Angelica Dahurica ethanolic extract improves impaired wound healing by activating angiogenesis in diabetes

• Published in: PloS one 2017-05, Vol.12 (5), p.e0177862-e0177862
• Main Authors: Zhang, Xiao-Na, Ma, Ze-Jun, Wang, Ying, Sun, Bei, Guo, Xin, Pan, Cong-Qing, Chen, Li-Ming
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Acarbose; Activation; Adhesion; AKT protein; Amputation; Analysis; Androstadienes - pharmacology; Angelica - metabolism; Angiogenesis; Animal models; Animals; Aorta; Aorta - metabolism; Apoptosis; Arginase; Arteriosclerosis; Atherosclerosis; Attenuation; Biochemistry; Biology and Life Sciences; Blood; Blood flow; Blood vessels; Cell adhesion & migration; Cell Line; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemicals; Chinese medicine; Circulation; Coagulation; Complications; Condensates; Constrictions; Coronary artery disease; Degradation; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - pathology; DNA; Drying; Enzyme Activation - drug effects; Ethanol; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids - pharmacology; Glucose; Growth factors; Health care; Heart; Heart diseases; Herbal medicine; Herbs; Human Umbilical Vein Endothelial Cells; Humans; Hypertension; Infiltration; Inflammation; Inhibition; Interleukin 1; Ischemia; Kinases; Meadows; Medicine; Medicine and Health Sciences; Medicine, Chinese Traditional; Metabolism; Mice; Mounting; Neovascularization, Physiologic - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type III - antagonists & inhibitors; Nitric Oxide Synthase Type III - metabolism; Pharmacology; Physiological aspects; Plant extracts; Plant Extracts - therapeutic use; Population studies; Protein kinase; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Side effects; Signal Transduction - drug effects; Skin; Solvents; Streptozocin; Traditional Chinese medicine; Ulcers; Vascular endothelial growth factor; Vasodilation; Wound healing; Wound Healing - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0177862

Abnormal angiogenesis plays an important role in impaired wound healing and development of chronic wounds in diabetes mellitus. Angelica dahurica radix is a common traditional Chinese medicine with wide spectrum medicinal effects. In this study, we analyzed the potential roles of Angelica dahurica ethanolic extract (ADEE) in correcting impaired angiogenesis and delayed wound healing in diabetes by using streptozotocin-induced diabetic rats. ADEE treatment accelerated diabetic wound healing through inducing angiogenesis and granulation tissue formation. The angiogenic property of ADEE was subsequently verified ex vivo using aortic ring assays. Furthermore, we investigated the in vitro angiogenic activity of ADEE and its underlying mechanisms using human umbilical vein endothelial cells. ADEE treatment induced HUVECs proliferation, migration, and tube formation, which are typical phenomena of angiogenesis, in dose-dependent manners. These effects were associated with activation of angiogenic signal modulators, including extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, endothelial nitric oxide synthase (eNOS) as well as increased NO production, and independent of affecting VEGF expression. ADEE-induced angiogenic events were inhibited by the MEK inhibitor PD98059, the PI3K inhibitor Wortmannin, and the eNOS inhibitor L-NAME. Our findings highlight an angiogenic role of ADEE and its ability to protect against impaired wound healing, which may be developed as a promising therapy for impaired angiogenesis and delayed wound healing in diabetes.