J Proteome Res.:中药蜈蚣药效分子群和药理学活性揭秘

    蜈蚣是一味传统的重要动物药材，其中药药用已有几千年的历史。根据《中国药典》和《中华本草》记述，蜈蚣具有祛风止痉、通络止痛、攻毒散结的功效，可用于惊风、癫痫、痉挛抽搐、中风口歪、半身不遂、破伤风、风湿顽痹、偏头痛以及毒物咬伤等的治疗。虽然蜈蚣的药用价值被国内外医学专家所重视，用蜈蚣配成的中成药和处方在百余种以上，但由于缺乏系统全面的对蜈蚣药效分子群的识别和相应的药理学活性解析的研究，使得蜈蚣蕴含的丰富的天然药用活性物质未能得到充分认识，成为有效利用蜈蚣药用价值和创新药物研发的重要瓶颈。

    中国科学院昆明动物研究所动物模型与人类疾病机理重点实验室生物毒素与人类疾病课题组在张云和李文辉研究员带领下，采用先进的现代生物化学与分子生物学研究技术和手段，对蜈蚣的药效分子群和药理学活性进行了迄今为止最全面系统的揭秘,新识别了400余种蜈蚣肽类生物活性物质。该课题组进一步与华中科技大学分子生物物理重点实验室丁久平课题组合作，揭示了许多蜈蚣肽类生物活性物质可作用于不同的细胞膜离子通道（包括钠、钾、钙离子通道等）而发挥药理学作用。人类离子通道是产生生物电信号和胞内钙离子信号的膜蛋白分子，离子通道功能的紊乱可导致人体几乎所有组织和器官的多种疾病，是目前药物开发中排名第二的药物靶点。上述研究成果不仅科学地诠释了传统中药蜈蚣的药理药效学基础，从分子水平直接证明蜈蚣药用的有效性，也提供了蜈蚣中药材更科学的标准制定、炮制和应用的科学依据。该研究同时识别了一些导致过敏、出血等相关副作用的物质，为安全利用蜈蚣药材提供了有益指导。一大批结构新颖的离子通道调节剂的发现，也为基于蜈蚣药效成分的现代创新药物研发打下坚实基础，具有重要的生物医学基础研究和临床应用价值。文章已在线发表于美国化学联合会官方杂志 Journal of Proteome Research 。该研究受到国家973计划项目、国家基金委－云南省联合基金重点项目以及国家基金委面上项目的资助

doi: 10.1021/pr300881d

PMC:
PMID:

Venomic and Transcriptomic Analysis of Centipede Scolopendra subspinipes dehaani

Liu ZC, Zhang R, Zhao F, Chen ZM, Liu HW, Wang YJ, Jiang P, Zhang Y, Wu Y, Ding JP, Lee WH, Zhang Y.

Centipedes have venom glands in their first pair of limbs and their venoms contain a large number of components with different biochemical and pharmacological properties. However, information about the compositions and functions of their venoms is largely unknown. In this study, Scolopendra subspinipes dehaani venoms were systematically investigated by transcriptomic and proteomic analysis coupled with biological function assays. After random screening approximately 1500 independent clones, 1122 full length cDNA sequences, which encoding 543 different proteins, were cloned from a constructed cDNA library using a pair of venom gland from a single centipede species. Neurotoxins, ion channel acting components and venom allergens were the main fractions of the crude venom as revealed by transcriptomic analysis. Meanwhile, 40 proteins/peptides were purified and characterized from crude venom of S. subspinipes dehaani. The N-terminal amino acid sequencing and mass spectrum results of 29 out of these 40 proteins or peptides matched well with their corresponding cDNAs. The purified proteins/peptides showed different pharmacological properties, including: (1) platelet aggregating activity; (2) anticoagulant activity; (3) phospholipase A(2) activity; (4) trypsin inhibiting activity; (5) voltage-gated potassium channel activities; (6) voltage-gated sodium channel activities; (7) voltage-gated calcium channel activities. Most of them showed no significant similarity to other protein sequences deposited in the known public database. This work provides the largest number of protein or peptide candidates with medical-pharmaceutical significance and reveals the toxin nature of centipede S. subspinipes dehaani venom.