ACNO hydrogel enhances diabetic wound healing by modulating the Bcl-2/Bax/Caspase-3/PARP pathway

Centella asiatica (L.) Urban, one of the authentic medicinal materials from Guizhou Province in China, has been traditionally applied for the treatment of contusions and fractures, as well as for promoting wound healing. Preliminary research suggests that asiaticoside-nitric oxide hydrogel (ACNO) exhibits the potential to enhance the healing of diabetic wounds (DWs); however, the underlying molecular mechanisms require further elucidation. Here, we aim to identify ACNO's anti-apoptotic targets and its mode of action in DWs treatment. ACNO was applied topically on db/db and db/m mice with DWs. Wound healing was evaluated through photography, histology, and molecular analyses including molecular docking, RT-qPCR, and western blotting. The impact of ACNO on cell migration and apoptosis was assessed in hyperglycosylated HFF-1 cells using CCK-8, scratch, and cloning assays, with molecular mechanisms confirmed using a Bcl-2 inhibitor. ACNO hydrogel promotes wound epithelialization and angiogenesis in diabetic mice, and also regulates abnormal apoptosis of wound cells. In vitro studies showed that ACNO promoted the proliferation and migration of hyperglycosylated HFF-1 cells and enhanced their anti-apoptotic capacity in vitro. Further experimental studies showed that ACNO hydrogel enhances the healing process of DWs by modulating the Bcl-2/Bax/Caspase-3/PARP signaling cascade, which stimulates cell growth and movement, encourages the formation of new blood vessels, and diminishes cell death. This discovery presents a pioneering approach to harnessing the potential of traditional chinese medicine for the management of persistent and challenging injuries, including DWs.