Six New Methyl Apiofuranosides from the Bark of Phellodendron chinense Schneid and Their Inhibitory Effects on Nitric Oxide Production.

A chemical investigation on 70% EtOH extract from the bark of Phellodendron chinense Schneid (Rutaceae) led to six new methyl apiofuranosides (1-6), and ten known compounds (7-16). All these compounds were characterized by the basic analysis of the spectroscopic data including extensive 1D-, 2D-NMR (HSQC, HMBC), and high-resolution mass spectrometry, and the absolute configurations were determined by both empirical approaches and NOESY. Inhibitory effects of compounds 1-9 and 11-16 on nitric oxide production were investigated in lipopolysaccharide (LPS)-mediated RAW 264.7 cells, as a result, most of these isolates inhibited nitric oxide (NO) release, and among them 9, 11, and 12 displayed the strongest inhibition on NO release at the concentration of 12.5 µM.

MicroRNA-30b Regulates High Phosphorus Level-Induced Autophagy in Vascular Smooth Muscle Cells by Targeting BECN1.

BACKGROUND/AIMS: Autophagy is an evolutionarily conserved mechanism that affects the survival and functions of vascular smooth muscle cells (VSMCs). We explored the role of microRNAs (miRNAs) in regulating autophagy in VSMCs exposed to high phosphorus (Pi) levels. METHODS: VSMCs were isolated from the thoracic aorta of rats and were cultured primarily. Real-time PCR was used to measure the mRNA expression of indicated genes. Western blotting was performed to detect the protein expression of autophagy-related markers. RESULTS: We found that treatment with high Pi levels (1 and 3 mM) activated LC3II expression and promoted autophagic flux in VSMCs. Conversely, treatment with an autophagy inhibitor decreased LC3II expression. Pi stimulation dysregulated the expression of several miRNAs such as miR-18a, miR-21, miR-23a, miR-30b, and miR-31a. However, miR-30b overexpression decreased Pi-induced expression of autophagy-related marker genes such as BECN1, ATG5, and LC3b, whereas miR-30b downregulation increased Pi-induced expression of these genes. In addition, we found that miR-30b directly targeted BECN1. CONCLUSIONS: These data suggest that miR-30b plays an important role in the regulation of high Pi level-induced autophagy in VSMCs by targeting BECN1.

Phenolic compounds from Bletilla striata.

Two new malic acid derivatives, namely eucomic acid 1-methyl ester (2) and 6'''-acetylmilitaline (7), together with ten known compounds (1, 3-6, 8-12), were isolated from the dry tubers of Bletilla striata (Thunb.) Reichb. F., a perennial traditional Chinese medicinal herb, which was used for the treatment of pneumonophthisis, pneumonorrhagia, tuberculosis, and hemorrhage of the stomach or lung. Their structures were elucidated by spectroscopic analyses, including 1D-, 2D-NMR, and HR-ESI-MS.

High phosphorus level leads to aortic calcification via ß-catenin in chronic kidney disease.

AIMS: Vascular calcification is a risk factor for causing cardiovascular events and has a high prevalence among chronic kidney disease (CKD) patients. However, the molecular mechanism underlying this pathogenic process is still obscure. METHODS: Vascular smooth muscle cells (VSMCs) were induced by a concentration of phosphorus (Pi) of 2.5 mM, and were subjected to cell calcification analyses. The effect of high Pi on the Wnt/ß-catenin pathway was measured using a TOP/FOP-Flash reporter assay. The transcriptional regulation of ß-catenin on PIT1 (a type III sodium-dependent phosphate cotransporter) was confirmed by promoter reporter and chromatin immunoprecipitation assays. The 5/6 nephrectomized rat was used as an in vivo model and was fed a high Pi diet to induce aortic calcification. Serum levels of phosphate, calcium, creatine, and blood urea nitrogen were measured, and abdominal aortic calcification was examined. RESULTS: High Pi induced VSMC calcification, downregulated expression levels of VSMC markers, and upregulated levels of osteogenic markers. High Pi activated the Wnt/ß-catenin pathway and ß-catenin activity. ß-Catenin was involved in the process of high Pi-induced VSMC calcification. Further investigation revealed that ß-catenin transcriptionally regulated Pit1, a necessary player in VSMC osteogenic phenotype change and calcification. The in vivo study showed that ß-catenin was involved in rat abdominal aortic calcification induced by high Pi. When knockdown expression of ß-catenin in the rat model was investigated, we found that aortic calcification was reduced. CONCLUSION: These results suggest that ß-catenin is an important player in high phosphorus level-induced aortic calcification in CKD.

ω-3 fatty acids therapy for IgA nephropathy: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of omega-3 fatty acids (O3FA) in IgA nephropathy remains a controversial issue. The aim of the current updated meta-analysis is to assess the efficacy of O3FA treatment for adult IgA nephropathy. METHODS: We searched PubMed/MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials that compared O3FA treatments with placebo or no treatment in adult IgA nephropathy. Outcomes of interest were effects on urine protein excretion (UPE) and renal function. RESULTS: Five RCTs (239 patients) were included for analysis. Compared with control groups, O3FA treatments did not show significant benefits for reducing UPE (standardized mean difference (SMD), -0.111; 95% confidence interval (CI), -0.369 - 0.147) or improving glomerular filtration rate (GFR) or estimated GFR (SMD, 0.177; 95% CI, -0.082 - 0.435), although the pooled results slightly favored O3FA. On the other hand, a lower risk of an increase of 50% or more in serum creatinine and ESRD were found in O3FA-treated IgA nephropathy patients (RR 0.189; 95% CI 0.068 - 0.524, p = 0.001; RR 0.236; 95% CI 0.094 - 0.594, p = 0.002), but the two outcomes were reported in only two trials. CONCLUSION: The current metaanalysis suggests that there are insufficient data to confirm the efficacy of O3FA treatments for proteinuria and renal function in IgA nephropathy. Further large scale trials are needed to shed more light on this issue.

Determination of atropisomeric configurations of macrocyclic bisbibenzyls by HPLC-CD/UV and quantum chemical calculations.

Isoriccardin C (1) and riccardin D (2), isolated from the liverwort Reboulia hemisphaerica, were first characterized to be a mixture of two enantiomeric atropisomers by online chiral high-performance liquid chromatography-circular dichroism (HPLC-CD) analysis. Exemplarily for bisbibenzyls of the diarylether-biphenyl type, the absolute atropisomeric configurations of compunds 1 and 2 were determined by the analysis of their CD data coupled with quantum chemical CD calculations.

Aromatic compounds from the liverwort Conocephalum japonicum.

Two undescribed dimeric ArC2 derivatives, cis- and trans-1,2-bis(3,4-dimethoxyphenyl)cyclobutane (1 and 2), one new monoterpenes esters, 2alpha,5beta-dihydroxybornane-2-cis-cinnamate (3), along with eight known compounds, 2alpha,5beta-dihydroxybornane-2-trans-cinnamate (4), perrottetin E (5), isoriccardin C (6), marchantin A (7), marchantin E (8), marchantin C (9), and isomarchantin C (10) were isolated from the liverwort Conocephalum japonicum. All the structures were established by extensive spectroscopic analysis. The isolated compounds 3-10 were evaluated for their cytotoxicity against the human KB cell line with IC50 values ranging from 16.5 to 50.2 microM.