Gypenoside LXXV Alleviates Colitis by Reprograming Macrophage Polarization via the Glucocorticoid Receptor Pathway.

An imbalance in the macrophage phenotype is closely related to various inflammatory diseases. Here, we discovered that gypenoside LXXV (GP-75), a type of saponin from Gynostemma pentaphyllum, can reprogram M1-like macrophages into M2-like ones. On a mechanistic level, GP-75 inhibits NF-κB-COX2 signaling by targeting the glucocorticoid receptor (GR). Administration of GP-75, either orally or by intraperitoneal injection, significantly alleviates ulcerative colitis in mice, a pathogenesis associated with macrophage polarization. Clodronate liposomes, which deplete macrophages in mice, as well as GR antagonist RU486, abrogate the anticolitis effect of GP-75, thus confirming the pivotal role of macrophages in GP-75 function. We also showed that GP-75 has no toxicity in mice. Overall, this is the first report that demonstrates the effect of GP-75 on macrophage reprograming and as an agent against colitis. Because G. pentaphyllum is gaining popularity as a functional food, our findings offer new perspectives on the use of gypenosides as potential nutraceuticals for medical purposes.

Simultaneous Determination of 25 Ginsenosides by UPLC-HRMS via Quantitative Analysis of Multicomponents by Single Marker.

A method using UPLC-HRMS has been developed for a rapid, simultaneous qualitative and quantitative analysis of twenty-five ginsenosides. Chromatographic separation was achieved on a C18 analytical column with an elution gradient comprising 0.1% aqueous formate/acetonitrile as the mobile phase. HRMS detection acquired full mass data for quantification and fullms-ddms2 (i.e., data-dependent scan mode) yielded product ion spectra for identification. Furthermore, quantitative analysis of multiginsenosides by single marker (QAMS) was developed and validated using a relative correction factor. Under optimal conditions, we could simultaneously separate eight groups of isomers of the 25 ginsenosides. Good linearity was observed over the validated concentration range for each analyte (r 2 > 0.9924), showing excellent sensitivity (LODs, 0.003-0.349 ng/mL) and lower limit quantification (LOQs, 0.015-1.163 ng/mL). The LC-MS external standard method (ESM) and QAMS were compared and successfully applied to analyze the ginsenoside content from Panax ginseng roots. Overall, our UPLC-HRMS/QAMS approach provides high precision, stability, and reproducibility and can be used for high-throughput analysis of complex ginsenosides and quantitative analysis of multiple components and quality control of traditional Chinese medicines (TCM).

Lack of association between the Angiogenin (ANG) rs11701 polymorphism and amyotrophic lateral sclerosis risk: a meta-analysis.

To perform a meta-analysis to help resolve the controversy of whether the Angiogenin (ANG) rs11701 polymorphism is associated with amyotrophic lateral sclerosis (ALS) risk. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang and SinoMed was conducted for eligible studies published up to Jun 5, 2015. The strength of the association between the polymorphism and ALS susceptibility was estimated by odds ratio (OR) and associated 95 % confidence interval (CI). The pooled ORs were assessed for the dominant model (TG + GG vs. TT), recessive model (GG vs. TG + TT), heterozygote model (TG vs. TT), homozygote model (GG vs. TT) and allele model (G vs. T). Ten eligible articles were identified, which reported 14 case-control studies and a total of 5807 cases and 3861 controls. Analysis of pooled ORs and 95 % CIs suggested lack of association between the ANG rs11701 polymorphism and risk for ALS, Familial ALS or Sporadic ALS (all p value for z test >0.05). A stratified analysis according to Caucasian or Han Chinese origin further showed that the rs11701 polymorphism was not associated with the disease risk in Caucasians or Han Chinese. There is no difference in the polymorphism frequencies between patients with FALS or SALS. The ANG rs11701 polymorphism was not associated with risk for ALS, FALS or SALS. There is no difference between the polymorphism frequencies in patients with FALS or SALS. Further well-designed studies with larger populations are required to validate these results.

Lack of association between the ATP13A2 A746T variant and Parkinson's disease susceptibility in Han Chinese: a meta-analysis.

PURPOSE: To perform a meta-analysis to help resolve the controversy of whether the ATP13A2 A746T variant is associated with Parkinson's disease (PD) susceptibility in Han Chinese. METHODS: Six literature databases were searched for case-control studies published up to October 2014: Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang and SinoMed. RESULTS: Five eligible articles were identified, which reported six case-control studies and a total of 1703 cases and 2050 controls. The overall results suggested low frequencies of the A746T variant in Han Chinese patients (9/1703, 0.55%) and controls (6/2050, 0.29%). We failed to find evidence of significant differences in variant frequencies among Han Chinese, Uyghur and Japanese patients (p = 0.263). Analysis of pooled odds ratios (ORs) and 95% confidence interval (CIs) revealed no association between the A746T variant and overall PD risk (GA vs. GG: OR 1.78, 95%CI 0.71-4.46, p = 0.216; allele A vs. G: OR 1.90, 95%CI 0.77-4.69, p = 0.167). CONCLUSION: The ATP13A2 A746T variant is rare in Han Chinese patients and controls and is not associated with PD susceptibility in this ethnic group. Variant frequencies do not differ significantly among Han Chinese, Uyghur and Japanese patients. Further well-designed studies with larger samples are needed to validate these results.

Association between the Angiogenin (ANG) K17I variant and amyotrophic lateral sclerosis risk in Caucasian: a meta-analysis.

The study purpose is to perform a meta-analysis to help resolve the debate of whether the Angiogenin (ANG) K17I variant is associated with amyotrophic lateral sclerosis (ALS) risk in Caucasian. Three literature databases were searched for eligible studies published up to January 8, 2015: PubMed, Embase and Web of Science using the following search terms: amyotrophic lateral sclerosis or ALS and Angiogenin or ANG. Five eligible articles were identified, which reported 6 case-control studies and a total of 2326 cases and 3799 controls. The overall results suggested low frequencies of the K17I variant in Caucasian patients (10/2326, 0.43 %) and controls (6/3799, 0.16 %). There is no difference in the variant frequencies between patients with FALS or SALS (p = 0.069). Analysis of pooled odds ratios (ORs) and 95 % confidence intervals (CIs) revealed that the ANG K17I variant increases the risk for ALS (AT vs. AA: OR 2.65, 95 % CI 1.05-6.66, p = 0.038) and familial ALS (FALS) (AT vs. AA: OR 11.81, 95 % CI 2.11-66.15, p = 0.005) but not for sporadic ALS (SALS) (AT vs. AA: OR 1.63, 95 % CI 0.55-4.82, p = 0.378). The ANG K17I variant is rare in Caucasian patients and controls and increases the risk for ALS and FALS but not for SALS in Caucasian populations. Further well-designed studies with larger samples are needed to validate these results.