Multi-glycoside of Tripterygium wilfordii Hook. f. attenuates glomerulosclerosis in a rat model of diabetic nephropathy by exerting anti-microinflammatory effects without affecting hyperglycemia

Wu,Wei; Yang,Jing-Jing; Yang,Hai-Ming; Huang,Meng-Meng; Fang,Qi-Jun; Shi,Ge; Mao,Zhi-Min; Han,Wen-Bei; Shen,Shan-Mei; Wan,Yi-Gang

doi:10.3892/ijmm.2017.3068

Multi-glycoside of Tripterygium wilfordii Hook. f. attenuates glomerulosclerosis in a rat model of diabetic nephropathy by exerting anti-microinflammatory effects without affecting hyperglycemia

Authors:
- Wei Wu
- Jing-Jing Yang
- Hai-Ming Yang
- Meng-Meng Huang
- Qi-Jun Fang
- Ge Shi
- Zhi-Min Mao
- Wen-Bei Han
- Shan-Mei Shen
- Yi-Gang Wan
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Affiliations: Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, P.R. China, Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China, Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210008, P.R. China, Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China
Published online on: July 17, 2017 https://doi.org/10.3892/ijmm.2017.3068
Pages: 721-730
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) has been proven to be clinically effective in relieving microinflammation in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain unclear. In the process of early DN, microinflammation and activation of p38 mitogen‑activated protein kinase (MAPK) and canonical nuclear factor (NF)-κB signaling pathways are the important mechanisms by which hyperglycemia contributes to glomerulosclerosis (GS). Therefore, this study aimed to examine the ameliorative effects of GTW on GS, and then to clarify its anti‑microinflammatory mechanisms by inhibiting p38 MAPK and NF-κB signaling activities in the kidney. All rats were divided into 4 groups: the sham group, the sham + GTW group, the vehicle group and the GTW group. The suitable dose of GTW and vehicle were daily administered for 8 weeks after the induction of DN by unilateral nephrectomy combined with intraperitoneal injections of streptozotocin (STZ). The general status of the rats, biochemical parameters, renal histological changes and macrophages in glomeruli, as well as expression of the key proteins in the p38 MAPK and canonical NF-κB signaling pathways and inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and transforming growth factor (TGF)-β1 in the kidney were examined, respectively. The results revealed that, GTW improved the general condition and biochemical parameters of the rats, but did not lower blood glucose; GTW attenuated GS and suppressed glomerular microinflammation including the infiltration of ED1+ cells in glomeruli and the protein overexpression of TNF-α, IL-1β and TGF-β1 in the kidney; GTW inhibited the protein overexpression of key signaling molecules of p38 MAPK and canonical NF-κB pathways in the kidney including phosphorylated p38 MAPK, phosphorylated inhibitor protein IκB and NF-κB (p65). On the whole, we expounded that GTW, as a natural regulator in vivo, alleviates GS without affecting hyperglycemia, by exerting anti-microinflammatory effects, including reducing macrophage infiltration in glomeruli, suppressing TNF-α, IL-1β and TGF-β1 overexpression in the kidney and inhibiting p38 MAPK and NF-κB signaling activities.

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