ArticleOncotarget2018
Two birds, one stone: hesperetin alleviates chemotherapy-induced diarrhea and potentiates tumor inhibition.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.Nutrition & metabolism · 2026Review
- KLF13-mediated CES2 upregulation via p300-dependent acetylation sensitizes gastric cancer cells to irinotecan.iScience · 2025Article
- Managing Irinotecan-Induced Diarrhea: A Comprehensive Review of Therapeutic Interventions in Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Intestinal human carboxylesterase 2 (CES2) expression rescues drug metabolism and most metabolic syndrome phenotypes in global Ces2 cluster knockout mice.Acta pharmacologica Sinica · 2025Article
- Exploring the Effects and Potential Mechanisms of Hesperidin for the Treatment of CPT-11-Induced Diarrhea: Network Pharmacology, Molecular Docking, and Experimental Validation.International journal of molecular sciences · 2024Article
- Chemotherapy: how to reduce its adverse effects while maintaining the potency?Medical oncology (Northwood, London, England) · 2023Review
- Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment.Molecules (Basel, Switzerland) · 2023Review
- Converging multi-modality datasets to build efficient drug repositioning pipelines against Alzheimer's disease and related dementias.Medical review (2021) · 2022Article
- Covalent CES2 Inhibitors Protect against Reduced Formation of Intestinal Organoids by the Anticancer Drug Irinotecan.Current drug metabolism · 2022Article
- Artificial intelligence unifies knowledge and actions in drug repositioning.Emerging topics in life sciences · 2021Review
- Human carboxylesterases and fluorescent probes to image their activity in live cells.RSC medicinal chemistry · 2021Review
- Comprehensive bioinformatics study reveals targets and molecular mechanism of hesperetin in overcoming breast cancer chemoresistance.Molecular diversity · 2020Article
- Herbal Medicines for Irinotecan-Induced Diarrhea.Frontiers in pharmacology · 2019Review
- Optimization of Regioselective α-Glucosylation of Hesperetin Catalyzed by Cyclodextrin Glucanotransferase.Molecules (Basel, Switzerland) · 2018Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
Chemotherapy-induced diarrhea (CID), with clinical high incidence, adversely affects the efficacy of cancer treatment and patients' quality of life. Our study demonstrates that the citrus flavonoid hesperetin (Hst) has a superior potential as a new agent to prevent and alleviate CID. In the animal model for irinotecan (CPT-11) induced CID, Hst could selectively inhibit intestinal carboxylesterase (CES2) and thus reduce the local conversion of CPT-11 to cytotoxic SN-38 which causes intestinal toxicity. Oral administration of Hst manifested an excellent anti-diarrhea efficacy, prohibiting 80% of severe and 100% of mild diarrhea in the CPT-11 administered tumor-bearing mice. In addition, a significant attenuation of intestinal inflammation contributed to the anti-diarrhea effect of Hst. Moreover, Hst was found to work synergistically with CPT-11 in tumor inhibition by suppressing the tumor's STAT3 activity and recruiting tumoricidal macrophages into the tumor microenvironment. The anti-intestinal inflammation and anti-STAT3 properties of Hst would contribute its broad benefits to the management of diarrhea caused by other chemo or targeted agents, and more importantly, enhance and reinforce the anti-tumor effects of these agents, to improve patient outcomes.
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Registered trials
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 OpenQuestion graph.