Asperosaponin VI promotes angiogenesis and accelerates wound healing in rats via up-regulating HIF-1α/VEGF signaling

• Published in: Acta pharmacologica Sinica 2018-03, Vol.39 (3), p.393-404
• Main Authors: Wang, Cheng-gui, Lou, Yi-ting, Tong, Min-ji, Zhang, Li-lian, Zhang, Zeng-jie, Feng, Yong-zeng, Li, Shi, Xu, Hua-zi, Mao, Cong
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Biomedical and Life Sciences; Biomedicine; Blood vessels; Cell Movement - physiology; Cell Proliferation - physiology; Cells, Cultured; Collagen; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - pharmacology; Endothelial cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - physiology; Hypoxia-inducible factor 1a; Immunology; Internal Medicine; Medical Microbiology; Neovascularization, Physiologic - physiology; Original; original-article; Pharmacology/Toxicology; Rats; Saponins - pharmacology; Signal Transduction - drug effects; Traditional Chinese medicine; Umbilical vein; Up-Regulation - drug effects; Vaccine; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - physiology; Vascularization; Wound healing; Wound Healing - drug effects
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2017.161

Wound therapy remains a clinical challenge due to the complexity of healing pathology and high demand of achieving functional and aesthetically satisfactory scars. Newly formed blood vessels are essential for tissue repair since they can support cells at the wound site with nutrition and oxygen. In this study, we investigated the effects of Asperosaponin VI (ASA VI) isolated from a traditional Chinese medicine, the root of Dipsacus asper Wall, in promoting angiogenesis, as well as its function in wound therapeutics. Treatment of human umbilical vein endothelial cells (HUVECs) with ASA VI (20–80 μg/mL) dose-dependently promoted the proliferation, migration and enhanced their angiogenic ability in vitro , which were associated with the up-regulated HIF-1α/VEGF signaling. Full-thickness cutaneous wound model rats were injected with ASA VI (20 mg·kg −1 ·d −1 , iv) for 21 d. Administration of ASA VI significantly promoted the cutaneous wound healing, and more blood vessels were observed in the regenerated tissue. Due to rapid vascularization, the cellular proliferation status, granulation tissue formation, collagen matrix deposition and remodeling processes were all accelerated, resulting in efficient wound healing. In summary, ASA VI promotes angiogenesis of HUVECs in vitro via up-regulating the HIF-1α/VEGF pathway, and efficiently enhances the vascularization in regenerated tissue and facilitates wound healing in vivo . The results reveal that ASA VI is a potential therapeutic for vessel injury-related wounds.