Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells.
Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells.
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DOI：
10.3389/fphar.2023.1196210
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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目的：慢传输型便秘(STC)是一种常见的胃肠道疾病，以肠道微生物区系改变和肠嗜铬细胞(ECs)数量减少为特征。黄芪甲苷(AS-IV)是一种低药物渗透性的皂苷，对STC患者有良好的治疗作用。然而，AS-IV调控STC的具体机制仍不清楚。在这项研究中，我们旨在研究AS-IV对STC的影响及其涉及肠道微生物区系的相关机制。方法：采用洛哌丁胺诱导的STC小鼠模型，观察AS-IV对STC的影响。我们测量了AS-IV治疗的STC小鼠的排便频率、肠道流动性、内皮细胞丢失和结肠病变。我们还分析了AS-IV治疗后肠道微生物区系和代谢产物的变化。此外，我们还研究了特定肠道微生物与改变的粪便代谢产物之间的关系，如3-溴酪氨酸(3-Bry)。我们还进行了体外实验，研究了3-Bry对氯哌丁胺诱导的内皮细胞caspase依赖的凋亡以及p38MAPK和ERK信号通路的激活的影响。结果：AS-IV治疗可促进STC小鼠排便，改善肠道运动，抑制ECs丢失，减轻结肠病变。AS-IV治疗还影响肠道微生物区系和代谢物，特定的肠道微生物和改变的粪便代谢物之间存在显著相关性，如3-Bry。此外，3-Bry可能通过抑制氯哌丁胺诱导的p38MAPK和ERK信号通路的激活，减少caspase依赖的内皮细胞的凋亡，保护细胞存活。结论：AS-IV治疗STC的作用机制可能与肠道微生物区系和内皮细胞的变化有关。这些结果为AS-IV作为益生素治疗STC提供了依据。AS-IV调节肠道微生物区系和ECs的具体机制值得进一步研究。
Purpose: Slow transit constipation (STC) is a common gastrointestinal disorder characterized by altered gut microbiota and reduced number of enterochromaffin cells (ECs). Astragaloside IV (AS-IV), a low drug permeability saponin, has showed beneficial effects on patients with STC. However, the specific mechanism by which AS-IV regulates STC remains unclear. In this study, we aimed to investigate the effect of AS-IV on STC and its associated mechanisms involving gut microbiota. Methods: The effect of AS-IV on STC was evaluated on STC mice induced with loperamide. We measured defecation frequency, intestinal mobility, ECs loss, and colonic lesions in STC mice treated with AS-IV. We also analyzed the changes in gut microbiota and metabolites after AS-IV treatment. Moreover, we investigated the relationship between specific gut microbes and altered fecal metabolites, such as 3-bromotyrosine (3-BrY). We also conducted in vitro experiments to investigate the effect of 3-BrY on caspase-dependent apoptosis of ECs and the activation of the p38 MAPK and ERK signaling pathways induced by loperamide. Results: AS-IV treatment promoted defecation, improved intestinal mobility, suppressed ECs loss, and alleviated colonic lesions in STC mice. AS-IV treatment also affected gut microbiota and metabolites, with a significant correlation between specific gut microbes and altered fecal metabolites such as 3-BrY. Furthermore, 3-BrY may potentially reduce caspase-dependent apoptosis of ECs and protect cell survival by inhibiting the activation of the p38 MAPK and ERK signaling pathways induced by loperamide. Conclusion: Our findings suggest that changes in gut microbiota and ECs mediated the therapeutic effect of STC by AS-IV. These results provide a basis for the use of AS-IV as a prebiotic agent for treating STC. The specific mechanism by which AS-IV regulates gut microbiota and ECs warrants further investigation.
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影响因子：
29.4
作者：
Zhao, Risheng;Coker, Olabisi Oluwabukola;Yu, Jun
通讯作者：
Yu, Jun
影响因子：
11.5
作者：
Pannemans, Jasper;Masuy, Imke;Tack, Jan
通讯作者：
Tack, Jan
影响因子：
64.5
作者：
Bellono NW;Bayrer JR;Leitch DB;Castro J;Zhang C;O'Donnell TA;Brierley SM;Ingraham HA;Julius D
通讯作者：
Julius D
DOI：
10.1523/jneurosci.1145-09.2009
发表时间：
2009-08-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Liu MT;Kuan YH;Wang J;Hen R;Gershon MD
通讯作者：
Gershon MD
DOI：
10.1073/pnas.1804938115
发表时间：
2018-08-07
影响因子：
11.1
作者：
Alcaino C;Knutson KR;Treichel AJ;Yildiz G;Strege PR;Linden DR;Li JH;Leiter AB;Szurszewski JH;Farrugia G;Beyder A
通讯作者：
Beyder A