Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang, 712000, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
J Ethnopharmacol. 2019 May 23;236:136-146. doi: 10.1016/j.jep.2019.01.042. Epub 2019 Mar 6.
Licorice and Yuanhua are both famous herbs in Traditional Chinese Medicine (TCM), and their combination is used by some TCM doctors to treat renal and gastrointestinal diseases as well as tumors. On the other hand, the compatibility theory of TCM warns that toxic effects might be triggered by Licorice-Yuanhua combination. The usability of Licorice-Yuanhua combination has long been controversial due to lack of evidence and mechanism illustration. Colonic hydrogen sulfide (HS) metabolism imbalance is closely related with colonic inflammation, tumor promotion and many other diseases.
This study was carried out to investigate if licorice-Yuanhua combination could induce potential toxic effects in the aspect of colonic HS metabolism.
Normal mice were treated with high or low doses of Licorice, Yuanhua and Licorice-Yuanhua combination. Fecal HS concentration was measured by colorimetric method, colon sulfomucin production was compared through tissue staining, fecal microbiota and microbial metagenomes were analyzed by 16S rDNA sequencing and data mining.
Data shows that although licorice cannot change colonic HS concentration, it can exacerbate Yuanhua induced HS rising. Licorice or Yuanhua increases colon sulfomucin production, and their combination further enhances this effect. 16S rDNA sequencing analysis revealed that licorice or Yuanhua has little influence on gut microbiota, however, licorice-Yuanhua combination can impact gut microbiota structural balance and increase the abundance of Desulfovibrio genus and other related genera. Moreover, the combination extensively changes microbial metagenomes, influencing 1172 genes that cannot be changed by individual licorice or Yuanhua. By searching in KEGG database, ten genes are annotated with HS producing gene, and these genes are remarkably increased by licorice-Yuanhua combination, more significantly than licorice or Yuanhua.
This study provides evidences and mechanisms for licorice induced risks, which is related with colonic HS metabolism disturbance, gut microbiota and microbial metagenomes. More risk assessment should be evaluated when licorice was used in combination with foods, herbs or drugs. The study provides an example where healthy risks can be induced by combination of food additive, herbs or drugs, through regulating gut microbiota and its metagenomes.
甘草和芫花都是中药（TCM）中的著名草药，一些 TCM 医生将它们组合使用来治疗肾脏和胃肠道疾病以及肿瘤。另一方面，TCM 的配伍理论警告说，甘草-芫花组合可能会引发毒性作用。由于缺乏证据和机制说明，甘草-芫花组合的可用性一直存在争议。结肠内硫化氢（HS）代谢失衡与结肠炎症、肿瘤促进等多种疾病密切相关。
本研究旨在探讨甘草-芫花组合是否会在结肠 HS 代谢方面引起潜在的毒性作用。
正常小鼠分别用高、低剂量的甘草、芫花和甘草-芫花组合进行处理。采用比色法测定粪便中 HS 浓度，组织染色比较结肠黏蛋白的产生，通过 16S rDNA 测序和数据挖掘分析粪便微生物群和微生物宏基因组。
数据表明，甘草虽然不能改变结肠 HS 浓度，但能加重芫花引起的 HS 升高。甘草或芫花增加结肠黏蛋白的产生，两者的组合进一步增强了这种作用。16S rDNA 测序分析显示，甘草或芫花对肠道微生物群影响不大，但甘草-芫花组合会影响肠道微生物群结构平衡，增加脱硫弧菌属和其他相关属的丰度。此外，该组合广泛改变了微生物宏基因组，影响了 1172 个不能被单独的甘草或芫花改变的基因。通过在 KEGG 数据库中搜索，有 10 个基因被注释为产生 HS 的基因，甘草-芫花组合显著增加了这些基因，比甘草或芫花更为显著。
本研究为甘草引起的风险提供了证据和机制，这与结肠 HS 代谢紊乱、肠道微生物群和微生物宏基因组有关。当甘草与食物、草药或药物联合使用时，应进行更多的风险评估。该研究提供了一个例子，即通过调节肠道微生物群及其宏基因组，食物添加剂、草药或药物的组合可能会引起健康风险。
