Wen Gu

Antidiabetic effect of total saponins from Polygonatum kingianum in streptozotocin-induced daibetic rats.

BACKGROUND Polygonatum kingianum has been used in the prevention and treatment of diabetes, hyperlipidemia and related metabolic syndrome in Asian counties for centuries. In this study, the blood glucose regulation activity and mechanism of total saponins from P. kingianum (TSPK) were investigated in streptozotocin (STZ)-induced diabetic rats in this research. METHODS TSPK (0.025g/kg and 0.1mg/kg) was administrated by gavage to STZ-induced diabetic rats for 8 weeks. Changes of body weight, food intakes, blood glucose, serum insulin and lipid indexes were observed. Genome-wide expression profiling was applied to explore the gene expression alternation after treated with TSPK. Expressions of adenosine monophosphate activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK), the relative transcript level of glucose kinase and glucose-6-phosphatase (GK/G6P) in the liver were investigated. Meanwhile, contents of AMPK, and glucose transporter subtype-4 (GLUT4) in skeletal muscle, and peroxysome proliferator-activated receptor (PPAR-γ) in adipose tissue were investigated. RESULTS TSPK could effectively alleviate hyperglycemia and hyperlipidemia in diabetic rats. Genome-wide expression profiling showed that TSPK up-regulated the expression of GLUT4 while down-regulated the expression of G6P in insulin signal pathway. In the liver, the expression of AMPK and GK are increased. Further more, TSPK promoted the expressions of GLUT4 in skeletal muscle, and PPAR-γ in adipose tissue, respectively. CONCLUSION These results provide possible mechanisms for the antidiabetic effects of TSPK. TSPK could promote not only glycogenesis but also glucose utilization in peripheral tissue. Our results suggested that TSPK may be used as adjuvant therapy to control blood glucose and insulin resistance in type 2 diabetic individuals.

Intake of total saponins and polysaccharides from Polygonatum kingianum affects the gut microbiota in diabetic rats

BACKGROUND The gut microbiota has been reported to play a critical role in metabolic diseases, including in diabetes. Polygonatum kingianum has been used in the treatment of diabetes and related diseases in China for centuries. Total saponins (TSPK) and total polysaccharides (PSPK) were reported to be major types of active constituents of P. kingianum. This research aims at investigation of their therapeutical mechanisms on diabetes based on the regulation of gut microbiota. STUDY DESIGN Type 2 diabetes (T2D) rats were induced by high-fat diet (HFD) and streptozotocin-injection from male Sprague-Dawley (SD) rats. The blood biochemical indicators were measured. Intestinal microbial diversities and the overall structural changes in gut microbiota and the contents of the short chain fatty acids (SCFAs) were discussed. METHODS T2D rats were treated with TSPK (0.025 and 0.1g/kg) and PSPK (0.1g/kg) for 56 days. Major biochemical indexes, such as fasting blood glucose (FBG), fasting insulin (FINS) and lipopolysaccharide (LPS), were measured. Intestinal microbial diversities and the overall structural changes in gut microbiota were discussed based on the sequencing results on V4 region of 16S rDNA. Moreover, the contents of the SCFAs in faeces, which were fermentation products produced from gut microbiota were determined by gas chromatography (GC). RESULTS Oral administration of TSPK and PSPK prevented the increase of FBG. TSPK (0.025g/kg) enhancing the content of FINS at the end of research. Furthermore, TSPK and PSPK improved the intestinal microecology by decreasing the abundances of Bacteroidetes and Proteobacteria, and increasing that of Firmicutes. However, TSPK.L, PSPK and TSPK.H displayed discrepant regulation roles on Firmicutes. TSPK.L and PSPK significantly increased the abundance of Ruminococcaceae family and Ruminococcus genus in Firmicutes phylum, however, TSPK.H increased the abundances of Veillonellaceae family and Anaerovibrio genus. 57 Key variables, altered after treated by TSPK and PSPK, correlated to the alternations of FBG, FINS, LPS and body weight were identified. In addition, TSPK.L, PSPK and TSPK.H showed different adjustment on the contents of SCFAs. CONCLUSION These results suggested that, compared to the normal rats, the structure of gut microbiota was significantly changed in diabetic rats. Oral administration with TSPK and PSPK could prevent T2D by its regulation role on the gut microbiota.

Naturally Occurring Stilbenoid TSG Reverses Non-Alcoholic Fatty Liver Diseases via Gut-Liver Axis.

The gut-liver axis is largely involved in the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether 2, 3, 5, 4′-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) could reverse NAFLD induced by a high-fat diet (HFD) and whether it did so via the gut-liver axis. Results showed that TSG could reduce the accumulation of FFA and it did so by reducing the expression of L-FABP and FATP4. TSG regulated gut microbiota balanced and increased the protein expression of ZO-1 and occludin, which could improve the function of the intestinal mucosal barrier and reduce serum LPS content by about 25%. TSG reduced TL4 levels by 56% and NF-κB expression by 23% relative to the NAFLD model group. This suggests that prevention of NAFLD by TSG in HFD-fed rats is mediated by modulation of the gut microbiota and TLR4/NF-κB pathway, which may alleviate chronic low-grade inflammation by reducing the exogenous antigen load on the host.

Screening for the bioactive constituents of traditional Chinese medicines—progress and challenges

The search for lead compounds from traditional Chinese medicines (TCMs) may be promising for new drug development. Screening efficiency and efficacy is chiefly determined by the validity of the selected screening tools. Recently, many experimental screening tools have been developed to identify lead compounds. This review provides a toolbox of the experimental screening methods and models that have been applied to discover new lead compounds and drugs from TCMs. The merits and limitations of these tools are summarized, assisting readers in the rapid retrieval of useful information and providing reference values for selecting appropriate screening tools for different research.

Volatile Oil from Amomi Fructus Attenuates 5-Fluorouracil-Induced Intestinal Mucositis

Amomi Fructus has been used to treat digestive diseases in the context of traditional Chinese medicine, so we evaluated the effects of a volatile oil from Amomum villosum (VOA) on intestinal mucositis induced by 5-fluorouracil (5-FU). We measured the effect of VOA and its main active constituent, bornyl acetate (BA), on body weight, food intake, diarrhea, inflammatory cytokines, the mucosal barrier, and gut microbiota. VOA and BA significantly increased the rats’ body weight, relieved diarrhea, and reversed histopathological changes in the gut and inflammation. VOA significantly inhibited apoptosis and alleviated the endoenteritis by downregulating p38 MAPK and caspase-3 expression. VOA and BA strengthened the intestinal mucosal barrier by increasing zonula occludin-1 and occludin expression. VOA and BA reduced the amount of pathogenic bacteria and increased the abundance of probiotics. Thus, VOA prevented the development and progression of intestinal mucositis after chemotherapy.

In Vivo Lipid Regulation Mechanism of Polygoni Multiflori Radix in High-Fat Diet Fed Rats

Mechanisms of the water extracts of Polygoni Multiflori Radix (PMR) and its processed products (PMRP) on liver lipid metabolism were observed in this paper. Aqueous extract of PMR and PMRP was given to nonalcoholic fatty liver model rats, respectively. PMR was better in reducing the contents of very low density lipoprotein (VLDL) than PMRP and the positive control groups. In the aspect of regulating TG, medium dose PMR reduced the activity of diacylglycerol acyltransferase (DGAT) to 1536 ± 47.69 pg/mL (P < 0.001) and promoted the expression of hepatic lipase (HL) to 23.59 ± 0.2758 U/mL (P < 0.05). HL promotion ability of medium dose PMR was similar with the simvastatin positive control. Both medium and high dose of PMR showed significant alterations in TC, which were related to the downregulation effects on hydroxyl methyl-glutaryl coenzyme A reductase (HMGCR) and upregulation effects on cholesterol 7-alpha-hydroxylase or cytochrome P450 7A (CYP7A). Quantitative relationships research indicated that the prominent effect on inhibiting the content of HMGCR (r = 0.756, P < 0.05) was strongly positive correlated with to the TC regulation effects. Effects of PMR on enhancing decomposition rate or reducing de novo synthesis rate of TG and TC were better than PMRP.

Intestinal Transportations of Main Chemical Compositions of Polygoni Multiflori Radix in Caco-2 Cell Model

Context. Polygoni Multiflori Radix (PMR) is originated from the root of Polygonum multiflorum Thunb. and used in oriental countries for centuries. However, little researches pay close attention to the absorption of its major constituents. Objective. Transepithelial transport of TSG, RL, PL, and four anthraquinones is carried out. Materials and Methods. Caco-2 cell monolayer, which represented a well-established model for the study of intestinal transport of nutrients and xenobiotics, was used in this paper. Results. The apparent permeability coefficients (P app) in the Caco-2 cell monolayers were TSG (2.372 × 10−9) < EG (2.391 × 10−9) < EN (2.483 × 10−9) < PL (4.917 × 10−9) < RN (1.707 × 10−8) < RL (1.778 × 10−8) < AE (1.952 × 10−8). Thus, RN, RL, and AE were considered partly absorbed, while other constituents were hardly absorbed. Discussion and Conclusion. Glycosides showed poor permeabilities than aglycones. In the meantime, TSG and EN gave out poor recovery rates in this assay, which indicated that TSG and EN may accumulate or metabolise in the Caco-2 cells. In silico prediction indicated that Gibbs energy (r = 0.751, p < 0.05) and heat of form (r = 0.701, p < 0.05) were strongly positively correlated with P app.

2,3,5,4'‑tetrahydroxy‑stilbene‑2‑O‑β‑D‑glucoside attenuates methionine and choline‑deficient diet‑induced non‑alcoholic fatty liver disease

Previous studies have suggested that 2,3,5,4′-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) prevents progression of non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet. The present study aimed to evaluate whether TSG could reverse NAFLD induced by a methionine and choline-deficient (MCD) diet and identify the possible mechanism of action. C57BL6/J mice were fed a MCD diet and were treated with TSG, fenofibrate, and resveratrol for 9 weeks. Regulatory effects of several cytokines and enzymes, including Nod-like receptor protein 3, apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), caspase-1, interleukin (IL)-18, IL-1β, and gut microbiota balance were investigated. TSG significantly reduced NAFLD biochemical indexes, including total cholesterol, triglyceride, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, aspartate aminotransferase and free fatty acid. Middle dosage (TSG.M, 35 mg/kg) of TSG reduced the expression of ASC and caspase-1. Furthermore, TSG displayed gut microbiota regulatory effects on MCD-induced NAFLD mice. The results of the present study suggested that TSG prevented the occurrence and development of MCD diet-induced NAFLD. The data further indicated that TSG may serve as a promising lead compound that may aid with intervention in NAFLD therapy.

Volatile Oil of Amomum villosum Inhibits Nonalcoholic Fatty Liver Disease via the Gut-Liver Axis

Background The dried mature fruit of Amomum villosum has been historically used in China as food and in the auxiliary treatment of digestive system disorders. Numerous studies have shown that gastrointestinal function is closely related to the development of nonalcoholic fatty liver disease via the “gut-liver” axis. Objective The present study aimed to explore whether the mechanism underlying the regulation of lipid accumulation in nonalcoholic fatty liver disease (NAFLD) may affect related disorders using the active ingredients in A. villosum. Design Male Sprague-Dawley rats on a high-fat diet (HFD) to induce NAFLD were administered water extract of A. villosum (WEAV), volatile oil of A. villosum (VOAV), or bornyl acetate. After treatment, serum and liver total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. The regulatory role of A. villosum in the microecology of the intestines was assessed using the V4 region of the 16S rDNA sequencing. The expression of the intestinal tight junction proteins occludin and ZO-1 was also measured. The influence of A. villosum on TLR4-mediated chronic low-grade inflammation was evaluated based on the concentrations of key proteins of the TLR4/NF-кB signaling pathway. Results. A. villosum effectively inhibited endogenous lipid synthesis, reduced TG, TC, and FFA accumulation, regulated the expression of LDL-C, and decreased lipid accumulation in liver tissues. VOAV effectively regulated the intestinal microflora, improved chronic low-grade inflammation by promoting ZO-1 and occludin protein expressions, and inhibited the TLR4/NF-кB signaling pathway. Conclusion The present study provides scientific basis for the potential application of A. villosum in NAFLD prevention and treatment. Additional chemical constituents other than bornyl acetate also contributed to the preventive effects of A. villosum on NAFLD.