Dual targeting of human and bacterial hyaluronidases by skincare bioactives: Mechanistic basis and functional evidence.

Summary

Multiple skincare bioactives (e.g., EGCG, retinol, ascorbic acid, hydroquinone) bind and inhibit both human and bacterial hyaluronidases, supported by bioinformatics, molecular dynamics, enzyme assays, and MIC testing. Conserved catalytic residues across species provide a mechanistic rationale for dual targeting of HAases to preserve HA and modulate skin microbiota.

Key Findings

• Human–bacterial HAases share conserved catalytic residues despite limited overall sequence similarity (notably in Streptococcus and Cutibacterium acnes isoforms).
• EGCG, retinol, ascorbic acid, hydroquinone, and rosmarinic acid showed strong predicted binding to both human and bacterial HAases; MD confirmed stable EGCG binding.
• Enzyme assays: ROL, EGCG, HQ, and AA inhibited S. agalactiae HAase by ~85–99%; AA, EGCG, AzA, AT, SA inhibited C. acnes HAase by ~94–100%.
• MICs: HQ, EGCG, ROL inhibited Streptococcus agalactiae (32–512 μg/mL); HQ, kojic acid, AzA inhibited C. acnes (1024–2048 μg/mL).

Clinical Implications

Supports selecting or combining actives (e.g., EGCG, AA, retinol, AzA) to protect HA while considering safety (e.g., hydroquinone use constraints), with potential benefits for aging, barrier repair, and acne-prone skin.

Limitations

• Lack of in vivo/clinical skin outcomes and formulation-level pharmacokinetics
• Some actives (e.g., hydroquinone) have regulatory/safety constraints and MICs may exceed practical topical concentrations

Future Directions

Validate in ex vivo human skin and controlled clinical trials measuring HA content, elasticity, microbiome shifts, and optimize formulations for synergistic dual HAase inhibition.