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代谢组学揭示了半夏的心脏毒性机制及其炮制减毒作用。

Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing.

机构信息

Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science, Beijing, China.

出版信息

Sci Rep. 2016 Oct 4;6:34692. doi: 10.1038/srep34692.

DOI:10.1038/srep34692
PMID:27698376
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5048190/
Abstract

Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR.

摘要

半夏是一种常用的中药材，但已有大量关于其毒性的报道。根据传统的中医理论，炮制可以降低药物的毒性。本研究旨在确定炮制是否降低生半夏的毒性，并探讨生半夏毒性的潜在机制和炮制的减毒作用。采用生化和组织病理学方法评价生半夏和炮制品的毒性。采用 LC-TOF-MS 分析大鼠血清代谢物。代谢组学数据的 IPA 分析突出了生半夏诱导毒性和炮制减毒作用涉及的生物学途径和网络功能，并通过分子方法进行了验证。结果表明，生半夏引起心脏毒性，炮制降低了毒性。mTOR 信号通路抑制和 TGF-β 通路激活参与了生半夏的心脏毒性，自由基清除可能是炮制减毒作用的原因。本研究为生半夏心脏毒性的机制和炮制的减毒作用提供了新的见解。本研究为半夏的传统炮制理论提供了科学依据，有助于优化炮制工艺和半夏的临床联合应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/7490ebf0ef94/srep34692-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/18ba3f95695b/srep34692-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/7490ebf0ef94/srep34692-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/9781b17625fc/srep34692-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/d3ef1b54300b/srep34692-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/f37a0eeb7236/srep34692-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/ed1054d93db0/srep34692-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/659912f0c68a/srep34692-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/27e0932d1aa8/srep34692-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/18ba3f95695b/srep34692-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3c4/5048190/7490ebf0ef94/srep34692-f8.jpg

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