Objective:To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel.Methods:In this study,the sodium urate and LPS were used on rats and ...Objective:To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel.Methods:In this study,the sodium urate and LPS were used on rats and mice to construct the model.Bee venom gelemicroneedle combination effect on the model is to determine the role of microneedle gel permeation by observing inflammation factors.Results:Compared with the model group,the bee venom gelemicroneedle combination group can reduce the level of serum nitric oxide of the acute gouty inflammation model caused by sodium urate,and on LPS induced mouse model of acute inflammation effect and the micro.Conclusions:Bee venom can significantly suppress the occurrence of gouty arthritis inflammation in rats and mice LPS inflammatory reaction.Choose the 750 mm microneedle with 10N force on skin about 3 minutes,bee venom can play the optimal role,and the anti-inflammatory effect is obvious.Microneedles can promote the percutaneous absorption of the active macromolecules bee venom gel.展开更多
Objective To examine whether microinjection of morphine into the rat thalamic nucleus submedius (Sm) could depress the bee venom (BV)-induced nociceptive behaviours. Methods In inflammatory pain model induced by BV su...Objective To examine whether microinjection of morphine into the rat thalamic nucleus submedius (Sm) could depress the bee venom (BV)-induced nociceptive behaviours. Methods In inflammatory pain model induced by BV subcutaneous injection into rat unilateral hind paw,the inhibitory effects of morphine microinjection into thalamic nucleus submedius (Sm) on the spontaneous nociceptive behavior,heat hyperalgesia and tactile allodynia,and the influence of naloxone on the morphine effects were observed in the rat. Results A single dose of morphine (5.0 μg,0.5 μL) applied into the Sm ipsilateral to the BV injected paw significantly depressed the spontaneous paw flinching response. Morphine also significantly increased the heat paw withdrawal latencies in the bilateral hind paw and the tactile paw withdrawal threshold in the ipsilateral hind paw 2 hours after BV injection. All these depressive effects could be effectively antagonized by pre-treatment with the opioid receptor antagonist naloxone (1.0 μg,0.5 μL) in the Sm 5min prior to morphine administration. Naloxone alone injected to the Sm had no effect on the BV-induced nociceptive behavior. Conclusion These results suggest that Sm is involved in opioid receptor-mediated anti-nociception in the rat with the BV-induced inflammatory pain. Together with results from previous studies,it is likely that this effect is produced by activation of the Sm-ventrolateral orbital cortex-periaqueductal gray pathway,leading to activation of the brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal cord level.展开更多
Subcutaneous injection of bee venom causes long-term neural activation and hypersensitization in the dorsal horn of the spinal cord,which contributes to the development and maintenance of various pain-related behavior...Subcutaneous injection of bee venom causes long-term neural activation and hypersensitization in the dorsal horn of the spinal cord,which contributes to the development and maintenance of various pain-related behaviors.The unique behavioral 'phenotypes' of nociception and hypersensitivity identified in the rodent bee venom test are believed to reflect a complex pathological state of inflammatory pain and might be appropriate to the study of phenotype-based mechanisms of pain and hyperalgesia.In this review,the spinal processing of the bee venom-induced different 'phenotypes' of pain and hyperalgesia will be described.The accumulative electrophysiological,pharmacological,and behavioral data strongly suggest that different 'phenotypes' of pain and hyperalgesia are mediated by different spinal signaling pathways.Unraveling the phenotype-based mechanisms of pain might be useful in development of novel therapeutic drugs against complex clinic pathological pain.展开更多
OBJECTIVE:To evaluate the efficacy of bee venom acupuncture in humeroscapularis(PHS)patients.METHODS:One hundred and twenty patients diagnosed with PHS were assigned into four groups:BV1(0.01 mg/kg),BV2(0.005 mg/kg),B...OBJECTIVE:To evaluate the efficacy of bee venom acupuncture in humeroscapularis(PHS)patients.METHODS:One hundred and twenty patients diagnosed with PHS were assigned into four groups:BV1(0.01 mg/kg),BV2(0.005 mg/kg),BV3(0.0025 mg/kg),and control group(vitamin B1 plus novocain 3%injection)with 15 d of treatment.The outcomes of the study including visual analogue scale(VAS)score andβ-endorphin,inflammatory cytokines including interleukin-10(IL-10),IL-1βand tumor necrosis factorα(TNF-α)and shoulder function score were assessed at baseline,after 10 and 15 d of treatment.RESULTS:All four groups reported statistically significant improvement in VAS score,motion range,and shoulder function score(P<0.01),only the BV3 group showed significant increase of anti-inflammatory(IL-10)and decrease of pro-inflammatory(IL-1β,TNF-α)cytokines after treatment(P<0.05).The BV3 group presented a significant difference between all outcomes compared to the control and other groups.CONCLUSION:BV3 groups showed better recovery including reduced pain,improved motor function and normalized inflammatory cytokines than current therapy used in Vietnam and other groups.展开更多
OBJECTIVE:To evaluate the anti-diabetic efficacy of orally administered bee wax coated water-soluble fraction of bee venom(BWCBVA)drug over orally administered bee wax(BW)and intraperitoneally administered whole bee v...OBJECTIVE:To evaluate the anti-diabetic efficacy of orally administered bee wax coated water-soluble fraction of bee venom(BWCBVA)drug over orally administered bee wax(BW)and intraperitoneally administered whole bee venom(BV)in streptozotocin(STZ)-induced diabetic rats.METHODS:Diabetes induced by intraperitoneal administration of 60 mg/kg STZ was treated with BWCBVA,BW,and BV for 21 d.The biochemical,protein and histological changes,and physical characteristics of BWCBVA were then analyzed.RESULTS:The BWCBVA group shows significantly decreased blood glucose level as compared to the BW and intraperitoneally administered whole BV treated group.Moreover,BWCBVA significantly normalizes the serum biochemical parameters and increases the body weight.Also,administration of BWCBVA significantly reverses the altered liver expression of phosphatidylinositide 3-kinases-p85 and liver glucokinase.Histological analysis of the pancreas an increase in the islet cell numbers and decrease inβ-cell damage.Co-administering BWCBVA 0.25 mg/kg with nifedipine(6.8 mg/kg)and nicorandil(13.8 mg/kg)to the diabetic rats results in insulin secretion through enhanced calcium ion influx.High performance liquid chromatography and gas chromatography was performed to identify the pharmacologically important compounds present in BWCBVA.CONCLUSION:Our results indicate that BWCBVA,an orally administered colon specific drug delivery system,can be effective in treating diabetes mellitus.展开更多
Background:Neuroinflammation and accumulation ofβ-amyloid(Aβ)play a significant role in the onset and progression of Alzheimer’s disease(AD).Our previous study demonstrated that signal transducer and activator of t...Background:Neuroinflammation and accumulation ofβ-amyloid(Aβ)play a significant role in the onset and progression of Alzheimer’s disease(AD).Our previous study demonstrated that signal transducer and activator of transcription-3(STAT3)plays a major role in neuroinflammation and amyloidogenesis.Methods:In the present study,we investigated the inhibitory effect of bee venom phospholipase A2(bvPLA2)on memory deficiency in Tg2576 mice,which demonstrate genetic characteristics of AD and the mechanism of its action at the cellular and animal level.For in vivo study,we examined the effect of bvPLA2 on improving memory by conducting several behavioral tests with the administration of bvPLA2(1 mg/kg)to Tg2576 mice.For in vitro study,we examined the effect of bvPLA2 on amyloidogenesis and neuroinflammation by treating bvPLA2 on LPSactivated BV2 cells.Results:We found that bvPLA2 alleviated memory impairment in Tg2576 mice,as demonstrated in the behavioral tests assessing memory.In the bvPLA2-treated group,Aβ,amyloid precursor protein(APP),and β-secretase 1(BACE1)levels and β-secretase activity were significantly decreased.Expression of pro-inflammatory cytokines and inflammation-related proteins decreased in the brain of bvPLA2-treated group,whereas anti-inflammatory cytokines increased.In addition,bvPLA2 reduced STAT3 phosphorylation in the brains of the bvPLA2-treated group.At the cellular level,bvPLA2 inhibits production of nitric oxide,pro-inflammatory cytokines,and inflammation-related proteins including p-STAT3.Additionally,bvPLA2 inhibits the production of Aβin cultured BV-2 cells.Results from the docking experiment,pull-down assay,and the luciferase assay show that bvPLA2 directly binds STAT3 and,thus,regulates gene expression levels.Moreover,when the STAT3 inhibitor and bvPLA2 were administered together,the anti-amyloidogenic and anti-inflammatory effects were further enhanced than when they were administered alone.Conclusion:These results suggest that bvPLA2 could restore memory by inhibiting the accumulation of Aβ and inflammatory responses via blockage of STAT3 activity.展开更多
Aim: The present study aimed to examine whether apipuncture (stimulation of acupuncture points with bee venom)at ST36 and GV3 acupoints promotes neuroprotection and reduces neuroinflammation by modulating M1 and M2 ph...Aim: The present study aimed to examine whether apipuncture (stimulation of acupuncture points with bee venom)at ST36 and GV3 acupoints promotes neuroprotection and reduces neuroinflammation by modulating M1 and M2 phenotype polarization.Methods: Wistar rats were treated with bee venom (BV) (0.08 mg/kg) injection at acupoints ST36 and GV3 [BV (ST36 + GV3)-spinal cord injury (SCI)] or BV injection at non-acupoints [BV (NP)-SCI] or no treatment (CTL-SCI)after SCI by compression. The spinal cord mRNA expression of iNOS, Arg-1 and TGF-β was measured by real time PCR and the levels of IBA-1;BCL-2;NeuN e CNPase was measured by western blotting. Locomotor performance was measured by Basso, Beattie, and Bresnahan (BBB) and grid-walking tests.Results: Apipuncture treatment was able to (1) ameliorate locomotor performance;(2) reduce inflammatory markers (Cox-2 levels) and activation of microglia and macrophages;(3) reduce the polarization of the M1 phenotype marker (iNOS) and increase M2 (Arg-1 and TGF-β) phenotypic markers;(4) promote neuroprotection by reducing the death of neurons and oligodendrocytes;and (5) increase the expression of the anti-apoptotic factor BCL-2.Conclusion: Apipuncture treatment induces locomotor recovery and neuroprotection after the compression model of spinal cord injury. Further, it reduces neuroinflammation by decreasing M1 polarization and increasing M2 phenotype.展开更多
BACKGROUND:Shoulder pain is a common complication of stroke.Bee venom acupuncture(BVA)is increasingly used in the treatment of post-stroke shoulder pain.OBJECTIVE:To summarize and evaluate evidence on the effectivenes...BACKGROUND:Shoulder pain is a common complication of stroke.Bee venom acupuncture(BVA)is increasingly used in the treatment of post-stroke shoulder pain.OBJECTIVE:To summarize and evaluate evidence on the effectiveness of BVA in relieving shoulder pain after stroke.SEARCH STRATEGY:Nine databases,namely MEDLINE,EMBASE,the Cochrane Library,the China National Knowledge Infrastructure(CNKI),the Japan Science and Technology Information Aggregator,Electronic(J-STAGE),and four Korean medical databases,namely,the National Assembly Library,the Research Information Service System,the National Discovery for Science Leaders,and OASIS,were searched from their inception through August 2014 without language restrictions.INCLUSION CRITERIA:Randomized controlled trials(RCTs)were included if BVA was used at acupoints as the sole treatment,or as an adjunct to other treatments,for shoulder pain after stroke.DATA EXTRACTION AND ANALYSIS:Two review authors independently selected trials for inclusion,assessed methodological quality and extracted data.RESULTS:A total of 138 potentially relevant articles were identifi ed,4 of which were RCTs that met our inclusion criteria.The quality of studies included was generally low,and a preponderance of positive results was demonstrated.All four trials reported favorable effects of BVA on shoulder pain after stroke.Two RCTs assessing the effects of BVA on post-stroke shoulder pain,as opposed to saline injections,were included in the meta-analysis.Pain was signifi cantly lower for BVA than for saline injections(standardized mean difference on 10-cm visual analog scale:1.46 cm,95%CI=0.30–2.62,P=0.02,n=86)CONCLUSION:This review provided evidence suggesting that BVA is effective in relieving shoulder pain after stroke.However,further studies are needed to confi rm the role of BVA in alleviating post-stroke shoulder pain.Future studies should be conducted with large samples and rigorous study designs.展开更多
OBJECTIVE:Acne vulgaris is a chronic dermatologic problem with multiple factors involved in its pathogenesis.Alternative solutions to acne treatment were instigated by antibiotic resistance despite of its extensive us...OBJECTIVE:Acne vulgaris is a chronic dermatologic problem with multiple factors involved in its pathogenesis.Alternative solutions to acne treatment were instigated by antibiotic resistance despite of its extensive use.Purified bee venom(PBV)has been proposed as a promising candidate for that purpose.The present study was designed to confirm the antibacterial effect of PBV and access the efficacy of cosmetics containing PBV in subjects with acne vulgaris.METHODS:The skin bacterium Propionibacterium acnes was incubated with PBV at various concentrations and bacterial growth was evaluated using the colony forming unit(CFU)assay.The mechanism of PBV employed in killing P.acnes was examined by scanning electron microscopy(SEM)and transmission electron microscopy(TEM).In addition,a total of 12 subjects were randomized in a double-blind,controlled trial to receive either cosmetics containing PBV or cosmetics without PBV for two weeks.Evaluations included lesion counts and skin microorganism.RESULTS:PBV exhibited antimicrobial activity in a concentration-dependent manner,reducing the number of P.acnes CFU by approximately 6 logs at a concentration of 0.5 mg.When PBV concentration was higher than 1.0 mg,no P.acnes colonies were spotted on an agar.TEM and SEM of untreated P.acnes illustrated the normal pleomorphic structure,whereas the PBVtreated bacterium lost the integrity of surface architecture.Significant difference(P=0.027)in the grading levels based on numbers of lesion counts for inflammatory and noninflammatory was observed in favour of the PBV group compared with the control group.In terms of average decrement of skin microorganism,subjects receiving cosmetics containing PBV experienced a significant 57.5%decrease of adenosine triphosphate levels,whereas participants receiving cosmetics without PBV experienced a nonsignificant decrease of 4.7%.CONCLUSION:These results show that the in vitro actions of antimicrobial activity of PBV were translated in vivo.Cosmetics containing PBV provided a certain degree of efficacy in terms of lesion counts and skin microorganism concentration compared with cosmetics without PBV in subjects with acne vulgaris.PBV may be a good candidate compound for developing therapeutic drug for the treatment of acne vulgaris.展开更多
Bee venom phospholipase A2(BvPLA2) is a lipolytic enzyme that catalyzes the hydrolysis of the sn-2 acyl bond of glycerophospholipids to liberate free fatty acids and lysophospholipids.In this work,a new BvPLA2(AccPLA2...Bee venom phospholipase A2(BvPLA2) is a lipolytic enzyme that catalyzes the hydrolysis of the sn-2 acyl bond of glycerophospholipids to liberate free fatty acids and lysophospholipids.In this work,a new BvPLA2(AccPLA2) gene from the Chinese honeybee(Apis cerana cerana) venom glands was inserted into bacmid to construct a recombinant transfer vector.Tn-5B-4(Tn) cells were transfected with the recombinant bacmid DNA for expression.Sodium dodecylsulfate-polyacrylamide gel electrophoresis(SDS-PAGE) analysis revealed a double band with molecular weights of 16 and 18 kDa.Products of hexahistidine AccPLA2 fusion protein accumulated up to 5.32% of the total cellular proteins.The AccPLA2 fusion protein was cross reactive with the anti-AmPLA2(BvPLA2 of the European honeybee,Apis mellifera) polyclonal serum.The reaction resulted in a double glycosylation band,which agrees with the band generated by the native AmPLA2 in Western blot analysis.The PLA2 activity of the total extracted cellular protein in the hydrolyzing egg yolk is about 3.16 μmol/(min·mg).In summary,the recombinant AccPLA2 protein,a native BvPLA2-like structure with corresponding biological activities,can be glycosylated in Tn cells.These findings provided fundamental knowledge for potential genetic engineering to produce AccPLA2 in the pharmaceutical industry.展开更多
The medical use of bee venom for rheumatoid arthritis ( RA ) has a very long tradition. In this study, isolation and purification of polypeptides from bee venom were carried out on sephadex chromatography, heparin sep...The medical use of bee venom for rheumatoid arthritis ( RA ) has a very long tradition. In this study, isolation and purification of polypeptides from bee venom were carried out on sephadex chromatography, heparin sepharose CL6B chromatography and HPLC. Several fractions were extracted, and their effects on activation of splenocyte and THP-1 cell were studied. The inhibitory fraction was selected for further studies. Finally, BV I-2H that the HPLC elution profiles was a single peak was isolated by C8 column. ESI-MS detection results showed that BY I-2H was a fraction of bee venom, and the molecular weight of the major component was 644.8. BY I -2H could inhibit ConA-induced splenocyte proliferation, IL-1 production and interfere with splenocyte cycle in mice. Moreover, BV I-2H could inhibit PMA-induced TNFa production in THP-1 cells, which was due to its inhibitory effects on TNFa mRNA expression and protein phosphorylation of IκBα. Our studies indicated that BY I -2H was one of the anti-inflammatory展开更多
OBJECTIVE:To investigate the safety of hair essence containing 0.05%purified bee venom(HE-PBV)on the skin and eyes of New Zealand White rabbits.METHODS:HE-PBV which contained 0.05%PBV,purified water,and glycerin,was u...OBJECTIVE:To investigate the safety of hair essence containing 0.05%purified bee venom(HE-PBV)on the skin and eyes of New Zealand White rabbits.METHODS:HE-PBV which contained 0.05%PBV,purified water,and glycerin,was used as the test substance.The skin-irritation test(SIT)and eye-irritation test(EIT)were conducted according to the Draize method.On the SIT,HE-PBV(0.5 m L)dropped gauze was attached both intact and abraded skin for 24 h.The other side of the skin was used as control.After 24 and 72 h,the treatment site was observed and scored according to evaluation criteria for skin reactions.On the EIT,the rabbits were divided into two groups:eye-washed(three rabbits)and non-eye-washed(six rabbits).HE-PBV(0.1 m L)was squirted into the right eye of rabbits.The left eye was untreated and used as a control.Then,20-30-s later,the eyes of rabbits in the eye-washed group were washed with^50 m L of physiologic(0.9%)salt solution.Then,1,2,3,4 and 7 d after the start of the EIT,the eyes and behavior of the rabbits were observed.The degree of eye irritation elicited by HE-PBV was determined in three steps and then the criteria of the classification of eye-irritation scores.RESULTS:The SIT revealed erythema and edema at the site of HE-PBV application.At 72 h,the body weight of rabbits was reduced slightly,but other symptoms(except erythema and edema)were not observed.The Primary Irritation Index score was0.6,and HE-PBV was deemed to be a slight irritant.The EIT did not show mortality or body-weight fluctuation,but hyperemic conjunctiva and eyelid closure were noted after HE-PBV administration.Except for these results,the score for the ophthalmic response on days 1,2,3,4 and 7 was 0,and HE-PBV was deemed to be a non-irritant.CONCLUSION:These data suggest that HE-PBV did not elicit eye irritation,but was a slight irritant to the skin of rabbits;the latter slight would have been due to the excipients used in manufacture of the hair essence because PBV has been shown to be safe.展开更多
This study evaluated the therapeutic effects of the phytomedicine,ethyl acetate fraction of the Cynanchum peniculatum (EACP) and bee venom (BV) of the honey bee (Apis mellifera) for the treatment of experimental stifl...This study evaluated the therapeutic effects of the phytomedicine,ethyl acetate fraction of the Cynanchum peniculatum (EACP) and bee venom (BV) of the honey bee (Apis mellifera) for the treatment of experimental stifle osteoarthritis (OA) in 24 skeletally mature mixed small breed dogs (age 2 to 6 years,weight 2. 8 to 9 kg). One year after induction of OA,the animals were randomly allocated in 2 groups; the EACP-group received 10% solution of EACP 0. 5mL plus 0. 2 mL lidocaine; and the BV-group received 10% solution of BV 0. 5 mL plus 0. 2 mL lidocaine intraarticularly twice in a week in the OA-induced stifles for one month. The joint tissue specimens,synovial fluid (SF) and blood samples were collected prior to and 12 months after induction of OA,and one month posttreatment. TRAP levels in SF and serum were measured using a spectrophotometer,and TRAP-positive cells in joint tissues were identified by enzyme histochemistry. TIMP-2 in SF and serum was detected by ELISA. Histochemistry revealed an increased number of TRAP positive cells in tissues from OA-affected joints which was decreased after one month treatment with BV and EACP. After one-month administration of EACP and BV,the levels of TRAP in SF of the index stifles as well as that in the serum were significantly decreased (P<0. 05),whereas,the levels of TIMP-2 in SF of the index stifles as well as that in the serum were increased indicating the therapeutic effects of the EACP and BV on improvement of the conditions of OA.The intraarticular administration of EACP and BV were found effective for the treatment of OA in the dog.展开更多
目的:探讨小鼠疼痛模型的昼夜节律和注射用蜂毒(Bee venom for injection,BVI)镇痛作用的昼夜差异及其相关机制。方法:采用热板法、辐射热甩尾法建立小鼠疼痛模型,在6个授时(Zeitgeber time,ZT)时间点(ZT2、ZT6、ZT10、ZT14、ZT18、ZT22...目的:探讨小鼠疼痛模型的昼夜节律和注射用蜂毒(Bee venom for injection,BVI)镇痛作用的昼夜差异及其相关机制。方法:采用热板法、辐射热甩尾法建立小鼠疼痛模型,在6个授时(Zeitgeber time,ZT)时间点(ZT2、ZT6、ZT10、ZT14、ZT18、ZT22)测量痛阈并分析其昼夜节律。将合格昆明小鼠随机分为注射用蜂毒大剂量(Bee venom for injection-High dose,BVI-H)、注射用蜂毒中剂量(Bee venom for injection-Medium dose,BVI-M)、注射用蜂毒低剂量(Bee venom for injection-low dose,BVI-L)、吗啡(Morphine,MOR)和模型(Model,MOD)组;每组再根据小鼠痛阈的昼夜节律分为两个亚组,分别在痛阈的峰值和谷值2个时间点给药。观察各组对热板法、辐射热甩尾法和扭体法疼痛模型小鼠行为学影响的动态变化;ELISA法检测血清P物质(Substances P,SP)、β-内啡肽(Beta-endorphin,β-EP)和IL-1β(interleukin-1β,IL-1β)水平。结果:小鼠疼痛模型的痛阈显示出峰值在明中期(ZT6)、谷值在暗后期(ZT22)的昼夜节律。BVI三个剂量组和MOR组均显示出明显的镇痛作用,并且BVI在热板法和扭体法模型的镇痛作用具有剂量依赖性。在热板法和辐射热法疼痛模型中,BVI于ZT22给药比ZT6给药显示出更强的镇痛作用。蜂毒对疼痛模型小鼠血清β-EP水平未显示上调作用;但可明显降低血清SP含量,且具有ZT22给药低于ZT6给药的昼夜变化(P<0.05);对扭体法和辐射热法(仅ZT22给药组)疼痛模型小鼠血清IL-1β水平显著下调,而在热板法则显示IL-1β水平明显增高。结论:小鼠的痛阈存在峰值在明中后期、谷值在暗后期的昼夜节律;BVI对小鼠多种疼痛模型均具有镇痛作用,且存在昼夜差异;BVI的镇痛作用及其昼夜变化可能与调节内源性疼痛介质有关。展开更多
基金the Beijing Science and Technology New Star Program(grant No.2015A048)the Young Teacher Special of Beijing University of Chinese Medicine(1000061221025)National Science and Technology Major New Drug Projects(2014ZX09301306-009).
文摘Objective:To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel.Methods:In this study,the sodium urate and LPS were used on rats and mice to construct the model.Bee venom gelemicroneedle combination effect on the model is to determine the role of microneedle gel permeation by observing inflammation factors.Results:Compared with the model group,the bee venom gelemicroneedle combination group can reduce the level of serum nitric oxide of the acute gouty inflammation model caused by sodium urate,and on LPS induced mouse model of acute inflammation effect and the micro.Conclusions:Bee venom can significantly suppress the occurrence of gouty arthritis inflammation in rats and mice LPS inflammatory reaction.Choose the 750 mm microneedle with 10N force on skin about 3 minutes,bee venom can play the optimal role,and the anti-inflammatory effect is obvious.Microneedles can promote the percutaneous absorption of the active macromolecules bee venom gel.
基金supported by the National Natural Science Foundation of China (No.3027045330570592)
文摘Objective To examine whether microinjection of morphine into the rat thalamic nucleus submedius (Sm) could depress the bee venom (BV)-induced nociceptive behaviours. Methods In inflammatory pain model induced by BV subcutaneous injection into rat unilateral hind paw,the inhibitory effects of morphine microinjection into thalamic nucleus submedius (Sm) on the spontaneous nociceptive behavior,heat hyperalgesia and tactile allodynia,and the influence of naloxone on the morphine effects were observed in the rat. Results A single dose of morphine (5.0 μg,0.5 μL) applied into the Sm ipsilateral to the BV injected paw significantly depressed the spontaneous paw flinching response. Morphine also significantly increased the heat paw withdrawal latencies in the bilateral hind paw and the tactile paw withdrawal threshold in the ipsilateral hind paw 2 hours after BV injection. All these depressive effects could be effectively antagonized by pre-treatment with the opioid receptor antagonist naloxone (1.0 μg,0.5 μL) in the Sm 5min prior to morphine administration. Naloxone alone injected to the Sm had no effect on the BV-induced nociceptive behavior. Conclusion These results suggest that Sm is involved in opioid receptor-mediated anti-nociception in the rat with the BV-induced inflammatory pain. Together with results from previous studies,it is likely that this effect is produced by activation of the Sm-ventrolateral orbital cortex-periaqueductal gray pathway,leading to activation of the brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal cord level.
基金grants from National Natural Science Foundation of China(No.30325023,30670692)Natural Science Foundation of Beijing Education Committee(No.KZ200510025016)+1 种基金National Basic Research Development Program(973)of China(No.2006CB500808)Innovation Research Team Program of Ministry of Education,China(No.IRT0560)
文摘Subcutaneous injection of bee venom causes long-term neural activation and hypersensitization in the dorsal horn of the spinal cord,which contributes to the development and maintenance of various pain-related behaviors.The unique behavioral 'phenotypes' of nociception and hypersensitivity identified in the rodent bee venom test are believed to reflect a complex pathological state of inflammatory pain and might be appropriate to the study of phenotype-based mechanisms of pain and hyperalgesia.In this review,the spinal processing of the bee venom-induced different 'phenotypes' of pain and hyperalgesia will be described.The accumulative electrophysiological,pharmacological,and behavioral data strongly suggest that different 'phenotypes' of pain and hyperalgesia are mediated by different spinal signaling pathways.Unraveling the phenotype-based mechanisms of pain might be useful in development of novel therapeutic drugs against complex clinic pathological pain.
文摘OBJECTIVE:To evaluate the efficacy of bee venom acupuncture in humeroscapularis(PHS)patients.METHODS:One hundred and twenty patients diagnosed with PHS were assigned into four groups:BV1(0.01 mg/kg),BV2(0.005 mg/kg),BV3(0.0025 mg/kg),and control group(vitamin B1 plus novocain 3%injection)with 15 d of treatment.The outcomes of the study including visual analogue scale(VAS)score andβ-endorphin,inflammatory cytokines including interleukin-10(IL-10),IL-1βand tumor necrosis factorα(TNF-α)and shoulder function score were assessed at baseline,after 10 and 15 d of treatment.RESULTS:All four groups reported statistically significant improvement in VAS score,motion range,and shoulder function score(P<0.01),only the BV3 group showed significant increase of anti-inflammatory(IL-10)and decrease of pro-inflammatory(IL-1β,TNF-α)cytokines after treatment(P<0.05).The BV3 group presented a significant difference between all outcomes compared to the control and other groups.CONCLUSION:BV3 groups showed better recovery including reduced pain,improved motor function and normalized inflammatory cytokines than current therapy used in Vietnam and other groups.
文摘OBJECTIVE:To evaluate the anti-diabetic efficacy of orally administered bee wax coated water-soluble fraction of bee venom(BWCBVA)drug over orally administered bee wax(BW)and intraperitoneally administered whole bee venom(BV)in streptozotocin(STZ)-induced diabetic rats.METHODS:Diabetes induced by intraperitoneal administration of 60 mg/kg STZ was treated with BWCBVA,BW,and BV for 21 d.The biochemical,protein and histological changes,and physical characteristics of BWCBVA were then analyzed.RESULTS:The BWCBVA group shows significantly decreased blood glucose level as compared to the BW and intraperitoneally administered whole BV treated group.Moreover,BWCBVA significantly normalizes the serum biochemical parameters and increases the body weight.Also,administration of BWCBVA significantly reverses the altered liver expression of phosphatidylinositide 3-kinases-p85 and liver glucokinase.Histological analysis of the pancreas an increase in the islet cell numbers and decrease inβ-cell damage.Co-administering BWCBVA 0.25 mg/kg with nifedipine(6.8 mg/kg)and nicorandil(13.8 mg/kg)to the diabetic rats results in insulin secretion through enhanced calcium ion influx.High performance liquid chromatography and gas chromatography was performed to identify the pharmacologically important compounds present in BWCBVA.CONCLUSION:Our results indicate that BWCBVA,an orally administered colon specific drug delivery system,can be effective in treating diabetes mellitus.
基金This work was supported by the National Research Foundation of Korea(NRF)grant funded by Korea government(MSIP)(No.MRC,2017R1A5A2015541)was supported by Korea Institute for Advancement of Technology(KIAT)as the research project for World Class 300 R&D(WC300 R&D,No.S2563418).
文摘Background:Neuroinflammation and accumulation ofβ-amyloid(Aβ)play a significant role in the onset and progression of Alzheimer’s disease(AD).Our previous study demonstrated that signal transducer and activator of transcription-3(STAT3)plays a major role in neuroinflammation and amyloidogenesis.Methods:In the present study,we investigated the inhibitory effect of bee venom phospholipase A2(bvPLA2)on memory deficiency in Tg2576 mice,which demonstrate genetic characteristics of AD and the mechanism of its action at the cellular and animal level.For in vivo study,we examined the effect of bvPLA2 on improving memory by conducting several behavioral tests with the administration of bvPLA2(1 mg/kg)to Tg2576 mice.For in vitro study,we examined the effect of bvPLA2 on amyloidogenesis and neuroinflammation by treating bvPLA2 on LPSactivated BV2 cells.Results:We found that bvPLA2 alleviated memory impairment in Tg2576 mice,as demonstrated in the behavioral tests assessing memory.In the bvPLA2-treated group,Aβ,amyloid precursor protein(APP),and β-secretase 1(BACE1)levels and β-secretase activity were significantly decreased.Expression of pro-inflammatory cytokines and inflammation-related proteins decreased in the brain of bvPLA2-treated group,whereas anti-inflammatory cytokines increased.In addition,bvPLA2 reduced STAT3 phosphorylation in the brains of the bvPLA2-treated group.At the cellular level,bvPLA2 inhibits production of nitric oxide,pro-inflammatory cytokines,and inflammation-related proteins including p-STAT3.Additionally,bvPLA2 inhibits the production of Aβin cultured BV-2 cells.Results from the docking experiment,pull-down assay,and the luciferase assay show that bvPLA2 directly binds STAT3 and,thus,regulates gene expression levels.Moreover,when the STAT3 inhibitor and bvPLA2 were administered together,the anti-amyloidogenic and anti-inflammatory effects were further enhanced than when they were administered alone.Conclusion:These results suggest that bvPLA2 could restore memory by inhibiting the accumulation of Aβ and inflammatory responses via blockage of STAT3 activity.
基金This work was supported by FAPERJ(Research support foundation in the state of Rio de Janeiro)(grand number.111.616/2010)
文摘Aim: The present study aimed to examine whether apipuncture (stimulation of acupuncture points with bee venom)at ST36 and GV3 acupoints promotes neuroprotection and reduces neuroinflammation by modulating M1 and M2 phenotype polarization.Methods: Wistar rats were treated with bee venom (BV) (0.08 mg/kg) injection at acupoints ST36 and GV3 [BV (ST36 + GV3)-spinal cord injury (SCI)] or BV injection at non-acupoints [BV (NP)-SCI] or no treatment (CTL-SCI)after SCI by compression. The spinal cord mRNA expression of iNOS, Arg-1 and TGF-β was measured by real time PCR and the levels of IBA-1;BCL-2;NeuN e CNPase was measured by western blotting. Locomotor performance was measured by Basso, Beattie, and Bresnahan (BBB) and grid-walking tests.Results: Apipuncture treatment was able to (1) ameliorate locomotor performance;(2) reduce inflammatory markers (Cox-2 levels) and activation of microglia and macrophages;(3) reduce the polarization of the M1 phenotype marker (iNOS) and increase M2 (Arg-1 and TGF-β) phenotypic markers;(4) promote neuroprotection by reducing the death of neurons and oligodendrocytes;and (5) increase the expression of the anti-apoptotic factor BCL-2.Conclusion: Apipuncture treatment induces locomotor recovery and neuroprotection after the compression model of spinal cord injury. Further, it reduces neuroinflammation by decreasing M1 polarization and increasing M2 phenotype.
基金supported by a grant(12-D-02,13-B-04)from the Korea National Rehabilitation Center
文摘BACKGROUND:Shoulder pain is a common complication of stroke.Bee venom acupuncture(BVA)is increasingly used in the treatment of post-stroke shoulder pain.OBJECTIVE:To summarize and evaluate evidence on the effectiveness of BVA in relieving shoulder pain after stroke.SEARCH STRATEGY:Nine databases,namely MEDLINE,EMBASE,the Cochrane Library,the China National Knowledge Infrastructure(CNKI),the Japan Science and Technology Information Aggregator,Electronic(J-STAGE),and four Korean medical databases,namely,the National Assembly Library,the Research Information Service System,the National Discovery for Science Leaders,and OASIS,were searched from their inception through August 2014 without language restrictions.INCLUSION CRITERIA:Randomized controlled trials(RCTs)were included if BVA was used at acupoints as the sole treatment,or as an adjunct to other treatments,for shoulder pain after stroke.DATA EXTRACTION AND ANALYSIS:Two review authors independently selected trials for inclusion,assessed methodological quality and extracted data.RESULTS:A total of 138 potentially relevant articles were identifi ed,4 of which were RCTs that met our inclusion criteria.The quality of studies included was generally low,and a preponderance of positive results was demonstrated.All four trials reported favorable effects of BVA on shoulder pain after stroke.Two RCTs assessing the effects of BVA on post-stroke shoulder pain,as opposed to saline injections,were included in the meta-analysis.Pain was signifi cantly lower for BVA than for saline injections(standardized mean difference on 10-cm visual analog scale:1.46 cm,95%CI=0.30–2.62,P=0.02,n=86)CONCLUSION:This review provided evidence suggesting that BVA is effective in relieving shoulder pain after stroke.However,further studies are needed to confi rm the role of BVA in alleviating post-stroke shoulder pain.Future studies should be conducted with large samples and rigorous study designs.
基金supported by a grant from BioGreen21 Program, Rural Development Administration (Code#:PJ009519), Republic of Korea
文摘OBJECTIVE:Acne vulgaris is a chronic dermatologic problem with multiple factors involved in its pathogenesis.Alternative solutions to acne treatment were instigated by antibiotic resistance despite of its extensive use.Purified bee venom(PBV)has been proposed as a promising candidate for that purpose.The present study was designed to confirm the antibacterial effect of PBV and access the efficacy of cosmetics containing PBV in subjects with acne vulgaris.METHODS:The skin bacterium Propionibacterium acnes was incubated with PBV at various concentrations and bacterial growth was evaluated using the colony forming unit(CFU)assay.The mechanism of PBV employed in killing P.acnes was examined by scanning electron microscopy(SEM)and transmission electron microscopy(TEM).In addition,a total of 12 subjects were randomized in a double-blind,controlled trial to receive either cosmetics containing PBV or cosmetics without PBV for two weeks.Evaluations included lesion counts and skin microorganism.RESULTS:PBV exhibited antimicrobial activity in a concentration-dependent manner,reducing the number of P.acnes CFU by approximately 6 logs at a concentration of 0.5 mg.When PBV concentration was higher than 1.0 mg,no P.acnes colonies were spotted on an agar.TEM and SEM of untreated P.acnes illustrated the normal pleomorphic structure,whereas the PBVtreated bacterium lost the integrity of surface architecture.Significant difference(P=0.027)in the grading levels based on numbers of lesion counts for inflammatory and noninflammatory was observed in favour of the PBV group compared with the control group.In terms of average decrement of skin microorganism,subjects receiving cosmetics containing PBV experienced a significant 57.5%decrease of adenosine triphosphate levels,whereas participants receiving cosmetics without PBV experienced a nonsignificant decrease of 4.7%.CONCLUSION:These results show that the in vitro actions of antimicrobial activity of PBV were translated in vivo.Cosmetics containing PBV provided a certain degree of efficacy in terms of lesion counts and skin microorganism concentration compared with cosmetics without PBV in subjects with acne vulgaris.PBV may be a good candidate compound for developing therapeutic drug for the treatment of acne vulgaris.
基金Project (No 2007AA10Z324) supported by the National High-Tech Research and Development Program (863) of China
文摘Bee venom phospholipase A2(BvPLA2) is a lipolytic enzyme that catalyzes the hydrolysis of the sn-2 acyl bond of glycerophospholipids to liberate free fatty acids and lysophospholipids.In this work,a new BvPLA2(AccPLA2) gene from the Chinese honeybee(Apis cerana cerana) venom glands was inserted into bacmid to construct a recombinant transfer vector.Tn-5B-4(Tn) cells were transfected with the recombinant bacmid DNA for expression.Sodium dodecylsulfate-polyacrylamide gel electrophoresis(SDS-PAGE) analysis revealed a double band with molecular weights of 16 and 18 kDa.Products of hexahistidine AccPLA2 fusion protein accumulated up to 5.32% of the total cellular proteins.The AccPLA2 fusion protein was cross reactive with the anti-AmPLA2(BvPLA2 of the European honeybee,Apis mellifera) polyclonal serum.The reaction resulted in a double glycosylation band,which agrees with the band generated by the native AmPLA2 in Western blot analysis.The PLA2 activity of the total extracted cellular protein in the hydrolyzing egg yolk is about 3.16 μmol/(min·mg).In summary,the recombinant AccPLA2 protein,a native BvPLA2-like structure with corresponding biological activities,can be glycosylated in Tn cells.These findings provided fundamental knowledge for potential genetic engineering to produce AccPLA2 in the pharmaceutical industry.
文摘The medical use of bee venom for rheumatoid arthritis ( RA ) has a very long tradition. In this study, isolation and purification of polypeptides from bee venom were carried out on sephadex chromatography, heparin sepharose CL6B chromatography and HPLC. Several fractions were extracted, and their effects on activation of splenocyte and THP-1 cell were studied. The inhibitory fraction was selected for further studies. Finally, BV I-2H that the HPLC elution profiles was a single peak was isolated by C8 column. ESI-MS detection results showed that BY I-2H was a fraction of bee venom, and the molecular weight of the major component was 644.8. BY I -2H could inhibit ConA-induced splenocyte proliferation, IL-1 production and interfere with splenocyte cycle in mice. Moreover, BV I-2H could inhibit PMA-induced TNFa production in THP-1 cells, which was due to its inhibitory effects on TNFa mRNA expression and protein phosphorylation of IκBα. Our studies indicated that BY I -2H was one of the anti-inflammatory
基金Supported by Korea Institute of Planning and Evaluation for Technology in Food,Agriculture,Forestry and Fisheries through an Agri-Bio industry Technology Development Program funded by Ministry of Agriculture,Food and Rural Affairs(114070-3).
文摘OBJECTIVE:To investigate the safety of hair essence containing 0.05%purified bee venom(HE-PBV)on the skin and eyes of New Zealand White rabbits.METHODS:HE-PBV which contained 0.05%PBV,purified water,and glycerin,was used as the test substance.The skin-irritation test(SIT)and eye-irritation test(EIT)were conducted according to the Draize method.On the SIT,HE-PBV(0.5 m L)dropped gauze was attached both intact and abraded skin for 24 h.The other side of the skin was used as control.After 24 and 72 h,the treatment site was observed and scored according to evaluation criteria for skin reactions.On the EIT,the rabbits were divided into two groups:eye-washed(three rabbits)and non-eye-washed(six rabbits).HE-PBV(0.1 m L)was squirted into the right eye of rabbits.The left eye was untreated and used as a control.Then,20-30-s later,the eyes of rabbits in the eye-washed group were washed with^50 m L of physiologic(0.9%)salt solution.Then,1,2,3,4 and 7 d after the start of the EIT,the eyes and behavior of the rabbits were observed.The degree of eye irritation elicited by HE-PBV was determined in three steps and then the criteria of the classification of eye-irritation scores.RESULTS:The SIT revealed erythema and edema at the site of HE-PBV application.At 72 h,the body weight of rabbits was reduced slightly,but other symptoms(except erythema and edema)were not observed.The Primary Irritation Index score was0.6,and HE-PBV was deemed to be a slight irritant.The EIT did not show mortality or body-weight fluctuation,but hyperemic conjunctiva and eyelid closure were noted after HE-PBV administration.Except for these results,the score for the ophthalmic response on days 1,2,3,4 and 7 was 0,and HE-PBV was deemed to be a non-irritant.CONCLUSION:These data suggest that HE-PBV did not elicit eye irritation,but was a slight irritant to the skin of rabbits;the latter slight would have been due to the excipients used in manufacture of the hair essence because PBV has been shown to be safe.
文摘This study evaluated the therapeutic effects of the phytomedicine,ethyl acetate fraction of the Cynanchum peniculatum (EACP) and bee venom (BV) of the honey bee (Apis mellifera) for the treatment of experimental stifle osteoarthritis (OA) in 24 skeletally mature mixed small breed dogs (age 2 to 6 years,weight 2. 8 to 9 kg). One year after induction of OA,the animals were randomly allocated in 2 groups; the EACP-group received 10% solution of EACP 0. 5mL plus 0. 2 mL lidocaine; and the BV-group received 10% solution of BV 0. 5 mL plus 0. 2 mL lidocaine intraarticularly twice in a week in the OA-induced stifles for one month. The joint tissue specimens,synovial fluid (SF) and blood samples were collected prior to and 12 months after induction of OA,and one month posttreatment. TRAP levels in SF and serum were measured using a spectrophotometer,and TRAP-positive cells in joint tissues were identified by enzyme histochemistry. TIMP-2 in SF and serum was detected by ELISA. Histochemistry revealed an increased number of TRAP positive cells in tissues from OA-affected joints which was decreased after one month treatment with BV and EACP. After one-month administration of EACP and BV,the levels of TRAP in SF of the index stifles as well as that in the serum were significantly decreased (P<0. 05),whereas,the levels of TIMP-2 in SF of the index stifles as well as that in the serum were increased indicating the therapeutic effects of the EACP and BV on improvement of the conditions of OA.The intraarticular administration of EACP and BV were found effective for the treatment of OA in the dog.
文摘目的:探讨小鼠疼痛模型的昼夜节律和注射用蜂毒(Bee venom for injection,BVI)镇痛作用的昼夜差异及其相关机制。方法:采用热板法、辐射热甩尾法建立小鼠疼痛模型,在6个授时(Zeitgeber time,ZT)时间点(ZT2、ZT6、ZT10、ZT14、ZT18、ZT22)测量痛阈并分析其昼夜节律。将合格昆明小鼠随机分为注射用蜂毒大剂量(Bee venom for injection-High dose,BVI-H)、注射用蜂毒中剂量(Bee venom for injection-Medium dose,BVI-M)、注射用蜂毒低剂量(Bee venom for injection-low dose,BVI-L)、吗啡(Morphine,MOR)和模型(Model,MOD)组;每组再根据小鼠痛阈的昼夜节律分为两个亚组,分别在痛阈的峰值和谷值2个时间点给药。观察各组对热板法、辐射热甩尾法和扭体法疼痛模型小鼠行为学影响的动态变化;ELISA法检测血清P物质(Substances P,SP)、β-内啡肽(Beta-endorphin,β-EP)和IL-1β(interleukin-1β,IL-1β)水平。结果:小鼠疼痛模型的痛阈显示出峰值在明中期(ZT6)、谷值在暗后期(ZT22)的昼夜节律。BVI三个剂量组和MOR组均显示出明显的镇痛作用,并且BVI在热板法和扭体法模型的镇痛作用具有剂量依赖性。在热板法和辐射热法疼痛模型中,BVI于ZT22给药比ZT6给药显示出更强的镇痛作用。蜂毒对疼痛模型小鼠血清β-EP水平未显示上调作用;但可明显降低血清SP含量,且具有ZT22给药低于ZT6给药的昼夜变化(P<0.05);对扭体法和辐射热法(仅ZT22给药组)疼痛模型小鼠血清IL-1β水平显著下调,而在热板法则显示IL-1β水平明显增高。结论:小鼠的痛阈存在峰值在明中后期、谷值在暗后期的昼夜节律;BVI对小鼠多种疼痛模型均具有镇痛作用,且存在昼夜差异;BVI的镇痛作用及其昼夜变化可能与调节内源性疼痛介质有关。
