Exosome-like nanoparticles derived from Salvia miltiorrhiza promote diabetic wound healing by reducing oxidative stress and inflammation.

Chronic non-healing wounds remain a major cause of amputation and mortality for diabetic patients. Therefore, finding effective treatment options has become a significant issue that biomedical research needs to address. Nanovesicles that resemble exosomes participate in intercellular communication in plants and may transfer bioactive substances between animals and plants with implications for regenerative medicine. Salvia miltiorrhiza, a traditional medicinal plant, has been used for centuries to treat cardiovascular diseases, infections, inflammation, and wounds. However, little is known of exosome-like nanovesicles derived from Salvia miltiorrhiza (SmELNs), including any actions to promote wound healing in diabetic patients. SmELNs were isolated and identified in the current work and assessment of their impact on proliferation, migration and angiogenesis in vitro indicated the potential to promote diabetic wound healing. In diabetic mouse wound models, subcutaneous SmELN rescued the delayed wound healing caused by streptozotocin-induced diabetes, promoted the formation of new blood vessels and did not damage internal organs in vivo. Subsequent studies further revealed that SmELN reduced reactive oxygen species production in response to high blood sugar and reduced secretion of inflammatory factors, IL-6, IL-1β and TNF-α. These findings suggest that the SmELN-enriched preparation represents a promising natural nanotherapeutic candidate for diabetic wound repair, potentially through attenuation of oxidative stress and inflammatory responses.