Hypoglycemic mechanisms of Polygonatum sibiricum polysaccharide in db/db mice via regulation of glycolysis/gluconeogenesis pathway and alteration of gut microbiota.

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.

Effects of Granule Dendrobii on chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

BACKGROUND: Dendrobium officinale is an herb of Traditional Chinese Medicine (TCM) commonly used for treating stomach diseases. One formula of Granule Dendrobii (GD) consists of Dendrobium officinale and American Ginseng (Radix Panacis quinquefolii), and is a potent TCM product in China. Whether treatment with GD can promote gastric acid secretion and alleviate gastric gland atrophy in chronic atrophic gastritis (CAG) requires verification. AIM: To determine the effect of GD treatment on CAG and its potential cellular mechanism. METHODS: A CAG model was induced by feeding rats N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 12 wk. After oral administration of low, moderate, and high doses of GD in CAG rats for 8 wk, its effects on body weight, gastric mucosa histology, mucosal atrophy, intestinal metaplasia, immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2, and hemoglobin and red blood cells were examined. RESULTS: The body weights of MNNG-induced CAG model rats before treatment (143.5 ± 14.26 g) were significantly lower than that of healthy rats (220.2 ± 31.20 g, P < 0.01). At the 8th week of treatment, the body weights of rats in the low-, moderate-, and high-dose groups of GD (220.1 ± 36.62 g) were significantly higher than those in the untreated group (173.3 ± 28.09 g, all P < 0.01). The level of inflammation in gastric tissue of the high-dose group (1.68 ± 0.54) was significantly reduced (P < 0.01) compared with that of the untreated group (3.00 ± 0.00, P < 0.05). The number and thickness of gastric glands in the high-dose group (31.50 ± 6.07/mm, 306.4 ± 49.32 µm) were significantly higher than those in the untreated group (26.86 ± 6.41/mm, 244.3 ± 51.82 µm, respectively, P < 0.01 and P < 0.05), indicating improved atrophy of gastric mucosa. The areas of intestinal metaplasia were significantly lower in the high-dose group (1.74% ± 1.13%), medium-dose group (1.81% ± 0.66%) and low-dose group (2.36% ± 1.08%) than in the untreated group (3.91% ± 0.96%, all P < 0.01). The expression of PCNA in high-dose group was significantly reduced compared with that in untreated group (P < 0.01). Hemoglobin level in the high-dose group (145.3 ± 5.90 g/L), medium-dose group (139.3 ± 5.71 g/L) and low-dose group (137.5 ± 7.56 g/L) was markedly increased compared with the untreated group (132.1 ± 7.76 g/L; P < 0.01 or P < 0.05). CONCLUSION: Treatment with GD for 8 wk demonstrate that GD is effective in the treatment of CAG in the MNNG model by improving the histopathology of gastric mucosa, reversing gastric atrophy and intestinal metaplasia, and alleviating gastric inflammation.

Myricanol 5-fluorobenzyloxy ether regulation of survivin pathway inhibits human lung adenocarcinoma A549 cells growth in vitro.

BACKGROUND: This study aimed to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and its underlying mechanisms in human lung adenocarcinoma A549 cells in vitro. METHODS: 5FEM was obtained by the chemical modification of myricanol with fluorobenzyloxy ether at the OH(5) position. The cytotoxicity, cell apoptosis, cell cycle, mitochondrial membrane potential (ΔΨm), scratch test, colony formation, and the expression levels of the key survivin pathway-related genes in A549 were evaluated. RESULTS: 5FEM could significantly inhibit A549 cell growth; induce cell apoptosis; increase G0/G1 population; reduce ΔΨm; inhibit cell migration and colony formation; upregulate caspase-9, P21, and Bax expression levels; and downregulate PARP, survivin, and Bcl-2 expression level. CONCLUSION: These results enhanced our understanding of 5FEM and aid the discovery of novel myricanol derivatives as potential antitumor agents.

Regulation of microRNAs by rape bee pollen on benign prostate hyperplasia in rats.

The miRNAs are dysregulated in BPH. Rape bee pollen (RBP) is used to improve benign prostatic hyperplasia (BPH). Whether RBP treats BPH by regulating the dysregulated miRNAs remains unclear. Here, we identified miRNAs regulated along with the improvement of BPH by RBP in posterior lobes of prostate in rats. Firstly, to screened miRNAs might relate to improvement of BPH by RBP, we compared differentially expressed miRNAs between BPH model group and RBP group by high-throughput sequencing. As a result, 10 known miRNAs and 17 novel miRNA were up-regulated in RBP group, and 6 known and 13 novel miRNAs were down-regulated. Secondly, among the known miRNAs, we identified those that might relate to BPH by RT-qPCR, while only rno-miR-184 was screened, so we compared it among normal control group, BPH model group and RBP group. The results showed that rno-miR-184 was significantly lower expressed in BPH group, but up-regulated along with the improvement of BPH by RBP. Moreover, expression level of rno-miR-184 was no difference between RBP group and normal control level. Therefore, we considered that RBP might improve BPH through regulating expression of miRNAs like rno-miR-184 in prostate in rats.

[Effect of two kinds of fermented food on blood glucose and lipids in induced diabetic mice].

OBJECTIVES: To investigate the effect of two kinds of fermented food, noni juice and natto, on blood glucose and lipids in induced diabetic mice. METHODS: Female (ICR) mice were induced into diabetes by an injection of alloxan (55 mg/kg, i. v.). After 72 hours, those mice whose fasting blood glucose levels were over 12.00 mmol/L and urine sugar was strongly positive (+ + +) were regarded as diabetical model and were randomly divided into three groups (n=10):diabetical model (DM) group, noni juice (NJ) group and natto (NT) group. Another ten normal female ICR mice were taken as normal control (NC) group. The mice in NJ and NT groups were gavaged with noni juice (25.0 ml/kg) and natto (0.6 g/kg) respectively. The other two groups were given normal saline (25.0 ml/kg). Continuous gavage administration was given for 30 days, the water-drinking volume and food-intake were recorded. After 1.5 h of the last administration, the glucose tolerance of mice was measured. Finally, the changes in glycated serum protein(GSP), insulin(Ins) and blood lipids of blood samples of mice, taken from the femoral artery, were determined. RESULTS: Compared to the NC group, the water-drinking amount and food-intake, GSP and total cholesterol (TC), triglyceride(TG) and low density lipoprotein (LDL) in DM group were increased significantly (P<0.01), while glucose tolerance, Ins and high density lipoprotein (HDL) were decreased significantly (P<0.01). However, when it came to DM group, NJ and NT could significantly (P<0.01 or P<0.05) reduce, GSP, TG and LDL, meanwhile improve glucose tolerance, Ins and HDL (P<0. 01). CONCLUSIONS: Both noni juice and natto could reduce the blood glucose levels in induced diabetical mice and improve blood lipids, which suggested that they may have certain application value in prevention and treatment of diabetic mellitus.

Study on the inhibition of Mfn1 by plant-derived miR5338 mediating the treatment of BPH with rape bee pollen.

BACKGROUND: Recent studies have found that plant derived microRNA can cross-kingdom regulate the expression of genes in humans and other mammals, thereby resisting diseases. Can exogenous miRNAs cross the blood-prostate barrier and entry prostate then participate in prostate disease treatment? METHODS: Using HiSeq sequencing and RT-qPCR technology, we detected plant miRNAs that enriched in the prostates of rats among the normal group, BPH model group and rape bee pollen group. To forecast the functions of these miRNAs, the psRobot software and TargetFinder software were used to predict their candidate target genes in rat genome. The qRT-PCR technology was used to validate the expression of candidate target genes. RESULTS: Plant miR5338 was enriched in the posterior lobes of prostate gland of rats fed with rape bee pollen, which was accompanied by the improvement of BPH. Among the predicted target genes of miR5338, Mfn1 was significantly lower in posterior lobes of prostates of rats in the rape bee pollen group than control groups. Further experiments suggested that Mfn1 was highly related to BPH. CONCLUSIONS: These results suggesting that plant-derived miR5338 may involve in treatment of rat BPH through inhibiting Mfn1 in prostate. These results will provide more evidence for plant miRNAs cross-kingdom regulation of animal gene, and will provide preliminary theoretical and experimental basis for development of rape bee pollen into innovative health care product or medicine for the treatment of BPH.

The mechanistic antitumor study of myricanol 5-fluorobenzyloxy ether in human leukemic cell HL-60.

AIM: The aim of the study was to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and the underlying mechanism in human leukemic cells HL-60. MATERIALS & METHODS: 5FEM was obtained by chemical modification of myricanol with fluorobenzyloxy ether at the OH(5) position. The cytotoxicity, cell apoptosis, cell cycle and the expression of key apoptosis-related genes in HL-60 were evaluated. RESULTS & CONCLUSION: 5FEM can significantly inhibited growth of HL-60 cells, increased the G2/M population and upregulated the expression of Bax, Fas, FasL, caspase-9 and p21 and downregulated that of Bcl-2 and survivin. The results enhance our understanding of 5FEM and aid the discovery of novel myricanol derivatives as potential antitumor agents.

Identification of Dietetically Absorbed Rapeseed (Brassica campestris L.) Bee Pollen MicroRNAs in Serum of Mice.

MicroRNAs (miRNAs) are a class of small noncoding RNA that, through mediating posttranscriptional gene regulation, play a critical role in nearly all biological processes. Over the last decade it has become apparent that plant miRNAs may serve as a novel functional component of food with therapeutic effects including anti-influenza and antitumor. Rapeseed bee pollen has good properties in enhancing immune function as well as preventing and treating disease. In this study, we identified the exogenous miRNAs from rapeseed bee pollen in mice blood using RNA-seq technology. We found that miR-166a was the most highly enriched exogenous plant miRNAs in the blood of mice fed with rapeseed bee pollen, followed by miR-159. Subsequently, RT-qPCR results confirmed that these two miRNAs also can be detected in rapeseed bee pollen. Our results suggested that food-derived exogenous miRNAs from rapeseed bee pollen could be absorbed in mice and the abundance of exogenous miRNAs in mouse blood is dependent on their original levels in the rapeseed bee pollen.