Na Han , Taotao Wang , Sheng Chang , Rong Gao , Yuanyuan Wen , Zhihui Liu , Haoying Xi , Jianxiu Zhai , Ruimao Feng , Sikai Li , Jun Yin
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The detoxificaion mechanism of Cin on Strychni Semen (SS)-induced neurotoxicity in SK was performed based on the analysis of intestinal absorption, liver metabolism, serum metabolomics, and gut microbiota. The mercury accumulation of SK was assayed using human hair by ICP-MS.</p></div><div><h3>Results</h3><p>Cin was found to inhibit the neurotoxicity of SS in SK. Our study shows that Cin could inhibit SS's absorption in small intestine and promote its metabolism in the liver. A serum metabolomics study showed that taurine and hypotaurine metabolism and retrograde endocannabinoid signaling pathway were associated with Cin attenuation. Association analysis with gut microbiota suggested that Cin could downregulate four key metabolites, including 12‑hydroxy arachidonic acid, GM4(d18:1/18:0), C16 sphinganine, and LysoPC(18:1(11Z)/0:0), by downregulating Lachnospiraceae_NK4A136 and upregulating Prevotella to inhibit the toxic effects of SS. In addition, the danger of mercury poisoning in a longer time administration of SK was evaluated using human hair, and no visible increase in mercury was observed.</p></div><div><h3>Conclusion</h3><p>As a new discovery in compatibility, Cin was proved to be capable of inhibiting the neurotoxicity not only in SK but also in Cin-SS combination, displaying vital roles in Traditional Chinese Medicines.</p></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":null,"pages":null},"PeriodicalIF":6.7000,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A discovery in traditional Chinese medicine compatibility: Cinnabaris suppresses the Strychni Semen-induced neurotoxicity in Shang-Ke-Jie-Gu tablet\",\"authors\":\"Na Han , Taotao Wang , Sheng Chang , Rong Gao , Yuanyuan Wen , Zhihui Liu , Haoying Xi , Jianxiu Zhai , Ruimao Feng , Sikai Li , Jun Yin\",\"doi\":\"10.1016/j.phymed.2024.156029\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Cinnabaris, as a commonly used mineral drugs, is a classic sedative medicine. 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引用次数: 0
摘要
背景辰砂是一种常用的矿物药，是典型的镇静药。目的 我们的研究评估了含或不含朱砂的尚可解毒片（SK）的毒性，并阐明了朱砂的相关作用机制。根据对肠道吸收、肝脏代谢、血清代谢组学和肠道微生物群的分析，研究了 Cin 对 Strychni Semen（SS）诱导的 SK 神经毒性的解毒机制。研究结果表明，Cin 可抑制石杉碱甲对石杉碱甲的神经毒性。我们的研究表明，Cin 可以抑制 SS 在小肠中的吸收，并促进其在肝脏中的代谢。血清代谢组学研究表明，牛磺酸和低牛磺酸代谢以及逆行内大麻素信号通路与 Cin 的衰减有关。与肠道微生物群的关联分析表明，Cin可通过下调Lachnospiraceae_NK4A136和上调Prevotella来下调12-羟基花生四烯酸、GM4(d18:1/18:0)、C16鞘氨醇和LysoPC(18:1(11Z)/0:0)等四种关键代谢物，从而抑制SS的毒性作用。此外，还利用人体毛发评估了较长时间服用 SK 后汞中毒的危险性，结果显示汞含量没有明显增加。
A discovery in traditional Chinese medicine compatibility: Cinnabaris suppresses the Strychni Semen-induced neurotoxicity in Shang-Ke-Jie-Gu tablet
Background
Cinnabaris, as a commonly used mineral drugs, is a classic sedative medicine. Shang-Ke-Jie-Gu tablet is a famous Chinese patent medicine with Cinnabaris, However, the function of Cin in the prescription hasn't been clarified.
Purpose
Our study evaluated the toxicity of Shang-Ke-Jie-Gu tablet (SK) with or without Cinnabaris, and illuminate the related mechanisms that why cinnabaris is necessary.
Methods
The toxicity of SK and Cin free Shang-Ke-Jie-Gu tablet (CFSK) was evaluated by physical and behavioral tests and histological examinations. The detoxificaion mechanism of Cin on Strychni Semen (SS)-induced neurotoxicity in SK was performed based on the analysis of intestinal absorption, liver metabolism, serum metabolomics, and gut microbiota. The mercury accumulation of SK was assayed using human hair by ICP-MS.
Results
Cin was found to inhibit the neurotoxicity of SS in SK. Our study shows that Cin could inhibit SS's absorption in small intestine and promote its metabolism in the liver. A serum metabolomics study showed that taurine and hypotaurine metabolism and retrograde endocannabinoid signaling pathway were associated with Cin attenuation. Association analysis with gut microbiota suggested that Cin could downregulate four key metabolites, including 12‑hydroxy arachidonic acid, GM4(d18:1/18:0), C16 sphinganine, and LysoPC(18:1(11Z)/0:0), by downregulating Lachnospiraceae_NK4A136 and upregulating Prevotella to inhibit the toxic effects of SS. In addition, the danger of mercury poisoning in a longer time administration of SK was evaluated using human hair, and no visible increase in mercury was observed.
Conclusion
As a new discovery in compatibility, Cin was proved to be capable of inhibiting the neurotoxicity not only in SK but also in Cin-SS combination, displaying vital roles in Traditional Chinese Medicines.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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