Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"

LI Dan; LIU Xiaoxia; WANG Xiaofen; HE Zuxin; WEI Junnan; LIU Yanqing; GAO Yuxuan; LUO Ping; WANG Fang

doi:10.13422/j.cnki.syfjx.20260161

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Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"

更新时间：2026-04-28

- Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 10, Pages: 201-209(2026)
- 作者机构：
  
  1.江西中医药大学质谱诊疗与慢病康复研究中心，南昌 330004
  2.四川川济康制药有限公司，四川绵阳 622651
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20260161
  CLC： R242;R943.1;R256
- Received：05 November 2025，
  
  Revised：2026-01-04，
  
  Accepted：20 January 2026，
  
  Online First：22 January 2026，
  
  Published：20 May 2026
- 稿件说明：
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李丹,刘晓霞,王晓芬等.基于“脾主运化”理论探究枳实汁制白术改善慢传输型便秘的干预作用及“菌群-代谢”协同调控机制[J].中国实验方剂学杂志,2026,32(10):201-209.

LI Dan,LIU Xiaoxia,WANG Xiaofen,et al.Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(10):201-209.
李丹,刘晓霞,王晓芬等.基于“脾主运化”理论探究枳实汁制白术改善慢传输型便秘的干预作用及“菌群-代谢”协同调控机制[J].中国实验方剂学杂志,2026,32(10):201-209. DOI： 10.13422/j.cnki.syfjx.20260161.

LI Dan,LIU Xiaoxia,WANG Xiaofen,et al.Exploring Intervention Effect of Atractylodis Macrocephalae Rhizoma Processed with Aurantii Fructus Immaturus Juice on Slow-transit Constipation and Its "Microbiota-Metabolism" Synergistic Regulation Mechanism Based on Theory of "Spleen Governing Transportation and Transformation"[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(10):201-209. DOI： 10.13422/j.cnki.syfjx.20260161.

摘要

目的

基于“脾主运化”理论，探讨建昌帮特色品种枳实汁制白术改善慢传输型便秘（STC）的干预作用及“菌群-代谢”协同调控机制，阐明其炮制理论的科学内涵。

方法

将动物随机分为空白组、模型组、阳性药（莫沙必利）组及枳实汁制白术低、中、高剂量组。除空白组外，其余5组均采用盐酸洛哌丁胺构建STC模型。造模后给予干预处理，其中莫沙比利组剂量为3 mg·kg

-1

，枳实汁制白术低、中、高剂量组分别为3.9、7.8、15.6 g·kg

-1

，各组连续给药15 d，收集粪便、结肠组织和血清。通过测定粪便含水率与小肠推进率；采用苏木素-伊红（HE）染色观察结肠组织病理形态；酶联免疫吸附测定法（ELISA）检测血清中白细胞介素（IL）-6、肿瘤坏死因子-

（TNF-

）、IL-2的表达水平；结合16S rRNA测序分析小鼠粪便菌群结构、转录组学测序筛选结肠组织差异表达基因并进行基因本体（GO）、京都基因与基因组百科全书（KEGG）富集分析，最后采用Spearman相关性分析差异菌群与差异基因的关联性。

结果

与空白组比较，模型组鼠肠道推进率和粪便含水率均显著降低（

0.01），血清中IL-6、TNF-

和IL-2水平显著升高（

0.01）；HE染色结果显示，模型组鼠结肠黏膜上皮细胞破损脱落、杯状细胞减少。与模型组比较，各给药组均不同程度地改善结肠黏膜细胞情况，显著降低血清中IL-6、TNF-

和IL-2水平（

0.01），其中枳实汁制白术高剂量组可显著升高动物肠道推进率和粪便含水率（

0.05，

0.01）。进一步通过转录组学分析发现，模型组与空白组、枳实汁制白术高剂量组两两比较共筛选出104个差异基因，富集于花生四烯酸

代谢、醛固酮调节钠重吸收等与STC发病密切相关的通路。16S rRNA测序结果表明，枳实汁制白术可逆转模型小鼠肠道菌群结构失衡，提高菌群物种丰富度，下调副萨特氏菌属等促炎菌丰度，并富集毛螺菌科NK4A136群、瘤胃球菌科等有益菌，而上述类群均为肠道重要的产丁酸盐菌。Spearman相关性分析显示，枳实汁制白术组富集的有益菌群与花生四烯酸代谢通路基因呈负相关，与醛固酮调节钠重吸收通路基因呈正相关，而模型组促炎菌呈现除相反的相关性。

结论

枳实汁制白术可通过调控肠道菌群、花生四烯酸介导的炎症代谢及醛固酮调控的水盐调节通路，发挥对STC的协同治疗效果。

Abstract

Objective

Based on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus

juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory.

Methods

Animals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg

-1

）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg

-1

）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-

， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses

. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes.

Results

Compared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（

0.01）， while serum levels of IL-6， TNF-

， and IL-2 were significantly elevated（

0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-

， and IL-2（

0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（

0.05，

0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as

Parasutterella

， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in

the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends.

Conclusion

AMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

关键词

Keywords

references

XUE X ， ZENG H ， CHEN D B ， et al . Comparing the short-term clinical outcomes and therapeutic effects of different colectomies in patients with refractory slow-transit constipation in eastern countries：A network meta-analysis ［J］. Updates Surg ， 2024 ， 76 （ 2 ）： 411 - 422 .

BARBERIO B ， JUDGE C ， SAVARINO E V ， et al . Global prevalence of functional constipation according to the Rome criteria：A systematic review and Meta-analysis ［J］. Lancet Gastroenterol Hepatol ， 2021 ， 6 （ 8 ）： 638 - 648 .

黄云，王学红 . 便秘发病机制概述［J］. 中国现代医药杂志， 2017 ， 19 （ 10 ）： 105 - 108 .

HUANG Y ， WANG X H . Overview of the pathogenesis of constipation ［J］. Chin J Mod Med ， 2017 ， 19 （ 10 ）： 105 - 108 .

LOCKE 3 R G ， ZINSMEISTER R A ， FETT L S ， et al . Overlap of gastrointestinal symptom complexes in a US community ［J］. Neurogastroenterol Motil ， 2005 ， 17 （ 1 ）： 29 - 34 .

RAJINDRAJITH S ， RANATHUNGA N ， JAYAWICKRAMA N ， et al . Behavioral and emotional problems in adolescents with constipation and their association with quality of life ［J］. PLoS One ， 2020 ， 15 （ 10 ）： e0239092 .

CAMILLERI M ， FORD A C ， MAWE G M ， et al . Chronic constipation ［J］. Nat Rev Dis Primers ， 2017 ， 3 （ 1 ）： 17095 .

张喻然，王波 . 济川煎加味联合腹针对慢传输型便秘（脾肾阳虚型）疗效及对血清SP和NO水平的干预影响［J］. 中国中西医结合消化杂志， 2018 ， 26 （ 3 ）： 238 - 242 .

ZHANG Y R ， WANG B . Clinical effect of modified Jichuanjian combined with abdominal acupuncture in the treatment of slow transit constipation （deficiency of spleen and kidney Yang type） and its influence on serum SP and NO ［J］. Chin J Integr Tradit West Med Dig ， 2018 ， 26 （ 3 ）： 238 - 242 .

王衮 . 博济方［M］. 北京：商务印书馆， 1959 ： 30 .

WANG G . Bongji Fang ［M］. Beijing ： Commercial Press ， 1959 ： 30 .

陈嘉谟 . 本草蒙筌［M］. 北京：人民卫生出版社， 1988 ： 31 - 32 .

CHEN J M . Bencao Mengquan ［M］. Beijing ： People's Medical Publishing House ， 1988 ： 31 - 32 .

WANG L F ， WANG F ， ZHANG X F ， et al . Transdermal administration of volatile oil from Citrus aurantium -Rhizoma Atractylodis Macrocephalae alleviates constipation in rats by altering host metabolome and intestinal microbiota composition ［J］. Oxid Med Cell Longev ， 2022 ， 2022 ： 9965334 .

GAO F ， SU J ， LI J ， et al . 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 ［J］. Phytomedicine ， 2025 ， 145 ： 156977 .

贡钰霞，王浩，侯毅，等 . 大剂量生白术配伍枳实对慢传输型便秘大鼠结肠5-HT3R、5-HT4R表达的影响［J］. 中国中西医结合杂志， 2019 ， 39 （ 8 ）： 988 - 992 .

GONG Y X ， WANG H ， HOU Y ， et al . Effects of high-dose raw Rhizoma Atractylodis Macrocephala combined with Fructus Aurantii Immaturus on the expression of 5-HT3R and 5-HT4R in colon of rats with slow transit constipation ［J］. Chin J Integr Tradit West Med ， 2019 ， 39 （ 8 ）： 988 - 992 .

陈文东，王孝停，黄琪，等 . 生白术与炒白术对功能性便秘大鼠肠道微生物群落结构的影响及作用机制［J］. 中草药， 2025 ， 56 （ 14 ）： 5098 - 5107 .

CHEN W D ， WANG X T ， HUANG Q ， et al . Effect and mechanism of raw Atractylodes macrocephala and fried Atractylodes macrocephala on intestinal microbial community structure in rats with functional constipation ［J］. Chin Tradit Herb Drugs ， 2025 ， 56 （ 14 ）： 5098 - 5107 .

轩宏达，沈胜楠，李林林，等 . 基于差异成分追踪策略探究白术“枳实汁制”炮制品的抗炎“增效”机制［J］. 中国实验方剂学杂志， 2026 ， 32 （ 1 ）： 228 - 237 .

XUAN H D ， SHEN S N ， LI L L ， et al . Exploring anti-inflammatory synergistic mechanism of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice based on differential component tracking strategy ［J］. Chin J Exp Tradit Med Form ， 2026 ， 32 （ 1 ）： 228 - 237 .

王芳，于欢，李风琴，等 . 枳实制白术的炮制工艺优选及HPLC特征图谱分析［J］. 中国实验方剂学杂志， 2018 ， 24 （ 17 ）： 6 - 13 .

WANG F ， YU H ， LI F Q ， et al . Optimization of processing technology of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus and analysis of its HPLC fingerprint ［J］. Chin J Exp Tradit Med Form ， 2018 ， 24 （ 17 ）： 6 - 13 .

王芳，杨明，钟凌云，等 . 一种枳实制白术的炮制工艺：中国， CN201710202918.8 ［P］. 2017-09-01 .

WANG F ， YANG M ， ZHONG L Y ， et al . A kind of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus concoction process ： China ， CN201710202918.8 ［P］. 2017-09-01 .

门唤钊 . 枳术汤对脾虚型便秘小鼠结肠cAMP、PKA及AQP3影响的实验研究［D］. 沈阳：辽宁中医药大学， 2021 .

MEN H Z . Experimental study on the effects of Zhizhu decoction on colonic cAMP，PKA and AQP3 in spleen-deficiency constipation mice ［D］. Shenyang ： Liaoning University of Traditional Chinese Medicine ， 2021 .

李静，何牟，李玲，等 . 白术挥发油化学成分及药理作用研究进展［J］. 中成药， 2024 ， 46 （ 3 ）： 881 - 889 .

LI J ， HE M ， LI L ， et al . Research progress on chemical constituents and pharmacological activities of Baizhu（ Atractylodes macrocephala Koidz.） essential oil ［J］. Chin Tradit Pat Med ， 2024 ， 46 （ 3 ）： 881 - 889 .

宗阳，孙明明，乐音子，等 . 白术-枳实配伍治疗慢传输型便秘的研究概述［J］. 中国药房， 2018 ， 29 （ 16 ）： 2300 - 2304 .

ZONG Y ， SUN M M ， LE Y Z ， et al . Overview of Atractylodis Macrocephalae Rhizoma-Aurantii Fructus Immaturus combination in the treatment of slow-transit constipation ［J］. Chin Pharm ， 2018 ， 29 （ 16 ）： 2300 - 2304 .

于红珍，付明海，吉小平，等 . 简述胃肠动力调节机制的研究进展［J］. 世界华人消化杂志， 2020 ， 28 （ 23 ）： 1183 - 1191 .

YU H Z ， FU M H ， JI X P ， et al . Progress in research of gastrointestinal motility regulation ［J］. World Chin J Digestol ， 2020 ， 28 （ 23 ）： 1183 - 1191 .

AKASAKA H ， RUAN K . Identification of the two-phase mechanism of arachidonic acid regulating inflammatory prostaglandin E 2 biosynthesis by targeting COX-2 and mPGES-1 ［J］. Arch Biochem Biophys ， 2016 ， 603 ： 29 - 37 .

WANG B ， WU L J ， CHEN J ， et al . Metabolism pathways of arachidonic acids：Mechanisms and potential therapeutic targets ［J］. Signal Transduct Tar ， 2021 ， 6 （ 1 ）： 94 .

王广军，梁群 . 从经典源流探析脓毒症热毒论治［J］. 疑难病杂志， 2023 ， 22 （ 1 ）： 106 - 109 .

WANG G J ， LIANG Q . Analysis on the treatment of sepsis from the classical heat toxin of traditional Chinese medicine ［J］. J Diffic Complicat Case ， 2023 ， 22 （ 1 ）： 106 - 109 .

LINZ D ， WIRTH K ， LINZ W ， et al . Antihypertensive and laxative effects by pharmacological inhibition of sodium-proton-exchanger subtype 3-mediated sodium absorption in the gut ［J］. Hypertension ， 2012 ， 60 （ 6 ）： 1560 - 1567 .

刘海涛，施家希，黄娟，等 . 补中益气汤对脾虚泄泻大鼠小肠黏膜修复及葡萄糖吸收相关转运体的影响［J］. 中药材， 2017 ， 40 （ 5 ）： 1178 - 1183 .

LIU H T ， SHI J X ， HUANG J ， et al . Effects of Buzhong Yiqi decoction on small intestinal mucosal repair and glucose absorption transporters in rats with spleen deficiency diarrhea ［J］. J Chin Med Mater ， 2017 ， 40 （ 5 ）： 1178 - 1183 .

GAO X Y ， GUO K F ， LIU S F ， et al . A potential use of vidarabine：Alleviation of functional constipation through modulation of the adenosine A2A receptor-MLC signaling pathway and the gut microbiota ［J］. Int J Mol Sci ， 2024 ， 25 （ 23 ）： 12810 - 12810 .

HUANG J Q ， LIN B ， ZHANG Y ， et al . Bamboo shavings derived O -acetylated xylan alleviates loperamide-induced constipation in mice ［J］. Carbohydr Polym ， 2022 ， 276 ： 118761 .

LI R ， LI M ， LI B ， et al . Cannabis sativa L.alleviates loperamide-induced constipation by modulating the composition of gut microbiota in mice ［J］. Front Pharmacol ， 2022 ， 13 ： 1033069 .

ZHONG Y B ， KANG Z P ， WANG M X ， et al . Curcumin ameliorated dextran sulfate sodium-induced colitis via regulating the homeostasis of DCs and Treg and improving the composition of the gut microbiota ［J］. J Funct Foods ， 2021 ， 86 ： 104716 .

LI L ， YAN Z ， YANG W X ， et al . Rotenone induces parkinsonism with constipation symptoms in mice by disrupting the gut microecosystem，inhibiting the PI3K/Akt signaling pathway and gastrointestinal motility ［J］. Int J Mol Sci ， 2025 ， 26 （ 5 ）： 2079 .

ZHANG Q ， ZHONG D ， SUN R ， et al . Prevention of loperamide induced constipation in mice by KGM and the mechanisms of different gastrointestinal tract microbiota regulation ［J］. Carbohydr Polym ， 2020 ，256（prepublish）：117418.

WANG L L ， HU L J ， XU Q ， et al . Bifidobacteria exert species-specific effects on constipation in BALB/c mice ［J］. Food Funct ， 2017 ， 8 （ 10 ）： 3587 - 3600 .

ZHANG C Y ， WANG L L ， LIU X M ， et al . Bifidobacterium longum subsp. longum relieves loperamide hydrochloride-induced constipation in mice by enhancing bile acid dissociation ［J］. Food Funct ， 2025 ， 16 （ 1 ）： 297 - 313 .

YANG Z D ， YE S M ， XU Z M ， et al . Dietary synbiotic ameliorates constipation through the modulation of gut microbiota and its metabolic function ［J］. Food Res Int ， 2021 ， 147 ： 110569 .

SINGH V ， LEE G ， SON H ， et al . Butyrate producers，"the sentinel of gut"：Their intestinal significance with and beyond butyrate，and prospective use as microbial therapeutics ［J］. Front Microbiol ， 2023 ， 13 ： 1103836 .

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