Protective effects of Radix Isatidis polysaccharide ameliorates obesity via promotion AMPK pathway in high-fat-diet-induced obese rats and 3T3-L1 adipocyte cells.

OBJECTIVES: The purpose of this paper is to ascertain the effect and mechanism of Radix Isatidis polysaccharide (RIP) on obesity. METHODS: High fat diet (HFD)-induced obese rats and the MDI-induced 3T3-L1 adipocyte cells were established to evaluate the ameliorated obesity effect and mechanism from RIP. KEY FINDINGS: Experiments in vivo show that oral administration of RIP has significant preventive effects on HFD-induced obesity and metabolic disorders in rats. With treatment of RIP (20, 40 and 80 mg/kg BW), the body weight, fat accumulation, adipocyte cell size, serum lipid levels and antioxidant enzyme activity were progressively improved. On the other hand, the treatment of 3T3-L1 cells with RIP (25, 50 and 100 mg/L) led to a decrease in lipid accumulation and glucose consumption. In addition, during adipogenesis in 3T3-L1 cells, RIP remarkably down-regulated mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein-α (C/EBPα), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase and glycerol-3-phosphate dehydrogenase. Furthermore, after RIP treatment, the protein expression of PPARγ, C/EBPα, FAS, HMG-CoA reductase and acetyl-CoA synthetase-1 (AceCS1) were significantly decreased and the expression of p-AMPK was increased. CONCLUSION: These results highlight the potential of RIP for obesity interventions and suggest that RIP inhibited adipocyte differentiation and lipid synthesis by activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signalling pathway and down-regulating the expression of major adipogenic transcription factors, PPARγ, C/EBPα, etc.

Exogenous Plant gma-miR-159a, Identified by miRNA Library Functional Screening, Ameliorated Hepatic Stellate Cell Activation and Inflammation via Inhibiting GSK-3ß-Mediated Pathways.

PURPOSE: Plant-derived exogenous microRNAs (miRNAs) regulate human physiological functions by blocking the translation of target mRNAs. Although several computational approaches have been developed to elucidate the interactions of cross-species miRNAs and their targets in mammals, the number of verified plant miRNAs is still limited, and the biological roles of most exogenous plant miRNAs remain unknown. METHODS: A miRNA mimic library-based phenotypic screening, which contained 8394 plant mature miRNAs published in the official database miRbase, was performed to identify more novel bioactive plant miRNAs for the prevention of hepatic fibrosis. Inhibition of candidates for the activation of hepatic stellate cells (HSCs) and the underlying mechanisms were evaluated in TGF-ß1- and PDGF-exposed HSC models. The protective effects of the candidates against CCl4-induced liver fibrosis were evaluated in a mouse model. RESULTS: Among the 8394 plant mature miRNAs reported in the official database miRBase, five candidates were found to effectively inhibit the differentiation of HSCs. gma-miR-159a (miR159a) exerted the strongest inhibitory activities on both TGF-ß1- and PDGF-induced HSC activation and proliferation by inhibiting the GSK-3ß-mediated NF-κB and TGF-ß1 pathways. Moreover, miR159a was mainly accumulated in the liver after intravenous injection, and it reduced CCl4-induced hepatic fibrosis and inflammation in mice. CONCLUSION: Results indicated that miR159a has the therapeutic potential for preventing hepatic fibrosis. This study provides a novel strategy for achieving natural nucleic acid drugs.

Effect of Radix isatidis polysaccharide on alleviating insulin resistance in type 2 diabetes mellitus cells and rats.

OBJECTIVES: The objective of this paper was to explore the effects of Radix isatidis polysaccharide (RIP) extracted from Radix isatis on alleviating insulin resistance. METHODS: The insulin resistance models of 3T3-L1 preadipocytes and type 2 diabetic rats were established to evaluate the insulin resistance activity of RIP. KEY FINDINGS: Radix isatidis polysaccharide within the concentration range of 25-100 µg/ml could reduce cell supernatant glucose and TNF-α levels (P < 0.01) and increase the expression of PI-3K P85, Glut4, IRS-1 and Akt protein in symptoms of IR 3T3-L1 preadipocytes. In the meantime, RIP contributed to relieve the weight loss of diabetic rats whose liver weight and liver index were decreased due to the effects of RIP. Experiments in rats also showed that RIP had capacity in reduced serum TC, TG, LDL-C, FFA, FBG, FINS, MDA, ALT, AST activities and increased serum HDL-C, SOD, ISI (P < 0.05 or 0.01). In addition, the oral glucose tolerance in rats was improved (P < 0.05) and liver damage was restored due to RIP. CONCLUSIONS: Radix isatidis polysaccharide significantly alleviates insulin resistance in 3T3-L1 preadipocytes and type 2 diabetic rats. These beneficial effects of RIP may associate with their roles in improving the glucose metabolism, lipid metabolism and oxidative stress.

PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics (Review).

The platelet­derived growth factor (PDFG) signaling pathway exerts persistent activation in response to a variety of stimuli and facilitates the progression of hepatic fibrosis. Since this pathway modulates a broad spectrum of cellular processes, including cell growth, differentiation, inflammation and carcinogenesis, it has emerged as a therapeutic target for hepatic fibrosis and liver­associated disorders. The present review exhibits the current knowledge of the role of the PDGF signaling pathway and its pathological profiles in hepatic fibrosis, and assesses the potential of inhibitors which have been investigated in the experimental hepatic fibrosis model, in addition to the clinical challenges associated with these inhibitors.

Studies on anti-angiogenesis of ginsenoside structure modification HRG in vitro.

This study investigates the anti-angiogenic effect of 3ß, 12ß, 20(S)-trihydroxy dammarane-3-O-ß-d-glucopyranosyl(1-2)-ß-d-glucopyranoside(HRG), a new chemical compound obtained by structure modification on Ginseng saponins Rg3, associated with the regulation of matrix metalloproteinases(MMPs) and its upstream signal-regulated molecule of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b-FGF) in vitro, which plays an critical role in angiogenesis during the process of carcinoma. In our study, to investigate the anti-angiogenesis effect of HRG in HUVECs, we utilized cell proliferation assay, tube formation assay, wound-healing assay, Semi-quantitative reverse transcription PCR, and Western blot assay. Our results demonstrated that HRG plays a major role in the regulation of proliferation, migration and tube formation of HUVECs by suppressing the expression of VEGF and b-FGF in both transcriptional and post-transcriptional levels. In addition, the expression of MMP-2 and MMP-9, which were related to the ECM degradation, were down-regulated after administration of HRG as well. Overall, our results revealed that HRG strongly inhibited the process of angiogenesis and shows better effectiveness than Rg3.

Baicalein attenuates vinorelbine-induced vascular endothelial cell injury and chemotherapeutic phlebitis in rabbits.

Chemotherapy is one of the major strategies for cancer treatment. Several antineoplastic drugs including vinorelbine (VRB) are commonly intravenously infused and liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. In this study, the mechanism of baicalein (BCN) was investigated on VRB-induced phlebitis in vivo and vascular endothelial cell injury in vitro. Treatment with BCN obviously attenuated vascular endothelial cell loss, edema, inflammatory cell infiltration and blood clots, and reduced the serum levels of TNF-α, IL-1ß, IL-6 and ICAM-1 in the rabbit model of phlebitis induced by intravenous injection of VRB compared with vehicle. Further tests in vitro demonstrated that BCN lessened VRB-induced endothelial cell apoptosis, decreased intracellular ROS levels, suppressed phosphorylation of p38 and eventually inhibited activation of NF-κB signaling pathway. And these effects could be reversed by p38 agonist P79350. These results suggested that BCN exerted the protective effects against VRB-induced endothelial disruption in the rabbit model of phlebitis via inhibition of intracellular ROS generation and inactivation of p38/NF-κB pathway, leading to the decreased production of pro-inflammatory cytokines. Thus, BCN could be used as a potential agent for the treatment of phlebitis.

Selaginella uncinata flavonoids ameliorated ovalbumin-induced airway inflammation in a rat model of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Selaginella uncinata (Desv.) Spring, known as "Cuiyuncao", is a perennial herb widely distributed in the Southeast Asian countries. In the folk medicine, the local minority commonly use it to treat cough and asthma for centuries. AIM OF THE STUDY: This study was carried out to investigate the protective mechanisms of total flavonoids from S. uncinata (SUF) on airway hyperresponsiveness, cytokine release and bitter taste receptors (T2Rs) signaling with emphasis on inflammatory responses in a rat model of ovalbumin (OVA)-induced asthma. MATERIALS AND METHODS: Rats were sensitized and challenged with OVA to induce typical asthmatic reactions. Pathological changes of lung tissue were examined by HE staining. The serum levels of T cell-associated cytokines (IFN-γ, IL-4, IL-5 and IL-13), total IgE and OVA-specific IgE were determined by enzyme-linked immunosorbent assay (ELISA). Gene expressions of T2R10, IP3R1 and Orai1 in lung tissue were assayed by fluorescence quantitative real-time polymerase chain reaction (FQ-PCR) while protein expressions of NFAT1 and c-Myc were assayed by western blot analysis. The activation of SUF was investigated on tansgentic T2R10-GFP HEK293 cells. RESULTS: SUF treatment attenuated airway hyperresponsiveness and goblet cell hyperplasia compared with OVA-challenged asthmatic rats. The serum levels of IL-4, IL-5 and IL-13 as well as total and OVA-specific IgE were decreased while serum IFN-γ was increased in SUF-treated rats. SUF treatment significantly up-regulated T2R10 gene expression, down-regulated IP3R1 and Orai1 gene expression. SUF further suppressed eotaxin, NFAT1 and c-Myc protein expression in lung tissues of OVA-challenged rats. CONCLUSIONS: These results imply that SUF exerts anti-inflammatory function through the T2R10/IP3R1/NFAT1 dependent signaling pathway, and may warrant further evaluation as a possible agent for the treatment of asthma.

Efficacy and safety of carbon dioxide insufflation versus air insufflation for endoscopic retrograde cholangiopancreatography: A meta-analysis update.

BACKGROUND AND OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for visualising the biliary tree and pancreatic ducts, and carbon dioxide (CO2) insufflation during ERCP is considered an alternative technique to air insufflation for relieving post-procedural abdominal discomfort (abdominal pain and distension). The aim of the present study was to evaluate the effect of CO2 insufflation on the remission of abdominal discomfort and the potential side effects by conducting a meta-analysis. METHODS: The method recommended by the Cochrane Collaboration was employed to conduct a meta-analysis of randomised controlled trials (RCTs) of CO2 insufflation versus air insufflation during ERCP. The PubMed, EMBASE, Cochrane Library, ISI Web of Science and China Biology Medicine disc (CBMdisc) databases were comprehensively searched. RESULTS: Nine high-quality RCTs were reviewed. The updated meta-analysis showed that the CO2 groups achieved a lower abdominal pain score [1-hour (SMD: -1.44, 95% CI: -2.76, -0.15), 3-hour (SMD: -1.17, 95% CI: -2.18, -0.16) and 6-hour (SMD: -1.39, 95% CI: -2.68, -0.10)], a lower abdominal distension score [1-hour (SMD: -1.05, 95% CI: -1.73, -0.38), 3-hour (SMD: -0.63, 95% CI: -1.10, -0.16) and 6-hour (SMD: -0.54, 95% CI: -0.99, -0.08)] and a lower overall rate of complications (OR: 0.59; 95% CI: 0.37, 0.93). There was no significant difference between the groups regarding abdominal discomfort immediately after recovery or 24-hour post-procedure. There was no evidence to indicate higher pressure of CO2 (pCO2) values in the CO2 groups during the procedure when the patients were under sedation anaesthesia. CONCLUSIONS: Compared to air insufflation, CO2 insufflation is currently the preferred method for ERCP and decreases post-procedural abdominal pain and distension without significant side effects.

Tolvaptan regulates aquaporin-2 and fecal water in cirrhotic rats with ascites.

AIM: To investigate the role of tolvaptan in regulating aquaporin (AQP)-2 expression and fecal water content in cirrhotic rats with ascites. METHODS: Cirrhosis with ascites was induced in rats by repetitive dorsal injection of CCl4 for 14 wk. In total, 84 cirrhotic rats with ascites divided into three groups (vehicle, 3 mg/kg and 5 mg/kg tolvaptan), and then further divided into five subgroups (days 1, 2, 3, 4, and 5). Blood samples were obtained to measure vasopressin and sodium concentrations. Rats were killed and colonic mucosa was scraped for analysis of protein expression and AQP-2 transcriptional level. The whole layer was fixed for hematoxylin&eosin (HE) staining and feces were collected for determination of fecal water content. CONCLUSION: Compared with vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2 to a similar level in each treatment group. AQP-2 showed significant upregulation in cirrhotic rats with ascites compared with an untreated control group (100% ± 22.9% vs 22.2% ± 10.23%, P < 0.01). After administration of tolvaptan, AQP-2 expression began to decrease significantly from day 2 in each treatment group, but no significant difference was finally found between the treatment groups. Fecal water content in the distal colon was increased by 5 mg/kg tolvaptan on day 1 (66.8% ± 9.3% vs 41.4% ± 6.3%, in the vehicle group, P < 0.05). Fecal water content returned to baseline at day 4 at the latest in both treatment groups, and did not correspond to the change in AQP-2 expression. HE staining of the colonic mucosa showed no mucosal damage related to tolvaptan. CONCLUSION: Upregulation of AQP-2 in the distal colon is found in cirrhotic rats with ascites. Tolvaptan inhibits its expression and may decrease water reabsorption and induce diarrhea.