ABSTRACT
Polygonatum rhizoma polysaccharide (PP) is a main ingredient of Polygonatum rhizoma , which is both food and traditional herbal medicine. In this study, we aimed to investigate the hypoglycemic effect of PP and the underlying mechanisms in db/db mice. Our finding showed that PP significantly ameliorates diabetic symptoms by reducing glucose levels in blood and urine and increasing insulin and leptin abundance in the serum. Histopathological examination revealed that PP improved the pathological state and increased hepatic glycogen storage in liver. Additionally, RT-qPCR results indicated that PP significantly down-regulated the expression of phosphoenolpyruvate carboxykinase 1. Furthermore, 16s rRNA sequencing results demonstrated that PP intervention resulted in an increase in beneficial bacteria genus and a reduction in harmful genus. Redundancy analysis revealed the correlation between intestinal flora and clinical factors. Taken together, these results suggest that PP has a significant hypoglycemic effect on type 2 diabetes (T2D) through up-regulating serum insulin and leptin, as well as hepatic glycogen storage, and down-regulating hepatic phosphoenolpyruvate carboxykinase 1 expression, as well as modulating gut microbiota composition. In conclusion, this study investigated the mechanisms of PP in the treatment of diabetes in db/db mice. To the best of our knowledge, this is the first study to explore the positive and negative correlations between gut microbiota and clinical factors, such as oxidative stress injury in liver and glucose related indicators in the blood.
ABSTRACT
BACKGROUND & AIM: Previous studies showed a vitamin D deficiency in patients with Behçet's disease, suggesting potential benefits of vitamin D supplementation in the prevention and treatment of Behçet's disease. Interpretation of these studies may be limited by reverse causality or confounding bias. We aim to determine the causal association between serum 25-hydroxyvitamin D [25(OH)D] and the risk of Behçet's disease by Mendelian randomization. METHODS: An allele score formed by four variants (rs2282679, rs10741657, rs12785878 and rs6013897) that were associated with serum 25(OH)D level, was examined using data of genome-wide association study (GWAS) on 999 Behçet's disease and 4417 healthy individuals of Chinese ancestry and validated using data of GWAS on 1215 Behçet's disease and 1278 controls of Turkish ancestry. The primary outcome was the risk of Behçet's disease, evaluated by an inverse variance weighted average of the associations with genetically determined 25(OH)D levels. RESULTS: The inverse variance weighted estimate showed that genetically increased 25(OH)D level was associated with a higher risk of Behçet's disease. In the Chinese cohort, the odds ratio for Behçet's disease in one standard deviation increase of natural log-transformed 25(OH)D level was 3.82 (95% CI: 1.27-11.42). Data from Turkish cohort confirmed the association with Behçet's disease (OR, 95% CI: 4.18, 1.15-15.12). In overall combination of Chinese and Turkish cohorts, the odds ratio for Behçet's disease per standard deviation increase of natural log-transformed 25(OH)D level was estimated to be 3.96 (95% CI: 1.72-9.13; P = 0.001). No significant evidence of pleiotropy and heterogeneity was detected. CONCLUSIONS: On the basis of evidence in 7909 human beings, this study provides the newest indication that a lifelong higher 25(OH)D level is associated with an increased risk of Behçet's disease. Special attention should be paid to the potential harm of long-term or high-dose use of vitamin D supplements in clinical practice.