The failure of wound healing often causes lower limb disability and
amputation of diabetic patients. Current strategies for diabetic
wound management often fail to achieve the expected outcomes, and emerging alternatives are urgently needed. Recent advances in the identification of active compounds from traditional
herbal medicines provide promising
therapeutics for tissue repair and regeneration. In this study, the pro-healing effects of
tetramethylpyrazine (
TMP, a natural
alkaloid found in Ligusticum chuanxiong Hort) for diabetic
wounds were for the first time demonstrated. The cutaneous healing was mainly achieved by
TMP-mediated macrophage polarization from pro-inflammatory to pro-healing phenotype. In addition, the
topical administration of
TMP was facilitated by the
hyaluronic acid (HA)
hydrogel for promoting the full-thickness
wounds in the experimental diabetic mice. Consequently,
TMP-loaded HA
hydrogel (
TMP-HA) profoundly accelerated the
wound closure in comparison with
TMP-loaded
INTRASITE Gel (it is a commercial
hydrogel), which was evident with the
inflammation mitigation, the angiogenesis enhancement, and the
collagen deposition. Our work reveals the macrophage-modulatory function of
TMP for diabetic wound healing and demonstrates great potential of
TMP-HA for clinical application.