Weikangning therapy in functional dyspepsia and the protective role of Nrf2

Abstract

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.

Quercetin Improves Mitochondrial Function and Inflammation in H2O2-Induced Oxidative Stress Damage in the Gastric Mucosal Epithelial Cell by Regulating the PI3K/AKT Signaling Pathway

“…More ROS will be produced after mitochondrial injury, which accelerates cell apoptosis [ 6 ]. Evidence demonstrated that oxidative stress-induced damage in gastric mucosal epithelial cells is related to the pathogenesis and development of FD [ 7 ]. Antioxidant agent mitoTEMPO showed gastroprotection by preventing mitochondrial apoptosis and mitochondrial oxidative stress-mediated proinflammation [ 8 ].…”

Effects and mechanisms of traditional Chinese medicines on functional dyspepsia: A review

“…The results showed that Banxia Xiexin Decoction could effectively improve the total dyspepsia symptom score and the single dyspepsia symptom score of FD patients, without adverse reactions. Chang et al used Weikangning Capsule to treat patients with FD ( Chang et al, 2017 ). The results showed that Weikangning Capsule can significantly improve the clinical symptoms of patients with FD compared with western medicines, and can improve the mood of patients to a certain extent, alleviate anxiety and depression psychological disorders, and improve the quality of life.…”

Precise and systematic survey of the efficacy of multicomponent drugs against functional dyspepsia

“…The Xiaoyao pill improved the Hamilton Rating Scale for Depression score, motilin and gastrin levels, as well as the rate of gastric emptying 10 . Though some action modes of TCMs have been revealed 7 , further investigations are still needed to determine their precise functionary mechanisms and find new intervention targets. Moreover, due to the complexity of multiple constituents from TCMs, accompanied by complicated synergistic effect processes, their precise localization in the clinic is also ambiguous, thus hindering their widespread use.…”