2. Academic Validation
  3. Garcinol promotes wound healing in diabetic mice by regulating inflammation and NLRP3 inflammasome-mediated pyroptosis via the PI3K/Akt/NF-κB pathway

Garcinol promotes wound healing in diabetic mice by regulating inflammation and NLRP3 inflammasome-mediated pyroptosis via the PI3K/Akt/NF-κB pathway

  • Int Immunopharmacol. 2025 Apr 4:151:114352. doi: 10.1016/j.intimp.2025.114352.
Zihao Li 1,  Kai Lin 2,  Yilong Wang 3,  Junnan Mao 1,  Yihu Yin 2,  Zi Li 4,  Fulin Wang 4,  Xiangtao Zeng 1,  Qiubo Li 1,  Xuan Wang 4,  Zhi Li 4,  Ronghui Miao 4,  Cai Lin 5,  Cong Mao 6
Affiliations

Affiliations

  • 1 Key Laboratory of Orthopedics of Zhejiang Province, Department of Orthopedics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Department of Burn and Wound Healing Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 2 Department of Burn and Wound Healing Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 3 Laboratory Animal Centre, Wenzhou Medical University, Wenzhou 325000, China.
  • 4 Key Laboratory of Orthopedics of Zhejiang Province, Department of Orthopedics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
  • 5 Department of Burn and Wound Healing Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: 13025092850@163.com.
  • 6 Key Laboratory of Orthopedics of Zhejiang Province, Department of Orthopedics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. Electronic address: maocong@wmu.edu.cn.
PMID: 40022821 DOI: 10.1016/j.intimp.2025.114352
Abstract

Diabetic wounds, characterized by chronic inflammation and impaired angiogenesis, often lead to severe complications such as persistent infections and an elevated risk of amputation, significantly affecting a patient's quality of life. Garcinol, a polyisoprenylated benzophenone derived from the rind of Garcinia indica, exhibits potent anti-inflammatory, angiogenic, and antioxidant effects in various disease models. However, its potential to enhance diabetic wound healing remains unclear. In this research, we firstly used network pharmacology analysis to identify the potential targets of Garcinol in treating diabetic wounds. Cellular study results revealed that Garcinol therapy alleviated high glucose-induced cellular dysfunction and increased the angiogenic potential of human umbilical vein endothelial cells (HUVECs). Additionally, Garcinol substantially downregulated the levels of inflammatory cytokines secreted by macrophages through inhibiting the PI3K/Akt/NF-κB signaling pathway, which was further validated using the PI3K/Akt Agonist 740 YP. Furthermore, inhibiting PI3K signaling also resulted in a marked reduction of NLRP3 inflammasome-mediated Pyroptosis in macrophages compared to control. In vivo study using a full-thickness diabetic wound model confirmed that Garcinol treatment promoted diabetic wound healing by improving angiogenesis, inhibiting inflammation and Pyroptosis, whereas the addition of 740 YP reduced the beneficial effects of Garcinol. Overall, our findings suggested that Garcinol enhanced diabetic wound healing via its anti-inflammatory ability, suppression of Pyroptosis, and enhancement of angiogenesis. These results highlight the potential of Garcinol as a therapeutic agent for diabetic wounds.

Keywords

Angiogenesis; Diabetic wound healing; Garcinol; Inflammation; Pyroptosis.

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