Rhein Inhibits Proliferation, Extracellular Matrix Deposition, and Inflammation in Mesangial Cells via ROS/Akt Signaling Pathway

Author:

Xiong Rongbing1,Hu Xiaodi2,Hu Shuangyan1,Yao Minqi2,Fu Xiaojun1ORCID

Affiliation:

1. Department of Nephrology, Jinhua Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Jinhua, China

2. Zhejiang Chinese Medical University, Hangzhou, China

Abstract

It has been reported that rhein, a Chinese herbal compound, has a potent anti-inflammatory effect on various diseases. However, it remains elusive whether rhein has a protective effect on chronic kidney disease (CKD) and what its underlying mechanism may be. In the present study, we evaluated whether rhein could prevent lipopolysaccharide (LPS)-induced proliferation, expression of extracellular matrix (ECM) proteins, and inflammation in rat mesangial cells (MCs), and whether these effects were mediated by reactive oxygen species (ROS) and Akt signaling. We also investigated the protective effect of rhein on renal function in a rat CKD model. Results showed that rhein significantly suppressed LPS-initiated proliferation in MCs in a cell counting kit-8 (CCK8) assay. Meanwhile, rhein significantly inhibited LPS-induced expression of ECM proteins and inflammation, as indicated by the decreased expression of fibronectin, α smooth muscle actin (α-SMA), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6), and interferon γ (IFN-γ). Of note, rhein significantly enhanced LPS-induced production of reactive oxygen species (ROS) and inhibited LPS-induced Akt phosphorylation. Furthermore, the inhibitory effect of rhein on Akt phosphorylation was inhibited by H2O2 scavenger catalase. Importantly, the protective effect of rhein was almost totally lost in the presence of phosphatidylinositol 3-kinase (PI3K) protagonist insulin-like growth factor 1 (IGF-1). Finally, rhein significantly decreased 24 h urinary protein, serum creatinine (SCr), and blood urea nitrogen (BUN) in CKD rats. Collectively, these results suggested that rhein improved CKD through inhibition of proliferation, ECM synthesis, and inflammation via ROS/Akt signaling in MCs.

Funder

National Natural Science Foundation of Zhejiang Province

Publisher

SAGE Publications

Subject

Complementary and alternative medicine,Plant Science,Drug Discovery,Pharmacology,General Medicine

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