Evidence mapPaperPMID 42499504Full record

ArticleFrontiers in pharmacology2026

Paeoniflorin alleviates CKD-associated constipation by modulating TPH1/AHR-related signaling and suppressing NLRP3/GSDMD-mediated pyroptosis.

Jun Qiu, Zhimin Ao, Fenghua Yao, Jianing Zhang, Yong Wen, Yu Zhan

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Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Jun Qiu *Department of Nephrology, Fifth Medical Center of the Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.
Zhimin Ao *Hospital of Chengdu University of TCM, Anorectal Department, Chengdu, Sichuan, China.
Fenghua Yao *Department of Nephrology, First Medical Center of the Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.
Jianing ZhangDepartment of Nephrology, First Medical Center of the Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.
Yong WenHospital of Chengdu University of TCM, Anorectal Department, Chengdu, Sichuan, China.
Yu ZhanTraditional Chinese Medicine Department, Fifth Medical Center of the Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Constipation is a common complication of chronic kidney disease (CKD) and contributes to a vicious cycle linking intestinal dysfunction and renal injury, yet effective targeted therapies remain limited. Paeoniflorin (PF), a major bioactive constituent of Paeonia lactiflora Pall., has reported renoprotective and gastrointestinal regulatory effects, but its role in CKD-associated constipation remains unclear. Methods: In this study, we investigated the therapeutic effects and underlying mechanisms of PF in an adenine-induced mouse model of CKD-associated constipation. Constipation-related phenotypes, renal function, renal and colonic histopathology, intestinal barrier markers, TPH1/AHR-related signaling, renal NLRP3/GSDMD-mediated pyroptosis, gut microbial composition, PCS-related metabolic alterations, and molecular docking with key enzymes involved in the tyrosine-p-cresol-PCS pathway were assessed. Results: PF dose-dependently improved constipation-related phenotypes and renal dysfunction, and the high-dose PF group was selected for subsequent mechanistic analyses. High-dose PF attenuated renal fibrosis, restored colonic mucosal architecture, and increased the expression of tight junction proteins. Mechanistically, PF upregulated TPH1 and AHR expression, suggesting modulation of TPH1/AHR-related signaling. In renal tissues, PF suppressed NLRP3/GSDMD-mediated pyroptosis and improved the expression of KCNK3 and OAT3. PF also selectively reshaped gut microbial composition and was associated with microbial functional changes related to amino acid metabolism and inflammatory signaling. In addition, PF was associated with PCS-related metabolic alterations and showed potential interactions with key enzymes involved in the tyrosine-p-cresol-PCS pathway. Discussion: These findings indicate that PF alleviated CKD-associated constipation and improved renal injury, possibly through integrated modulation of intestinal barrier integrity, gut microbial composition, TPH1/AHR-related signaling, and renal pyroptosis-related signaling. PF may therefore represent a potential pharmacological candidate for CKD-associated constipation.

Indexed as

CKD-associated constipationNLRP3/GSDMD pyroptosispaeoniflorinp-cresyl sulfateTPH1/AHR-related signaling

Identifiers

PMID42499504
PMCPMC13396008

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.