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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

Natural products and extracellular vesicle-associated miRNA networks in perianal infectious wound healing: a critical ethnopharmacological appraisal

  1. 1Xi’an Hospital of Traditional Chinese Medicine
  2. 2Southern Medical University

Abstract

Perianal infectious wounds form a contaminated, moist, mechanically disturbed repair niche that differs from standard cutaneous wounds. This critical narrative review evaluates whether natural-product pharmacology and extracellular vesicle (EV)-associated miRNA biology can be linked credibly in this setting. A structured PubMed search updated through 29 September 2026, supplemented by Google Scholar citation tracking, identified direct human perianal studies, anatomically relevant and infection-relevant animal studies, and mechanistically relevant in vitro and in silico evidence. Core studies were appraised on two separate axes: clinical/model proximity and methodological credibility, including material identity and taxonomic validity, chemical characterization, exposure, comparators and controls, model fidelity, EV characterization, causal miRNA evidence, and assay-interference risk. Direct human ethnopharmacological evidence now includes several randomized postoperative studies, although blinding, material standardization, comparator quality, endpoint selection, and mechanistic depth remain heterogeneous. Early-phase mesenchymal stromal cell EV studies provide perianal feasibility and fistula-closure signals without controlled comparative efficacy. A 2025 Wugu Qilin study provides direct human treatment-associated evidence from wound-fluid vesicle-enriched miRNA profiling involving miR-93-3p/EIF4EBP1, but it did not demonstrate EV-mediated transfer to recipient cells. Astragaloside IV-conditioned endothelial progenitor-cell EV studies provide stronger nonperianal cargo-level evidence, whereas curcumin-loaded macrophage EVs primarily support vesicle-assisted delivery. No study establishes the full causal sequence from chemically defined natural-product exposure through rigorously characterized EV cargo alteration and transfer of a defined miRNA to a necessary recipient-cell effect and improved healing in an anatomically faithful perianal model. Direct clinical and translational evidence is therefore present, but the natural product-EV-miRNA mechanism remains unproven; the most immediate needs are material standardization, clinically derived wound-fluid EV profiling, mixed-biofilm models, causal cargo perturbation, assay-interference controls, and stage-adapted local delivery.

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BibTeX
@article{yang2026natural,
  title = {{Natural products and extracellular vesicle-associated miRNA networks in perianal infectious wound healing: a critical ethnopharmacological appraisal}},
  author = {Wei Yang and Ruizhen Zhang and Jiamin Hang and Yujie Su and Yulong Ma and Qiang Song and Cong Wang and Xi Zhang},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1917327},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1917327/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Natural products and extracellular vesicle-associated miRNA networks in perianal infectious wound healing: a critical ethnopharmacological appraisal
AU  - Wei Yang
AU  - Ruizhen Zhang
AU  - Jiamin Hang
AU  - Yujie Su
AU  - Yulong Ma
AU  - Qiang Song
AU  - Cong Wang
AU  - Xi Zhang
PY  - 2026
DA  - 2026/10/29
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1917327
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1917327/full
AB  - Perianal infectious wounds form a contaminated, moist, mechanically disturbed repair niche that differs from standard cutaneous wounds. This critical narrative review evaluates whether natural-product pharmacology and extracellular vesicle (EV)-associated miRNA biology can be linked credibly in this setting. A structured PubMed search updated through 29 September 2026, supplemented by Google Scholar citation tracking, identified direct human perianal studies, anatomically relevant and infection-relevant animal studies, and mechanistically relevant in vitro and in silico evidence. Core studies were appraised on two separate axes: clinical/model proximity and methodological credibility, including material identity and taxonomic validity, chemical characterization, exposure, comparators and controls, model fidelity, EV characterization, causal miRNA evidence, and assay-interference risk. Direct human ethnopharmacological evidence now includes several randomized postoperative studies, although blinding, material standardization, comparator quality, endpoint selection, and mechanistic depth remain heterogeneous. Early-phase mesenchymal stromal cell EV studies provide perianal feasibility and fistula-closure signals without controlled comparative efficacy. A 2025 Wugu Qilin study provides direct human treatment-associated evidence from wound-fluid vesicle-enriched miRNA profiling involving miR-93-3p/EIF4EBP1, but it did not demonstrate EV-mediated transfer to recipient cells. Astragaloside IV-conditioned endothelial progenitor-cell EV studies provide stronger nonperianal cargo-level evidence, whereas curcumin-loaded macrophage EVs primarily support vesicle-assisted delivery. No study establishes the full causal sequence from chemically defined natural-product exposure through rigorously characterized EV cargo alteration and transfer of a defined miRNA to a necessary recipient-cell effect and improved healing in an anatomically faithful perianal model. Direct clinical and translational evidence is therefore present, but the natural product-EV-miRNA mechanism remains unproven; the most immediate needs are material standardization, clinically derived wound-fluid EV profiling, mixed-biofilm models, causal cargo perturbation, assay-interference controls, and stage-adapted local delivery.
SN  - 1663-9812
ER  -