Study on the effects of the atractylodes macrocephala koidz-raphanus sativus l herb pair in alleviating senile constipation via the gut microbiota-SCFAs-5-HT axis

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-14 DOI:10.1016/j.phymed.2025.156977

Fan Gao , Jie Su , Jin Li , Changsheng Gan , Xiaohu Jin, Hengpu Zhou, Xingyu Liu, Jingjing Yu, Meiqiu Yan, Suhong Chen, Guiyuan Lv

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Abstract

Background

Senile constipation is a common functional gastrointestinal disorder that severely affects the quality of life in elderly populations. Chronic constipation can lead to colonic dysfunction and related complications. Atractylodes macrocephala Koidz. and Raphanus sativus L. are traditional Chinese medicinal herbs known for their "Qi-replenishing and spleen-strengthening" and "digestion-promoting and stagnation-relieving" properties, respectively. The herb pair (BZLF) is effective in treating senile constipation. However, the underlying mechanisms by which BZLF alleviating senile constipation remain unclear and require further investigation.

Purpose

This study aims to explore how BZLF alleviates senile constipation by promoting intestinal motility via the gut microbiota-short-chain fatty acids (SCFAs)-(5-hydroxytryptamine) 5-HT axis.

Methods

A mouse model of senile constipation was established by feeding aged mice a low-fiber diet. The therapeutic effects of BZLF were evaluated by assessing defecation frequency, fecal water content, time to first black stool, small intestine transit rate, and gastric emptying rate. Histological changes in the colon were observed using HE staining and AB-PAS staining. Immunohistochemistry and immunofluorescence were used to detect intestinal barrier-related protein expression in colonic tissues. Serum and colonic hormone levels were measured by ELISA. Western blotting and RT-qPCR were employed to analyze the expression of 5-HT signaling pathway-related proteins and mRNA. Gut microbiota composition was analyzed using 16S rDNA sequencing, and SCFAs levels were detected via GC/MS.

Results

BZLF improved defecation function and promoted intestinal motility in the mouse model of senile constipation. BZLF repaired intestinal barrier damage and increased serum levels of motilin (MTL), gastrin (GAS), endothelin (ET), and acetylcholine (ACH), thereby regulating gastrointestinal hormone imbalances. BZLF modulated gut microbiota dysbiosis in senile constipated mice by significantly increasing the abundance of beneficial bacteria (Lactobacillus and Ruminococcus) and suppressing the overgrowth of harmful bacteria (Escherichia-Shigella). Additionally, BZLF elevated SCFAs levels, particularly butyrate, in feces, which activated the 5-HT signaling pathway to alleviate constipation.

Conclusion

BZLF significantly alleviates senile constipation. Its mechanism of action is likely related to the modulation of gut microbiota composition, promotion of SCFAs production, and subsequent activation of the 5-HT signaling pathway. This study provides strong theoretical support for the development of BZLF as a potential anti-constipation herbal medicine and offers new therapeutic strategies for the treatment of senile constipation.

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通过肠道微生物群- scfas -5- ht轴研究苍术-白术对老年性便秘的缓解作用

背景老年性便秘是一种常见的功能性胃肠疾病，严重影响老年人的生活质量。慢性便秘可导致结肠功能障碍及相关并发症。苍术。和Raphanus sativus L.是传统的中草药，分别以“补气健脾”和“化瘀化瘀”的特性而闻名。中药对（BZLF）治疗老年性便秘疗效显著。然而，BZLF缓解老年性便秘的潜在机制尚不清楚，需要进一步研究。目的探讨茯苓多糖通过肠道菌群-短链脂肪酸(SCFAs)-（5-羟色胺）5-HT轴促进肠道蠕动，缓解老年性便秘的机制。方法采用低纤维饮食法建立小鼠老年性便秘模型。通过排便次数、粪便含水量、首黑便时间、小肠转运率、胃排空率等指标评价BZLF治疗效果。采用HE染色和AB-PAS染色观察结肠组织学变化。采用免疫组织化学和免疫荧光法检测结肠组织中肠屏障相关蛋白的表达。ELISA法测定血清和结肠激素水平。采用Western blotting和RT-qPCR分析5-HT信号通路相关蛋白和mRNA的表达。采用16S rDNA测序分析肠道菌群组成，GC/MS检测SCFAs水平。结果茯苓多糖能改善老年便秘小鼠的排便功能，促进肠道蠕动。BZLF可修复肠屏障损伤，提高血清胃动素（MTL）、胃泌素（GAS）、内皮素（ET）和乙酰胆碱（ACH）水平，从而调节胃肠激素失衡。BZLF通过显著增加有益菌（乳杆菌和瘤胃球菌）的丰度和抑制有害菌（埃希氏菌-志贺氏菌）的过度生长来调节老年便秘小鼠肠道菌群失调。此外，BZLF可提高粪便中SCFAs水平，尤其是丁酸盐水平，从而激活5-HT信号通路，缓解便秘。结论茯苓汤对老年便秘有明显的缓解作用。其作用机制可能与调节肠道菌群组成、促进SCFAs产生以及随后激活5-HT信号通路有关。本研究为bzzlf作为一种潜在的抗便秘中药的开发提供了强有力的理论支持，并为治疗老年性便秘提供了新的治疗策略。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

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.