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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00978

Paeoniflorin inhibits mesangial cell proliferation and inflammatory response in rats with mesangial proliferative glomerulonephritis through PI3K/AKT/GSK-3β pathway

 Bihao Liu1, Jin Lin2, Lixia Bai1, Yuan zhou1, Ruirui Lu1, Peichun Zhang1, Dandan Chen1, Honglian Li1, Jianping Song1,  Xusheng Liu1, Yidan Wu1,  Junbiao Wu1, Chunling Liang1 and  Jiuyao Zhou1*
  • 1Guangzhou University of Chinese Medicine, China
  • 2Guangdong Food and Drug Vocational College, China

Mesangial proliferative glomerulonephritis (MsPGN) is the most common type of chronic kidney diseases in China, characterized by mesangial cells proliferation and inflammatory response. Paeoniflorin, an effective composition extracted from Radix Paeoniae Alba, has been used for various kinds of kidney diseases for many years. However, there are no studies reporting the effects of paeoniflorin on MsPGN. The present study is aimed to investigate whether paeoniflorin plays a role in MsPGN and confirm the underlying molecular mechanisms. Our results manifest that paeoniflorin strongly promoted renal function, restrained 24 h urinary protein and dyslipidemia in a MsPGN rat model. Moreover, paeoniflorin attenuates mesangial cells proliferation and inflammation both in MsPGN rats and human mesangial cells (HMCs) treated with lipopolysaccharide (LPS). In detail, paeoniflorin decreased the numbers of mesangial cells and expressions of proliferation marker Ki67 in MsPGN rats. Paeoniflorin also inhibited HMCs proliferation and blocked cell cycle progression. In addition, the contents of inflammatory factors and the expressions of macrophage marker CD68 were decreased after paeoniflorin treatment. Furthermore, we found that the protective effect of paeoniflorin is accompanied by a strong inhibition of phosphatidylinositol 3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3β pathway, which is enhanced by PI3K inhibitor LY294002, and suppressed by PI3K agonist insulin-like growth factor 1 (IGF-1). In conclusion, these results demonstrate that paeoniflorin ameliorated MsPGN by inhibiting mesangial cells proliferation and inflammatory response through PI3K/AKT/GSK-3β pathway.

Keywords: Mesangial proliferative glomerulonephritis, paeoniflorin, mesangial cells proliferation, Inflammatory Response, PI3K/Akt/GSK-3β pathway

Received: 22 Nov 2018; Accepted: 31 Jul 2019.

Copyright: © 2019 Liu, Lin, Bai, zhou, Lu, Zhang, Chen, Li, Song, Liu, Wu, Wu, Liang and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Jiuyao Zhou, Guangzhou University of Chinese Medicine, Guangzhou, China, zhoujiuyao@tom.com