Asperosaponin VI promotes flap survival through HIF-1α/VEGF-associated angiogenesis.

BACKGROUND: Skin flap transplantation is a vital procedure in clinical tissue repair and reconstruction; however, postoperative ischemic necrosis remains a challenging complication. Dipsacus asper Wall. is a classic traditional Chinese herb renowned for its ability to strengthen tendons and bones, promote fracture healing, and accelerate soft tissue repair, suggesting its potential value in microcirculation restoration and wound regeneration. This study aims to evaluate the potential of Asperosaponin VI (ASA VI) to improve flap survival, which is a critical concern in reconstructive surgery. METHODOLOGY: RNA-seq of sham and untreated flap tissues was performed to characterize transcriptomic changes associated with ischemic necrosis. These data were then integrated with network pharmacology, molecular docking, and molecular dynamics simulations to generate hypotheses on potential targets and pathways of ASA VI. A rat McFarlane flap model was established to systematically evaluate the therapeutic effects of ASA VI across multiple dimensions, including blood flow perfusion, angiogenesis, inflammatory responses, and oxidative stress. In vitro validation was conducted in human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation (OGD). RESULTS: Transcriptomic analysis revealed that flap ischemic necrosis is closely associated with angiogenesis-related pathways, most notably the HIF-1α signaling pathway. ASA VI significantly promoted the survival of rat dorsal random-pattern flaps, enhanced angiogenesis and blood perfusion, and suppressed inflammatory responses. In vitro, ASA VI alleviated oxidative stress injury and increased viability in OGD-induced HUVECs; however, these protective effects were attenuated by HIF-1α siRNA. CONCLUSIONS: ASA VI improves random-pattern flap survival and is associated with enhanced HIF-1α/VEGF-related angiogenic signaling.