title: Calycosin Rebalances Advanced Glycation End Products-Induced Glucose Uptake Dysfunction of Hepatocyte In Vitro.
abstract: Diabetes mellitus (DM) often accompanies liver dysfunction. Astragali Radix is a traditional Chinese herbal medicine that is widely administrated to ameliorate the symptoms of diabetes as well as liver dysfunction, but its acting mechanism is still not yet fully recognized. Advanced glycation end products (AGEs) play a key role in promoting diabetic organ dysfunction. Both hyperglycemia and AGEs can induce insulin resistance, hepatocyte damage and liver dysfunction. We designed this study to explore the effects of the phytoestrogen Calycosin, a major active component of Astragali Radix, on AGEs-induced glucose uptake dysfunction in the hepatocyte cell line and relevant mechanisms. MTT and BrdU methods were applied to evaluate cell viability. 2-NBDG was used to observe glucose uptake by a live cell imaging system. Immunofluorescence method was carried out to investigate GLUT1, GLUT4, and RAGE protein expressions on cell membrane. cAMP content was determined by an EIA method. We found Calycosin concentration-dependently ameliorated AGEs-induced hepatocyte viability damage. AGEs dramatically reduced basal glucose uptake in hepatocytes, and this reduction could be reversed by Calycosin administration. By immunofluorescence detection, we observed that Calycosin could inhibit AGEs-induced GLUT1 expression down-regulation via estrogen receptor (ER). Furthermore, Calycosin decreased AGEs-promoted RAGE and cAMP elevation in hepatocytes. These findings strongly suggest that Calycosin can ameliorate AGEs-promoted glucose uptake dysfunction in hepatocytes; the protection of cell viability and ER-RAGE and GLUT1 pathways play a significant role in this modulation.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, The Institute for Translational Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, P.R. China.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, The Institute for Translational Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xiong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, The Institute for Translational Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, P.R. China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou, P.R. China.
authors.forename: Bao
authors.initials: B
authors.lastname: He
authors.affiliation: Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou, P.R. China.
authors.forename: Zhaoguang
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: University Hospital, Macau University of Science and Technology Foundation, Macau, P.R. China.
authors.forename: Gejin
authors.initials: G
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, The Institute for Translational Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, P.R. China.|Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Guangzhou, P.R. China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D048789:Phytoestrogens / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats
chemical_list: D017127:Glycation End Products, Advanced; D007529:Isoflavones; D048789:Phytoestrogens; D010936:Plant Extracts; C121707:7,3'-dihydroxy-4'-methoxyisoflavone; D005947:Glucose
keywords: Advanced Glycation End Products; Calycosin; Glucose Uptake; Hepatocyte; Radix Astragali