Indole-3-Carboxylic Acid From the Endophytic Fungus Lasiodiplodia pseudotheobromae LPS-1 as a Synergist Enhancing the Antagonism of Jasmonic Acid Against Blumeria graminis on Wheat.

The discovery of natural bioactive compounds from endophytes or medicinal plants against plant diseases is an attractive option for reducing the use of chemical fungicides. In this study, three compounds, indole-3-carbaldehyde, indole-3-carboxylic acid (3-ICA), and jasmonic acid (JA), were isolated from the EtOAc extract of the culture filtrate of the endophytic fungus Lasiodiplodia pseudotheobromae LPS-1, which was previously isolated from the medicinal plant, Ilex cornuta. Some experiments were conducted to further determine the antifungal activity of these compounds on wheat powdery mildew. The results showed that JA was much more bioactive than indole-3-carbaldehyde and 3-ICA against Blumeria graminis, and the disease severity caused by B. graminis decreased significantly with the concentration increase of JA treatment. The assay of the interaction of 3-ICA and JA indicated that there was a significant synergistic effect between the two compounds on B. graminis in each of the ratios of 3-ICA to JA (3-ICA:JA) ranging from 1:9 to 9:1. When the compound ratio of 3-ICA to JA was 2:8, the synergistic coefficient was the highest as 22.95. Meanwhile, a histological investigation indicated that, under the treatment of JA at 500 µg/ml or 3-ICA:JA (2:8) at 40 µg/ml, the appressorium development and haustorium formation of B. graminis were significantly inhibited. Taken together, we concluded that JA plays an important role in the infection process of B. graminis and that 3-ICA as a synergist of JA enhances the antagonism against wheat powdery mildew.

Serum ω-3 Polyunsaturated Fatty Acids and Potential Influence Factors in Elderly Patients with Multiple Cardiovascular Risk Factors.

Recent clinical trials failed to demonstrate that ω-3 polyunsaturated fatty acid (PUFA) supplement reduced cardiovascular events, which contradicted previous evidence. However, serum ω-3 PUFA concentrations of participants remained unclear in those studies. We aimed to investigate the definite relationship between serum concentrations of ω-3 PUFAs and coronary artery disease (CAD), and to explore the potential influence factors of ω-3 PUFAs. We selected Chinese in-patients (n = 460) with multiple cardiovascular risk factors or an established diagnosis of CAD. Serum ω-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were measured by liquid chromatography mass spectrometry. Serum concentrations of ω-3 PUFAs in CAD patients were lower than that in patients with cardiovascular risk factors. Furthermore, high serum DHA concentration was an independent protective factor of CAD after adjustment for confounding factors (OR: 0.52, p = 0.014). Alcohol intake (p = 0.036) and proton pump inhibitor (PPI) usage (p = 0.027) were associated with a decreased serum ω-3 PUFA concentration. We conclude that serum concentrations of ω-3 PUFAs may associate with a decreased CAD proportion, and DHA may serve as a protective factor of CAD. Serum ω-3 PUFA concentrations may be reduced by alcohol intake and certain drugs like PPIs.

Synthesis of Pyrido-Fused Quinazolinone Derivatives via Copper-Catalyzed Domino Reaction.

A simple and efficient synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones by Cu(OAc)2·H2O-catalyzed reaction of easily available substituted isatins and 2-bromopyridine derivatives has been developed. The reaction involves C-N/C-C bond cleavage and two C-N bond formations in a one-pot operation. This methodology is complementary to previously reported synthetic procedures, and two plausible reaction mechanisms are discussed.

Evening -versus morning- dosing drug therapy for chronic kidney disease patients with hypertension: a systematic review.

BACKGROUND/AIMS: There is a strong correlation between non-dipping status and cardiovascular events in chronic kidney disease (CKD) patients. Our study is designed to identify the effect of evening administration of antihypertensive drugs to hypertensive CKD patients. METHODS: A comprehensive search of Medline, Embase, the Chinese Biomedical Literature Database, Wanfang Data, Chinese National Knowledge Infrastructure, and the Cochrane Central Register of Controlled Trials was performed in July 2014. Concurrent controlled or crossover trials (including randomized and non-randomized experimental trials) designed to evaluate the effects of evening- versus morning-dosing hypertensive drug regimens on clinical outcomes in CKD patients with hypertension were included. All statistical analyses were performed using the RevMan software, which is available free from the Cochrane Collaboration. RESULTS: Seven trials involving 1277 patients were identified, and the randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) were classified into two groups. Taking at least one blood pressure-lowering medication at bedtime was not shown to reduce total death (P=0.056) or cardiovascular death (P=0.059) but was shown to reduce total events (P<0.001) and major cardiovascular events (P<0.001) in both RCTs and non-RCTs. Compared with a morning dosing regimen, taking antihypertensive drug in the evening significantly lowered nighttime systolic blood pressure (SBP) (P<0.0001) and diastolic blood pressure (P<0.05) in patients in the RCTs but did not affect blood pressure in patients in the non-RCTs (P<0.05). There is limited evidence from one non-RCT that taking an antihypertensive drug (benazepril 10 mg) in the evening did not increase adverse events (P=0.72) or withdrawals due to adverse events (P=0.64). CONCLUSIONS: A regimen of antihypertensive drugs in the evening should be considered for CKD patients with hypertension to lower nighttime blood pressure and help prevent total events and cardiovascular mortality. More studies are needed to verify the results of this study.

Shenyuan, an extract of American Ginseng and Corydalis Tuber formula, attenuates cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and oxidative stress in a porcine model of acute myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of American Ginseng and Corydalis Tuber has been widely used for treatment of cardiovascular diseases due to their anti-ischemic and anti-arrhythmic effects. The aim of this study is to evaluate the anti-apoptotic effect of Shenyuan, which is composed of the bioactive components extracted from the mixture of American Ginseng and Corydalis Tuber, and to explore potential mechanisms involved in the regulation of apoptosis. MATERIALS AND METHODS: A porcine model of acute myocardial infarction (AMI) was established by ligation of the left anterior descending coronary artery. Thirty-eight pigs were randomized into six groups: Group S, sham (n=6); Group C, AMI controls (n=8); Group L, AMI+low-dose Shenyuan (240 mg/kg·d, n=6); Group M, AMI+moderate-dose Shenyuan (320 mg/kg·d, n=6); Group H, AMI+high-dose Shenyuan (400 mg/kg·d, n=6); Group B, AMI+Metoprolol Tartrate (1 mg/kg·d, n=6). The treatment of Shenyuan or Metoprolol started one week before AMI and continued for another two weeks after AMI. RESULTS: Treatment with all doses of Shenyuan as well as Metoprolol produced a significant decrease of apoptotic index (P < 0.05), which was confirmed by TUNEL staining method. This anti-apoptotic effect was accompanied by less release of cardiac enzymes and limit of infarct size. In Group H, levels of MDA, 8-iso-prostaglandin F2α, GRP78/bip, calregulin, CHOP/GADD153, Bax, caspase-3, cleaved caspase-3 and activity of caspase-3 were reduced, while GSH, SOD, Bcl-2 and the Bcl-2/Bax ratio were significantly increased (P < 0.05). In groups M and L, some results did not show statistical difference. There was no statistical difference in cardiac function between treatment groups and Group C. CONCLUSION: Shenyuan treatment significantly inhibited ERS and oxidative stress, balanced the Bcl-2/Bax ratio, suppressed activation of caspase-3, and finally exerted an anti-apoptotic effect in pigs with a large anterior wall AMI. This was accompanied by less release of cardiac enzymes and limit of infarct size. Shenyuan treatment inhibited apoptosis and may have a therapeutic role in improving the natural process of AMI.

Effective Components of Panax quinquefolius and Corydalis tuber Protect Myocardium through Attenuating Oxidative Stress and Endoplasmic Reticulum Stress.

Both oxidative stress and endoplasmic reticulum stress (ERS) have been implicated in carcinogenesis and neurological diseases, while there are few reports about the mechanisms of them in the progression of acute myocardial infarction (AMI). This study examined oxidative stress and ERS in a rat model of AMI and evaluated their role in therapy by metoprolol and effective components of Panax quinquefolius and Corydalis tuber (EPC). In the present study a rat model of AMI was established by ligation of the left anterior descending coronary artery. After oral administration of metoprolol or low-to-high doses of EPC for 2 weeks, serum malondialdehyde (MDA), superoxide dismutase (SOD), and 8-iso-prostaglandin F2 α (8-iso-PGF2 α ) were detected using enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR and Western blotting were used to examine mRNA and protein expressions of the hallmarks of ERS-glucose-regulated protein-78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP). We confirmed that both metoprolol and moderate-to-high dose of EPC decreased 8-iso-PGF2 α serum level and downregulated the mRNA and protein expressions of GRP78 and CHOP in myocardium, while EPC also increased SOD serum level. These results indicated that metoprolol and EPC protect the myocardium by attenuating oxidative stress and ERS induced by myocardial infarction, highlighting the ERS pathways as potential therapeutic targets for AMI.

Xuezhikang, extract of red yeast rice, improved abnormal hemorheology, suppressed caveolin-1 and increased eNOS expression in atherosclerotic rats.

BACKGROUND: Xuezhikang is the extract of red yeast rice, which has been widely used for the management of atherosclerotic disease, but the molecular basis of its antiatherosclerotic effects has not yet been fully identified. Here we investigated the changes of eNOS in vascular endothelia and RBCs, eNOS regulatory factor Caveolin-1 in endothelia, and hemorheological parameters in atherosclerotic rats to explore the protective effects of Xuezhikang. METHODOLOGY/PRINCIPAL FINDINGS: Wistar rats were divided into 4 groups (n = 12/group) group C, controls; group M, high-cholesterol diet (HCD) induced atherosclerotic models; group X, HCD+Xuezhikang; and group L, HCD +Lovastatin. In group X, Xuezhikang inhibited oxidative stress, down-regulated caveolin-1 in aorta wall (P<0.05), up-regulated eNOS expression in vascular endothelia and erythrocytes (P<0.05), increased NOx (nitrite and nitrate) in plasma and cGMP in erythrocyte plasma and aorta wall (P<0.05), increased erythrocyte deformation index (EDI), and decreased whole blood viscosity and plasma viscosity (P<0.05), with the improvement of arterial pathology. CONCLUSIONS/SIGNIFICANCE: Xuezhikang up-regulated eNOS expression in vascular endothelia and RBCs, increased plasma NOx and improved abnormal hemorheology in high cholesterol diet induced atherosclerotic rats. The elevated eNOS/NO and improved hemorheology may be beneficial to atherosclerotic disease.

Xuezhikang, extract of red yeast rice, inhibited tissue factor and hypercoagulable state through suppressing nicotinamide adenine dinucleotide phosphate oxidase and extracellular signal-regulated kinase activation.

Xuezhikang, extract of red yeast rice, is a traditional Chinese medicine with multiple cardioprotective effect. It contains a family of naturally occurring statins, such as lovastatin. Tissue factor (TF) is overexpressed in macrophages of lipid core plaques, which display high procoagulant activity and seem to be a potentially target for anti-atherothrombosis. Therefore, the purpose of this study was to explore the effect and possible molecular mechanisms of xuezhikang on inhibiting TF expression and hypercoagulable state and the differences compared with lovastatin. Our results showed that xuezhikang significantly suppressed oxidized low-density lipoprotein-induced TF expression in macrophages in a concentration-dependent manner. Xuezhikang reduced nicotinamide adenine dinucleotide phosphate oxidase activity by decreasing membrane translocation of p47 through inhibition of extracellular signal-regulated kinase 1/2 activation. Nicotinamide adenine dinucleotide phosphate inhibitor (diphenyleneiodonium) also inhibited the oxidized low-density lipoprotein-induced TF expression, similar to the effects of xuezhikang. Furthermore, consistent with the severity of aortic atherosclerosis, xuezhikang (300 mg·kg·d) significantly reduced blood coagulation activation and TF expression in high-cholesterol diet-induced atherosclerotic rats. In addition, xuezhikang was more potent than lovastatin on inhibiting the expression of TF and nicotinamide adenine dinucleotide phosphate oxidase activation. These observations provide evidences that inhibition of xuezhikang on hypercoagulation and TF expression may partly account for its cardioprotective benefits.