Research Papers:

Combination therapy of chitosan, gynostemma, and motherwort alleviates the progression of experimental rat chronic renal failure by inhibiting STAT1 activation

Wenxia Bai, Shudong Wang, Shanshan An, Mengjie Guo, Guangming Gong, Wenya Liu, Shaoxin Ma, Xin Li, Jihua Fu and Wenbing Yao _

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Oncotarget. 2018; 9:15498-15511. https://doi.org/10.18632/oncotarget.24125

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Wenxia Bai1, Shudong Wang3, Shanshan An2, Mengjie Guo4, Guangming Gong3, Wenya Liu3, Shaoxin Ma2, Xin Li2, Jihua Fu2,* and Wenbing Yao1,*

1Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China

2Department of Physiology, China Pharmaceutical University, Nanjing, China

3Department of Pharmaceutics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China

4School of Medicine and Life Sciences, Nanjing University of Traditional Chinese Medicine, Nanjing, China

*These authors have contributed equally to this work

Correspondence to:

Wenbing Yao, email: [email protected]

Jihua Fu, email: [email protected]

Keywords: chronic renal failure; STAT1

Received: August 13, 2017     Accepted: September 23, 2017     Epub: January 10, 2018     Published: March 20, 2018


This study aimed to investigate the effect of single and combination therapy using chitosan (K), gynostemma (J), and motherwort (Y) on an experimental rat model of chronic renal failure (CRF) induced by adenine and the underlying mechanisms. CRF rats were treated with individual or combinational therapy with two or three of these agents. Biochemical indicators showed that the levels of blood urea nitrogen, creatinine and uric acid decreased and the levels of albumin and hemoglobin increased by single or combination therapy of these drugs. Drug treatment also decreased oxidative stress damage of renal tissues in CRF rats. Histopathological lesions were attenuated in each drug treatment group by various degrees. Additionally, drug treatment affected the expression of extracellular matrix (ECM) proteins including plasminogen activator inhibitor 1, collagen I, matrix metalloprotease-1, and tissue inhibitor of metalloproteinases 1. In particular, the combination therapy of K, J, and Y was superior to the respective monotherapy, which supported the prescription of KJY combination. We further studied the inhibitory effect of KJY on LPS-induced inflammation in RAW264.7 macrophages. The results showed that KJY inhibited LPS-induced secretion of inflammatory cytokines (Interferon-gamma, Interleukin-1 Beta, chemokine (C-X-C motif) ligand 10, cyclooxygenase-2 and Tumor necrosis factor-α in RAW264.7 macrophages. Combination therapy of KJY suppressed the protein expression of Cyclooxygenase-2 and inducible nitric oxide synthase in vivo and in vitro. Further study indicated that KJY inhibited STAT1 activation by down regulating p-STAT1 to exert anti-inflammatory effect and improve renal function in rats with chronic renal failure.

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