TY - JOUR
T1 - Weikangning therapy in functional dyspepsia and the protective role of Nrf2
AU - Chang, Yujuan
AU - Wei, Wei
AU - Tong, Li
AU - Liu, Yanjun
AU - Zhou, Aimin
AU - Chen, Jiande
AU - Wei, Ruhan
AU - Zhang, Ping
AU - Su, Xiaolan
N1 - Funding Information:
The present study was supported by the National Natural Science Fund (grant no. 81273746).
Publisher Copyright:
© 2017, Spandidos Publications. All rights reserved.
PY - 2017/10
Y1 - 2017/10
N2 - Functional dyspepsia (FD) is a non-organic gastrointestinal disorder that has a marked negative impact on quality of life. Compared with conventional pharmacological therapies, the traditional Chinese medicine weikangning (WKN) is a safe and effective treatment for FD. The present study aimed to determine the molecular mechanisms underlying the efficacy of WKN. The effect of different concentrations of WKN on the proliferation of the human gastric mucosal epithelial cell line GES-1 was assessed. The optimal WKN concentration to promote cell proliferation was determined, and this concentration was used to examine the effect of WKN compared with a domperidone-treated positive control group on the antioxidant capacity of GES-1 cells. The effect of WKN treatment on the growth and antioxidant activity of GES-1 cells was also assessed following nuclear factor erythroid 2 like 2 (Nrf2) knockdown. The optimal WKN dose for promoting cell growth was determined to be 0.025 mg/ml; at this concentration the expression of the antioxidant proteins glutathione S-transferase P and superoxide dismutase 2 (SOD2) were significantly elevated (P<0.0001). Furthermore, the amount of reduced glutathione and activity of SOD2 were significantly increased (P<0.0001 and P<0.01, respectively), and malondialdehyde content was significantly decreased, compared with the controls (P<0.001). With WKN treatment, the transcription of Nrf2 and its downstream genes were significantly upregulated (P<0.01), and the level and nuclear distribution of Nrf2 protein was also markedly increased. Following Nrf2 silencing, the protective antioxidant effects of WKN treatment were impaired and GES-1 cell proliferation decreased. The results of the present study suggest that the efficacy of WKN in protecting gastric mucosal epithelial cells in FD is antioxidant-dependent and mediated by Nrf2 activation.
AB - Functional dyspepsia (FD) is a non-organic gastrointestinal disorder that has a marked negative impact on quality of life. Compared with conventional pharmacological therapies, the traditional Chinese medicine weikangning (WKN) is a safe and effective treatment for FD. The present study aimed to determine the molecular mechanisms underlying the efficacy of WKN. The effect of different concentrations of WKN on the proliferation of the human gastric mucosal epithelial cell line GES-1 was assessed. The optimal WKN concentration to promote cell proliferation was determined, and this concentration was used to examine the effect of WKN compared with a domperidone-treated positive control group on the antioxidant capacity of GES-1 cells. The effect of WKN treatment on the growth and antioxidant activity of GES-1 cells was also assessed following nuclear factor erythroid 2 like 2 (Nrf2) knockdown. The optimal WKN dose for promoting cell growth was determined to be 0.025 mg/ml; at this concentration the expression of the antioxidant proteins glutathione S-transferase P and superoxide dismutase 2 (SOD2) were significantly elevated (P<0.0001). Furthermore, the amount of reduced glutathione and activity of SOD2 were significantly increased (P<0.0001 and P<0.01, respectively), and malondialdehyde content was significantly decreased, compared with the controls (P<0.001). With WKN treatment, the transcription of Nrf2 and its downstream genes were significantly upregulated (P<0.01), and the level and nuclear distribution of Nrf2 protein was also markedly increased. Following Nrf2 silencing, the protective antioxidant effects of WKN treatment were impaired and GES-1 cell proliferation decreased. The results of the present study suggest that the efficacy of WKN in protecting gastric mucosal epithelial cells in FD is antioxidant-dependent and mediated by Nrf2 activation.
KW - Antioxidant capacity
KW - Functional dyspepsia
KW - Gastric mucosal epithelial cell
KW - Nuclear factor erythroid 2 like 2
KW - Traditional Chinese medicine
KW - Weikangning
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U2 - 10.3892/etm.2017.4892
DO - 10.3892/etm.2017.4892
M3 - Article
AN - SCOPUS:85028599654
SN - 1792-0981
VL - 14
SP - 2885
EP - 2894
JO - Experimental and Therapeutic Medicine
JF - Experimental and Therapeutic Medicine
IS - 4
ER -