# Cordyceps militaris Enhances Wound Repair Through Regulation of HIF-1α, TGF-β1, and SIRT1/Nrf2/HO-1 Signaling in Diabetic Skin

## TL;DR

Cordyceps militaris helps heal diabetic wounds by reducing inflammation and boosting tissue repair through specific molecular pathways.

## Contribution

This study reveals the novel role of Cordyceps militaris in diabetic wound healing via HIF-1α, TGF-β1, and SIRT1/Nrf2/HO-1 signaling.

## Key findings

- Cordyceps militaris treatment accelerated wound closure and improved skin barrier integrity in diabetic models.
- The extract reduced inflammatory markers IL-6 and TNF-α while activating antioxidant pathways.
- It enhanced extracellular matrix remodeling through increased MMP-1 and MMP-2 expression.

## Abstract

Chronic diabetic wounds are characterized by persistent inflammation, impaired angiogenesis, oxidative stress, and defective tissue remodeling, leading to delayed healing. Cordyceps militaris, a medicinal fungus with known anti-inflammatory and antioxidant properties, has shown therapeutic potential in metabolic disorders; however, its role in diabetic wound repair remains unclear. In this study, we evaluated the wound-healing effects of an aqueous extract of C. militaris using in vitro keratinocyte models and a streptozotocin-induced diabetic mouse model. C. militaris treatment significantly accelerated wound closure, improved epidermal regeneration, and enhanced skin barrier integrity. Mechanistically, C. militaris restored HIF-1α and TGF-β1 expression, promoted cell proliferation and fibroblast activation, and increased the expression of matrix metalloproteinases MMP-1 and MMP-2, indicating enhanced extracellular matrix remodeling. In parallel, excessive inflammatory responses were attenuated, as evidenced by reduced IL-6 and TNF-α levels, along with activation of SIRT1/Nrf2/HO-1 antioxidant signaling pathways. Collectively, these findings demonstrate that C. militaris promotes a balanced wound-healing microenvironment and represents a promising natural therapeutic candidate for the treatment of diabetic wounds.