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全面的粪便代谢组学和肠道微生物群用于评估人参治疗气虚型肝癌的机制。

Comprehensive fecal metabolomics and gut microbiota for the evaluation of the mechanism of Panax Ginseng in the treatment of Qi-deficiency liver cancer.

机构信息

Changchun University of Chinese Medicine, Changchun, 130117, China.

Jilin Provincial Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

出版信息

J Ethnopharmacol. 2022 Jun 28;292:115222. doi: 10.1016/j.jep.2022.115222. Epub 2022 Mar 24.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Qi deficiency liver cancer (QDLC) is an important part of liver cancer research in traditional Chinese medicine (TCM). In the course of its treatment, Panax ginseng is often selected as the main Chinese herbal medicine, and its function has special significance in the tumor treatment of Qi deficiency constitution. However, its mechanism is not clear.

AIM OF THE STUDY

The research tried to evaluate the mechanism of Panax ginseng in the treatment of QDLC through fecal metabonomics and gut microbiota on the basis of previous pharmacodynamic evaluation.

MATERIALS AND METHODS

Firstly, biomarkers and related metabolic pathways were screened and identified by metabonomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Then, 16S rRNA sequencing technique was used to investigate the composition, β diversity and key differences of gut microbiota. Finally, the relationship among phenotypes, gut microbiota and fecal metabolites was comprehensively analyzed by spearman correlation coefficient.

RESULTS

31 pharmacodynamic potential biomarkers and 20 synergistic potential biomarkers of effective parts of Panax ginseng on QDLC were screened and identified by fecal metabonomics. And then, 6 major metabolic pathways were searched, including bile acid biosynthesis, unsaturated fatty acid biosynthesis, tryptophan metabolism, arachidonic acid metabolism, pyrimidine metabolism, vitamin B6 metabolism. In the study of gut microbiota, at the genus level, 25 species of bacteria with significant differences of effective parts on QDLC and 23 species of bacteria with significant differences of synergistic action of ginsenosides and polysaccharides were screened. In addition, Spearman correlation analysis showed that there was a complex potential relationship among phenotype, gut microbiota and fecal metabolites during the development of QDLC and Panax ginseng intervention, which was mainly reflected in the close potential relationship between bacteria and fecal metabolites such as bile acids, unsaturated fatty acids and indole compounds.

CONCLUSION

Through the changes of fecal endogenous metabolites and intestinal bacteria, the mechanism of Panax ginseng on QDLC were preliminarily clarified.

摘要

民族药理学相关性

气虚肝癌(QDLC)是中医(TCM)肝癌研究的重要组成部分。在治疗过程中,人参常被选为主要中药,其功能在气虚体质的肿瘤治疗中具有特殊意义。然而,其机制尚不清楚。

研究目的

本研究在前药效评价的基础上,尝试通过粪便代谢组学和肠道微生物群来评估人参治疗 QDLC 的机制。

材料和方法

首先,通过代谢组学和京都基因与基因组百科全书(KEGG)数据库筛选和鉴定生物标志物和相关代谢途径。然后,采用 16S rRNA 测序技术研究肠道微生物群的组成、β多样性和关键差异。最后,通过 Spearman 相关系数综合分析表型、肠道微生物群和粪便代谢物之间的关系。

结果

通过粪便代谢组学筛选和鉴定了人参对 QDLC 的 31 种药效潜在生物标志物和 20 种协同作用有效部位的潜在生物标志物。然后,搜索了 6 条主要代谢途径,包括胆汁酸生物合成、不饱和脂肪酸生物合成、色氨酸代谢、花生四烯酸代谢、嘧啶代谢、维生素 B6 代谢。在肠道微生物群研究中,在属水平上,筛选出 25 种有效部位对 QDLC 有显著差异的细菌和 23 种人参皂苷和多糖协同作用有显著差异的细菌。此外,Spearman 相关分析表明,在 QDLC 发展和人参干预过程中,表型、肠道微生物群和粪便代谢物之间存在复杂的潜在关系,主要反映在细菌与胆汁酸、不饱和脂肪酸和吲哚类化合物等粪便代谢物之间的密切潜在关系。

结论

通过粪便内源性代谢物和肠道细菌的变化,初步阐明了人参对 QDLC 的作用机制。

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