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ArticleNaunyn-Schmiedeberg's archives of pharmacology2026

Mechanistic insights into the antidiarrheal action of phlorizin: modulation of TLR4/NF-κB, PI3K/AKT, and HIF-1 signalling with antispasmodic and antimicrobial effects.

Ravi Kushwah, Smita Jain, Meenal Sahu, Chinchu Praisthy Lj, Siddharth Maurya, Taufik Ansari, Mansi, Ashwini Kumar Mishra, Aleksey Kuznetsov

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In one paragraph

Article in Naunyn-Schmiedeberg's archives of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Ravi KushwahDepartment of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Kishangarh, Rajasthan, India.
Smita JainDepartment of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Kishangarh, Rajasthan, India. smitajain1994@gmail.com.ORCID http://orcid.org/0000-0002-3374-5792
Meenal SahuDepartment of Bioscience & Biotechnology, Banasthali Vidyapith, Banasthali, Rajasthan, India.
Chinchu Praisthy LjDepartment of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Kishangarh, Rajasthan, India.
Siddharth MauryaDepartment of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Kishangarh, Rajasthan, India.
Taufik AnsariDepartment of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Kishangarh, Rajasthan, India.
MansiDepartment of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Kishangarh, Rajasthan, India.
Ashwini Kumar MishraDepartment of Pharmacology, School of Pharmacy & Technology Management, SVKM's NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India.
Aleksey KuznetsovDepartment of Pharmacology, School of Pharmacy & Technology Management, SVKM's NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India. aleksey.kuznetsov@usm.cl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study comprehensively evaluated the antidiarrheal potential of phlorizin, a natural dihydrochalcone glycoside abundant in apple peels, using an integrated approach combining network pharmacology, molecular docking, density functional theory (DFT) analyses, antimicrobial assays, and ex vivo spasmolytic evaluations. Network pharmacology identified 52 overlapping targets between phlorizin and diarrhoea-associated genes, significantly enriched in TLR4/NF-κB, PI3K/AKT, and HIF-1 signalling pathways, implicating roles in inflammation regulation, epithelial protection, and cellular metabolism. Molecular docking revealed strong binding affinities of phlorizin with key target proteins including PIK3R1 (- 11.8 kcal/mol), SLC2A1/GLUT1 (- 10.3 kcal/mol), NF-κB1 (- 6.9 kcal/mol), TLR4 (- 6.6 kcal/mol), and NOS2 (- 6.4 kcal/mol)-stabilized by multiple hydrogen bonds and favourable MMGBSA energies (- 49.14 to - 69.65 kcal/mol). DFT analysis (B3LYP-GD3/6-311G(d,p)) demonstrated notable thermodynamic stability (ΔE < 4 kcal/mol between conformers), a dipole moment of 10.6 D, and significant charge localisation on hydroxyl oxygens (- 0.55 to - 0.76 e), supporting strong hydrogen bonding and electrostatic interactions within protein binding pockets. Antimicrobial evaluation showed dose-dependent inhibition of Escherichia coli and Bacillus subtilis, with optical density (OD

Indexed as

AntidiarrhealsAnti-Infective AgentsPhlorhizinAnimalsDiarrheaHypoxia-Inducible Factor 1MaleMolecular Docking SimulationNetwork PharmacologyNF-kappa BPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionToll-Like Receptor 4AntidiarrhealsAnti-Infective AgentsHypoxia-Inducible Factor 1NF-kappa BPhlorhizinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktToll-Like Receptor 4Antibacterial mechanismDFTDiarrhoeaGene ontologyGlycosideMolecular dockingNetwork pharmacologyProtein–protein interaction

Identifiers

What Socratic holds

Textmetadata
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Registered trials

None linked

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.