells through a decrease in BCL2 expression and an increase in BAX and caspase-3 (CASP3) expression. It is suggested that BV inhibits the proliferation of rheumatoid synovial cells through induction of apoptosis by CASP3 activation.

PMID: 15922390 [PubMed - indexed for MEDLINE]

3: J Ethnopharmacol. 2005 Jun 3;99(2):245-52. Epub 2005 Apr 11.

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Effect of bee venom on aromatase expression and activity in leukaemic FLG 29.1 and primary osteoblastic cells.

Kim KS, Choi US, Lee SD, Kim KH, Chung KH, Chang YC, Park KK, Lee YC, Kim CH.

Department of Acupuncture, Biochemistry and Molecular Biology, College of Oriental Medicine, Dongguk University and National Research Laboratory for Glycobiology, Kyungju, Kyungbuk 780-714, Korea.

The effect of bee venom aqua-acupuncture (BVA) (api-toxin), a traditional immunosuppressive Korean aqua-acupuncture, on the bone function in human osteoblastic cells was studied. To provide insights into the effect of BVA on aromatase activity in bone-derived cells, we examined the human leukaemic cell line FLG 29.1, which is induced to differentiate toward the osteoclastic phenotype by TPA and TGF-beta1, and the primary first-passage osteoblastic cells (hOB). Southern blot of RT-PCR products with a 32P-labeled cDNA probe for the human aromatase demonstrated that FLG 29.1 and hOB cells express aromatase mRNA. Gene expression and enzyme activity were stimulated in a time-dependent fashion by 5.0 microl/ml BV and by either 1-50 nM TPA or 0.01-0.5 ng/ml TGF-beta1, with maximal responses after 2-3 h exposure. After 24 h incubation of the cells in the absence of these stimuli the aromatase mRNA and the protein were barely detectable. These findings demonstrate that cells of the osteoclastic lineage synthesize aromatase in vitro by the local cytokine of TGF-beta1 and BVA. These can offer an explanation for the lack of development of osteoarthritis in BVA-treated patients.

PMID: 15894134 [PubMed - indexed for MEDLINE]

4: Arthritis Rheum. 2004 Nov;50(11):3504-15.

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Antiarthritic effect of bee venom: inhibition of inflammation mediator generation by suppression of NF-kappaB through interaction with the p50 subunit.

Park HJ, Lee SH, Son DJ, Oh KW, Kim KH, Song HS, Kim GJ, Oh GT, Yoon do Y, Hong JT.

College of Pharmacy, Chungbuk National University, 48 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.

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 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. RESULTS: 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. CONCLUSION: Target inactivation of NF-kappaB by directly binding to the p50 subunit is an important mechanism of the antiarthritic effects of BV.

PMID: 15529353 [PubMed - indexed for MEDLINE]

5: Am J Chin Med. 2004;32(3):361-7.

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Anti-inflammatory effect of bee venom on type II collagen-induced arthritis.

Lee JD, Kim SY, Kim TW, Lee SH, Yang HI, Lee DI, Lee YH.

Research Group of Pain and Neuroscience in Vision 2000 Project East-West Medical Research Institute, Kyung Hee University, Seoul, Korea. ljdacu@khmc.or.kr

Bee venom (BV) has been used to relieve pain and reduce inflammation in traditional Oriental medicine, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). We previously reported that the BV injection into a traditional acupuncture point (Zusanli) reduced arthritis-associated edema and nociceptive responses in Freund's adjuvant-induced arthritis in rats (Kwon et al., 2001). This study was designed to evaluate the anti-inflammatory and anti-cytokine effect of BV on a murine type-II collagen-induced arthritis (CIA) model. Male mice were immunized by spontaneous injection of 100 microg of an emulsion of bovine type-II collagen and complete Freund's adjuvant (CFA), with a booster injection after 2 weeks. In the experimental group, 0.1 ml BV was injected at acupuncture point (Zusanli) near both knees twice a week for a total of 5 times. In the control group, normal saline was injected at the same frequencies. These injections began 5 weeks after the first collagen injection. Starting the 3rd week after the first collagen injection, we examined limb swelling and severity of arthritis twice a week. At 8 weeks, mice were sacrificed and synovial tissue was examined with the light microscope and serum cytokines (IL-1beta and TNF-alpha) were measured by ELISA. The incidence of arthritis, the mean arthritis index and the number of arthritic limbs were significantly lower in the treatment compared to the control group (63% versus 75%, 3.4% versus 8.5%, 23% versus 75%, respectively). Among the serum proinflammatory cytokines, the production of TNF-alpha in the BV group was suppressed compared to the control group (59 +/- 4.5 versus 99.5 +/- 6.5, p < 0.05), but IL-1beta was not suppressed. The examination of the histopathology of the joints of murine CIA showed decreased inflammation signs and less lymphocyte infiltration after BV acupuncture therapy. Acupuncture therapy with BV suppressed the development of arthritis and caused inhibition of the immune responses in type-II collagen-induced arthritis.

PMID: 15344419 [PubMed - indexed for MEDLINE]

6: Zhong Yao Cai. 2003 Jun;26(6):456-8.

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[Advances in the study of bee venom and its clinical uses]

[Article in Chinese]

Liu H, Tong F.

College of Zoological Sciences, Zhejiang University, Hangzhou 310029, Zhejiang, China.

Publication Types:

·       Review

PMID: 14669739 [PubMed - indexed for MEDLINE]

7: Am J Chin Med. 2002;30(1):73-80.

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The effect of whole bee venom on arthritis.

Kang SS, Pak SC, Choi SH.

College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.

This study was performed to assess the clincotherapeutic effect of whole venom of honeybee (Apis mellifera) in adjuvant-induced arthritic rat. Ninety Sprague-Dawley male rats were injected with complete Freund's adjuvant (CFA). Adjuvant arthritis was produced by a single subcutaneous injection of I mg Mycobacterium butyricum suspended in 0.1 ml paraffin oil into the right hind paw. Righting reflex was uniformly lost and considered to be the point of arthritis development on day 14 after CFA injection. The experiments were divided into three groups. When arthritis was developed in the rat, tested groups were administered with prednisolone (10 mg/kg, p.o.) or honeybee venom (one bee, s.c.) every other day for another 14 days. Control group was injected with 0.1 ml of physiological saline solution subcutaneously. Clinical and hematological values with histopathological findings were observed during the drug administration. In treatment groups, the development of inflammatory edema and polyarthritis was suppressed. No significant differences of hind paw edema volume and lameness score between prednisolone and honeybee venom groups were observed during treatment. White blood cell counts of control group showed leucocytosis that was significantly different from the two treatment groups (p < 0.01). Erosions of articular cartilage and inflammatory cell infiltrations into interphalangeal joint were effectively suppressed in treated groups. In conclusion, whole honeybee venom was found to suppress arthritic inflammation in the rat. This may be an alternative treatment of arthritic agony in humans.

PMID: 12067099 [PubMed - indexed for MEDLINE]

8: Life Sci. 2002 May 31;71(2):191-204.

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The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats.

Kwon YB, Lee HJ, Han HJ, Mar WC, Kang SK, Yoon OB, Beitz AJ, Lee JH.

Department of Veterinary Physiology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Suwon, South Korea.

We recently demonstrated that bee venom (BV) injection into the Zusanli acupoint produced a significantly more potent anti-inflammatory and antinociceptive effect than injection into a non-acupoint in a Freund's adjuvant induced rheumatoid arthritis (RA) model. However, the precise BV constituents responsible for these antinociceptive and/or anti-inflammatory effects are not fully understood. In order to investigate the possible role of the soluble fraction of BV in producing the anti-arthritic actions of BV acupuncture, whole BV was extracted into two fractions according to solubility (a water soluble fraction, BVA and an ethylacetate soluble fraction, BVE) and the BVA fraction was further tested.Subcutaneous BVA injection (0.9 mg/kg/day) into the Zusanli acupoint was found to dramatically inhibit paw edema and radiological change (i.e. new bone proliferation and soft tissue swelling) caused by Freund's adjuvant injection. BVA treatment also reduced the increase in serum interleukin-6 caused by RA induction to levels observed in non-arthritic animals. In addition, BVA therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). Finally, BVA treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. In contrast, BVE treatment (0.05 mg/kg/day) failed to show any anti-inflammatory or antinociceptive effects on RA.The results of the present study demonstrate that BVA is the effective fraction of whole BV responsible for the antinociception and anti-inflammatory effects of BV acupuncture treatment. Thus it is recommended that this fraction of BV be used for long-term treatment of RA-induced pain and inflammation. However, further study is necessary to clarify which constituents of the BVA fraction are directly responsible for these anti-arthritis effects.

PMID: 12031688 [PubMed - indexed for MEDLINE]

9: Am J Chin Med. 2001;29(2):187-99.

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The analgesic efficacy of bee venom acupuncture for knee osteoarthritis: a comparative study with needle acupuncture.

Kwon YB, Kim JH, Yoon JH, Lee JD, Han HJ, Mar WC, Beitz AJ, Lee JH.

Department of Veterinary Physiology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Suwon, Korea.

The aim of this investigation was to determine whether bee venom (BV) administered directly into an acupoint was a clinically effective and safe method for relieving the pain of patients with knee osteoarthritis (OA) as compared to traditional needle acupuncture. We evaluated the efficacy of BV acupuncture using both pain relief scores and computerized infrared thermography (IRT) following 4 weeks of BV acupuncture treatment. We observed that a significantly higher proportion of subjects receiving BV acupuncture reported substantial pain relief as compared with those receiving traditional needle acupuncture therapy. Furthermore, the IRT score was significantly improved and paralleled the level of pain relief.

Publication Types:

·       Clinical Trial

·       Randomized Controlled Trial

PMID: 11527062 [PubMed - indexed for MEDLINE]

10: Pain. 2001 Feb 15;90(3):271-80.

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Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses.

Kwon YB, Lee JD, Lee HJ, Han HJ, Mar WC, Kang SK, Beitz AJ, Lee JH.

Department of Veterinary Physiology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Suwon 441-744, South Korea.

Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). While several investigators have evaluated the anti-inflammatory effect of BV treatment, the anti-nociceptive effect of BV treatment on inflammatory pain has not been examined. Previous studies in experimental animals suggest that the therapeutic effect of BV on arthritis is dependent on the site of administration. Because of this potential site specificity, the present study was designed to evaluate the anti-nociceptive effect of BV injections into a specific acupoint (Zusanli) compared to a non-acupoint in an animal model of chronic arthritis. Subcutaneous BV treatment (1 mg/kg per day) was found to dramatically inhibit paw edema caused by Freund's adjuvant injection. Furthermore, BV therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. the nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). These anti-nociceptive/anti-inflammatory effects of BV were observed from 12 days through 21 days post-BV treatment. In addition, BV treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. Finally, injection of BV into the Zusanli acupoint resulted in a significantly greater analgesic effect on arthritic pain as compared to BV injection in to a more distant non-acupoint. The present study demonstrates that BV injection into the Zusanli acupoint has both anti-inflammatory and anti-nociceptive effects on Freund's adjuvant-induced arthritis in rats. These findings raise the possibility that BV acupuncture may be a promising alternative medicine therapy for the long-term treatment of rheumatoid arthritis.

PMID: 11207399 [PubMed - indexed for MEDLINE]

11: Blood. 2000 Dec 1;96(12):3809-15.

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Secreted phospholipase A(2) induces vascular endothelial cell migration.

Rizzo MT, Nguyen E, Aldo-Benson M, Lambeau G.

Signal Transduction Laboratory, Methodist Research Institute and Arthritis Care Center, Clarian Health, Indianapolis, IN 46201, USA. mrizzo@clarian.com

Secreted phospholipase A(2) (sPLA(2)) regulates a variety of cellular functions. The present investigation was undertaken to elucidate the potential role of sPLA(2) in endothelial cell (EC) migration. Bovine aortic endothelial cells (BAECs) exposed to sPLA(2) placed in the lower compartment of a modified Boyden chamber displayed increased migration compared to cells exposed to vehicle. The effect of sPLA(2) on EC migration was time and dose dependent. Migration of BAECs was observed at 30 minutes, increased over 1 to 2 hours, and declined thereafter. At 2 hours of stimulation, sPLA(2) (0.01-2 micromol/L) induced 1.2- to 3-fold increased cell migration compared with media alone. Among the different sPLA(2)s tested, bee venom, Naja naja, and porcine and human pancreatic PLA(2)s all evoked a migratory response in ECs. Moreover, human synovial fluid, obtained from patients with arthritis and containing sPLA(2) activity, induced EC migration. Migration of ECs was significantly reduced after exposure to a catalytic site mutant of pancreatic sPLA(2) with decreased lipolytic activity as compared to wild-type sPLA(2). Similarly, pretreatment of human synovial fluid with p-bromophenacyl bromide, an irreversible inhibitor of sPLA(2), markedly decreased the ability of human synovial fluid to stimulate EC migration. Moreover, migration of ECs was stimulated on exposure to hydrolytic products of sPLA(2) activity including arachidonic acid, lysophosphatidic acid, and lysophosphatidylcholine. These findings suggest that sPLA(2) plays a physiologic role in induction of EC migration. Moreover, the effects of sPLA(2) on EC migration are mediated, at least in part, by its catalytic activity.
(Blood. 2000;96:3809-3815)

PMID: 11090064 [PubMed - indexed for MEDLINE]

12: J Pharmacol Exp Ther. 1999 Apr;289(1):166-72.

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Effects of petrosaspongiolide M, a novel phospholipase A2 inhibitor, on acute and chronic inflammation.

Garcia-Pastor P, Randazzo A, Gomez-Paloma L, Alcaraz MJ, Paya M.

Departamento de Farmacologia, Universidad de Valencia, Facultad de Farmacia, Valencia, Spain.

The marine product petrosaspongiolide M is a novel inhibitor of phospholipase A2 (PLA2), showing selectivity for secretory PLA2 versus cytosolic PLA2, with a potency on the human synovial enzyme (group II) similar to that of manoalide. This compound was more potent than manoalide on bee venom PLA2 (group III) and had no effect on group I enzymes (Naja naja and porcine pancreatic PLA2). Inhibition of PLA2 was also observed in vivo in the zymosan-injected rat air pouch, on the secretory enzyme accumulated in the pouch exudate. Petrosaspongiolide M decreased carrageenan paw edema in mice after the oral administration of 5, 10, or 20 mg/kg. This marine metabolite (0.01-1.0 micromol/pouch) induced a dose-dependent reduction in the levels of prostaglandin (PG)E2, leukotriene B4, and tumor necrosis factor-alpha in the mouse air pouch injected with zymosan 4 h after the stimulus. It also had a weaker effect on cell migration. The inflammatory response of adjuvant arthritis was reduced by petrosaspongiolide M, which also inhibited leukotriene B4 levels in serum and PGE2 levels in paw homogenates. In contrast with indomethacin, this marine compound did not reduce PGE2 levels in stomach homogenates. Petrosaspongiolide M is a new inhibitor of secretory PLA2 in vitro and in vivo, with anti-inflammatory properties in acute and chronic inflammation.

PMID: 10087000 [PubMed - indexed for MEDLINE]

13: Biochem Biophys Res Commun. 1997 Sep 18;238(2):436-42.

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Melittin binds to secretory phospholipase A2 and inhibits its enzymatic activity.

Saini SS, Peterson JW, Chopra AK.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1019, USA.

Synthetic melittin inhibited the enzymatic activity of secretory phospholipase A2 (PLA2) from various sources, including bee and snake venoms, bovine pancreas, and synovial fluid from rheumatoid arthritis patients, irrespective of substrate (e.g., [14C]-phosphatidylcholine or phosphatidylethanolamine vesicles and [3H]-oleic acid-labeled E.coli). A Lineweaver-Burk analysis showed that melittin was a noncompetitive inhibitor of bee venom PLA2, causing a change in Vmax from 200 to 50 units/min/mg of protein. The Km remained unchanged (0.75 nmole). Melittin inhibited approximately 50% of purified bee venom PLA2 activity in a 30:1 molar ratio (melittin:enzyme). Because the enzyme kinetics indicated a PLA2-melittin interaction, a melittin-sepharose affinity column was used to purify a PLA2 from human serum. Further, an enzyme-linked assay was developed to quantitate PLA2 activity in biological fluids using avidin-peroxidase and ELISA plates coated with biotinylated melittin. These observations may have potential therapeutic significance, as well as provide a convenient basis for the isolation and quantitation of PLA2.
Copyright 1997 Academic Press.

PMID: 9299527 [PubMed - indexed for MEDLINE]

14: Clin Exp Immunol. 1993 Oct;94(1):156-62.

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Modulation of alpha 1-acid glycoprotein (AGP) gene induction following honey bee venom administration to adjuvant arthritic (AA) rats; possible role of AGP on AA development.

Yiangou M, Konidaris C, Victoratos P, Hadjipetrou-Kourounakis L.

Faculty of Sciences, School of Biology, Department of Genetics, Development and Molecular Biology, Aristotle University of Thessaloniki, Greece.

Honey bee venom (HBV) administration to adjuvant arthritic (AA) rats resulted in a significant suppression of arthritis and in suppression of the hepatic acute phase alpha 1-acid glycoprotein (AGP) gene induction at the early stages of disease development. AGP administration in AA rats resulted in acceleration of arthritis development and in increase of severity and duration of the disease. IL-1, IL-6, tumour necrosis factor (TNF) and glucocorticoids alone are not responsible for the HBV-mediated AGP gene down-regulation. These results indicate that AGP gene expression in AA and HBV-treated AA rats involves the interaction of several factors, and that AGP plays a role for AA development in rats.

PMID: 8403499 [PubMed - indexed for MEDLINE]

15: Agents Actions. 1989 Jun;27(3-4):425-7.

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Rheumatoid arthritis synovial fluid phospholipase A2 activating protein (PLAP) stimulates human neutrophil degranulation and superoxide ion production.

Bomalaski JS, Baker D, Resurreccion NV, Clark MA.

V.A. Medical Center, Medical College of Pennsylvania, University of Pennsylvania, Philadelphia 19104.

Rheumatoid arthritis is characterized by excessive eicosanoid production, and phospholipase enzymes are the rate limiting step in eicosanoid synthesis. We have shown previously that cells from patients with rheumatoid arthritis express enhanced phospholipase A2 enzyme activities. Recently, we have isolated a phospholipase A2 activating protein termed PLAP from rheumatoid synovial fluid. This novel human protein shares biochemical and antigenic similarities with melittin, a bee venom phospholipase activating protein. Because melittin has been shown to induce neutrophil degranulation and superoxide formation, and because exuberent release of lysosomal enzymes and superoxide have been implicated in the pathogenesis of rheumatoid arthritis, we examined the role of PLAP on inducing these neutrophil functions.

PMID: 2552770 [PubMed - indexed for MEDLINE]

16: J Rheumatol. 1988 Dec;15(12):1878.

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Bee venom and adjuvant arthritis.

Somerfield SD, Brandwein S.

Publication Types:

·       Letter

PMID: 3230576 [PubMed - indexed for MEDLINE]

17: J Rheumatol. 1988 Jul;15(7):1126-8.

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Bee venom, adjuvant induced disease and interleukin production.

Hadjipetrou-Kourounakis L, Yiangou M.

Laboratory of General Biology, Aristotelian University of Thessaloniki, Greece.

Interleukin production and the in vitro mitogenic responses from honey bee venom treated normal rat splenocytes were reduced considerably compared to controls. Addition of interleukin-1 (IL-1) or interleukin-2 (IL-2) supernatants to these cultures in vitro resulted in an increase of their responses to normal levels. These results suggest that in vivo honey bee venom treatment affects the production of IL-1 by macrophages directly. Honey bee venom treatment affects adjuvant induced disease development by inhibiting certain macrophage functions and thus indirectly inhibiting the activation of T and B cells, and possibly the activation of an endogenous virus which might be involved in adjuvant induced disease induction.

PMID: 3262759 [PubMed - indexed for MEDLINE]

18: N Z Med J. 1986 Apr 23;99(800):281-3.

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Bee venom and arthritis: magic, myth or medicine?

Somerfield SD.

PMID: 3010202 [PubMed - indexed for MEDLINE]

19: J Rheumatol. 1986 Apr;13(2):477.

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Bee venom and arthritis.

Somerfield SD.

Publication Types:

·       Letter

PMID: 3014144 [PubMed - indexed for MEDLINE]

20: J Rheumatol. 1984 Oct;11(5):720.

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Bee venom and adjuvant induced disease.

Hadjipetrou-Kourounakis L, Yiangou M.

Publication Types:

·       Letter

PMID: 6512799 [PubMed - indexed for MEDLINE]

21: Arthritis Rheum. 1983 Aug;26(8):1023-8.

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The public's perceptions and misperceptions of arthritis.

Price JH, Hillman KS, Toral ME, Newell S.

A telephone survey of a random sample of 300 respondents indicated that the respondents relied mainly on the mass media for their information about arthritis. Almost half of the respondents believed arthritis could be caused by "poor diet" or "cold, wet climates." Furthermore, quack or unproven "treatment" for arthritis, such as bee venom (83%), vitamins (76%), copper bracelets (74%), special diets (57%), and DMSO (54%) were all supported by more than half of the respondents. However, a followup to the random survey, using only diagnosed arthritis patients as respondents, did not reveal as high a level of actual use of unproven treatments. Numerous factors were found which imply that the lay public is not as well informed about arthritis as arthritis patients are, and that sustained, community-wide educational efforts about arthritis are greatly needed.

PMID: 6882478 [PubMed - indexed for MEDLINE]

22: J Rheumatol. 1983 Jun;10(3):522.

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Bee venom and adjuvant arthritis.

Somerfield SD.

Publication Types:

·       Letter

PMID: 6887182 [PubMed - indexed for MEDLINE]

23: Med Welt. 1982 Aug 27;33(34):1174-7.

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[Bee venom containing Forapin in the treatment of mesenchymal diseases of the locomotor system. Report on treatment results in 211 patients]

[Article in German]

Mund-Hoym WD.

PMID: 7132669 [PubMed - indexed for MEDLINE]

24: J Rheumatol. 1982 Jul-Aug;9(4):649.

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Bee venom therapy of adjuvant arthritis.

Tannenbaum H, Greenspoon M.

Publication Types:

·       Letter

PMID: 7131471 [PubMed - indexed for MEDLINE]

25: Biochem Pharmacol. 1982 Mar 15;31(6):1139-46.

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Effect of honeybee (Apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat.

Eiseman JL, von Bredow J, Alvares AP.

The ability of honeybee venom to suppress Mycobacterium butyricum-induced arthritis was studied in Lewis rats. Bee venom, 2 mg.kg-1.day-1 for 24 days, suppressed but did not abolish the primary and secondary inflammatory responses to the adjuvant as monitored by decreases in the swelling of the left and right hind paws and adjuvant-induced arthritis on heme metabolism were also examined. Bee venom or adjuvant had no effect on hepatic delta-aminolevulinic acid synthase, porphyrin content, or ferrochelatase activity. However, with both treatments cytochrome P-450 and the associated enzymic activities of ethylmorphine N-demethylase and benzo[a]pyrene hydroxylase were depressed markedly. In contrast, both treatments caused several-fold enhancement of hepatic microsomal heme oxygenase activity. Adjuvant-treated rats receiving bee venom showed changes in heme metabolism which were of a magnitude similar to those observed when either agent was administered to the experimental animals. Although the bee venom appears to suppress adjuvant-induced arthritis to a greater extent in female than in male rats, the alterations in heme metabolism were similar in bee venom-treated male and female rats. The observed changes in heme metabolism elicited by the venom or by the adjuvant are strongly suggestive of perturbations of the immune system causing alterations in hepatic microsomal enzymes.

PMID: 6177321 [PubMed - indexed for MEDLINE]

26: Toxicon. 1982;20(1):317-21.

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Adolapin--a newly isolated analgetic and anti-inflammatory polypeptide from bee venom.

Shkenderov S, Koburova K.

Adolapin was isolated by a two-step procedure: gel filtration and chromatography on CM cellulose. The molecular mass of the polypeptide as determined by SDS electrophoresis and amino acid composition proved to be 11500 and 11092 respectively. Adolapin exhibited a potent analgesic effect demonstrated by the "writhing" test (ED50-0,016mg/kg) and by the Randall-Sellito's test (ED50-0,013 mg/kg). The anti-inflammatory activity of adolapin was most marked with regard to carrageenin, prostaglandin and adjuvant rat hind paw edemas and adjuvant polyarthritis. The adolapin effects are presumably due to its capacity to inhibit the prostaglandin synthase system, following a biphasic dose-response relationship. It is likely that central mechanisms are also involved in the analgetic action of adolapin.

PMID: 7080045 [PubMed - indexed for MEDLINE]

27: Agents Actions. 1979 Jun;9(2):205-11.

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Anti-arthritic effect of bee venom.

Chang YH, Bliven ML.

Bee venom, administered subcutaneously, suppressed the development of carrageenan-induced paw edema and adjuvant arthritis in the rat in a dose-related manner. A single dose of bee venom administered subcutaneously the day before or on the day of injection of complete Freund's adjuvant (CFA) effectively suppressed the development of polyarthritis. This suppressive effect decreased progressively as dosing was delayed. Bee venom was found to be most effective when mixed and injected (sub-plantar) together with CFA, the disease-inducing agent. Similarly, antigens such as egg albumin, when incorporated into CFA, and injected into the hind paw, prevented the development of arthritis. These results suggest that at least two mechanisms are involved in the anti-arthritic action of bee venom: (1) alteration of the immune response, probably via antigen competition, and (2) an anti-inflammatory action via corticosteroids or through an as yet undetermined mechanism.

PMID: 474306 [PubMed - indexed for MEDLINE]

28: Rev Med Liege. 1974 Apr 15;29(8):239.

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[Therapeutic properties of bee venom]

[Article in French]

Bacq ZM, Lecomte J, Leclercq M.

PMID: 4826387 [PubMed - indexed for MEDLINE]

29: Nature. 1973 Sep 21;245(5421):163-4.

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Letter: An anti-inflammatory peptide from bee venom.

Billingham ME, Morley J, Hanson JM, Shipolini RA, Vernon CA.

PMID: 4582672 [PubMed - indexed for MEDLINE]

30: Ann Rheum Dis. 1973 Sep;32(5):466-70.

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Effect of bee venom on experimental arthritis.

Zurier RB, Mitnick H, Bloomgarden D, Weissmann G.

PMID: 4751783 [PubMed - indexed for MEDLINE]

31: Res Commun Chem Pathol Pharmacol. 1972 Sep;4(2):339-52.

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Influence of bee venom in the adjuvant-induced arthritic rat model.

Lorenzetti OJ, Fortenberry B, Busby E.

PMID: 4538551 [PubMed - indexed for MEDLINE]

32: Feldsher Akush. 1972 May;37(5):38-9.

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[Treatment with bee venom]

[Article in Russian]

Gorobets GN.

PMID: 4482902 [PubMed - indexed for MEDLINE]

33: Clin Chim Acta. 1967 Jul;17(1):119-23.

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The specificity of the anti-hyaluronidase developed in beekeepers serum against bee venom hyaluronidase.

Barker SA, Walton KW, Weston PD.

PMID: 4166652 [PubMed - indexed for MEDLINE]

34: Ind Med Surg. 1966 Dec;35(12):1045-9.

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Standardized bee venom (SBV) therapy of arthritis. Controlled study of 50 cases with 84 percent benefit.

Steigerwaldt F, Mathies H, Damrau F.

Publication Types:

·       Clinical Trial

·       Controlled Clinical Trial

PMID: 5332533 [PubMed - indexed for MEDLINE]

35: Kazan Med Zh. 1962 Jul-Aug;4:73-5.

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[Treatment of patients with spondyloarthritis deformans with bee venom.]

[Article in Russian]


PMID: 14488023 [PubMed - OLDMEDLINE for Pre1966]

36: Sov Med. 1961 Jun;25:94-101.

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[Bee venom in the treatment of infectious non-specific (rheumatoid) arthritis.]

[Article in Russian]


PMID: 13734638 [PubMed - OLDMEDLINE for Pre1966]

37: Sov Med. 1959 Feb;23(2):133-4.

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[Use of bee venom in polyarthritis.]

[Article in Russian]


PMID: 13646994 [PubMed - OLDMEDLINE for Pre1966]