Sulforaphane promotes diabetic wound healing by regulating macrophage efferocytosis and polarization.
AI Summary
This study investigated sulforaphane's potential for treating diabetic wounds, a common complication characterized by delayed healing and chronic inflammation. Researchers used diabetic mice and human cell cultures to examine how sulforaphane affects wound healing processes. The study found that topical application of sulforaphane accelerated wound healing in diabetic mice through specific immune system mechanisms. The compound enhanced macrophage efferocytosis (the process by which immune cells clear dead cells) and promoted M2 macrophage polarization, which reduces inflammation at wound sites. Mechanistically, sulforaphane activated the Nrf2 pathway, leading to increased production of heme oxygenase 1 and enhanced MERTK receptor function. In laboratory experiments using human immune cells, sulforaphane improved the ability of macrophages to clear dead cells and reduced inflammatory responses. These findings suggest sulforaphane from broccoli sprouts could potentially serve as a therapeutic agent for chronic diabetic wounds, though human clinical trials would be needed to confirm these benefits.
Key Findings
- Topical sulforaphane application accelerated wound healing in diabetic mice by enhancing impaired macrophage efferocytosis and promoting M2 macrophage polarization
- Sulforaphane promoted phagocytosis of dead cells by human macrophages and reduced resulting inflammatory responses in laboratory studies
- The compound works by activating the Nrf2 pathway, leading to upregulation of heme oxygenase 1 and enhancement of MERTK receptor function
- Sulforaphane enhanced macrophage polarization toward the anti-inflammatory M2 phenotype and reduced LPS-induced inflammatory responses
Abstract
Delayed wound healing frequently occurs as a complication of diabetes. Diabetic wounds that are difficult to heal are associated with chronic, persistent inflammation, characterized by impaired efferocytosis and a sustained pro-inflammatory state of macrophages at the wound site. Sulforaphane (SFN), a bioactive compound found in cruciferous vegetables, possesses anti-inflammatory and antioxidant activities. Numerous studies have shown that SFN can inhibit various inflammatory diseases such as atherosclerosis and psoriasis; however, its potential in treating diabetic wounds remains unknown. This study investigates the effects and potential mechanisms of SFN on diabetic wound healing. Network pharmacology approaches were employed to identify potential targets of SFN for diabetic wound treatment. Additionally, an STZ-induced diabetic mouse model (C57/B6) was used in in vivo studies to examine SFN's impact on diabetic wound healing. Simultaneously, immunofluorescence staining, immunohistochemical staining, Western blotting, and qPCR analysis were employed to detect phenotypes associated with macrophage efferocytosis and M2 polarization. Subsequently, the mechanism underlying SFN treatment was explored through in vitro experiments utilizing the THP-1 human monocyte cell line. The results demonstrated that topical SFN application accelerated wound healing in diabetic mice, partly through the enhancement of impaired macrophage efferocytosis and the promotion of M2 macrophage polarization, thereby reducing the inflammatory response at the wound site. SFN promoted the phagocytosis of apoptotic Jurkat cells by THP-1 differentiated macrophages, reducing the resulting inflammatory response. Mechanistic studies revealed that SFN promotes macrophage efferocytosis by activating nuclear factor E2-related factor 2 (Nrf2), leading to upregulation of heme oxygenase 1 (HO-1) expression and subsequent enhancement of mer proto-oncogene tyrosine kinase (MERTK), a recognition receptor for efferocytosis. Furthermore, SFN enhanced macrophage polarization toward the M2 phenotype and reduced the lipopolysaccharide (LPS)-induced inflammatory response in vitro. These data suggest that SFN could serve as an effective adjunct or novel therapeutic agent for treating chronic non-healing wounds in diabetes.
Authors
Yumeng Huang, Beizhi Wang, Zhouji Ma, Tianzhe Chen, Haiting Zou, Yutong Chen, Zheng Dong, Jingyi Chen, Hao Zhang, Youjun Ding, Qian Tan