Mechanism of Colla Corii Asini on Improving D-Galactose-Induced Skin Aging and Microvascular Homeostasis via the Tie2/Ang/VE-cadherin Signaling Axis
D-galactose-induced premature aging in mice and H2O2-stressed human umbilical vein endothelial cells (HUVEC) were used to evaluate Colla Corii Asini (CCA) at 270.3 mg/kg (8-week oral gavage) and 62.5–250.0 μg/mL (24-h pretreatment), respectively. CCA restored skin architecture, increased epidermal/dermal thickness and collagen volume fraction (P<0.01, 0.001), improved perfusion, reduced disorganized angiogenesis, elevated PDGFRβ and serum Ang1/Ang2 ratio (P<0.001), and suppressed IL-1β, CXCL1, and TNF-α (P<0.001). In HUVEC, CCA reduced SA-β-gal positivity and ROS (P<0.001), downregulated SASP/inflammatory genes (P<0.01, 0.001), upregulated p-Tie2 and VE-cadherin (P<0.001), downregulated p53, p21, Tie2, and VEGFA (P<0.05, 0.001), increased Ang1/Ang2 (P<0.05, 0.01), and enhanced pericyte recruitment and endothelial barrier integrity. The data indicate that CCA mitigates skin aging and microvascular instability through modulation of the Tie2/Ang/VE-cadherin axis, providing a multi-target natural intervention for age-related microcirculatory dysfunction.