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

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.