Thermostable potassium channel-inhibiting neurotoxins in processed scorpion medicinal material revealed by proteomic analysis: Implications of its pharmaceutical basis in traditional Chinese medicine
Thermostable potassium channel-inhibiting neurotoxins in processed scorpion medicinal material revealed by proteomic analysis: Implications of its pharmaceutical basis in traditional Chinese medicine
复制标题
蛋白质组学分析揭示全蝎药材中的耐热钾通道抑制性神经毒素：其中药药学基础的意义
DOI：
10.1016/j.jprot.2019.103435
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发表时间：
2019-08-30
影响因子：
3.3
通讯作者：
Zhao, Xiaolu
中科院分区：
文献类型：
--
作者：
Yang, Fan;Wang, Danya;Zhao, Xiaolu
有毒蝎子的神经毒素作用于离子通道。这些神经毒素是否保留在用于中药原料的加工过的东亚钳蝎中尚不清楚。对加工后的药用蝎子原料中具有功能活性的毒素进行了全面的质谱学研究，发现22种全长和44种截短的耐热钾通道调节毒素保留了六个保守的半胱氨酸残基，能够形成毒性所需的三个二硫键。此外，还发现了广泛的降解毒素片段，表明它们的相对热不稳定使毒性得以降低。此外，对Jurkat细胞产生IL-2的抑制和迟发性超敏反应(DTH)反应的降低表明，该提取物在体外和体内都具有免疫调节活性。我们的工作首次描绘了蝎子炮制药材中具有功能活性的蝎子毒素图，有助于揭示蝎子炮制药材的药学基础。生物学意义：中国以蝎子为药材已有一千多年的历史。这是众所周知的中医“以毒攻毒”战略的一个例子。在过去的30年里，对中国蝎子的广泛调查表明，蝎子毒液中的神经毒素是主要的毒性成分，它们针对细胞膜上的各种离子通道。然而，这些神经毒素是否保留在用于中药的加工马氏东亚钳蝎中仍是未知的。我们的研究描述了钾通道调节神经毒素在炮制蝎子体内的热稳定性和不稳定性，有助于理解以毒治病战略背后的药学基础。
The neurotoxins of venomous scorpion act on ion channels. Whether these neurotoxins are retained in processed Buthus martensii Karsch scorpions used in traditional Chinese medicine materials is unknown. Comprehensive mass spectrometry-based proteomic characterization of functionally active toxins in the processed medicinal scorpion material revealed 22 full-length and 44 truncated thermostable potassium channel-modulatory toxins that preserved six conserved cysteine residues capable of forming the three disulfide bonds necessary for toxicity. Additionally, a broad spectrum of degraded toxin fragments was found, indicating their relative thermal instability which enabled toxicity reduction. Furthermore, the suppression of interleukin-2 (IL-2) production in Jurkat cells and the reduced delayed-type hypersensitivity (DTH) response demonstrated that the extracts have immunoregulatory activity both in vitro and in vivo. Our work describes the first "map" of functionally active scorpion toxins in processed scorpion medicinal material, which is helpful to unveil the pharmaceutical basis of the processed scorpion medicinal material in traditional Chinese medicine.Biological significance: Scorpions have been used as medicinal materials in China for more than one thousand years. This is an example of the well-known "Combat poison with poison" strategy common to traditional Chinese medicine. In the past 30 years, extensive investigations of Chinese scorpions have indicated that the neurotoxins in the scorpion venom are the main toxic components and they target various ion channels in cell membranes. However, whether these neurotoxins are retained in processed Buthus martensii Karsch scorpions used for traditional Chinese medicine remains unknown. Our study described the thermal stability and instability of potassium channel-modulatory neurotoxins in processed scorpions and helps to understand the pharmaceutical basis underling the strategy of "combat poison with poison to cure diseases".