Liu Bihao, Lin Jin, Bai Lixia, Zhou Yuan, Lu Ruirui, Zhang Peichun, Chen Dandan, Li Honglian, Song Jianping, Liu Xusheng, Wu Yidan, Wu Junbiao, Liang Chunling, Zhou Jiuyao
Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
College of Chinese Materia Medica, Guangdong Food and Drug Vocational College, Guangzhou, China.
Front Pharmacol. 2019 Sep 9;10:978. doi: 10.3389/fphar.2019.00978. eCollection 2019.
Mesangial proliferative glomerulonephritis (MPGN) is the most common type of chronic kidney disease in China, characterized by mesangial cell proliferation and inflammatory response. Paeoniflorin, an effective composition extracted from Alba, has been used for various kinds of kidney diseases. However, there are no studies reporting the effects of paeoniflorin on MPGN. The present study aims to investigate whether paeoniflorin plays a role in MPGN and confirm the underlying molecular mechanisms. Our results manifested that paeoniflorin strongly restrained 24 h urinary protein and promoted renal function and dyslipidemia in a MPGN rat model. Moreover, paeoniflorin attenuated mesangial cell proliferation and inflammation both in MPGN rats and human mesangial cells (HMCs) treated with lipopolysaccharide (LPS). In detail, paeoniflorin decreased the number of mesangial cells and expressions of proliferation marker Ki67 in MPGN rats. Paeoniflorin also inhibited HMC proliferation and blocked cell cycle progression. In addition, the contents of inflammatory factors and the expressions of macrophage marker iNOS were decreased after paeoniflorin treatment. Furthermore, we found that the protective effect of paeoniflorin was accompanied by a strong inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3β pathway. Paeoniflorin enhanced the inhibitory effect of PI3K inhibitor LY294002 and suppressed the activated effect of PI3K agonist insulin-like growth factor 1 (IGF-1) on PI3K/AKT/GSK-3β pathway. In conclusion, these results demonstrated that paeoniflorin ameliorates MPGN by inhibiting mesangial cell proliferation and inflammatory response through the PI3K/AKT/GSK-3β pathway.
系膜增生性肾小球肾炎（MPGN）是中国最常见的慢性肾脏病类型，其特征为系膜细胞增殖和炎症反应。芍药苷是从白芍中提取的一种有效成分，已被用于治疗各种肾脏疾病。然而，尚无关于芍药苷对MPGN作用的研究报道。本研究旨在探讨芍药苷在MPGN中是否发挥作用，并确认其潜在的分子机制。我们的结果表明，在MPGN大鼠模型中，芍药苷能显著抑制24小时尿蛋白，改善肾功能和血脂异常。此外，芍药苷可减轻MPGN大鼠以及用脂多糖（LPS）处理的人系膜细胞（HMCs）中的系膜细胞增殖和炎症。具体而言，芍药苷减少了MPGN大鼠中系膜细胞的数量和增殖标志物Ki67的表达。芍药苷还抑制HMC增殖并阻断细胞周期进程。此外，芍药苷处理后炎症因子含量和巨噬细胞标志物诱导型一氧化氮合酶（iNOS）的表达降低。此外，我们发现芍药苷的保护作用伴随着对磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/糖原合成酶激酶（GSK）-3β通路的强烈抑制。芍药苷增强了PI3K抑制剂LY294002的抑制作用，并抑制了PI3K激动剂胰岛素样生长因子1（IGF-1）对PI3K/AKT/GSK-3β通路的激活作用。总之，这些结果表明芍药苷通过PI3K/AKT/GSK-3β通路抑制系膜细胞增殖和炎症反应，从而改善MPGN。
