Effects of cosmetics containing purified honeybee(Apis mellifera L.) venom on acne vulgaris

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 PBV- treated 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 drua for the treatment of acne vulaaris.

Anti-arthritic effects of microneedling with bee venom gel

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.

Spinal processing of bee venom-induced pain and hyperalgesia

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.

Inhibitory effects of microinjection of morphine into thalamic nucleus submedius on ipsilateral paw bee venom-induced inflammatory pain in the rat

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.

Structure of the Venom Apparatus of Large Carpenter Bees, Xylocopa fenestrata （Fabricius） （Hymenoptera： Apidae）

The venom apparatus in the large carpenter bees, Xylocopafenestrata （Fabricius） （Hymenoptera： Apidae） has been studied It consists of typical parts, i.e., the venom sac, free filament, Dufour gland, sting shaft and accessory sclerites. It is highly sclerotized and concealed by the 7th abdominal tergite and sternite. The venom sac serves as a reservoir for the venom which synthesized by the convoluted gland present in it, which is remarkably uniform to that of ants. The median duct extends from lower portion of venom sac, which measures 2.5 ±0.17 mm （mean ＋ SD） （n = 20） in length. The Dufour gland is a tube-like structure which is inserted in the sting-bulb. The triangular plate is attached at terminal portion of rami, which is in turn attached with lancets. The gonostyli are paired long and tubular structure with 5.29 ± 0.23 mm （n = 20） in length. The sting length is 5.29 ±0.23 mm （n = 20）. The fulcral arm is well-developed with an inverse Y-shaped structure present beneath the sting-bulb. Barbs on the sting shaft are weakly developed in X fenestrata but well developed in ants. The venom apparatus ofX. fenestrata when compared is similar to the bees but differs from that of the wasps and ants.

In Vitro Study on the Effect of Bee Venom on Some Cell Lines and Lumpy Skin Disease Virus

Bee venom （BV） was used from long time ago in the medical field as treatment of chronic joint affections. In the recent decades, the screening process of new sources of antimicrobials discovers its high advantageous characteristics for combating various types of microbes, as well as trials to discover its anti-cancer medicinal fields. Lumpy skin disease virus （LSDV） causes disease in cattle of economic importance, and this work aimed to find treatment as well as alternative inactivant for LSDV. The use of bee venom as antiviral was experimented in this work and exhibited satisfied inhibitory effects on LSDV, meanwhile, the antigenic properties was still intact. The viability of virus was tested in tissue culture cells lines and in embryonated chicken eggs. According to doses and time of exposure, the cell lines of Hep-2 （human larynx carcinoma） and MCF7 （breast carcinoma cell line） were treated with different concentrations of BV and examined after 24 h post-inoculation. The Hep-2 and MCF7 cell lines were treated with various concentrations of BV in descending doses as follow： 25, 20, 15, 10, 5 and 0.5 ug/mL of BV. Then bee venom pathological effects on Hep-2 cells and MCF7 cells were observed, such as apoptosis, retarded growths and cytolysis. The results indicate the possibilities of using bee venom as anti-neoplastic and antiviral.

蜂毒及其组分调节氧化应激的研究进展

蜂毒是天然生物毒素,有较强的生物活性,成分复杂,具有较重要的药用价值。其主要成分为蜂毒肽,具有多种药理活性。蜂毒及其组分的多重作用,部分与调节机体氧化应激密切相关,一方面可以通过抑制氧化应激改善辐射诱导的氧化应激损伤、减轻药物所致的肝肾肺功能受损、抑制肿瘤生长、促进神经功能恢复,另一方面也可能在某些情况下诱导氧化应激造成机体损伤。本文综述了蜂毒及其组分对氧化应激的调节作用,以期为其临床应用和进一步深入研究提供参考。

蜂毒PLA2原核表达及溶血作用研究

[目的]蜂毒(Bee_Venom,BV)是天然的动物药,药理效应广泛,成分较为复杂。磷脂酶A2(phospholipase A2,PLA2)是蜂毒的重要活性成分和主要过敏原,可与蜂毒肽发挥协同作用,诱发溶血。本研究旨在通过原核系统表达并纯化出蜂毒磷脂酶A2(BvPLA2)蛋白,并通过溶血试验对比蜂毒(bee venom,BV)、蜂毒肽(melittin)以及BvP⁃LA2的溶血效果。[方法]将已构建好的pET28a-BvPLA2融合表达载体转化到大肠杆菌BL21菌株中并通过IPTG低温诱导蛋白表达,对表达产物进行鉴定并纯化获得重组BvPLA2蛋白。采集小鼠眼球全血与生理盐水等体积混合配制成2%的红细胞混悬液,加入不同浓度的BvPLA2蛋白液、蜂毒液及蜂毒肽,通过酶标仪测定溶血率。[结果]经IPTG诱导后的表达产物在约15 kDa的分子量处呈现清晰的条带,与理论推算值一致。超声破碎后在上清及沉淀中均表达出特异性条带,且上清中的表达量与沉淀表达量基本一致。不同浓度的BvPLA2蛋白液均具有溶血效果,溶血率均超过5%,且低浓度BvPLA2溶血率较高。经对比得出,BvPLA2溶血率显著低于蜂毒和蜂毒肽(P<0.05)。[结论]通过原核表达系统成功诱导并纯化出可溶性目标蛋白BvPLA2,且BvPLA2具有一定的溶血效果,但溶血效果显著低于蜂毒和蜂毒肽。

马蜂蜇伤五例临床分析

马蜂蛰伤在临床工作中较为常见,患者的临床表现可仅表现为伤处的肿痛,但也有部分患者发生多脏器器官功能衰竭。因此,及时识别、早期救治马蜂蛰伤危急重症患者具有重要临床意义。本文回顾分析5例马蜂蛰伤患者的临床资料,结合国内外研究,对马蜂蛰伤后患者的临床表现进行小结,并进一步探讨可能造成病情危重的危险因素,以期为临床提供参考。

蜂毒多肽BVI-2对T细胞及THP-1细胞功能的影响

目的 :探讨蜂毒多肽BVI中有效的抗炎成份及其作用机制。方法 :观察蜂毒多肽对小鼠脾淋巴细胞转化、IL 1合成及THP 1细胞合成TNFα的影响。结果 :蜂毒多肽BV、BVI、BVI 2可抑制ConA(2 5 μg ml)诱导的小鼠脾淋巴细胞转化、IL 1合成及PMA(10 0ng ml)诱导的THP 1细胞合成TNFα。结论 :利用高效液相分离得到的蜂毒多肽BVI 2具有一定的抗炎作用。

蜂毒镇痛作用的昼夜变化及对外周血P物质β-内啡肽和IL-1β水平的影响

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。

动物毒液的抗菌活性研究进展

研究发现动物毒液中含有多种活性蛋白和多肽,具有广谱抗菌、抗病毒、抗癌、免疫调节等功能,目前针对蛇、蜜蜂、蝎子、蚂蚁和蜈蚣毒液的研究较为广泛,其毒液中所分泌的活性物质有望成为抗菌药物的来源。蛇毒中的磷脂酶A2和L-氨基酸氧化酶是发挥抗菌作用的主要活性物质,碱性磷脂酶A2可以杀灭金黄色葡萄球菌、鼻疽杆菌。L-氨基酸氧化酶在氧气的作用下产生过氧化氢,对巴氏杆菌、大肠杆菌、金黄色葡萄球菌、粪肠球菌有抑菌活性。蜂毒液的主要成分包括蜂毒素、磷脂酶A2和蜂毒肽,其中蜂毒肽和蜂毒素抗菌效果显著,对唾液链球菌、粪肠杆菌、沙门菌具有抗菌活性,蜂毒肽对耐甲氧西林金黄色葡萄球菌(MRSA)具有抗菌活性。蝎毒液作为生物活性肽的来源之一,分为二硫键桥肽(DBPs)和非二硫键桥肽(NDBPs),大部分非二硫键桥肽具有良好的抗菌效果,但部分非二硫键桥肽对真核细胞具有毒性作用。蚂蚁毒液富含生物活性蛋白和其他挥发性与非挥发性化合物,部分蚂蚁毒液肽对多种革兰阳性菌、革兰阴性菌表现出一定的抗菌活性。蜈蚣毒液分离出的抗菌肽主要有抗菌肽ScolopinⅠ、抗菌肽ScolopinⅡ和抗菌肽Scolopendrin 1,其中ScolopinⅠ和ScolopinⅡ对金黄色葡萄球菌及多重耐药菌株的生长均有抑制作用。在当前全球细菌耐药性问题日益严重的情况下,动物毒液作为一种潜在的原材料,为抗菌药物的研发提供了一个新思路,但由于动物毒液的毒性、稳定性等限制其作为药物直接进行应用,需通过改造、重组等手段进行改进,且多数研究还处于试验阶段。本文综述了蛇、蜜蜂、蚂蚁、蝎子、蜈蚣毒液的抗菌活性,旨在为开发新型、有效、低毒的抗菌药物提供参考。

蜂毒研究进展:炎症性皮肤病治疗新型药物候选库

炎症性皮肤病(inflammatory skin disease,ISD)的特点是持续的炎症浸润和缠绵难愈的皮肤病变。皮质类固醇激素是目前治疗ISD的主要药物,但因ISD复发性与顽固性等特点,长期服用这些激素药物对患者产生较大副作用。近年来,越来越多研究证实,蜂毒具有显著的抗炎、抗凋亡、抗纤维化、抗菌与抗氧化等作用,从而有效治疗ISD。本文就蜂毒主要活性组分及其抗炎机制,及蜂毒治疗包括痤疮、特应性皮炎、银屑病、过敏性接触性皮炎等ISD的新进展进行综述,为ISD的基础研究与临床治疗提供借鉴与参考。

2023年国内外蜂毒研究概况(1)

对2023年国内外蜂毒的研究概况进行了回顾,对公开发表的112篇中英文研究性论文的地域分布和研究领域进行了统计分析和评述,并重点介绍了蜂毒在化学成分、质量控制和生物学活性领域的研究新进展。

2023年国内外蜂毒研究概况(2)

对2023年国内外蜂毒的研究概况进行了回顾,对公开发表的112篇中英文研究性论文的地域分布和研究领域进行了统计分析和评述,并重点介绍了蜂毒在化学成分、质量控制和生物学活性领域的研究新进展。

毒蜂蜇伤患者血清指标与中医证候的相关性研究

目的 研究毒蜂蜇伤患者的中医证候分布及与血清指标的相关性。方法 回顾性分析238例毒蜂蜇伤患者的中医四诊信息,由3名中医师讨论确定患者的中医证候要素与中医复合证候,并应用Spearman相关性分析探索中医证候与血清指标的相关性。结果 毒蜂蜇伤患者的中医证候要素分布为:毒证>风证>内火>瘀血>痰湿,中医复合证候分布为:火毒证>风毒证>痰瘀互结证,风毒证与火毒证患者的病程显著短于痰瘀互结证,合并多器官功能障碍综合征(MODS)的比例显著高于痰瘀互结证,差异具有统计学意义(P <0.05)。风毒证、火毒证的C反应蛋白(CRP)、白细胞计数(WBC)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(LDH)、总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)、谷氨酰转肽酶(GGT)、肌酐(Scr)水平显著高于痰瘀互结证(P <0.05),火毒证的降钙素原(PCT)、尿素(BUN)水平显著高于风毒证与痰瘀互结证(P <0.05),痰瘀互结证的纤维蛋白原(FIB)、D2聚体(D-D)水平显著高于风毒证与火毒证(P <0.05)。结论 毒蜂蜇伤患者的血清相关指标与中医证候间存在相关性,在临床辨证论治中可参考血清指标水平。

蜂毒的主要成分及药理作用研究进展

蜂毒是一种天然生物毒素,主要成分包括蜂毒素、蜂毒肽、蜂毒明肽等。近年来,蜂毒的药理作用研究取得了显著进展。本文综述了蜂毒的主要成分及其药理作用的研究进展,包括抗炎、抗菌、抗病毒、抗肿瘤等方面。这些药理作用使得蜂毒在临床治疗中具有广泛的应用前景,其药理作用机制仍需进一步深入研究,以便更好地应用于临床实践。

蜂毒肽的生物活性及临床应用研究进展

本研究旨在系统探讨蜂毒肽的多种生物活性及其在临床应用中的潜力。蜂毒肽作为蜜蜂毒液的主要成分,因其广泛的药理作用和治疗潜力,近年来在生物医学领域引起了极大的关注。研究采用系统文献检索的方法,检索了从2004年至今的相关学术论文、专利和医学报告。关键词包括“蜂毒肽”、“抗菌”、“抗炎”、“抗肿瘤”、“临床应用”等。通过筛选和分析这些文献,提取出与蜂毒肽生物活性和临床应用相关的核心数据和结论。研究结果为蜂毒肽具有显著的抗菌和抗病毒活性。多项研究证实,蜂毒肽可以破坏细菌和病毒的细胞膜,抑制其生长和复制。其抗炎作用主要通过抑制炎症因子的释放和减少氧化应激反应来实现。蜂毒肽在抗肿瘤研究中表现出显著的效果,能够诱导肿瘤细胞凋亡,并在某些动物模型中显著抑制肿瘤生长。此外,蜂毒肽还显示出在治疗糖尿病、心血管疾病和神经退行性疾病中的潜力。在实际应用方面,蜂毒肽已被开发出多种产品,如抗菌喷雾、抗炎软膏等。然而,蜂毒肽在临床应用中仍面临一些挑战,如毒性控制、稳定性和靶向递送问题。研究结论为毒肽作为一种具有多种生物活性的天然产物,在临床应用领域具有广阔的前景,蜂毒肽其抗菌、抗病毒、抗炎和抗肿瘤作用为新药开发提供了重要的研究基础。综上所述,蜂毒肽有望成为未来治疗多种疾病的重要生物活性物质。

蜂针疗法治疗膝骨关节炎临床观察

目的观察蜂针疗法对膝骨关节炎(KOA)患者的临床疗效,为中医治疗KOA提供新方法。方法选取2020年1月至2023年6月绍兴市中心医院及宁波市第二医院中医科门诊患者150例肝肾亏虚型KOA患者为研究对象,按照随机数表法将患者分为观察组与对照组,每组各75例。观察组运用蜂针疗法调理;对照组运用塞来昔布胶囊200 mg,每日1次,餐后口服,氨基葡萄糖片0.75 g,每日2次,餐中口服。两组疗程均为5周。比较两组治疗前后西安大略麦克马斯特大学骨关节炎指数(WOMAC)评分、关节压痛视觉模拟量表(VAS)评分、50 m行走后膝关节压痛VAS评分与关节肿胀VAS评分。结果共有137例患者完成本研究,其中观察组70例,对照组67例。观察组治疗后的总有效率(82.86%)显著高于对照组(71.64%),差异有统计学意义(P<0.05)。治疗后两组关节肿胀VAS评分、50 m行走后膝关节压痛VAS评分、关节压痛VAS评分及WOMAC评分与治疗前相比明显降低,差异有统计学意义(P<0.05)。治疗后观察组关节肿胀VAS评分、50 m行走后膝关节压痛VAS评分、关节压痛VAS评分及WOMAC评分与对照组比较均显著降低,差异有统计学意义(P<0.05)。结论蜂针疗法在临床中可以明显改善KOA相关症状,并且比氨基葡萄糖片与塞来昔布胶囊具有更显著的临床效果。