X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway  

作　　者：Ming-Wei Du Xin-Lin Zhu Dong-Xing Zhang Xian-Zhen Chen Li-Hua Yang Jin-Zhou Xiao Wen-Jie Fang Xiao-Chun Xue Wei-Hua Pan Wan-Qing Liao Tao Yang 

机构地区：[1]Institute of Cardiovascular Disease,Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200120,China [2]Department of Dermatology,Shanghai Key Laboratory of Molecular Medical Mycology,Second Affiliated Hospital of Naval Medical University,Shanghai 200003,China [3]Department of Dermatology,Dongshan Hospital,Meizhou 514000,Guangdong Province,China [4]Department of Dermatology,Central Hospital Affiliated to Shandong First Medical University,Jinan 250000,Shandong Province,China [5]Department of Emergency,Naval Hospital of Eastern Theater,Zhoushan 316000,Zhejiang Province,China [6]Department of Pharmacy,905th Hospital of People’s Liberation Army of China(PLA)Navy,Shanghai 200052,China

出　　处：《World Journal of Diabetes》2024年第6期1299-1316,共18页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by the Shanghai Science and Technology Innovation Project,One Belt One Road International Joint Laboratory of Medical Mycology,No.21410750500。

摘　　要：BACKGROUND Diabetic foot ulcers(DFU),as severe complications of diabetes mellitus(DM),significantly compromise patient health and carry risks of amputation and mortality.AIM To offer new insights into the occurrence and development of DFU,focusing on the therapeutic mechanisms of X-Paste(XP)of wound healing in diabetic mice.METHODS Employing traditional Chinese medicine ointment preparation methods,XP combines various medicinal ingredients.High-performance liquid chromatography(HPLC)identified XP’s main components.Using streptozotocin(STZ)-induced diabetic,we aimed to investigate whether XP participated in the process of diabetic wound healing.RNA-sequencing analyzed gene expression differences between XP-treated and control groups.Molecular docking clarified XP’s treatment mechanisms for diabetic wound healing.Human umbilical vein endothelial cells(HUVECs)were used to investigate the effects of Andrographolide(Andro)on cell viability,reactive oxygen species generation,apoptosis,proliferation,and metastasis in vitro following exposure to high glucose(HG),while NF-E2-related factor-2(Nrf2)knockdown elucidated Andro’s molecular mechanisms.RESULTS XP notably enhanced wound healing in mice,expediting the healing process.RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment.HPLC identified 21 primary XP components,with Andro exhibiting strong Nrf2 binding.Andro mitigated HG-induced HUVECs proliferation,metastasis,angiogenic injury,and inflammation inhibition.Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation,with Nrf2 knockdown reducing Andro’s proliferative and endothelial protective effects.CONCLUSION XP significantly promotes wound healing in STZ-induced diabetic models.As XP’s key component,Andro activates the Nrf2/HO-1 signaling pathway,enhancing cell proliferation,tubule formation,and inflammation reduction.

关 键 词：Words:Diabetes mellitus Wound healing NF-E2-related factor-2/HO-1 signaling pathway ANDROGRAPHOLIDE 

分 类 号：R587.1[医药卫生—内分泌]