Gao Fan, Su Jie, Li Jin, Gan Changsheng, Jin Xiaohu, Zhou Hengpu, Liu Xingyu, Yu Jingjing, Yan Meiqiu, Chen Suhong, Lv Guiyuan
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310014, China.
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310014, China..
Phytomedicine. 2025 Jun 14;145:156977. doi: 10.1016/j.phymed.2025.156977.
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.
背景：老年便秘是一种常见的功能性胃肠疾病，严重影响老年人群的生活质量。慢性便秘可导致结肠功能障碍及相关并发症。白术和莱菔子是传统中药材，分别以“补气健脾”和“消食化积”著称。药对（白术-莱菔子）在治疗老年便秘方面有效。然而，白术-莱菔子缓解老年便秘的潜在机制尚不清楚，需要进一步研究。 目的：本研究旨在探讨白术-莱菔子如何通过肠道微生物群-短链脂肪酸（SCFAs）-（5-羟色胺）5-HT轴促进肠道蠕动来缓解老年便秘。 方法：通过给老年小鼠喂食低纤维饮食建立老年便秘小鼠模型。通过评估排便频率、粪便含水量、首次排黑便时间、小肠转运率和胃排空率来评价白术-莱菔子的治疗效果。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道屏障相关蛋白的表达。采用ELISA法检测血清和结肠激素水平。采用蛋白质免疫印迹法和RT-qPCR法分析5-HT信号通路相关蛋白和mRNA的表达。采用16S rDNA测序分析肠道微生物群组成，通过GC/MS检测SCFAs水平。 结果：白术-莱菔子改善了老年便秘小鼠模型的排便功能，促进了肠道蠕动。白术-莱菔子修复了肠道屏障损伤，提高了胃动素（MTL）、胃泌素（GAS）、内皮素（ET）和乙酰胆碱（ACH）的血清水平，从而调节胃肠激素失衡。白术-莱菔子通过显著增加有益菌（乳酸杆菌和瘤胃球菌）的丰度和抑制有害菌（大肠埃希菌-志贺菌属）的过度生长，调节老年便秘小鼠的肠道微生物群失调。此外，白术-莱菔子提高了粪便中SCFAs的水平，尤其是丁酸盐，激活了5-HT信号通路以缓解便秘。 结论：白术-莱菔子能显著缓解老年便秘。其作用机制可能与调节肠道微生物群组成、促进SCFAs产生以及随后激活5-HT信号通路有关。本研究为白术-莱菔子作为一种潜在的抗便秘草药的开发提供了有力的理论支持，并为老年便秘的治疗提供了新的治疗策略。
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