Olive Oil Phenols

Olive oils contain numerous substances that have a beneficial role in human health. Phenols are natural compounds that are present in extra-virgin olive oil (EVOO), and they are produced at the malaxation step of the olive oil production. The four most abundant phenols in EVOO are oleocanthal, oleacein, ligstroside aglycon, and oleuropein aglycon. These phenols exhibit significant biological effects in many diseases, participating in various cellular and biochemical processes. Oleocanthal can protect and prevent against the Alzheimer disease, demonstrates acute antiplatelet effects, which has a vital role against cancer, and can act like ibuprofen. Oleacein has antioxidant and anti-inflammatory activities and helps against atherosclerosis. Moreover, it acts as an antiaging factor and as a 5-lipoxygenase inhibitor. Ligstroside aglycon implicates to mechanisms against breast cancer, while oleuropein aglycon shows activities against the Alzheimer disease and breast cancer

2,3-cis-2R,3R-(−)-epiafzelechin-3-O-p-coumarate, a novel flavan-3-ol isolated from Fallopia convolvulus seed, is an estrogen receptor agonist in human cell lines

BACKGROUND: The plant genus Fallopia is well-known in Chinese traditional medicine and includes many species that contain bioactive compounds, namely phytoestrogens. Consumption of phytoestrogens may be linked to decreased incidence of breast and prostate cancers therefore discovery of novel phytoestrogens and novel sources of phytoestrogens is of interest. Although phytoestrogen content has been analyzed in the rhizomes of various Fallopia sp., seeds of a Fallopia sp. have never been examined for phytoestrogen presence. METHODS: Analytical chemistry techniques were used with guidance from an in vitro estrogen receptor bioassay (a stably transfected human ovarian carcinoma cell line) to isolate and identify estrogenic components from seeds of Fallopia convolvulus. A transiently transfected human breast carcinoma cell line was used to characterize the biological activity of the isolated compounds on estrogen receptors (ER) α and β. RESULTS: Two compounds, emodin and the novel flavan-3-ol, (−)-epiafzelechin-3-O-p-coumarate (rhodoeosein), were identified to be responsible for estrogenic activity of F. convolvulus seed extract. Absolute stereochemistry of rhodoeosein was determined by 1 and 2D NMR, optical rotation and circular dichroism. Emodin was identified by HPLC/DAD, LC/MS/MS, and FT/ICR-MS. When characterizing the ER specificity in biological activity of rhodoeosein and emodin, rhodoeosein was able to exhibit a four-fold greater relative estrogenic potency (REP) in breast cells transiently-transfected with ERβ as compared to those transfected with ERα, and emodin exhibited a six-fold greater REP in ERβ-transfected breast cells. Cell type-specific differences were observed with rhodoeosein but not emodin; rhodoeosein produced superinduction of reporter gene activity in the human ovarian cell line (> 400% of maximum estradiol [E2] induction) but not in the breast cell line. CONCLUSION: This study is the first to characterize the novel flavan-3-ol compound, rhodoeosein, and its ability to induce estrogenic activity in human cell lines. Rhodoeosein and emodin may have potential therapeutic applications as natural products activating ERβ, and further characterization of rhodoeosein is necessary to evaluate its selectivity as a cell type-specific ER agonist

Antifungal activity of selected Malassezia indolic compounds detected in culture

Background: Malassezia yeasts produce bioactive indolic substances when grown on L‐tryptophan agar. A panel of these substances was tested against commensal and opportunistic fungi, the Minimum Inhibitory Concentration (MIC) was determined and the potential for in loco antifungal activity on the skin was assessed. Materials and Methods: Eight indoles were included (malassezin, pityriacitrin, indirubin, indolo[3,2‐b]carbazole, 6‐formylindolo[3,2‐b]carbazole, tryptanthrin, 6‐hydroxymethylindolo[3,2‐b]carbazole and 6‐methylindolo[3,2‐b]carbazole) and were tested against 40 fungal strains [yeasts: Malassezia spp.(N = 9); Cryptococcus spp.(N = 10); Candida spp.(N = 7); Yarrowia lipolytica(N = 1); Exophialla dermatitidis (N = 2); moulds: Aspergillus spp.(N = 7); Fusarium spp.(N = 2); Rhizopus oryzae(N = 2)]. The concentration of 5/8 of the tested indoles on diseased skin was calculated from published data. Kruskal‐Wallis and Mann‐Whitney U tests were employed for group susceptibility evaluation in 33 strains. Results: The MIC range was 0.125‐32 μg/mL, and the median log2MIC was four. Indirubin was the most potent antifungal agent and differed significantly from the others. The highest median MIC was found for FICZ. Malassezia with Candida strains were more susceptible compared to Cryptococcus and Aspergillus, and this inhibitory activity was predicted to be valid also on human skin. Conclusions: Malassezia yeasts produce indolic species that inhibit an array of clinically significant yeasts and moulds

Differential effect of Pistacia vera extracts on experimental atherosclerosis in the rabbit animal model: an experimental study

<p>Abstract</p> <p>Background</p> <p>Lipid-enriched diets and oxidative stress are risk factors for the development of atherosclerosis. The effects of the methanolic (ME) and cyclohexane (CHE) extracts of the <it>Pistacia vera </it>nut, often included in the Mediterranean diet, were studied in the rabbit model of atherosclerosis.</p> <p>Methods and results</p> <p>Twenty-four New Zealand White rabbits received atherogenic diet (Control Group), supplemented with ME (Group ME) or CHE (Group CHE) for 3 months. Previously, a GC-MS and a UHPLC LC-DAD-ESI(-)-HRMS/MS method were developed to investigate the extracts' chemical profiles. Blood samples at baseline and monthly determined lipid profile, lipid peroxidation and liver function. The aorta, myocardium and liver were examined histologically at 3 months.</p> <p>Groups ME and CHE had significantly higher HDL- and non-significantly lower LDL-cholesterol median % changes from baseline than the Control Group. Triacylglycerol was significantly higher in Group CHE vs. Control. MDA values were significantly lower in Group ME vs. Control and CHE. ALT and AST were significantly higher in Group CHE vs. Control. γ-GT was lower in Group ME vs. Control. Aortic intimal thickness was significantly less in Groups ME and CHE vs. Control; Group ME atherosclerotic lesions were significantly less extensive vs. Groups Control and CHE. Only Group CHE had significant liver fatty infiltration.</p> <p>Conclusions</p> <p>During short-term administration concomitantly with atherogenic diet, both <it>P. vera </it>extracts were beneficial on HDL-, LDL-cholesterol and aortic intimal thickness. The ME additionally presented an antioxidant effect and significant decrease of aortic surface lesions. These results indicate that <it>P. vera </it>dietary inclusion, in particular its ME, is potentially beneficial in atherosclerosis management.</p

Kemijski sastav endemske biljke Centaurea austro-anatolica i ispitivanje antimikrobnog djelovanja protiv multi-rezistentnih bakterija

Hexane, chloroform, ethyl acetate and ethanolic extracts of the aerial parts of C. austro-anatolica Hub.-Mor. (Asteraceae) were evaluated against microorganisms, including multi-resistant bacteria, using a paper disc diffusion method. The chloroform extract exhibited significant antibacterial activity toward all bacteria tested. The chemical composition of the chloroform extract was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The major compounds of the extract were caryophyllene oxide (21.32 %), spathulenol (10.86 %), n-tricosanol (9.58 %) and geranyl isovalerate (8.71 %).Heksanski, kloroformski, etil-acetatni i etanolni ekstrakti vršnih dijelova biljke C. austro-anatolica Hub.-Mor. (Asteraceae) ispitivani su na antimikrobno djelovanje protiv multi-rezistentnih bakterija, koristeći difuzijsku metodu na papirnom disku. Kloroformski ekstrakt pokazao je značajno antibakterijsko djelovanje protiv svih testiranih bakterija. Kemijski sastav tog ekstrakta određivan je plinskom kromatografijom (GC) i plinskom kromatografijom-spektrometrijom masa (GC-MS). Najvažniji sastojci ekstrakta bili su kariofilen oksid (21,32 %), spatulenol (10,86 %), n-trikozanol (9,58 %) i geranil izovalerat (8,71 %)

An evaluation of indirubin analogues as phosphorylase kinase inhibitors

Phosphorylase kinase (PhK) has been linked with a number of conditions such as glycogen storage diseases, psoriasis, type 2 diabetes and more recently, cancer (Camus S. et al., Oncogene 2012, 31, 4333). However, with few reported structural studies on PhK inhibitors, this hinders a structure based drug design approach. In this study, the inhibitory potential of 38 indirubin analogues have been investigated. 11 of these ligands had IC50 values in the range 0.170 – 0.360 µM, with indirubin-3’-acetoxime (1c) the most potent. 7-bromoindirubin-3’-oxime (13b), an antitumor compound which induces caspase-independent cell-death (Ribas J. et al., Oncogene, 2006, 25, 6304) is revealed as a specific inhibitor of PhK (IC50 = 1.8 µM). Binding assay experiments performed using both PhK-holo and PhK-γtrnc confirmed the inhibitory effects to arise from binding at the kinase domain (γ subunit). High level computations using QM/MM-PBSA binding free energy calculations were in good agreement with experimental binding data, as determined using statistical analysis, and support binding at the ATP-binding site. The value of a QM description for the binding of halogenated ligands exhibiting -hole effects is highlighted. A new statistical metric, the ‘sum of the modified logarithm of ranks’ (SMLR), has been defined which measures performance of a model for both the “early recognition” (ranking earlier/higher) of active compounds and their relative ordering by potency. Through a detailed structure activity relationship analysis considering other kinases (CDK2, CDK5 and GSK-3α/β), 6’(Z) and 7(L) indirubin substitutions have been identified to achieve selective PhK inhibition. The key PhK binding site residues involved can also be targeted using other ligand scaffolds in future work