title: Schizandrin prevents damage of murine mesangial cells via blocking NADPH oxidase-induced ROS signaling in high glucose.
abstract: High glucose (HG) is the underlying factor contributing to long term complication of diabetes mellitus. Reactive oxygen species (ROS) have been postulated as a unifying mechanism for HG-induced complications. NADPH oxidase, producing superoxide anion, is the main source of ROS in diabetic nephropathy. In this study we report the inhibitory effect of schizandrin (Sch), an active ingredient of Fructus schisandrae, on HG-induced murine mesangial cells (MMCs) damage. Sch treatment significantly attenuated HG-induced proliferation and protein synthesis of MMCs in a dose dependent manner. The intracellular reactive oxygen species (ROS) level was also remarkably reduced by Sch as well as the enhanced NADPH oxidase activity, superoxide anion levels, NOX4 and p22phox protein expression, and phosphorylation of p47phox and p67phox. The phosphorylation level of mitogen activated kinase (MAPK) protein, phospho-Erk1/2 and -p38, and Akt was also significantly inhibited by Sch under HG condition. By using specific inhibitors, we found that Sch inhibits HG-induced mesangial cell proliferation and ECM overexpression via NADPH oxidase/PI3K-Akt-MAPK-dependent pathway in MMCs. Taken together; our demonstration of the ability of Sch to inhibit high glucose induced damage of MMCs has clinical implications in treatment of diabetic nephropathy.
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Seung-Il
authors.initials: SI
authors.lastname: Jeong
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Kwon
authors.forename: Kang-Yeol
authors.initials: KY
authors.lastname: Yu
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D024141:Collagen Type IV / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D051379:Mice; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011083:Polycyclic Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D024141:Collagen Type IV; D034242:Cyclooctanes; D005353:Fibronectins; D017705:Lignans; D011083:Polycyclic Compounds; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D019255:NADPH Oxidases; C011105:schizandrin; D005947:Glucose