Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis through PI3K/Akt Signaling Pathway.

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.

Anti-Toxoplasma gondii agent isolated from Orostachys malacophylla (Pallas) Fischer.

Botanical medicinal plants have aroused our interest to deal with Toxoplasmosis which can causes serious public health problems. Nipagic acid, gallic acid, ethyl gallate, phloretic acid, protocatechuic acid, methyl p-coumarate, arbutin, and homoprotocatechuic acid are first isolated from Orostachys malacophylla (Pallas) Fischer, their inhibition rate, survival rate, biochemical and viscera index are evaluated using gastric epithelia strain-1(GES-1). Among them, arbutin can effectively prolong the survival time of mice acutely infected with T. gondii, and exhibit the same curative effect as Spiramycin (Spi) group in terms of the glutathione (GSH) and malondialdehyde (MDA) content, alleviate hepatomegaly and splenomegaly. Structure-activity relationship (SAR) and molecular docking implies that phenolic hydroxyl group would be preferred for improvement of activity. In a summary, arbutin is a potential anti-T. gondii candidate for clinical application.

Arctigenin: pharmacology, total synthesis, and progress in structure modification.

Arctium lappa L. is a prevalent medicinal herb and a health supplement that is commonly used in Asia. Over the last few decades, the bioactive component arctigenin has attracted the attention of researchers because of its anti-inflammatory, antioxidant, immunomodulatory, multiple sclerosis fighting, antitumor, and anti-leukemia properties. After summarising the research and literature on arctigenin, this study outlines the current status of research on pharmacological activity, total synthesis, and structural modification of arctigenin. The purpose of this study is to assist academics in obtaining a more comprehensive understanding of the research progress on arctigenin and to provide constructive suggestions for further investigation of this useful molecule.

Research and Development of Natural Product Tanshinone I: Pharmacology, Total Synthesis, and Structure Modifications.

Salvia miltiorrhiza (S. miltiorrhiza), which has been used for thousands of years to treat cardiovascular diseases, is a well-known Chinese medicinal plant. The fat-soluble tanshinones in S. miltiorrhiza are important biologically active ingredients including tanshinone I, tanshinone IIA, dihydrotanshinone, and cryptotanshinone. Tanshinone I, a natural diterpenoid quinone compound widely used in traditional Chinese medicine, has a wide range of biological effects including anti-cancer, antioxidant, neuroprotective, and anti-inflammatory activities. To further improve its potency, water solubility, and bioavailability, tanshinone I can be used as a platform for drug discovery to generate high-quality drug candidates with unique targets and enhanced drug properties. Numerous derivatives of tanshinone I have been developed and have contributed to major advances in the identification of new drugs to treat human cancers and other diseases and in the study of related molecular mechanisms. This review focuses on the structural modification, total synthesis, and pharmacology of tanshinone I. We hope that this review will help understanding the research progress in this field and provide constructive suggestions for further research on tanshinone I.

Crowberry inhibits cell proliferation and migration through a molecular mechanism that includes inhibition of DEK and Akt signaling in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CCA) is a rare biliary adenocarcinoma related to poor clinical prognosis. Crowberry is an herbal medicine used to control inflammatory diseases and reestablish antioxidant enzyme activity. Although crowberry shows significant therapeutic efficacy in various tumors and diseases, its anticancer effects and specific molecular mechanisms in CCA are poorly understood. AIM OF THE STUDY: This study was conducted to characterize crowberry effects on CCA cells behavior. MATERIALS AND METHODS: The chemical profiles of crowberry extract was qualitatively analyzed by high-performance liquid chromatography (HPLC) and HPLC-tandem mass spectrometry. MTT, colony formation and EdU assays were performed to measure cell proliferation. The effect of crowberry treatment on CCA cell migration was assessed by wound healing and migration assays. Moreover, Hoechst staining assay and flow cytometry were performed to assess the cell apoptosis rate. Western blotting was used to assess the protein expression levels of key factors associated with apoptosis, the Akt signaling pathway, and the epithelial-mesenchymal transition. A xenograft model was established and immunohistochemical and H&E staining was performed to assess crowberry antitumor effects in vivo. RESULTS: Crowberry clearly inhibited CCA cells proliferation and migration in a dose-dependent manner and induced apoptosis in vitro. Crowberry inactivated the PI3K/Akt signaling pathway by regulating DEK in vitro and significantly inhibited tumor growth by downregulating the DEK expression in xenograft models. CONCLUSION: Crowberry inhibits CCA cells proliferation and migration through a molecular mechanism that includes inhibition of DEK and Akt signaling pathway inhibition in vitro and in vivo.

Anti-hypertensive and endothelia protective effects of Fufang Qima capsule on primary hypertension via adiponectin/adenosine monophosphate activated protein kinase pathway.

OBJECTIVE: To investigate the potential mechanism of the vascular remodeling effect and provide additional information about anti-hypertension activity of Fufang Qima capsule. METHODS: Spontaneous hypertensive rats (SHRs) were used to study the underlying mechanism of the anti-hypertension activity of QM. In this study, SHRs were randomly divided into 5 groups: model group, Telmisartan group (7.2 mg/kg, p.o.), and three QM groups (0.9298, 1.8596, and 3.7192 g/kg, p.o.). Wistar Kyoto rats (WKY) were used as normal control group. Blood pressure (BP), aorta, perivascular adipose tissue (PVAT) histology were investigated to evaluate the effect of QM. Nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) phosphorylation were measured. Adiponectin (APN) secretion, as well as APN signal pathway proteins including APN, adiponectin receptors (R1 and R2) and adenosine 5'-monophosphate-activated protein kinase (AMPK) were all analyzed. RESULTS: QM significantly reduced BP and ameliorated the vascular pathological change, i.e. intima media thicken and collagen fiber hyperplasia. Meanwhile, QM increased concentration of NO and the phosphorylation of eNOS in the aorta. The anti-hypertensive and endothelia-protective effect of QM could be attributed to activating APN/ AMPK pathway by up-regulating the expression of APN in PVAT and APN Receptor 2, AMPKα and phosphorylated AMPKα in the aorta. CONCLUSION: The QM alleviation effect mechanism for primary hypertension was via modulating the APN/AMPK signal pathway.

Rapid measurement of total polyphenol content in tea by kinetic matching approach on microfluidic paper-based analytical devices.

In this work, a facile kinetic matching approach for total polyphenol content (TPC) measurement was developed based on the adoption of microfluidic paper-based analytical devices with symmetric channel distribution. A set of Folin-Ciocalteu reactions performed on the same paper chip were activated all at the same time through synchronized filling of sodium carbonate solution among individual channels. Gallic acid was found valid as a standard compound for kinetic matching measurement of tea samples. TPC of tea infusions was successfully measured within ten minutes without any complexed time control procedure needed. Under the optimized conditions, the new developed method showed good linearity in the TPC range of 10-100 mg/L (r > 0.9955) and the inter-chip precision was 5.6% (n = 11). The results measured with the new developed approach were in good agreement with those with the conventional FC assay.

Assessment of Cultural Competence Among Nurses: The Need Of Hour.

Cultural competence and skills are the major part of professionalism a nurse should achieve to provide the best quality health care without hurting the culturally sensitive issues in all aspects. This review focused on the assessment of cultural competence and skills among nursing professionals. Assessment of these skills is very much necessary for accountability as well as improving the capability among the nurses or nursing professionals. Many tools are developed across the world including many region-specific. These tools can be employed for the self-assessment to know the self-competency and to assess the effectiveness of training programs among the professionals.

Influence of sulfate reduction on fraction and regeneration of phosphorus at sediment-water interface of urban malodorous river.

The effective control of the release of endogenous phosphorus is an urgent problem in the management of urban malodorous rivers. This research explored the fraction and regeneration of phosphorus of urban malodorous river in the context of sulfate reduction. It was found that sulfate reduction could promote sediment phosphorus release. The contents of total phosphorus (TP) and soluble reactive phosphorus (SRP) in the overlying water presented a decreasing trend after the initial increase during the operation of 120 days. The phosphorus release was positively related to the input of sulfate, and the maximum values of TP and SRP (14.01 mg/L and 12.27 mg/L, respectively) in the overlying water were observed when 8 mM Na2SO4 was added. Moreover, the addition of sulfate could significantly affect the distribution of phosphorus fraction in the sediment and promote the transformation of moderately active phosphorus (NaOH-P, D. HCI-P) to more active phosphorus Resin-P), which resulted in more release of phosphorus to the overlying water. In addition, it was observed that sulfate input could increase the relative abundance of phosphate solubilizing bacteria (PSB) and sulfate-reducing bacteria (SRB) from 0.69 to 1.1% and 4.92 to 9.03%, respectively.

Potential α-glucosidase inhibitor from Hylotelephium erythrostictum.

In light of the adequate sources for Hylotelephium erythrostictum, its active components have aroused research interest. 2-(3',4'-dihydroxyphenyl)-2,3-dihydro-4,6-dihydroxy-2-(methoxy)- 3-benzofuranone(1), apigenin(2), diosmetin(3), kaempferol(4), kaempferide(5), rhamnocitrin(6), quercetin(7), and gallic acid(8) were isolated from H. erythrostictum. Rarely occurring naturally, 1 is 2-methoxybenzofuranone type compound against α-glucosidase and exhibits a potential inhibitory effect on α-glucosidase(IC50 = 1.8 µM), with a Ki value of 709 nM. In silico molecular docking was performed for the investigation of the inhibition mechanism. H. erythrostictum is a potential source of antidiabetic agent. This information is useful in finding more potent antidiabetic candidates from medicinal plants for the clinical development of therapeutics.

Determination of polychlorinated biphenyls in tea using gas chromatography-tandem mass spectrometry combined with dispersive solid phase extraction.

A gas chromatography-tandem mass spectrometry method was developed for simultaneous determination of 38 polychlorinated biphenyls (PCBs) in tea. Sample preparation was based on a dispersive solid phase extraction procedure through an extraction of target compounds. An appropriate amount of polyvinylpolypyrrolidone was directly added in tea extractions to effectively remove polyphenols, and then tea extracts were cleaned up with primary secondary amine, florisil and graphitised carbon black. The method was validated, and linearity with correlation coefficients higher than 0.99 was obtained. Satisfactory recoveries at 2, 10, 50, and 100 µg kg-1 ranged from 71% to 117% with a maximum relative standard deviation of 23%, except for PCB 81, 77, 126 and 169, of which recoveries were in the range of 32%-63%. Limits of quantitation for PCBs were 2 or 10 µg kg-1, which was set as the lowest validated and spiked level meeting the acceptable accuracy and precision.

A method based on precolumn derivatization and ultra high performance liquid chromatography with high-resolution mass spectrometry for the simultaneous determination of phthalimide and phthalic acid in tea.

Phthalimide can be formed from either the degradation of folpet and phosmet, or reaction of phthalic anhydride with primary amino groups. Consequently, the sum of phthalimide and folpet, expressed as folpet-residue definition, is highly prone to false-positive levels of folpet in tea. An analytical method is thus urgently needed to investigate the residue level and source of phthalimide in tea. In this work, we developed an accurate method of determining phthalimide and phthalic acid (the indicator of phthalic anhydride) by acetonitrile extraction and 3-bromopropyltrimethylammonium bromide derivatization coupled with ultra high performance liquid chromatography and high-resolution mass spectrometry. The method was validated, and linearity (correlation coefficients > 0.99) was obtained. Satisfactory recoveries at 10, 20, 50, and 100 µg/kg ranged from 76 to 117%, and the intra- and interday accuracies were <23%. The limit of quantification for phthalimide and phthalic acid was 10 µg/kg. The developed method was further successfully used to determine phthalimide and phthalic acid in some tea samples. The positive rate of phthalimide and phthalic acid detected in the tea samples ranged from 30-75 and 50-90%, respectively.

A randomized, double-blind, multicenter, placebo-controlled clinical study on the efficacy and safety of Shenmai injection in patients with chronic heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenmai injection (SMI) is a traditional Chinese herbal medicine extracted from Panax ginseng (Panax ginseng C.A. Mey, steamed and dry) and Ophiopogon japonicus (Ophiopogon japonicus (L.f.) Ker-Gawl, root). It has been widely used for the treatment of chronic heart failure (CHF) in China. However, the evidence supporting its effects remains unclear due to lack of high quality trials. The aim of this study was to investigate the efficacy and safety of SMI in CHF patients with coronary artery disease (CAD). MATERIALS AND METHODS: This double-blind, multicenter study randomized 240 eligible patients equally to receive SMI or placebo (100ml/day) in addition to standard medicines for the treatment of CHF. The primary endpoint was the New York Heart Association (NYHA) functional classification. The secondary endpoints were 6-min walking distance (6MWD), short-form 36 (SF-36) hearth survey score, traditional Chinese medicines (TCM) syndrome score, left ventricular ejection fractions (LVEF) and B-type natriuretic peptide (BNP) level. RESULTS: During treatment of 1 week, the NYHA functional classification was gradually improved in both groups, but the SMI group demonstrated a significantly greater improvement compared with the placebo group (p=0.001). Moreover, the improvement in patients received SMI was superior to those in control group with respect to 6MWD, SF-36 score and TCM syndrome score. Treatment with SMI within 1 week was well tolerated with no apparent safety concerns. CONCLUSIONS: The integrative treatment with standard medicines plus SMI can further improve NYHA functional classification for patients with CHF and CAD. Therefore, SMI could be recommended in the combination therapy for CHF accompanied with CAD.

Antiparasitic effects of oxymatrine and matrine against Toxoplasma gondii in vitro and in vivo.

Toxoplasma gondii (T. gondii) is an important pathogen which can causes serious public health problems. Since the current therapeutic drugs for toxoplasmosis present serious host toxicity, research on effective and new substances of relatively low toxicity is urgently needed. This study was carried out to evaluate the anti-parasitic effect of oxymatrine (OM) and matrine (ME) against T. gondii in vitro and in vivo. In our study, the anti-T. gondii activities of ME and OM were evaluated in vitro using cell counting kit-8 assay, morphological observation and trypan blue exclusion assay. In vivo, mice were sacrificed four days post-infection and ascites were drawn out to determine the extent of tachyzoite proliferation. Viscera indexes and liver biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione (GSH) and malondialdehyde (MDA), were examined to evaluate the toxicity of compounds to mice. As a result, OM and ME showed anti-T. gondii activity but low selectivity toxicity to HeLa cells. Both compounds also significantly decreased the number of tachyzoites in peritoneal cavity and recovered the levels of ALT, AST, GSH and MDA in liver. Moreover, the mice treated with OM or ME achieved better results in viscera index and survival rate than that of spiramycin. These results suggest that OM and ME are likely the sources of new drugs for toxoplasmosis, and further studies will be necessary to compare the efficacy of drug combination, as well as identify its action of mechanism.

An update of novel screening methods for GPCR in drug discovery.

INTRODUCTION: G protein-coupled receptors (GPCRs) are the largest and most versatile group of cytomembrane receptors, comprising of approximately 300 non-sensory and druggable members. Traditional GPCR drug screening is based on radiometric competition binding assays, which are expensive and hazardous to human health. Furthermore, the paradox of high investment and low output, in terms of new drugs, highlights the need for more efficient and effective drug screening methods. AREAS COVERED: This review summarizes non-radioactive assays assessing the ligand-receptor binding including: the fluorescence polarization assay, the TR-FRET assay and the surface plasmon resonance assay. It also looks at non-radioactive assays that assess receptor activation and signaling including: second messenger-based assays and ß-arrestin recruitment-based assays. This review also looks at assays based on cellular phenotypic change. EXPERT OPINION: GPCR signaling pathways look to be more complicated than previously thought. The existence of receptor allosteric sites and multireceptor downstream effectors restricts the traditional assay methods. The emergence of novel drug screening methods such as those for assessing ß-arrestin recruitment and cellular phenotypic change may provide us with improved drug screening efficiency and effect.

5 alpha-reductase and aromatase inhibitory constituents from Brassica rapa L. pollen.

In the screening of biologically active constituents from Brassica rapa pollen, the supercritical CO(2) fluid extract (SFE-CO(2)) showed potent 5 alpha-reductase and aromatase inhibiting activity. The SFE-CO(2) extract was separated by various chromatographic methods to give two new phytosterol derivatives, 24-methylenecholesterol linolenate (1) and cycloeucalenol linolenate (2), as well as eight known compounds, 24-methylenecholesterol palmitate (3), cycloeucalenol (4), pollinastanol (5), 24-methylenecholesterol (6), linolenic acid (7), palmitic acid (8), monolinolein (9) and monopalmitin (10), compounds 7 and 9 showed potent 5 alpha-reductase inhibitory activity; compounds 1-6 and 10 showed potent aromatase inhibitory activity.