Dang-Gui-Bu-Xue decoction improves wound healing in diabetic rats by the activation of Notch signaling

Xian Zhang; Song Zhao; Xiaogui Zhao; Zhiwei Yang; Xiaodan Wang

doi:10.1016/j.heliyon.2024.e26711

Dang-Gui-Bu-Xue decoction improves wound healing in diabetic rats by the activation of Notch signaling

Heliyon. 2024 Feb 20;10(5):e26711. doi: 10.1016/j.heliyon.2024.e26711. eCollection 2024 Mar 15.

Authors

Xian Zhang¹, Song Zhao², Xiaogui Zhao³, Zhiwei Yang³, Xiaodan Wang¹

Affiliations

¹ College of Traditional Chinese Veterinary Medicine of Hebei Agricultural University, 289 Lingyusi Street, Baoding City, Hebei Province, China.
² JINYUBAOLING BIO-PHARMACEUTICAL Co.Ltd, 1 Jinyu Street, Shaerqin Industrial Park, Hohhot Economic and Technological Development Zone, Inner Mongolia Autonomous Region, China.
³ MDL Biotech. Co. Ltd (Beijing, China), 432, Building 4, Block1, 4th Floor, Buildionfg1, NO.19 Xianlongshan Road, Haidian District, Beijing, China.

Abstract

Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.

Keywords: Angiogenesis; Dang-Gui-Bu-Xue decoction; Diabetes; Notch signaling; Wound healing.