Cardiovascular

Baicalin-loaded chitosan hydrogel accelerates diabetic foot ulcer healing by regulating MAPK1 expression.

TL;DR

Baicalin-loaded carboxymethyl chitosan hydrogel accelerated diabetic foot ulcer healing by restoring cell viability and migration, reducing inflammation, lowering blood glucose, and regulating MAPK1 expression.

Key Findings

Baicalin restored high glucose-reduced HaCaT cell viability and migration in vitro.

  • HaCaT cells were exposed to high glucose (HG) conditions as an in vitro cell model of diabetic foot ulcer.
  • Baicalin was administered at a concentration of 100 µg/mL.
  • Cell viability was restored with statistical significance at p < 0.01.
  • Cell migration was restored with statistical significance at p < 0.001.

Baicalin decreased levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α in high glucose-exposed HaCaT cells.

  • Treatment was with baicalin at 100 µg/mL in HG-exposed HaCaT cells.
  • All three inflammatory cytokines (IL-6, IL-1β, and TNF-α) were reduced following baicalin treatment.
  • This finding supports an anti-inflammatory mechanism of action for baicalin in the DFU context.

Baicalin-loaded carboxymethyl chitosan hydrogel lowered blood glucose levels in streptozotocin-induced DFU rats.

  • In vivo model used streptozotocin-induced DFU rats.
  • Blood glucose was lowered from greater than 20 mM to approximately 10 mM.
  • This reduction was statistically significant at p < 0.001.
  • The therapeutic effects were evaluated over a 14-day period.

Baicalin-loaded carboxymethyl chitosan hydrogel accelerated wound closure in DFU rats.

  • Wound healing was assessed over 14 days in streptozotocin-induced DFU rats.
  • Wound closure was significantly accelerated compared to controls (p < 0.01).
  • The hydrogel formulation was a carboxymethyl chitosan-based delivery vehicle for baicalin.

Bioinformatic analysis identified MAPK1 as a key target of baicalin in DFU, and molecular docking confirmed strong binding affinity.

  • Bioinformatic analysis was used to identify MAPK1 as a key therapeutic target.
  • Molecular docking confirmed a strong binding affinity between baicalin and MAPK1 of less than -6 kcal/mol.
  • A binding affinity below -6 kcal/mol is generally considered indicative of strong molecular interaction.

Baicalin upregulated MAPK1 expression, and shRNA-mediated MAPK1 knockdown attenuated baicalin's therapeutic effects both in vitro and in vivo.

  • Baicalin treatment upregulated MAPK1 expression with statistical significance at p < 0.01.
  • shRNA-mediated knockdown of MAPK1 was used to verify the mechanistic role of MAPK1.
  • MAPK1 knockdown attenuated baicalin's therapeutic effects in vitro and in vivo at p < 0.001.
  • These results indicate that MAPK1 upregulation is a key mechanism through which baicalin promotes DFU healing.

What This Means

This research suggests that baicalin, a natural plant compound, can help heal diabetic foot ulcers (DFUs) — a serious and difficult-to-treat complication of diabetes. When delivered in a special gel made from chitosan (a material derived from shellfish shells), baicalin significantly reduced blood sugar levels and sped up wound closure in diabetic rats over a two-week period. In laboratory experiments using skin cells exposed to high glucose (mimicking diabetic conditions), baicalin improved cell survival and movement, and reduced levels of proteins associated with inflammation. The research also investigated how baicalin works at a molecular level. Using computer-based analysis and gene-silencing experiments, the researchers found that baicalin acts largely by increasing the activity of a protein called MAPK1. When MAPK1 was experimentally turned off using genetic techniques, most of the beneficial effects of baicalin were reversed, both in cell cultures and in living animals. Molecular modeling further confirmed that baicalin binds tightly to MAPK1, supporting its role as a direct target of the compound. This research suggests that baicalin delivered via a chitosan hydrogel could be a promising approach for treating diabetic foot ulcers, and that the MAPK1 signaling pathway is central to its mechanism of action. The authors note that further research into the molecular mechanisms and clinical applications is needed before this approach could be considered for use in humans.

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Citation

Zhang X, Zhang Y, Yang L, Fang S, Mei X. (2026). Baicalin-loaded chitosan hydrogel accelerates diabetic foot ulcer healing by regulating MAPK1 expression.. Journal of molecular histology. https://doi.org/10.1007/s10735-026-10840-0