蝎毒抗肿瘤及其相关机制研究进展

目前发现蝎类6科约800种,已报道具有医学意义的近50种,均属钳蝎科。其中在我国分布最广的是东亚钳蝎。全蝎,味甘、辛,有毒,归肝经,主要成分含蝎毒。蝎毒成分复杂,已知具有抗风湿、镇痛、改善心血管功能、抗癫痫等功效。近年来,国内学者对蝎毒抗肿瘤作用进行了初步研究,并探讨了其可能抑制肿瘤生长的机制,为其进一步与传统治疗方法结合治疗肿瘤提供了实验依据。现就蝎毒抗癌及相关机制方面的研究进展综述如下。     

蝎毒治疗白血病作用机制的研究进展

对蝎毒治疗白血病的机制进行阐述,蝎毒蛋白是蝎毒主要的活性成分,蝎毒能诱导人白血病K562细胞,HL-60细胞,Raji细胞凋亡,其作用机制可能与提高P53基因,降低Bcl-2基因表达有关.蝎毒及其分离组分通过减少白血病细胞从骨髓内的选出,抑制白血病细胞对血管内皮细胞的粘附及跨血管迁移,干预白血病细胞对细胞外基质的降解等方面干预白血病髓外浸润.同时蝎毒组分具有改善骨髓造血抑制,恢复免疫功能的作用.蝎毒是一种具有开发应用前景的抗白血病药物.     

阿米洛利对神经系统疾病治疗作用的研究进展

阿米洛利（amiloride）发挥药理学作用主要是通过抑制一些离子通道如Na＋/H＋交换器（NHE）,酸感受离子通道（ASICs）,Na＋/Ca2＋交换泵（NCX）等实现的,越来越多的研究表明其对神经系统多种疾病具有治疗作用,阿米洛利可有效减轻缺血性脑损伤、癫痫、偏头痛等发作时造成的酸中毒、Ca2＋超载、兴奋性毒性神经递质的释放,有望作为一种新型药物应用于神经系统疾病的治疗。     

钩藤治疗癫痫的主要作用机制研究进展

癫痫，为临床上最常见的神经系统疾病之一，对患者的身心健康造成了极大的威胁。中药钩藤具有息风定惊、清热平肝之效，为临床用于治疗癫痫的常用药。随着现代科学技术的发展，目前已有研究表明，钩藤可通过拮抗NMDA受体及抑制丝裂原活化蛋白激酶(MAPK)信号通路、调节离子通道、抑制胶质细胞增殖和S100B蛋白表达以减少神经元凋亡等机制发挥抗癫痫作用，本文对钩藤治疗癫痫的主要作用机制综述如下。     

龙血竭对免疫调节功能相关性Kv1.3通道的抑制作用

目的拟调查龙血竭对免疫调节功能相关性Kv1.3通道的影响。方法运用全细胞膜片钳实验检测龙血竭对Kv1.3通道电流及Jurkat细胞膜电位的影响;运用ELISA实验检测龙血竭对细胞炎性因子白细胞介素-2释放的影响。结果龙血竭对外源性表达在HEK293T细胞及内源性表达在Jurkat T细胞上的Kv1.3通道产生了浓度依赖性抑制作用;龙血竭尚可以诱导Jurkat T细胞膜电位发生去极化改变,抑制植物血凝素激活的Jurkat T细胞炎性因子白细胞介素-2的释放。结论该研究首次报道了Kv1.3通道是龙血竭赖以产生免疫抑制作用的受体靶蛋白,部分阐明了龙血竭产生免疫抑制效应原细胞和分子机制。     

蝎毒提取技术及应用前景探讨

全蝎是我国传统的名贵中药,药用已有上千年的历史。蝎毒为全蝎的主要活性成分,具有很高的药用价值,除具有全蝎的传统药效外,蝎毒对神经、消化、心脑血管系统疾病及恶性肿瘤等尤有疗效,蝎毒的研究日益为各国科学家重视,欧美一些国家已率先把蝎毒制剂用于临床,其价格昂贵,被称为"液体软黄金"。总结各种蝎毒提取技术优劣及其注意事项,蝎毒的具体应用范围以及存在的一些问题、蝎毒未来的发展前景等,为开发更加安全、有效的蝎毒新药提供思路和参考。     

基于网络药理学探讨全石榴“助胃火”治疗功能性胃肠病的作用机制

目的基于网络药理学探讨全石榴"助胃火"治疗功能性胃肠病的作用机制。方法通过TCMSP数据库、化学专业数据库、Swiss ADME平台筛选出主要活性成分,Swiss Target Prediction预测活性成分的潜在靶点,并与OMIM、DisGeNET、DiGSeE疾病靶点数据进行比对,获得治疗功能性胃肠病的潜在靶点,Matascape数据库平台对潜在靶点进行GO分析和KEGG Pathway富集分析,Cytoscape软件构建"活性成分-作用靶点-通路"网络。结果全石榴中34种活性成分、86个作用靶点与其缓解功能性胃肠炎相关,主要与Ca~(2+)转运、离子通道进程、神经递质传递等生物过程相关,涉及了细胞膜、神经元突触、离子通道等多种物质,并调节了神经-内分泌-免疫等相关信号通路。结论本文为全石榴"助胃火"治疗功能性胃肠炎的作用机制提供了新的思路方法,为后续机制研究指明了方向。     

火麻仁化学成分及治疗便秘机制研究进展

火麻仁为桑科植物大麻Cannabis sativa L.的干燥成熟果实，具有悠久的用药历史，为临床常用药，主产于甘肃、云南等地。其化学成分主要包括木脂素酰胺类、生物碱类、黄酮类、甾体和萜类、大麻素类、脂肪酸、其酯类等，并具有诸多药理作用，并在治疗功能性便秘方面发挥重要作用，其机制可能是通过调节肠道内微环境、神经递质、离子通道、Cajal间质细胞，影响肠道AQP蛋白表达，从而发挥抗便秘作用。本文通过查阅文献对近年国内外有关火麻仁化学成分及治疗便秘机制研究进展进行综述，以期为今后火麻仁治疗便秘活性成分、作用机制的研究以及火麻仁新药的研发提供参考。     

蝎毒及其提取物免疫调节作用的研究进展

蝎毒及其提取物具有抗肿瘤作用近年来得到广泛证实,蝎毒提取物的蛋白成分对肿瘤增殖及转移过程中免疫功能调节具有重要意义。蝎毒及其提取物可活化或提高巨噬细胞、NK细胞、淋巴细胞及树突状细胞功能,并能与放化疗联合产生良好的协同抗肿瘤效应。文章就蝎毒及其提取物对免疫系统的影响及可能的作用机制进行系统阐述。     

中医药信息

<正> 全蝎开发研究取得突破全蝎是名贵中药材之一。蝎毒不仅能治疗多种疾病,而且能抗癌治癌,对全蝎的开发利用国家已列入“星火计划”科研项目。为了开发利用这一名贵中药资源,有效提取蝎毒,湖南新宁县助理农艺师唐晓明,从1987年起,致力于蝎毒提取研究。他根据蝎子的生活习性和在受到电、光、声等刺激时不断排毒的生理特征,于最近研制成功中外独有的蝎毒提取器。采用该     

18β-Glycyrrhetinic acid potently inhibits Kv1.3 potassium channels and T cell activation in human Jurkat T cells

Ethnopharmacological relevance

Licorice has been extensively used in traditional medicines for treatment of many diseases, including inflammations and immunological disorders. Recent studies have shown that the anti-inflammatory and immunomodulation activities of licorice have been attributed to its active component, glycyrretinic acid (GA). GA consists of two isoforms, 18α- and 18β-. However, its mechanism remains poorly understood.

Aim of the study

We compared the effects of two isoforms on Kv1.3 channels in Jurkat T cells and further characterized the inhibition of Kv1.3 channels by 18β-GA in CHO cells. In addition, we examined the effects of 18β-GA on Kv1.3 gene expression, Ca²⁺ influx, proliferation, as well as IL-2 production in Jurkat T cells.

Materials and methods

Whole-cell patch-clamp technique was applied to record Kv1.3 currents in Jurkat T or CHO cells. Real-time PCR and Western blotting were used to detect gene expression. Fluo-4, CCK-8 kit and ELISA kit were used to measure Ca²⁺ influx, proliferation, and IL-2 secretion in Jurkat T cells, respectively.

Results

Superfusion of 18β-GA (10–100 µM) blocked Kv1.3 currents in Jurkat T cells, while 18α-GA at the same concentration had no effect. The 18β-GA induced inhibition had a voltage- and concentration-dependent manner with an IC₅₀ of 23.9±1.5 µM at +40 mV in CHO cells. Furthermore, 18β-GA significantly inhibited Kv1.3 gene expression. In addition, paralleling Kv1.3 inhibition, 18β-GA also inhibited Ca²⁺ influx, proliferation as well as IL-2 production in Jurkat T cells.

Conclusion

18β-GA blocks Kv1.3 channels, which probably involves its anti-inflammatory and immunomodulation effects.     

Curcumin Serves as a Human Kv1.3 Blocker to Inhibit Effector Memory T Lymphocyte Activities

Curcumin, the principal active component of turmeric, has long been used to treat various diseases in India and China. Recent studies show that curcumin can serve as a therapeutic agent for autoimmune diseases via a variety of mechanisms. Effector memory T cells (T_EM, CCR7^‐CD45RO⁺ T lymphocyte) have been demonstrated to play a crucial role in the pathogenesis of T cell‐mediated autoimmune diseases, such as multiple sclerosis (MS) or rheumatoid arthritis (RA). Kv1.3 channels are predominantly expressed in T_EM cells and control T_EM activities. In the present study, we examined the effect of curcumin on human Kv1.3 (hKv1.3) channels stably expressed in HEK‐293 cells and its ability to inhibit proliferation and cytokine secretion of T_EM cells isolated from patients with MS or RA. Curcumin exhibited a direct blockage of hKv1.3 channels in a time‐dependent and concentration‐dependent manner. Moreover, the activation curve was shifted to a more positive potential, which was consistent with an open‐channel blockade. Paralleling hKv1.3 inhibition, curcumin significantly inhibited proliferation and interferon‐γ secretion of T_EM cells. Our findings demonstrate that curcumin is able to inhibit proliferation and proinflammatory cytokine secretion of T_EM cells probably through inhibition of hKv1.3 channels, which contributes to the potency of curcumin for the treatment of autoimmune diseases. This is probably one of pharmacological mechanisms of curcumin used to treat autoimmune diseases. Copyright © 2012 John Wiley & Sons, Ltd.     

蝎毒素药用价值研究进展

传统中药采用全蝎及其毒液来治疗多种疑难杂症已有千年的历史,其主要药用活性成分来自蝎毒液的多肽和酶,特别是含量丰富的神经毒素多肽(俗称蝎毒素)。随着现代研究的深入,越来越多的毒液多肽成分逐渐从不同蝎种中分离出来,为新的药物设计与开发提供了众多的候选多肽分子。在神经、免疫、感染、心血管、肿瘤等方面疾病中,蝎毒液及其多肽成分都具有良好的治疗效果。此外,由于独特的结构与功能,蝎毒素也常作为分子骨架用于开发新的特异性药物。该文有针对性地阐述了具有良好药用前景的蝎毒素药理活性及其作用机制,为相关药物的进一步开发提供数据基础。     

蝎毒多肽干预急性白血病髓外浸润传变的机制

目的:观察蝎毒多肽(PESV)对人白血病NOD/SCID小鼠髓外浸润模型体内uPA、uPAR、MMP2、MMP9表达的影响,探讨PESV干预急性白血病髓外浸润传变的机制。方法:首先选取急性白血病患者骨髓单个核细胞注入经过铯-137源照射的NOD/SCID小鼠体内,建立人白血病NOD/SCID小鼠髓外浸润模型;对实验小鼠随机分组,用Real-time PCR及Western Blot检测PESV治疗后小鼠体内MMP2、MMP9 mRNA和蛋白表达水平,用ELISA法检测小鼠血清uPA及uPAR表达水平。结果:PESV能够抑制模型小鼠体内MMP2、MMP9 mRNA及蛋白水平表达,能够抑制uPA及uPAR过度表达,其抑制效果与PESV浓度具有相关性。结论:PESV通过干预细胞外基质降解机制,阻抑急性白血病髓外浸润传变进展。     

Screening of plants acting against Heterometrus laoticus scorpion venom activity on fibroblast cell lysis

The aqueous extracts of 64 plant species, listed as animal- or insect-bite antidotes in old Thai drug recipes were screened for their activity against fibroblast cell lysis after Heterometrus laoticus scorpion venom treatment. The venom was preincubated with plant extract for 30 min and furthered treated to confluent fibroblast cells for 30 min. More than 40% efficiency (test/control) was obtained from cell treatment with venom preincubated with extracts of Andrographis paniculata Nees (Acanthaceae), Barringtonia acutangula (L.) Gaertn. (Lecythidaceae), Calamus sp. (Palmae), Clinacanthus nutans Lindau (Acanthaceae), Euphorbia neriifolia L. (Euphorbiaceae), Ipomoea aquatica Forssk (Convolvulaceae), Mesua ferrea L. (Guttiferae), Passiflora laurifolia L. (Passifloraceae), Plectranthus amboinicus (Lour.) Spreng. (Labiatae), Ricinus communis L. (Euphorbiaceae), Rumex sp. (Polygonaceae) and Sapindus rarak DC. (Sapindaceae), indicating that they had a tendency to be scorpion venom antidotes. However, only Andrographis paniculata and Barringtonia acutangula extracts provided around 50% viable cells from extract treatments without venom preincubation. These two plant extracts are expected to be scorpion venom antidotes with low cytotoxicity.     

Effect of Eryngium creticum on the haemolytic activities of snake and scorpion venoms

Aqueous and ethanol extracts of the fresh and dried leaves and roots of Eryngium creticum were tested for their inhibition against snake and scorpion venoms. The fresh leaf extract gave a higher percentage inhibition of the haemolytic activity of the scorpion venom Leiurus quinquesteiartus compared with the dried leaf extract. Extracts of both fresh and dried roots gave 100% inhibition of the snake and scorpion venoms. However, ethanol extracts of the leaves and roots enhanced RBC haemolysis rather than inhibiting venom activities on red blood cells. © 1997 John Wiley & Sons, Ltd.     

蝎毒多肽抑制白血病干细胞龛内活化的实验研究

[目的]观察蝎毒多肽(PESV)抑制白血病干细胞(LSC)在骨髓龛内的活化效应。[方法]分离白血病/急性淋巴细胞白血病(AML/ALL)患者LSC,置于Transwell小室中,分为高中低剂量组及对照组,分别加入不同浓度蝎毒多肽后培养,计算不同浓度组及不同时间段的LSC迁移率。[结果]PESV组迁移率分别为(25.01±6.83)%、(36.85±3.83)%、(50.73±7.15)%,与对照组(49.10±6.12)%比较差异具有显著性(P<0.05),高剂量组迁移率高于中低剂量组。[结论]不同浓度PESV均有抑制白血病干细胞活化作用,抑制强度呈浓度依赖。     

使用爪蟾卵母细胞载体研究黄连素对Kv1.4通道C型失活的影响

目的以非洲爪蟾卵母细胞为载体研究黄连素对去N端Kv1.4(Kv1.4ΔN)通道C型失活特性的影响。方法将Kv1.4ΔN的mRNA注射入非洲爪蟾卵母细胞并于18~20℃下孵育,成功表达后使用双微电极钳制法记录电流,观察黄连素对Kv1.4ΔN电流失活、复活的影响。结果黄连素对Kv1.4ΔN峰电流的抑制作用呈浓度依赖性和电压依赖性。黄连素可显著加速Kv1.4通道的C型失活速度,通道失活后的恢复时间延长。结论黄连素能显著加快Kv1.4通道的C型失活速度并延长其恢复时间,其机制可能为黄连素改变了Kv1.4通道S5或S6区域的构象。