title: The protection of 4,4'-diphenylmethane-bis(methyl) carbamate from Cortex Mori on advanced glycation end product-induced endothelial dysfunction: via inhibiting AGE formation or blocking AGEs-RAGE axis?
abstract: Advanced glycation end products (AGEs) were implicated in the pathogenesis of endothelial dysfunction in diabetic vascular complications. Our previous study found that a novel compound 4,4'-diphenylmethane-bis(methyl) carbamate (CM1) from Cortex Mori (Morus alba L.) could attenuate AGE-induced endothelial dysfunction. The present study was conducted to explore the possible protective mechanisms of CM1 on AGE-induced endothelium damage. In binding experiments, fluorescence quenching and fluorescence polarization assays showed no significant difference or changes of AGEs on fluorescence intensity and polarization in the absence/presence of CM1. In AGE formation experiments, CM1 was incubated with AGE precursor compounds methylglyoxal (MGO), glyceraldehydes (Glycer) and glycolaldehyde (Glycol) in the formation system. However, high performance liquid chromatography (HPLC) analysis showed no new conjugated compounds formed in the reaction system. The results of ELISA analysis also showed that CM1 did not inhibit the AGE formation. However, the pretreatment with CM1 could significantly decrease AGE or high-mobility group box-1 (HMGB1, a ligand of RAGE)-induced cytotoxicity, apoptosis and reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVECs). Our results suggested that CM1 might block the AGEs-RAGE signal transduction rather than inhibit AGE formation or bind to AGEs and change its structure to prevent endothelial dysfunction in diabetic vascular complications.
authors.affiliation: Key Laboratory of New Drug Delivery Systems of Chinese Meteria Medica, Jiangsu Provincial Academy of Chinese Medicine, Jiangsu, Nanjing 210028, China. wenmoxiushi@163.com
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: Maomao
authors.initials: M
authors.lastname: Zhu
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhang
authors.forename: Junfei
authors.initials: J
authors.lastname: Gu
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Jia
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Tan
authors.forename: Chenglin
authors.initials: C
authors.lastname: Gao
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000517:prevention & control; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D031625:Morus / Q000737:chemistry*; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C572821:4,4'-diphenylmethane-bis(methyl)carbamate; D002219:Carbamates; D004365:Drugs, Chinese Herbal; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D017382:Reactive Oxygen Species
keywords: 4,4′-diphenylmethane-bis(methyl) carbamate; AGE formation; Diabetic vascular complications; Fluorescence polarization; Fluorescence quenching; RAGE