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Zhizhu Decoction Alleviates Intestinal Barrier Damage via Regulating SIRT1/FoxO1 Signaling Pathway in Slow Transit Constipation Model Mice

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To explore the possible effects and mechanism of Zhizhu Decoction (ZZD) on the pathophysiology of slow transit constipation (STC).

Methods

A total of 54 C57BL/6 mice was randomly divided into the following 6 groups by a random number table, including control, STC model (model), positive control, and low-, medium- and high-doses ZZD treatment groups (5, 10, 20 g/kg, namely L, M-, and H-ZZD, respectively), 9 mice in each group. Following 2-week treatment, intestinal transport rate (ITR) and fecal water content were determined, and blood and colon tissue samples were collected. Hematoxylin-eosin and periodic acid-Schiff staining were performed to evaluate the morphology of colon tissues and calculate the number of goblet cells. To determine intestinal permeability, serum levels of lipopolysaccharide (LPS), low-density lipoprotein (LDL) and mannose were measured using enzyme-linked immunosorbent assay (ELISA). Western blot analysis was carried out to detect the expression levels of intestinal tight junction proteins zona-occludens-1 (ZO-1), claudin-1, occludin and recombinant mucin 2 (MUC2). The mRNA expression levels of inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4, IL-10 and IL-22 were determined using reverse transcription-quantitative reverse transcription reaction. Colon indexes of oxidative stress were measured by ELISA, and protein expression levels of colon silent information regulator 1/forkhead box O transcription factor 1 (SIRT1/FoxO1) antioxidant signaling pathway were detected by Western blot.

Results

Compared with the model group, ITR and fecal moisture were significantly enhanced in STC mice in the M-ZZD and H-ZZD groups (P<0.01). Additionally, ZZD treatment notably increased the thickness of mucosal and muscular tissue, elevated the number of goblet cells in the colon of STC mice, reduced the secretion levels of LPS, LDL and mannose, and upregulated ZO-1, claudin-1, occludin and MUC2 expressions in the colon in a dose-dependent manner, compared with the model group (P<0.05 or P<0.01). In addition, ZZD significantly attenuated intestinal inflammation and oxidative stress and activated the SIRT1/FoxO1 signaling pathway (P<0.05 or P<0.01).

Conclusion

ZZD exhibited beneficial effects on the intestinal system of STC mice and alleviated intestinal inflammation and oxidative stress via activating SIRT1/FoxO1 antioxidant signaling pathway in the colon.

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Author information

Authors and Affiliations

  1. Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China

    Yong Wen &  Xue-gui Tang

  2. Department of Traditional Chinese Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuang Province, 646000, China

    Yong Wen

  3. Department of Anus and Intestine Surgery, Affiliated Hospital of Integrated Chinese Medicine and Western Medicine of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China

    Yu Zhan

  4. Department of Anus and Intestine Surgery, Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, Chengdu, 610075, China

    Yu Zhan

  5. Department of Integrated Traditional and Western Medicine Anorectal, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuang Province, 637000, China

    Shi-yu Tang, Fang Liu, Qiu-xiao Wang, Peng-fei Kong &  Xue-gui Tang

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  1. Yong Wen
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  2. Yu Zhan
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  3. Shi-yu Tang
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  4. Fang Liu
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Contributions

Wen Y, Zhan Y and Tang XG designed the research; Wen Y, Zhan Y and Tang SY performed the research; Liu F, Wang QX and Kong PF analyzed the data; Wen Y, Zhan Y and Tang XG wrote the paper. All authors read and agreed to the final version for publication.

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Correspondence to Xue-gui Tang.

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Additional information

Supported by the General Project of National Natural Science Foundation of China (No. 82074429)

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Wen, Y., Zhan, Y., Tang, Sy. et al. Zhizhu Decoction Alleviates Intestinal Barrier Damage via Regulating SIRT1/FoxO1 Signaling Pathway in Slow Transit Constipation Model Mice. Chin. J. Integr. Med. 29, 809–817 (2023). https://doi.org/10.1007/s11655-022-3539-2

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