A 60% Edible Ethanolic Extract of Ulmus davidiana Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis

As abnormal angiogenesis is associated with exacerbation of various diseases, precise control over angiogenesis is imperative. Vascular endothelial growth factor (VEGF), the most well-known angiogenic factor, binds to VEGF receptor (VEGFR), activates various signaling pathways, and mediates angiogenesis. Therefore, blocking the VEGF-induced angiogenic response-related signaling pathways may alleviate various disease symptoms through inhibition of angiogenesis. Ulmus davidiana is a safe natural product that has been traditionally consumed, but its effects on endothelial cells (ECs) and the underlying mechanism of action are unclear. In the present study, we focused on the effect of a 60% edible ethanolic extract of U. davidiana (U60E) on angiogenesis. U60E inhibited the VEGF-mediated proliferation, tube formation, and migration ability of ECs. Mechanistically, U60E inhibited endothelial nitric oxide synthase activation and nitric oxide production by blocking the protein kinase B signaling pathway activated by VEGF and consequently inhibiting proliferation, tube formation, and migration of ECs. These results suggest that U60E could be a potential and safe therapeutic agent capable of suppressing proangiogenic diseases by inhibiting VEGF-induced angiogenesis.

Potential Anti-Skin Aging Effect of (-)-Catechin Isolated from the Root Bark of Ulmus davidiana var. japonica in Tumor Necrosis Factor-α-Stimulated Normal Human Dermal Fibroblasts

Reactive oxygen species (ROS) are generated during skin aging, including intrinsic (chronologic aging) and extrinsic aging (photoaging). Therefore, antioxidants that inhibit ROS generation can delay skin aging. In this study, we evaluated the potential anti-skin aging effect of (-)-phenolic compounds isolated from the root bark of Ulmus davidiana var. japonica. We preferentially investigated the possible preventive effects of isolates against the degradation of skin extracellular matrix. Among the isolates, (-)-catechin suppressed the activity of collagenase MMP-1, and reversed the degradation of collagen induced by tumor necrosis factor-α (TNF-α) in normal human dermal fibroblast. This action mechanism of (-)-catechin was validated by the suppression of tumor necrosis factor-α-induced accumulation of ROS and activation of mitogen-activated protein kinases, protein kinase B (Akt), and cyclooxygenase-2 (COX-2). The proinflammatory cytokines upregulate inflammatory reactions, and ultimately promote aging-related reactions. In this milieu, we demonstrated that (-)-catechin decreased the expression and secretion of proinflammatory cytokines, including interleukin (IL)-1β and IL-6. In conclusion, (-)-catechin is a candidate to ameliorate both intrinsic and extrinsic skin aging.