APITOXINA ARTRITIS
| 1: Brain Res. 2006 Jan 31; [Epub ahead of print] |
Antinociceptive
effect and the mechanism of bee venom acupuncture (Apipuncture) on inflammatory
pain in the rat model of collagen-induced arthritis: Mediation by alpha(2)-Adrenoceptors.
Baek
YH, Huh
JE, Lee
JD, Choi
DY, Park
DS.
Department of Acupuncture and Moxibustion, College of Oriental Medicine, Kyung
Hee University, #1 Hoegidong, Dongdaemungu, Seoul 130-702, South Korea.
The antinociceptive effect and the mechanism of bee venom acupuncture (BVA)
on inflammatory pain, especially in the rat model of collagen-induced arthritis
(CIA), have not yet been fully studied. This study was designed to investigate
the antinociceptive effect and its mu-opioid and alpha(2)-adrenergic
mechanism of BVA in the CIA rat model. To induce CIA, male Sprague-Dawley
rats were immunized with bovine type II collagen emulsified in Freund's incomplete
adjuvant followed by a booster injection 14 days later. The antinociceptive
effect was evaluated by tail flick latency (TFL). After induction of arthritis,
the inflammatory pain threshold decreased as time passed, and there was no
big change of the pain threshold after 3 weeks. Three weeks after the first
immunization, BVA (0.25 mg/kg) injected into the Zusanli acupoint (ST(36)) showed the antinociceptive effect. Furthermore, the
antinociceptive effect of BVA was blocked by yohimbine (alpha(2)-adrenergic
receptor antagonist, 2 mg/kg, i.p) pretreatment, but not by naloxone (mu-opioid
receptor antagonist, 2 mg/kg, i.p.) pretreatment. These results suggest that
BVA can relieve inflammatory pain in CIA and the antinociceptive effect of
BVA can be mediated by alpha(2)-adrenergic receptor.
PMID: 16457792 [PubMed - as supplied by publisher]
| 2: In Vivo. 2005 Jul-Aug;19(4):801-5. |
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]
| 3: Toxicon. 2005 Jul;46(1):39-45. |
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]
| 4: J Ethnopharmacol. 2005 Jun 3;99(2):245-52. Epub 2005 Apr 11. |
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]
| 5: Evid Based Complement Alternat Med. 2005 Mar;2(1):79-84. |
An Overview of Bee Venom Acupuncture in the Treatment of Arthritis.
Lee
JD, Park
HJ, Chae
Y, Lim
S.
Bee venom acupuncture (BVA), as a kind of herbal acupuncture, exerts not only
pharmacological actions from the bioactive compounds isolated from bee venom
but also a mechanical function from acupuncture stimulation. BVA is growing
in popularity, especially in
PMID: 15841281 [PubMed - as supplied by publisher]
| 6: J Vet Sci. 2004 Dec;5(4):309-18. |
General pharmacological profiles of bee venom and its water soluble
fractions in rodent models.
Kim HW, Kwon YB, Ham TW, Roh DH, Yoon SY, Kang SY, Yang IS, Han HJ, Lee HJ, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Seoul 151-742, Korea.
Recently, the antinociceptive and anti-inflammatory efficacy of bee venom
(BV, Apis mellifera) has been confirmed in rodent models of inflammation and
arthritis. Interestingly, the antinociceptive and anti-inflammatory effect
of whole BV can be reproduced by two water-soluble fractions of BV (>20
kDa:BVAF1 and<10 kDa: BVAF3). Based on these scientific findings,
BV and its effective water-soluble fractions have been proposed as potential
anti-inflammatory and antinociceptive pharmaceuticals. While BV's anti-inflammatory
and antinociceptive properties have been well documented, there have been
no careful studies of potential, side effects of BV and its fractions when
administered in the therapeutic range (BV, 5 microgram/kg; BVAF1, 0.2 microgram/kg:
BVAF3, 3 microgram/kg; subcutaneous or intradermal). Such information is critical
for future clinical use of BV in humans. Because of this paucity of information,
the present study was designed to determine the general pharmacological/physiological
effects of BV and its fractions administration on the rodent central nervous,
cardiovascular, respiratory and gastrointestinal system. Subcutaneous BV and
its fractions treatment did not produce any significant effects on general
physiological functions at the highest dose tested (200-fold and 100-fold
doses higher than that used clinically, respectively) except writhing test.
These results demonstrate that doses of BV or BV subfractions in the therapeutic
range or higher can be used as safe antinociceptive and anti-inflammatory
agents.
PMID: 15613814 [PubMed - indexed for MEDLINE]
| 7: Toxicon. 2005 Jan;45(1):81-91. |
Microarray
analysis of gene expression in chondrosarcoma cells treated with bee venom.
Yin
CS, Lee
HJ, Hong
SJ, Chung
JH, Koh
HG.
Department of Acupuncture,
Bee venom (BV) has a broad array of clinical applications in Korean medicine,
including treatment of inflammatory conditions such as arthritis. The final
common pathway of many arthropathies is the destruction of articular cartilage
and consequent loss of articular function. Chondrocyte dysfunction plays a
key role in the pathogenesis of such disorders. To explore the global gene
expression profiles in a human chondrocyte-like cell line treated with BV,
microarray analysis was performed. The HTB-94 human chondrosarcoma cells were
treated with BV, lipopolysaccharide (LPS), or both. Of the 344 genes profiled
in this study, with a cut-off level of 4-fold change in the expression, (1)
35 were downregulated following BV treatment, (2) 16 were upregulated and
7 downregulated following LPS treatment, and (3) 32 were downregulated following
co-stimulation of BV and LPS. The results of the present study shows that
treatment of BV reversed the LPS-induced upregulation of such genes as interleukin-6
(IL-6) receptor, matrix metalloproteinase 15 (MMP-15), tumor necrosis factor
(ligand) superfamily-10, caspase-6 and tissue inhibitor of metalloproteinase-1
(TIMP-1). It is thought that microarrays will play an ever-growing role in
the advance of our understanding of the pharmacologic actions of BV in the
treatment of arthritis.
PMID: 15581686 [PubMed - indexed for MEDLINE]
| 8: Arthritis Rheum. 2004 Nov;50(11):3504-15. |
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.
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.
| 9: Am J Chin Med. 2004;32(3):361-7. |
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]
| 10: Zhong Yao Cai. 2003 Jun;26(6):456-8. |
[Advances in the
study of bee venom and its clinical uses]
[Article in Chinese]
Liu
H, Tong
F.
College of Zoological Sciences,
Publication Types:
· Review
PMID: 14669739 [PubMed - indexed for MEDLINE]
| 11: Arch Pharm Res. 2003 May;26(5):383-8. |
Inhibition of COX-2 activity and proinflammatory cytokines (TNF-alpha
and IL-1beta) production by water-soluble sub-fractionated parts from bee
(Apis mellifera) venom.
Nam KW, Je KH, Lee JH, Han HJ, Lee HJ, Kang SK, Mar W.
Natural Products Research Institute,
Bee venom is used as a traditional medicine for treatment of arthritis. The
anti-inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions
from bee venom (Apis mellifera) was studied using cyclooxygenase (COX) activity
and pro-inflammatory cytokines (TNF-alpha and IL-1beta) production, in vitro.
COX-2 is involved in the production of prostaglandins that mediate pain and
support the inflammatory process. The aqueous partition of bee venom showed
strong dose-dependent inhibitory effects on COX-2 activity (IC50 = 13.1 microg/mL),
but did not inhibit COX-1 activity. The aqueous partition was subfractionated
into three parts by molecular weight differences, namely, B-F1 (above 20 KDa),
B-F2 (between 10 KDa and 20 KDa) and B-F3 (below 10 KDa). B-F2 and B-F3 strongly
inhibited COX-2 activity and COX-2 mRNA expression in a dose-dependent manner,
without revealing cytotoxic effects. TNF-alpha and IL-1beta,
are potent pro-inflammatory cytokines and are early indicators of the inflammatory
process. We also investigated the effects of three subfractions on TNF-alpha
and IL-1beta production using ELISA method. All three subfractions, B-F1,
B-F2 and B-F3, inhibited TNF-alpha and IL-1beta production. These results
suggest the pharmacological activities of bee venom on anti-inflammatory process
include the inhibition of COX-2 expression and the blocking of pro-inflammatory
cytokines (TNF-alpha, and IL-1beta) production.
| 12: J Vet Med Sci. 2003 Mar;65(3):349-55. |
Acupoint
stimulation using bee venom attenuates formalin-induced pain behavior and
spinal cord fos expression in rats.
Kim HW, Kwon YB, Ham TW, Roh DH, Yoon SY, Lee HJ, Han HJ, Yang IS, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Seoul, South Korea.
In two previous reports, we have demonstrated that injection of bee venom
(BV) into an acupoint produces a significant antinociceptive and anti-inflammatory
effect in both a mouse model of visceral nociception and a rat model of chronic
arthritis. The present study was designed to evaluate the potential antinociceptive
effect of BV pretreatment on formalin-induced pain behavior and it associated
spinal cord Fos expression in rats. Adult Sprague-Dawley
rats were injected with BV directly into the Zusanli (ST36) acupoint or into
an arbitrary non-acupoint located on the back. BV pretreatment into the Zusanli
acupoint significantly decreased paw-licking time in the late phase of the
formalin test. In contrast, BV injected into a non-acupoint in the back region
did not suppress the paw-licking time. In addition, BV pretreatment into the
Zusanli acupoint markedly inhibited spinal cord Fos
expression induced by formalin injection. These findings indicate that BV
pretreatment into the Zusanli acupoint has an antinociceptive effect on formalin-induced
pain behavior.
PMID: 12679565 [PubMed - indexed for MEDLINE]
| 13: Am J Chin Med. 2002;30(1):73-80. |
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,
| 14: Life Sci. 2002 May 31;71(2):191-204. |
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]
| 15: Am J Chin Med. 2001;29(2):187-99. |
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,
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:
PMID: 11527062 [PubMed - indexed for MEDLINE]
| 16: Acupunct Electrother Res. 2001;26(1-2):59-68. |
Antinociceptive
effects of bee venom acupuncture (apipuncture) in rodent animal models: a
comparative study of acupoint versus non-acupoint stimulation.
Kwon YB, Kang MS, Kim HW, Ham TW, Yim YK, Jeong SH, Park DS, Choi DY, Han HJ, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Suwon, South Korea.
From a clinical perspective, the alternative forms of acupoint stimulation
including electroacupuncture, moxibustion and acupressure appear to have more
potent analgesic effects than manual needle acupuncture. Bee venom (BV) injection
has also been reported to produce persistent nociceptive stimulation and to
cause neuronal activation in the spinal cord. In previous study, we observed
that BV stimulation into acupoint, namely BV acupuncture or Apipuncture, produced
more potent anti-inflammatory and antinociceptive potency in rodent arthritis
model as comparing with that of non-acupoint injection. Based on previous
report, we decided to further investigate that BV injection into an acupoint
produces antinociception as a result of its potent chemical stimulatory effect
in both abdominal stretch assay and formalin test. Different doses of BV were
injected into an acupoint or a non-acupoint 30 min prior to intraplantar formalin
injection or intraperitoneal acetic acid injection. Using the abdominal stretch
assay, we found that the high dose of BV (1:100 diluted in 20microl saline)
produced a potent antinociceptive effect irrespective of the site of BV injection.
In contrast the antinociceptive effect observed in both the writhing and formalin
tests following administration of a low dose of BV (1:1000 diluted in 20microl
saline) was significantly different between acupoint and non-acupoint sites.
BV injection into an acupoint (Zhongwan, Cv. 12) was found to produce significantly
greater antinociception than non-acupoint injection (
| 17: J Vet Med Sci. 2001 Mar;63(3):251-9. |
Bee venom
pretreatment has both an antinociceptive and anti-inflammatory effect on carrageenan-induced
inflammation.
Lee JH, Kwon YB, Han HJ, Mar WC, Lee HJ, Yang IS, Beitz AJ, Kang SK.
Department
of Veterinary Physiology,
Although the injection of bee venom (BV) has been reported to evoke tonic
pain and hyperalgesia, there is conflicting evidence in the literature indicating
that BV can also exert an anti-inflammatory and antinociceptive
effects on inflammation. In this regard, BV has been traditionally
used in Oriental medicine to relieve pain and to treat chronic inflammatory
diseases such as rheumatoid arthritis. The present study was designed to test
the hypothesis that BV induces acute nociception under normal conditions,
but that it can serve as a potent anti-inflammatory and antinociceptive agent
in a localized inflammatory state. The experiments were designed to evaluate
the effect of BV pretreatment on carrageenan (CR)-induced acute paw edema
and thermal hyperalgesia. In addition, spinal cord Fos expression induced by peripheral inflammation was quantitatively
analyzed. In normal animals subcutaneous BV injection into the hindlimb was
found to slightly increase Fos expression in the
spinal cord without producing detectable nociceptive behaviors or hyperalgesia.
In contrast pretreatment with BV (0.8 mg/kg) 30 min prior to CR injection
suppressed both the paw edema and thermal hyperalgesia evoked by CR. In addition,
there was a positive correlation between the percent change in paw volume
and the expression of Fos positive neurons in the
spinal cord. These results indicate that BV pretreatment has both antinociceptive
and anti-inflammatory effects in CR-induced inflammatory pain. These data
also suggest that BV administration may be useful in the treatment of the
pain and edema associated with chronic inflammatory diseases.
PMID: 11307924 [PubMed - indexed for MEDLINE]
| 18: Pain. 2001 Feb 15;90(3):271-80. |
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.
| 19: Blood. 2000 Dec 1;96(12):3809-15. |
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
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]
| 20: J Pharmacol Exp Ther. 1999 Apr;289(1):166-72. |
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]
| 21: Biochem Biophys Res Commun. 1997 Sep 18;238(2):436-42. |
Melittin
binds to secretory phospholipase A2 and inhibits its enzymatic activity.
Saini SS, Peterson
JW, Chopra
AK.
Department of Microbiology and Immunology,
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]
| 22: J Immunol. 1995 Apr 15;154(8):4027-31. |
Phospholipase
A2-activating protein induces the synthesis of IL-1 and TNF in human monocytes.
Bomalaski
JS, Ford
T, Hudson
AP, Clark
MA.
Medical
Phospholipase A2-activating protein (PLAP) is an important mediator of eicosanoid
generation. PLAP can also be found in high concentrations in synovial fluid
from patients with rheumatoid arthritis, and injection of PLAP into animal
joints results in an inflammatory, rheumatoid-like lesion. We have demonstrated
previously that TNF-alpha and IL-1 beta stimulate formation of PLAP before
phospholipase A2 (PLA2) enzyme activation and production of eicosanoids. To
further explore the mechanisms found in the inflammatory response, we examined
the ability of PLAP to stimulate release of TNF and IL-1 from human peripheral
blood monocytes. TNF and IL-1 protein levels were measured by ELISA, and IL-1
and TNF mRNA were determined by Northern blotting. PLAP, PLAP peptide, and
melittin, a bee venom PLA2 activator with homology with PLAP, all increased
IL-1 and TNF production in a time- and dose-dependent manner. Heat-denatured
PLAP and actin (an irrelevant protein) failed to exert this effect. PLAP stimulation
of TNF and IL-1 could be enhanced with co-treatment of cells with free fatty
acids, such as arachidonic or linoleic acid, but it was not blocked completely
by PLA2 inhibitors. These results demonstrate not only that synthesis of PLAP
can be stimulated by cytokines, but also that PLAP may regulate cytokine synthesis
and thus perpetuate an immune or inflammatory response.
PMID: 7706741 [PubMed - indexed for MEDLINE]
| 23: Clin Exp Immunol. 1993 Oct;94(1):156-62. |
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]
| 24: Agents Actions. 1989 Jun;27(3-4):425-7. |
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.
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.
| 25: J Rheumatol. 1988 Dec;15(12):1878. |
Bee venom and adjuvant arthritis.
Somerfield SD,
Brandwein S.
Publication Types:
· Letter
PMID: 3230576 [PubMed - indexed for MEDLINE]
| 26: J Rheumatol. 1988 Jul;15(7):1126-8. |
Bee venom, adjuvant
induced disease and interleukin production.
Hadjipetrou-Kourounakis
L, Yiangou
M.
Laboratory of General Biology, Aristotelian
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]
| 27: Inflammation. 1986 Jun;10(2):175-82. |
Bee venom melittin
blocks neutrophil O2- production.
Somerfield
SD, Stach
JL, Mraz
C, Gervais
F, Skamene
E.
Bee venom (BV) is used in folk medicine to treat arthritis. It has antiinflammatory
effects in animal models of rheumatic disease. We have studied the effects
of BV on human neutrophil production of superoxide (O2-) and hydrogen peroxide,
finding potent, nontoxic, dose-dependent production inhibition. Melittin,
the major fraction of BV (50-70%) 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 poststimulation
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 serve as a prototype small (mol wt 1280), cationic,
amphipathic, calmodulin-binding, membrane-active, superoxide-production-inhibiting
peptide, providing a model for peptides which could have a role in in vivo
regulation of radical production.
PMID: 3011670 [PubMed - indexed for MEDLINE]
| 28: N Z Med J. 1986 Apr 23;99(800):281-3. |
Bee venom and arthritis:
magic, myth or medicine?
Somerfield SD.
PMID: 3010202 [PubMed - indexed for MEDLINE]
| 29: J Rheumatol. 1986 Apr;13(2):477. |
Bee venom and arthritis.
Somerfield
SD.
Publication Types:
· Letter
PMID: 3014144 [PubMed - indexed for MEDLINE]
| 30: J Rheumatol. 1984 Oct;11(5):720. |
Bee venom and adjuvant
induced disease.
Hadjipetrou-Kourounakis
L, Yiangou M.
Publication Types:
· Letter
PMID: 6512799 [PubMed - indexed for MEDLINE]
| 31: Arthritis Rheum. 1983 Aug;26(8):1023-8. |
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]
| 32: J Rheumatol. 1983 Jun;10(3):522. |
Bee venom and adjuvant arthritis.
Somerfield SD.
Publication Types:
· Letter
PMID: 6887182 [PubMed - indexed for MEDLINE]
| 33: Med Welt. 1982 Aug 27;33(34):1174-7. |
[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]
| 34: J Rheumatol. 1982 Jul-Aug;9(4):649. |
Bee venom therapy of adjuvant arthritis.
Tannenbaum H,
Greenspoon M.
Publication Types:
· Letter
PMID: 7131471 [PubMed - indexed for MEDLINE]
| 35: Biochem Pharmacol. 1982 Mar 15;31(6):1139-46. |
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]
| 36: Toxicon. 1982;20(1):317-21. |
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]
| 37: Agents Actions. 1979 Jun;9(2):205-11. |
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]
| 38: Rev Med Liege. 1974 Apr 15;29(8):239. |
[Therapeutic properties
of bee venom]
[Article in French]
Bacq
ZM, Lecomte
J, Leclercq
M.
PMID: 4826387 [PubMed - indexed for MEDLINE]
| 39: Nature. 1973 Sep 21;245(5421):163-4. |
Letter: An anti-inflammatory
peptide from bee venom.
Billingham
ME, Morley
J, Hanson
JM, Shipolini
RA, Vernon
CA.
PMID: 4582672 [PubMed - indexed for MEDLINE]
| 40: Ann Rheum Dis. 1973 Sep;32(5):466-70. |
Effect of bee venom on experimental arthritis.
Zurier
RB, Mitnick
H, Bloomgarden
D, Weissmann
G.
PMID: 4751783 [PubMed - indexed for MEDLINE]
| 41: Res Commun Chem Pathol Pharmacol. 1972 Sep;4(2):339-52. |
Influence of bee
venom in the adjuvant-induced arthritic rat model.
Lorenzetti
OJ, Fortenberry
B, Busby
E.
PMID: 4538551 [PubMed - indexed for MEDLINE]
| 42: Feldsher Akush. 1972 May;37(5):38-9. |
[Treatment with
bee venom]
[Article in Russian]
Gorobets
GN.
PMID: 4482902 [PubMed - indexed for MEDLINE]
| 43: Clin Chim Acta. 1967 Jul;17(1):119-23. |
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]
| 44: Ind Med Surg. 1966 Dec;35(12):1045-9. |
Standardized bee venom (SBV) therapy of arthritis. Controlled study of 50 cases with 84 percent
benefit.
Steigerwaldt F,
Mathies H, Damrau F.
Publication Types:
PMID: 5332533 [PubMed - indexed for MEDLINE]
| 45: Kazan Med Zh. 1962 Jul-Aug;4:73-5. |
[Treatment of patients with spondyloarthritis deformans with bee
venom.]
[Article in Russian]
PORIADIN VT.
PMID: 14488023 [PubMed - OLDMEDLINE for Pre1966]
| 46: Sov Med. 1961 Jun;25:94-101. |
[Bee venom in the treatment of infectious non-specific (rheumatoid)
arthritis.]
[Article in Russian]
PERTSULENKO VA.
PMID: 13734638 [PubMed - OLDMEDLINE for Pre1966]
| 47: Sov Med. 1959 Feb;23(2):133-4. |
[Use of bee venom in polyarthritis.]
[Article in Russian]
ISTOMINA
KV, KONEVTSEVA
TV.
PMID: 13646994 [PubMed - OLDMEDLINE for Pre1966]
| 48: Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1951;213(1-2):8-17. |
[Studies on the effect of bee venom and histamine in formaldehyde
arthritis in the rat.]
[Article in Undetermined Language]
NEUMANN
W, STRACKE
A.
PMID: 14869074 [PubMed - OLDMEDLINE for Pre1966]