Four new phenolics and antiparasitic secondary metabolites from Flacourtia rukam Zoll. & Mortizi.

Phytochemical investigation of Flacourtia rukam Zoll. & Mortizi (F. rukam) leaves and bark led to the isolation and characterization of seventeen compounds of which four phenolics were not previously described; 2-[(benzoyloxy)methyl]-phenyl-O-ß-xylosyl-(1→2)-ß-glucopyranoside (1), 2-[(benzoyloxy)methyl]-4-hydroxyphenyl-O-ß-xylosyl-(1→2)-ß-D-glucopyranoside (2), 2-hydroxy-5-(2-hydroxyphenoxy)phenoxy-ß-glucopyranoside (3) and biphenyl-1,1',2,2'-tetraol (5). Interestingly, the later compound is known as a synthetic but this is the first report for its isolation from nature. Chemical structures were established using extensive analysis of spectroscopic data (1 D and 2 D NMR and HRESIMS). Biphenyl-1,1,2,2'-tetrol (5) exhibited a good activity against Trypanosoma brucei trypomastigotes with IC50= 6.66 ug/mL. Compounds 2, 5, 9, 10, 11 and 12 showed a good in-vitro anti-inflammatory activity using proteinase inhibitory assay. On the contrary, all tested compounds were inactive as antileishmanial or antimalarial.

Zingiber officinale extract and omega-3 fatty acids ameliorate endoplasmic reticulum stress in a nonalcoholic fatty liver rat model.

Endoplasmic reticulum (ER) stress was reported to play a major role in non-alcoholic fatty liver disease (NAFLD) induction and progression. Here, we study the effect of Zingiber officinale and omega-3 fatty acids on ER stress for treating NAFLD. Male Wistar rats were fed on a normal diet (control group) or high-fat diet (HFD) for 8 weeks. The HFD rats were later treated with vehicle, omega-3 or with Z. officinale extract. HFD group demonstrated significantly more body weight gain and higher plasma lipid profile, glucose, and hepatic enzymes. The expressions of lipogenic ChREBP and ER stress genes CHOP, XBP1, and GRP78 were increased. This was accompanied by intrahepatic fat accumulation visualized by hepatic morphology and H&E-stained sections. Treatment with Z. officinale and omega-3 fatty acids reverted these changes into a normal healthy state. From these results, we prove that both therapeutic approaches can be potential drugs for treating NAFLD besides other ER stress-associated diseases. PRACTICAL APPLICATIONS: The effect of Zingiber officinale extract and omega-3 fatty acid on ER stress associated with NAFLD was investigated. The results revealed that Z. officinale extract and omega-3 fatty acids significantly inhibited ER stress and intrahepatic fat accumulation with the upper hand for Z. officinale extract. Both can be used as future promising therapies for the treatment of NAFLD patients and also treating different diseases that involve ER stress as a pathological modulator like diabetes mellitus, Alzheimer's disease, Parkinson's disease, and cancer.

Acylated Iridoids and Rhamnopyranoses from Premna odorata (Lamiaceae) as Novel Mesenchymal-Epithelial Transition Factor Receptor Inhibitors for the Control of Breast Cancer.

Phytochemical investigation of Premna odorata Blanco, Lamiaceae, leaves afforded three new acylated iridoid glycosides 1-3 and two new acylated rhamnopyranoses 9 and 10, in addition to ten known compounds. The structures of the new compounds were confirmed using extensive 1D and 2D NMR analysis. Molecular modeling study suggested the potential of the acylated rhamnopyranoses to bind at the c-Met kinase domain. Cell-free Z'-LYTE™ assay testing revealed the good c-Met phosphorylation inhibitory activity of 9, followed by 8, and 10, with IC50 values of 2.5, 6.9, and 12.7 µM, respectively. The (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay testing against the human c-Met expressing highly invasive MDA-MB-231 suggested compound 9 as the most active with IC50 value of 13.3 µM. Testing of compound 9 against multiple phenotypic breast cancer cell lines including MCF-7, BT-474 cells, and MDA-MB-468 proved enhanced activity against the highly c-Met expressing triple-negative breast cancer cell lines. Acylated rhamnopyranoses are potential novel c-Met inhibitors appropriate for future optimizations to control c-Met-dependent breast malignancies. Copyright © 2017 John Wiley & Sons, Ltd.

The fatty acid-rich fraction of Eruca sativa (rocket salad) leaf extract exerts antidiabetic effects in cultured skeletal muscle, adipocytes and liver cells.

CONTEXT: Eruca sativa Mill. (Brassicaceae), commonly known as rocket salad, is a popular leafy-green vegetable with many health benefits. OBJECTIVE: To evaluate the antidiabetic activities of this plant in major insulin-responsive tissues. MATERIALS AND METHODS: Five E. sativa leaf extracts of varying polarity were prepared (aqueous extract, 70% and 95% ethanol extracts, the n-hexane-soluble fraction of the 95% ethanol extract (ES3) and the defatted 95% ethanol extract). Eruca sativa extracts were investigated through a variety of cell-based in vitro bioassays for antidiabetic activities in C2C12 skeletal muscle cells, H4IIE hepatocytes and 3T3-L1 adipocytes. Guided by the results of these bioassays, ES3 was fractionated into the saponifiable (SM) and the unspaonifiable (USM) fractions. Glucose uptake was measured using [3H]-deoxy-glucose, while the effects on hepatic glucose-6-phosphatase (G6Pase) and adipogenesis were assessed using Wako AutoKit Glucose and AdipoRed assays, respectively. RESULTS: ES3 and its SM fraction significantly stimulated glucose uptake with EC50 values of 8.0 and 5.8 µg/mL, respectively. Both extracts significantly inhibited G6Pase activity (IC50 values of 4.8 and 9.3 µg/mL, respectively). Moreover, ES3 and SM showed significant adipogenic activities with EC50 of 4.3 and 6.1 µg/mL, respectively. Fatty acid content of SM was identified by GC-MS. trans-Vaccenic and palmitoleic acids were the major unsaturated fatty acids, while palmitic and azelaic acids were the main saturated fatty acids. DISCUSSION AND CONCLUSION: These findings indicate that ES3 and its fatty acid-rich fraction exhibit antidiabetic activities in insulin-responsive cell lines and may hence prove useful for the treatment of type 2 diabetes.

INVESTIGATION OF AMOEBICIDAL POTENTIAL OF ARACHIS HYPOGAEA L. PERICARP ON CYSTS OF ACANTHAMOEBA ASTRONYXIS T7 GENOTYPE.

Acanthamoeba is an opportunistic pathogen cauAing keratitis and fatal encephalitis. Early diagnosis, followed by intense treatment using a drugs mixture is a necessity for effective therapy. Many natural compounds have proved lethal effects, yet the search for original natural amebicidal agents is still of current concern. This study investigated the acanthamoebicidal effect of A. hypogaea L. pericarp; total ethanol extract and its successive fractions, n-hexane, dichloro-methane, ethyl acetate, and methanol as well as resveratrol. Acanthamoebae were isolated and cultivated on E. coli seeded non-nutrient agar, genotyped, and the in vitro acanthamoebicidal potentials of different concentrations of A. hypogaea L. pericarp; total extract ethanol and its successive fractions and resveratrol compound was investgated on cysts of A. astronyxis T7 genotype. The results showed variable degrees of lethal potentials were obtained by all examined A. hypogaea L. pericarp ethanol extract and its successive fractions, with the highest mean of non-viable cysts on the first and the second days. bf the study by total ethanol extract followed by the methanol fraction . On the third day of the study n-hexane and ethyl acetate gave the highest mean of non-viable cysts. Resveratrol showed the lowest mean of non-viable cysts count all through the study duration. Significantly higher difference was observed between all examined A. hypogaea L. pericarp extract and fractions and chlorohexidine, except for resveratrol compound the difference was found to be noinsignificant.

Preparation and application of reversed phase Chromatorotor for the isolation of natural products by centrifugal preparative chromatography.

A method of preparation of rotors with a reversed phase (RP) solid silica gel sorbent layer has been developed for centrifugal preparative chromatography (CPC), also known as rotational planar chromatography (RPC). The rotors consist of binder free RP solid SiO2 layers of different thicknesses packed between two supported circular glass discs and can be used in any appropriate device for centrifugal chromatography, like Chromatotron and CycloGraph. Polar and /or semi-polar compounds with close R(f) values, as well as extracts and column fractions were separated and/or purified in a preparative and/or semi-preparative scale using the RP rotors, eluted with mixtures of aqueous-based solvents. We herein report three examples of its application, using RP Chromatorotors, for the isolation of the diastereoisomeric alkaloids banistenosides I and II from Banisteriopsis caapi, saponins III and IV from Fagonia cretica, and the sesquiterpenes artemisinin (V) and artemisinic acid (VI) from Artemisia annua.

Efficacy of Citrus reticulata and Mirazid in treatment of Schistosoma mansoni

This work has been carried out to investigate the effect of Schistosoma mansoni infection on mice livers after treatment with the ethanolic extract of Citrus reticulata root or the oleo-resin extract from Myrrh of Commiphora molmol tree (Mirazid), as a new antishistosomal drug. Marker enzymes for different cell organelles were measured; succinate dehydrogenase (SDH); lactate dehydrogenase (LDH) and its isoenzymes; glucose-6-phosphatase (G-6-Pase); acid phosphatase (AP) and 5'- nucleotidase. Liver function enzymes; aspartate aminotransferase (AST); alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were also estimated. Parasitological studies through ova count and worm burden will also be taken into consideration. The results showed a marked reduction in SDH, LDH, AST, and ALT enzyme activities and a significant increase in G-6-Pase, AP, 5'- nucleotidase, and ALP after S. mansoni infection. A noticeable alteration in LDH subunits were also noticed. Treatment with C. reticulata or Mirazid improved all the previous enzyme activities with a noticeable reduction in ova count and worm burden.

Efficacy of Citrus reticulata and Mirazid in treatment of Schistosoma mansoni.

This work has been carried out to investigate the effect of Schistosoma mansoni infection on mice livers after treatment with the ethanolic extract of Citrus reticulata root or the oleo-resin extract from Myrrh of Commiphora molmol tree (Mirazid), as a new antishistosomal drug. Marker enzymes for different cell organelles were measured; succinate dehydrogenase (SDH); lactate dehydrogenase (LDH) and its isoenzymes; glucose-6-phosphatase (G-6-Pase); acid phosphatase (AP) and 5'- nucleotidase. Liver function enzymes; aspartate aminotransferase (AST); alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were also estimated. Parasitological studies through ova count and worm burden will also be taken into consideration. The results showed a marked reduction in SDH, LDH, AST, and ALT enzyme activities and a significant increase in G-6-Pase, AP, 5'- nucleotidase, and ALP after S. mansoni infection. A noticeable alteration in LDH subunits were also noticed. Treatment with C. reticulata or Mirazid improved all the previous enzyme activities with a noticeable reduction in ova count and worm burden.