title: Hyperoside downregulates the receptor for advanced glycation end products (RAGE) and promotes proliferation in ECV304 cells via the c-Jun N-terminal kinases (JNK) pathway following stimulation by advanced glycation end-products in vitro.
abstract: Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown. In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs) in the presence or absence of hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK) activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by hyperoside. Our findings suggest a novel role for hyperoside in the treatment and prevention of diabetes.
authors.affiliation: Sericulture & Agri-Food Research Institute, Guangdong Academy of Agricultural Sciences, NO. 133 Yiheng St. Dongguanzhuang Rd., Tianhe Ditrict, Guangzhou 510610, China. yuxiaozou@163.com.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Mosha Silas
authors.initials: MS
authors.lastname: Sethiel
authors.forename: Weizhi
authors.initials: W
authors.lastname: Shen
authors.forename: Sentai
authors.initials: S
authors.lastname: Liao
authors.forename: Yuxiao
authors.initials: Y
authors.lastname: Zou
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000008:administration & dosage*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C021304:hyperoside; D011794:Quercetin; D048031:JNK Mitogen-Activated Protein Kinases