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Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells.

ABSTRACT: 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.

SUBMITTER: Wan X

PROVIDER: S-EPMC10703044 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells.

Wan Xingyang X Zhou Qian Q Chen Huaxian H Li Zhen Z Mo Mianling M Liu Zhimin Z Zhang Heng H He Zhuojie Z Xiao Guozhong G Zheng Yihui Y Lin Hongcheng H Ren Donglin D

Frontiers in pharmacology 20231121

<b>Purpose:</b> 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. <b>Methods: ...[more]

PMID: 38074145

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Project description:BackgroundGestational diabetes mellitus (GDM), a severe pregnancy disorder, is a temporary form of diabetes that occurs during gestation. Astragaloside IV (AS IV), a natural and effective composition of Astragalus membranaceus, shows pharmacological effects against diabetes. On the contrary, the effects of AS IV on GDM development are still not clear. This study aims to investigate the role of AS IV in alleviating GDM in rats and determine whether AS IV exerts its anti-GDM properties through the regulation of gut microbiota and metabolite modulation.MethodsThere were six pregnant SD rats in each of the four groups. First, the GDM model was induced by the streptozotocin (STZ, 45 mg/kg) injection on gestational days (GDs) 1-4, and AS IV intervention (10 mg/kg/d) was administered from 6 days before pregnancy until delivery. The measurements of relevant indicators pertaining to GDM symptoms and reproductive outcomes, along with the 16S rRNA sequencing data and LC-MS-based metabolomic profiles, were assessed across all groups.ResultsAfter the 25-day intervention, the GDM model + AS IV group showed significantly decreased fasting blood glucose levels (p = 0.0003), mean insulin levels (p = 0.0001), and insulin resistance index (p = 0.0001). AS IV treatment also decreased the malformation rate (p = 0.0373) and increased the average fetal weight (p = 0.0020) of GDM rats. Compared to the control rats, GDM rats showed a significantly higher abundance of Blautia and Anaerobiospirillum. However, the dramatically elevated abundance of these microorganisms was markedly decreased by AS IV treatment. In contrast, compared to GDM rats without treatment, GDM rats treated with AS IV showed a significantly higher abundance of bacteria (p < 0.05), such as Methanobrevibacter, Dubosiella, and Romboutsia, which are beneficial to the rats. Additionally, we observed dramatically elevated production of metabolites, such as N-acetyl-l-leucine and lithocholic acid, after AS IV treatment through metabolomics analysis (p < 0.05). Furthermore, significant associations between most genera of gut bacteria and the altered levels of the metabolites connected to gut microbiota were also discovered.ConclusionOur study demonstrated that AS IV could be an effective nutritional intervention strategy for targeting gut microbiota and metabolome profiles in GDM and provided experimental evidence supporting the use of AS IV to treat GDM.

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Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells.

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Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells.

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