Phenolic constituents from the root bark of Morus alba L. and their cardioprotective activity in vitro. PUMID/DOI：DOI: 10.1016/j.phytochem.2016.12.006 Phytochemistry. 2017 Mar;135:128-134. A flavanone C-glycoside, steppogenin-5'-C-β-D-glucopyranoside, six prenylated 2-arylbenzofuran derivatives, moracin O-3″-O-β-D-glucopyranoside, moracin O-3'-O-β-D-xylopyranoside, moracin P-2″-O-β-D-glucopyranoside, moracin P-3'-O-β-D-glucopyranoside, moracin P-3'-O-α-L-arabinopyranoside and moracin P-3'-O-[β-D-glucopyranosyl-(1 → 2)]-α-L-arabinopyranoside, two phenolic acids, 2,4-dihydroxy-5-(4-hydroxybenzyl) benzoic acid and 2,4-dihydroxy-5-(3,4-dihydroxybenzyl) benzoic acid, as well as three known compounds, moracinoside C, moracin O, and moracin P were isolated from the root bark of Morus alba L. Their structures were ascertained on the basis of spectroscopic evidence. The protective effects of the compounds against doxorubicin-induced cardiomyopathy in H9c2 cells was investigated in vitro. Of all of the isolated compounds, moracin P-3'-O-β-D-glucopyranoside, moracin O and moracin P had a strong protective influence against doxorubicin-induced cell death with EC50 values of 9.5 ± 2.6, 4.5 ± 1.3, and 8.8 ± 2.4 μM, respectively. Bioactive Benzofuran Derivatives from Cortex Mori Radicis, and Their Neuroprotective and Analgesic Activities Mediated by mGluR?. PUMID/DOI：DOI:10.3390/molecules22020236 Molecules. 2017 Feb 8;22(2). pii: E236. Four new benzofuran-type stilbene glycosides and 14 known compounds including 8 benzofuran-type stilbenes and 6 flavonoids were isolated from the traditional Chinese medicine, Cortex Mori Radicis. The new compounds were identified as (9R)-moracin P 3'-O-α-l-arabinopyranoside (1), (9R)-moracin P 9-O-β-d-glucopyranoside (2), (9R)-moracin P 3'-O-β-d-glucopyranoside (3), and (9R)-moracin O 10-O-β-d-glucopyranoside (4) based on the spectroscopic interpretation and chemical analysis. Three benzofuran-type stilbenes, moracin O (5), R (7), and P (8) showed significant neuroprotective activity against glutamate-induced cell death in SK-N-SH cells. In addition, moracin O (5) and P (8) also demonstrated a remarkable inhibition of the acetic acid-induced pain. The molecular docking with metabotropic glutamate receptor 1 (mGluR?) results indicated that these neuroprotective benzofuran-type stilbenes might be the active analgesic components of the genus Morus, and acted by mediating the mGluR? pathway. Inhibitory effect of 2-arylbenzofurans from the Mori Cortex Radicis (Moraceae) on oxygen glucose deprivation (OGD)-induced cell death of SH-SY5Y cells. PUMID/DOI：DOI: 10.1007/s12272-011-0818-4 Arch Pharm Res. 2011 Aug;34(8):1373-80. Three known 2-arylbenzofurans, moracin P (1), moracin O (2) and mulberrofuran Q (3) were isolated from the MeOH extract of the Mori Cortex Radicis. These compounds 1-3 enhanced cell viability in dose-dependent manner against oxygen-glucose deprivation (OGD)-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay. (EC(50) values of 10.4, 12.6, and 15.9 礛, respectively). In addition, the compounds 1-3 were examined for their inhibitory effect on OGD-induced ROS production by FACS analysis. We observed these compounds reduced ROS production in OGD-induced cell death (IC(50) values of 1.9, 0.3 and 12.1 礛, respectively). Consequently, reactive oxygen species (ROS) were overexpressed in OGD-induced cells and all three compounds reduced ROS induced by OGD in dosedependent manner. Taken together, compounds 1-3 might protect neuronal cell death against the oxidative stress induced by OGD, though further studies in vitro and in vivo models are necessary. Inhibitory effects of constituents from Morus alba var. multicaulis on differentiation of 3T3-L1 cells and nitric oxide production in RAW264.7 cells. PUMID/DOI：DOI: 10.3390/molecules16076010 Molecules. 2011 Jul 19;16(7):6010-22. A new arylbenzofuran, 3',5'-dihydroxy-6-methoxy-7-prenyl-2-arylbenzofuran (1), and 25 known compounds, including moracin R (2), moracin C (3), moracin O (4), moracin P (5), artoindonesianin O (6), moracin D (7), alabafuran A (8), mulberrofuran L (9), mulberrofuran Y (10), kuwanon A (11), kuwanon C (12), kuwanon T (13), morusin (14), kuwanon E (15), sanggenon F (16), betulinic acid (17), uvaol (18), ursolic acid (19), β-sitosterol (20), oxyresveratrol 2-O-β-D-glucopyranoside (21), mulberroside A (22), mulberroside B (23), 5,7-dihydroxycoumarin 7-O-β-D-glucopyranoside (24), 5,7-dihydroxycoumarin 7-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside (25) and adenosine (26), were isolated from Morus alba var. multicaulis Perro. (Moraceae). Their structures were determined by spectroscopic methods. The prenyl-flavonoids 11-14, 16, triterpenoids 17,18 and 20 showed significant inhibitory activity towards the differentiation of 3T3-L1 adipocytes. The arylbenzofurans 1-10 and prenyl-flavonoids 11-16 also showed significant nitric oxide (NO) production inhibitory effects in RAW264.7 cells. Inhibition of HCV replicon cell growth by 2-arylbenzofuran derivatives isolated from Mori Cortex Radicis. PUMID/DOI：DOI: 10.1055/s-2007-990249 Planta Med. 2007 Nov;73(14):1481-5. Epub 2007 Oct 18. Medicinal herbs are increasingly used in the search for safe and efficient drug candidates for hepatitis C virus infection. In this study, we have investigated the anti-HCV effect of compounds from Mori Cortex Radicis. During a screening for extracts with anti-HCV affinity from medicinal plants (173 species), the methanol extract of Mori Cortex Radicis was selected. Fractionation of the extract by monitoring antiviral activity with a replicon cell-based assay resulted in the isolation of five compounds, mulberroside C ( 1), moracin P ( 2), moracin O ( 3), moracin M ( 4) and mulberrofuran K ( 5) from the ethyl acetate-soluble fraction. Compounds 1 approximately 4 showed significant inhibitory activities. Compounds 2 and 3 showed potent inhibitory activity (IC (50) 35.6 microM, 80.8 microM, respectively) in the replicon cell assay, which was confirmed by NS3 helicase inhibitory activity (IC (50) 42.9 microM, 27.0 microM, respectively).
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Subspecies of the African trypanosome, Trypanosoma brucei, which cause human African trypanosomiasis, are transmitted by the tsetse fly, with transmission-essential lifecycle stages occurring in both the insect vector and human host. During infection of the human host, the parasite is limited to using glycolysis of host sugar for ATP production. This dependence on glucose breakdown presents a series of targets for potential therapeutic development, many of which have been explored and validated as therapeutic targets experimentally. These include enzymes directly involved in glucose metabolism (e.g., the trypanosome hexokinases), as well as cellular components required for development and maintenance of the essential subcellular compartments that house the major part of the pathway, the glycosomes.
Glycolysis in the African Trypanosome: Targeting Enzymes and Their Subcellular Compartments for Therapeutic Development
April F. Coley, Heidi C. Dodson, Meredith T. Morris, and James C. Morris *
Streptococcus pneumoniae (pneumococcus) remains an important cause of morbidity and mortality. Pneumococcal vaccination is part of the South African pediatric public immunization program but the potential cost-effectiveness of such an intervention for adults is unknown. This study aimed to compare the cost-effectiveness of two widely used pneumococcal vaccines: pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23) in South African adults, 18 years and older. Four analyses were carried out in a) both the private and public health care sectors; and b) for the HIV-infected population alone and for the total mixed population (all HIV-infected and -uninfected people). A previously published global pharmacoeconomic model was adapted and populated to represent the South African adult population. The model utilized a Markov-type process to depict the lifetime clinical and economic outcomes of patients who acquire pneumococcal disease in 2015, from a societal perspective. Costs were sourced in South African rand and converted to US dollar (USD). The incremental cost divided by the incremental effectiveness (expressed as quality-adjusted life years gained) represented the incremental cost-effectiveness ratio for PCV13 compared to PPSV23. Results indicated that the use of PCV13 compared to PPSV23 is highly cost-effective in the public sector cohorts with incremental cost-effectiveness ratios of $771 (R11,106)/quality-adjusted life year and $956 (R13,773)/quality-adjusted life year for the HIV-infected and mixed populations, respectively. The private sector cohort showed similar highly cost-effective results for the mixed population (incremental cost-effectiveness ratio $626 (R9,013)/quality-adjusted life year) and the HIV-infected cohort (dominant). In sensitivity analysis, the model was sensitive to vaccine price and effectiveness. Probabilistic sensitivity analyses found predominantly cost-effective ICERs. From a societal perspective, these findings provide some guidance to policy makers for consideration and implementation of an immunization strategy for both the public and private sector and amongst different adult patient pools in South Africa.
The cost-effectiveness of using pneumococcal conjugate vaccine (PCV13) versus pneumococcal polysaccharide vaccine (PPSV23), in South African adults
Charles Feldman, Conceptualization, Investigation, Supervision, Writing - original draft,1,* Sipho K. Dlamini, Conceptualization, Investigation, Writing - review & editing,2 Shabir A. Madhi, Conceptualization, Investigation, Writing - review & editing,3,4 Susan Meiring, Conceptualization, Investigation, Writing - review & editing,5 Anne von Gottberg, Conceptualization, Investigation, Writing - review & editing,6,7 Janetta C. de Beer, Conceptualization, Formal analysis, Methodology, Writing - original draft,8 Margreet de Necker, Conceptualization, Formal analysis, Methodology, Writing - original draft,8 and Marthinus P. Stander, Conceptualization, Investigation, Writing - review & editing8
Recent theoretical works have proposed atomic clocks based on narrow optical transitions in highly charged ions. The most interesting candidates for searches of physics beyond the Standard Model are those which occur at rare orbital crossings where the shell structure of the periodic table is reordered. There are only three such crossings expected to be accessible in highly charged ions, and hitherto none have been observed as both experiment and theory have proven difficult. In this work we observe an orbital crossing in a system chosen to be tractable from both sides: Pr9+. We present electron beam ion trap measurements of its spectra, including the inter-configuration lines that reveal the sought-after crossing. With state-of-the-art calculations we show that the proposed nHz-wide clock line has a very high sensitivity to variation of the fine-structure constant, α, and violation of local Lorentz invariance; and has extremely low sensitivity to external perturbations.
Subject terms: Electronic structure of atoms and molecules, Exotic atoms and molecules
Detection of the 5p - 4f orbital crossing and its optical clock transition in Pr9+
H. Bekker,1,6 A. Borschevsky,2 Z. Harman,1 C. H. Keitel,1 T. Pfeifer,1 P. O. Schmidt,3,4 J. R. Crespo Lopez-Urrutia,1 and J. C. Berengutcorresponding author1,5