“Chronic diabetic wounds pose significant clinical challenges due to persistent inflammation, vascular insufficiency, and impaired tissue remodeling, leading to poor healing outcomes. The PI3K/Akt/eNOS signaling pathway is critical for regulating angiogenesis, apoptosis, and extracellular matrix organization-key processes disrupted in diabetic wounds.
Isovitexin, a natural flavonoid from plants like passionflower and Cannabis, exhibits well-documented antioxidant and anti-inflammatory properties. However, its therapeutic potential and mechanistic action in diabetic wounds, particularly regarding multi-targeted regulation of angiogenesis, collagen deposition, and apoptosis within the complex wound microenvironment, remain unexplored.
This study demonstrates that isovitexin accelerates diabetic wound healing. Using streptozotocin-induced diabetic rodent models and cell culture, we found isovitexin significantly promoted angiogenesis and vascular maturation, reduced oxidative damage and apoptosis, and improved collagen organization versus controls. Crucially, these effects were entirely abolished by the eNOS inhibitor L-NAME, confirming PI3K/Akt/eNOS pathway specificity. Whereas previous studies have largely focused on single-pathway interventions for diabetic wounds, the concurrent modulation of angiogenesis, matrix remodeling, and apoptosis remains unexplored.
Our study uniquely demonstrates that isovitexin activates the PI3K/Akt/eNOS pathway to synchronously enhance angiogenesis, promote collagen maturation, and inhibit apoptosis. This tripartite mechanism-uncovered for the first time-provides a novel therapeutic strategy to address the multifactorial pathology of diabetic wounds. Future research should prioritize clinical translation of these findings.”
https://pubmed.ncbi.nlm.nih.gov/40882326/
“This study demonstrates the therapeutic potential of isovitexin in promoting diabetic wound healing and clarifies its underlying mechanisms. In vitro, isovitexin improved endothelial cell function under hyperglycemic conditions. In vivo, it activated the PI3K/Akt/eNOS pathway, enhancing angiogenesis while reducing oxidative stress, inflammatory responses, and apoptosis. These coordinated mechanisms collectively contribute to accelerated wound closure and suggest therapeutic potential”
“Isovitexin, a natural flavonoid from plants like passionflower and Cannabis, exhibits well-documented antioxidant and anti-inflammatory properties. “
“Isovitexin significantly accelerates diabetic wound healing through coordinated activation of the PI3K/Akt/eNOS signaling pathway. This natural compound synchronously enhances angiogenesis, promotes collagen matrix remodeling, and suppresses oxidative stress-mediated apoptosis, addressing multifactorial pathology in diabetic wounds.”
https://www.sciencedirect.com/science/article/abs/pii/S0040816625003829?via%3Dihub