ArticleActa pharmaceutica Sinica. B2021
Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage.
Article in Acta pharmaceutica Sinica. B, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 82 citations in OpenAlex.
- Serum metabolic traits reveal therapeutic toxicities and responses of neoadjuvant chemoradiotherapy in patients with rectal cancer.Nature communications · 2022Trial
- Microbiota-Associated Amino Acid Metabolites in Inflammatory Bowel Disease: Emerging Key Players in the Host-Microbe Interface.Microorganisms · 2026Review
- Hepato-Cardiac Axis in Epirubicin Toxicity: Role of Kynurenine Pathway and N-Acetylcysteine Antioxidant Intervention.Journal of applied toxicology : JAT · 2026Article
- Enterococcus faecalis NBRC 100481 Protects the Intestinal Barrier via α-catenin/HMP-1 in Caenorhabditis elegans.Probiotics and antimicrobial proteins · 2026Article
- Comprehensive Analysis of miRNAs, mRNAs, and lncRNAs in Intestines of Breast- and Formula-Fed Pigs.Journal of animal physiology and animal nutrition · 2026Article
- The kynurenine pathway storm in epilepsy: mechanisms and therapeutic implications.Acta epileptologica · 2026Review
- Tryptophan metabolism alterations in neurological and psychiatric diseases: Molecular mechanisms and pharmacological targets.Metabolic brain disease · 2026Review
- Phocaeicola coprophilus-Derived 6-Methyluracil Attenuates Radiation-Induced Intestinal Fibrosis by Suppressing the IDO1-Kynurenine-AHR Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Kynurenic Acid/GPR35 Signaling Protects the Infarcted Heart by Suppressing Macrophage mtDNA-Triggered cGAS-STING Activation.Antioxidants (Basel, Switzerland) · 2026Article
- Mesaconate Alleviates Myocardial Ischemia/Reperfusion Injury and Cardiovascular Aging by Targeting GPR35 to Arrest Macrophage Inflammation.Inflammation · 2026Article
- Gliquidone alleviates DSS-induced ulcerative colitis in rats by targeting carnitine palmitoyltransferase 1A.Journal of pharmaceutical analysis · 2026Article
- Tryptophan metabolic gatekeeping in epithelial repair: GPR35-KLF5 circuitry decodes mucosal damage signals for repair programming.Cell death & disease · 2026Article
- Chronic stress drives liver cancer by impairing the hepatic kynurenine pathway and immune surveillance.Nature metabolism · 2026Article
- Reimagining AHR in Cancer: From Environmental Sensor to Novel Immunomodulatory Therapeutic Target.International journal of biological sciences · 2026Review
- Intestinal amino acid metabolic response and its roles in inflammatory bowel disease.Cell communication and signaling : CCS · 2025Review
- Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets.Acta pharmaceutica Sinica. B · 2025Review
- Kynurenic Acid Protects Against Myocardial Ischemia/Reperfusion Injury by Activating GPR35 Receptors and Preserving Mitochondrial Structure and Function.Biomolecules · 2025Article
- Mitochondrial Integrity and Kynurenine Pathway Enzyme Dynamics in the Hippocampus of Rats with Scopolamine-Induced Cognitive Deficits.International journal of molecular sciences · 2025Article
- Increased GPR35 expression is correlated with poor prognosis in prostate cancer.World journal of surgical oncology · 2025Article
- Liposomal Vardenafil and Linagliptin Combined with Irinotecan for Synergistic Colorectal Cancer Therapy.Pharmaceutical research · 2025Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity
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