{"title":"A discovery in traditional Chinese medicine compatibility: Cinnabaris suppresses the Strychni Semen-induced neurotoxicity in Shang-Ke-Jie-Gu tablet","authors":"","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. 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.</p></div><div><h3>Purpose</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</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":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S094471132400686X","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
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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