title: Astragaloside IV attenuates complement membranous attack complex induced podocyte injury through the MAPK pathway.
abstract: Membranous nephropathy (MN) is the most common cause of idiopathic nephrotic syndrome in adults and the cause is known to be due to the injury of podocytes located in the glomeruli. Astragalus membranaceus has been used for the treatment of patients with MN in China for a long time. The beneficial effect of Astragalus membranaceus on proteinuria of patients with MN has been well documented. However, the mechanism of astragalus membranaceu in alleviation of MN is still not completely understood. Therefore, in the current study, we employed a podocyte injury model induced by complement membranous attack complex to examine the mechanism of astragalus membraneceus in the treatment of MN. We found that complement membranous attack complex could increase lactate dehydrogenase (LDH) release from podocytes and astragaloside IV (AS-IV) could prevent LDH release from podocytes in a time- and dose-dependent pattern. Moreover, AS-IV restored podocyte morphology and cytoskeleton loss induced by complement membranous attack complex. Furthermore, AS-IV was able to reduce phosphorylation of JNK and ERK1/2 induced by complement membranous attack complex. In conclusion, the mechanism of Astragalus membranaceus in the treatment of MN may be related to its attenuation of podocyte injury through regulation of cytoskeleton and mitogen activated protein kinase.
authors.affiliation: Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.forename: Yueyi
authors.initials: Y
authors.lastname: Deng
authors.forename: Yiping
authors.initials: Y
authors.lastname: Chen
authors.forename: Junming
authors.initials: J
authors.lastname: Fan
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhang
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhong
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D027885:Astragalus propinquus / Q000737:chemistry; D002460:Cell Line; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D015433:Glomerulonephritis, Membranous / Q000473:pathology; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D010766:Phosphorylation; D050199:Podocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D020011:Protective Agents / Q000494:pharmacology; D011507:Proteinuria / Q000473:pathology; D012503:Saponins / Q000494:pharmacology*; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D015938:Complement Membrane Attack Complex; D020011:Protective Agents; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D007770:L-Lactate Dehydrogenase