RESUMEN
Objectives: Jian-Pi-Yin decoction (JPY), a prescription derived from the traditional Chinese medicine Shen-Ling-Bai-Zhu-San, has shown good clinical efficacy in the treatment of diarrhea caused by lactose intolerance. However, the mechanism of action of JPY in the treatment of diarrhea is not fully understood. Design: In this study, a rat diarrhea model was induced by high lactose feeding combined with standing on a small platform to investigate the ameliorating effect of JPY on hyper lactose-induced diarrhea in rats and its possible mechanism. Methods: The rat model of hyper lactose diarrhea was given high, medium, and low doses of JPY and the positive control drug Smida by gavage for 1 week. At the same time, NA+-H+ exchanger 3 (NHE3) inhibitor Tenapanor was administered orally for 3 weeks. Body weight, food intake, water intake, grip strength, and severity of diarrhea symptoms were measured in rats throughout the study. The serum, colon, and jejunum tissues of the model and drug-treated rats were collected for histopathological examination and analysis of relevant indicators. Results: JPY significantly alleviated the symptoms of fatigue, diet reduction and diarrhea in the model group. Glucagon-like peptide-1 (GLP-1) and cyclic adenosine monophosphate (cAMP) expression were also down-regulated after JPY treatment. JPY can significantly promote NHE3 in intestinal tissues of rats with diarrhea, and the mechanism is related to the decrease of GLP-1, inhibition of cAMP/PKA pathway activation, an increase of ubiquitin-specific protease 7 (USP7) and USP10 expression, and decrease of NHE3 ubiquitination and phosphorylation. Conclusion: JPY can reduce the expression of GLP-1, reduce the ubiquitination and phosphorylation of NHE3, regulate the expression of NHE3, at least partly improve ion transport in the intestinal epithelium, and improve the imbalance of electrolyte absorption, thus significantly reducing the diarrhea symptoms of rats with high lactose combined with small platform standing. Innovation: In this study, we explored the mechanism of intestinal GLP-1 activation of cAMP/PKA signaling pathway from multiple dimensions, and increased its expression by reducing phosphorylation and ubiquitination of NHE3, thereby treating chronic diarrhea associated with lactose intolerance.
RESUMEN
INTRODUCTION/AIM: To assess the effectiveness and safety of Traditional Chinese patent medicines (TCPMs) for managing impaired glucose tolerance (IGT). METHODS: Seven databases were searched to identify eligible trials published from incepting to May 1, 2016. Randomized controlled trials (RCTs) involving TCPM for IGT with a minimum follow-up duration of 6 months were included for analysis. Data extraction and quality assessment were performed by two reviewers independently. Data synthesis was analyzed using Review Manager 5.3 software. Subgroup analysis was carried out to assess the robustness of results of meta-analysis. RESULTS: Eighteen trials with a total of 3172 participants met the inclusion criteria. The methodological quality of the RCTs was variable. Comparing with receiving lifestyle modification (LM) alone, TCPM plus LM was significantly better at reducing the incidence of diabetes (risk ratio [RR] 0.45; 95% confidence interval [CI] 0.36-0.57, p < 0.00001) and normalizing the blood glucose (RR 0.72; 95% CI 0.64-0.82, p < 0.00001). TCPM plus LM was superior in decreasing the levels of 2hPG, body mass index (BMI), fasting insulin, and 2 h insulin compared with LM alone (2hPG: mean difference [MD] -1.13; 95% CI -1.68 to -0.58, p < 0.0001; BMI: MD -0.42; 95% CI -0.71 to -0.14, p = 0.004; fasting insulin: MD -2.44; 95% CI -3.79 to -1.09, p = 0.0004; and 2 h insulin: MD -8.26; 95% CI -8.47 to -8.05, p < 0.00001). Compared with placebo plus LM, TCPM plus LM was superior in reducing diabetes (RR 0.54; 95% CI 0.42-0.69, p < 0.00001) and normalizing blood glucose (RR 0.55; 95% CI 0.41-0.73, p < 0.00001; the interventions were also associated with a decline in the two-hour postprandial blood glucose (2hPG) levels (MD -1.45; 95% CI -2.11 to -0.79, p < 0.0001) and BMI levels (MD -1.12; 95% CI -2.00 to -0.24, p < 0.0001). There were no significant differences in adverse events between two groups. Subgroup analysis found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. CONCLUSIONS: The study indicated that TCPM combined with moderate lifestyle modification had significant effect on IGT. Further studies are needed to provide more reliable evidence. The PROSPERO registration is No. CRD42016039312.