Analysis of the flavonoid component of bioactive New Zealand mānuka (Leptospermum scoparium) honey and the isolation, characterisation and synthesis of an unusual pyrrole

The flavonoid components of New Zealand mānuka (Leptospermum scoparium) honey have been quantified in a series of 31 honeys of varying non-peroxide antibacterial activity to clarify discrepancies between previous studies reported in the literature. Total flavonoid content was 1.16 mg/100 g honey. The principal flavonoids present were pinobanksin, pinocembrin, luteolin and chrysin and together these represented 61% of the total flavonoid content. 1, 2-formyl-5-(2-methoxyphenyl)-pyrrole, which was weakly correlated with the non-peroxide antibacterial activity, was isolated from the flavonoid fraction and separately synthesised. 1 did not display inhibitory activity against Staphylococcus aureus in vitro and thus the origin of the correlation, which is still unknown, is not a direct contribution

Antioxidant activity and phenolic profile of selected organic and conventional honeys from Poland

Honey is a natural food product hypothesized to have significant health-beneficial value. The results of recent studies indicate that the biological activity of honey can also be ascribed to phenolic compounds and their antioxidant activity. The aims of this study were: To determine the phenolic profiles of several varieties of Polish honey and their correlation with various factors influencing the quality of honey, plus to verify the impact of production method (organic/conventional) and the pollen content on these profiles. In total, 11 organic and 11 conventional honey samples from Poland were investigated. The botanical origin of the samples was identified through melissopalynological analysis, whereas individual phenolic compounds were determined by the LC/MS analysis. The Folin-Ciocalteau assay was used for the determination of the total phenolic content (TPC). Moreover, the CIE L*a*b* color values were measured and matched with the above-mentioned parameters. The results of the study contribute to the discussion on the health benefits of organic farming. It was found that chrysin may act as a potential indicator compound. The study confirms the existence of the link between TPC and color, and it shows that there is a correlation between pinocembrin and galangin, two compounds that are reported to ameliorate insulin resistance

Effect of Chrysin on AGS human gastric cancer cell line

Background and Objective: Chrysin is a natural and active biological component which is extracted from plants, honey and propolis. Chrysin has anti-inflammatory, anticancer and antioxidant propertis. This study was done to evaluate the effect of chrysin on AGS human gastric cancer cell line. Methods: In this descriptive - analytic study, chrysin was dissolved in dimethyl sulfoxide (DMSO) and the cytotoxic effects of concentrations of 10, 15, 20, 30, 40 ,50, 60, 70, 80, and 100 µM/ml of chrysin on AGS cells was evaluated. Viability of the cells was determined with MTT assay after 24, 48 and 72 hours and compared to controls. Results: Chrysin inhibited the growth and proliferation of human gastric cancer AGS cell line. The antiproliferative effect of chrysin was dose and time dependent. The IC50 values were determined for 60, 30 and 20 µM, in incubation time of 24, 48 and 72 hour, respectively (P<0.05). Conclusion: Chrysin proved to have antiproliferative activity on human gastric cancer cells in culture mediu

Effects of Chrysin plant flavonoid on proliferation and apoptosis of gastric cancer cell line (AGS)

Introduction: Chrysin is a natural flavonoid antioxidant which its role in tumor cell death has been reported. The aim of this study was to investigate the mechanism of Chrysin effect on proliferation and apoptosis of gastric cancer cell line (AGS). Methods: Cells were cultured and treated with different concentrations of Chrysin (90, 80, 70, 60, 50 &mu;M) for 48 h and evaluated for cell viability. To examine the cytotoxic effect of drug in inducing apoptosis, staining with fluorescein isothiocyanate (FITC) and propidium iodide (PI) was used. The cells were treated for 48 h with different concentrations of Chrysin (50 of 90 &mu;M) and examined for the morphological changes. The one-way analysis of variance (ANOVA) and the Excel software were used for data analysis. Results: Different concentrations of Chrysin significantly inhibited the growth and proliferation of AGS cells (p&lt;0.05). The IC50 dose was determined to be 67.5&plusmn;0.66. Apoptosis induced by 50 and 70 &mu;M of Chrysin was significantly greater than in untreated cells (p&lt;0.05). Cells treated with high concentration of Chrysin (90 &mu;M) showed more prominent growth inhibition and cell shrinkage compared to cells treated with the lower concentrations of Chrysin. Conclusion: The results of this study showed that Chrysin effects on AGS cell line were significantly high and dose-dependent and might be helpful in the treatment of gastric cancer. Chrysin may therefore be considered a potential candidate for both cancer prevention and treatment. Further investigation is needed to validate the contribution of chrysin in tumor therapy in vivo.</p

Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells

With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the discovery of new neuroprotective treatments able to rescue neurons from cell injury is presently a matter of extreme importance and urgency. Here, we were inspired by the widely reported potential of natural flavonoids to build a library of novel flavones, chromen-4-ones and their C-glucosyl derivatives, and to explore their ability as neuroprotective agents with suitable pharmacokinetic profiles. All compounds were firstly evaluated in a parallel artificial membrane permeability assay (PAMPA) to assess their effective permeability across biological membranes, namely the blood-brain barrier (BBB). With this test, we aimed not only at assessing if our candidates would be well-distributed, but also at rationalizing the influence of the sugar moiety on the physicochemical properties. To complement our analysis, logD7.4 was determined. From all screened compounds, the p-morpholinyl flavones stood out for their ability to fully rescue SH-SY5Y human neuroblastoma cells against both H2O2- and Aβ1-42-induced cell death. Cholinesterase inhibition was also evaluated, and modest inhibitory activities were found. This work highlights the potential of C-glucosylflavones as neuroprotective agents, and presents the p-morpholinyl C-glucosylflavone 37, which did not show any cytotoxicity towards HepG2 and Caco-2 cells at 100 μM, as a new lead structure for further development against AD.Fundação para a Ciência e a Tecnologia-UID/Multi/0612/2019Unión Europea-D3i4AD), FP7-PEOPLE-2013-IAPP, GA 61234

2013 REU Poster: Small Molecule Evolution: A Biomimetic Approach to Small Molecule Lead Generation and Optimization

Poster presentation at REU Summer's End Research Symposium, 2013, by REU participant Tiara Bloodworth, MassBay Community College - Aaron Beeler group, Dr. Kristen Mascall lab mentor.The goal of my project was to determine the standard calibration curves of compounds in the small molecule evolution library. Solutions of several small molecules were prepared at various concentrations and analyzed using the nanoAcquity UPLC instrument. Diode array traces were collected for each solution, in which UV-active compounds showed up as a single peak in the chromatogram. These peaks were extracted at a single wavelength (usually max) to produce new traces, and peak area was determined. Plots of peak area against concentration were obtained for each small molecule, and the results showed a linear relationship between concentration and peak area at a single wavelength. Equations of the line were found and this data will be used to determine unknown concentrations of small molecules in solution after chemical reactions are performed. The information will be vital for the biological assessment of new compounds formed by chemical modification.NSF RE

Cytotoxic and antioxidant effect of chrysin on neonate mouse spermatogenic stem cells

Background: So far, many plants have been used for the treatment of infertility. Several studies have revealed that chrysin (as an active metabolite) improves animals' reproduction. Therefore, the objective of this study was to evaluate the effect of chrysin on Balb/C mice spermatogenic stem cells. Materials and Methods: In this in vitro experimental study Balb/C neonate spermatogonia stem cells cultured in DMEM-F12 medium were treated with various concentrations of chrysin (2.5, 5, 10, 20, 40 &micro;g/ml) for 6 and 12 days. Then the cytotoxicity was assessed using MTT, Akredin orange/Propodium Idid, DAPI and antioxidant concentration DCF-DA tests. Results: Chrysin showed no remarkable cytoxicity in concentrations less than 5 &micro;g/ml. While, after 6 days the viability of cells treated with chrysin 10, 20 and 40 &micro;g/ml was decreased to 30, 45 and 56 (P&lt;0.05 and P&lt;0.001, respectiely); after 12 days the viability of cells was decreased to 44, 56 and 65 (P&lt;0.05, P&lt;0.01 and P&lt;0.001, respectiely). DCF-DA results revealed a 80 antioxidant capacity of chrysin in 5 and 2.5&micro;g/ml concentrations. Conclusion: Lower concentrations of chrysin has protective effect on Balb/C mice spermatogenic through improving cell viability, decreasing cells apoptosis and inhibiting free radicals

Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy

The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents

Synthetic flavonoids as novel modulators of platelet function and thrombosis

Cardiovascular diseases represent a major cause of mortality and morbidity in the world and thrombotic conditions such as heart attacks and strokes are caused by unwarranted activation of platelets and subsequent formation of blood clots (thrombi) within the blood vessels during pathological circumstances. Therefore, platelets act as a primary therapeutic target to treat and prevent thrombotic conditions. Current treatments are limited due to intolerance and they are associated with severe side effects such as bleeding complications. Hence, the development of novel therapeutic strategies for thrombotic diseases is an urgent priority. Flavonoids are naturally occurring plant-derived molecules that exert numerous beneficial effects in humans through modulating the functions of distinct cell types. However, naturally occurring flavonoids suffer from several issues such as poor solubility, lipophilicity, and bioavailability, which hinder their efficacy and potency. Despite this, flavonoids act as versatile templates for the design and synthesis of novel molecules for various therapeutic targets. Indeed, several synthetic flavonoids have recently been developed to improve their stability, bioavailability and efficacy including for the modulation of platelet function. Here, we provide insight into the actions of certain natural flavonoids along with the advantages of synthetic flavonoids in the modulation of platelet function, haemostasis and thrombosis

Ekspresi Gen Aromatase pada Pengarahan Diferensiasi Kelamin Ikan Nila (Oreochromis Niloticus Linnaeus 1758) Menggunakan Madu [Aromatase Gene Expression Of Sex Reversal Nile Tilapia (Oreochromis Niloticus Linnaeus 1758) Using Honey]

Budi daya ikan nila dengan populasi jantan semua (monoseks) lebih memberikan keuntungan karena laju pertumbuhan-nya lebih cepat dan dapat mencegah pemijahan liar.Teknik pengarahan diferensiasi kelamin(sex reversal) digunakan untuk mengarahkan pembentukan jenis kelamin pada budi daya ikan.Penelitian ini dilakukan untuk mengevaluasi pe-ngaruh perendaman larva ikan nila menggunakan tiga sumber madu berbeda terhadap persentase ikan jantan dan ekspresi gen aromatase. Pada percobaan satu, 30 larva ikan nila berumur 12 hari setelah menetas direndam menggunakan madu hutan, madu ternak dan madu bakau, dengan dosis 10 ml L-1 air selama 10 jam. Ikan dipelihara dalam kondisi yang sama selama dua bulan. Hasil penelitian menunjukkan bahwa persentase ikan jantan tidak berbeda nyata antar perlakuan madu (p>0,05), tetapi semuanya berbeda nyata dengan kontrol (p<0,05). Pada percobaan kedua, larva ikan nila direndam dalam air mengandung dua bahan bioaktif madu, yakni chrysin dan kalium dengan dosis masing-masing 20 mg L-1 dan 0,026 g L-1. Ekspresi gen aromatase tipe gonad (aroma-g) dan tipe otak (aroma-o) dianalisis menggunakan metode RT-PCR. Sampel jaringan diambil pada waktu 1, 6, 12, 24, dan 48 jam pascaperlakuan madu, chrysin, dan kalium, serta setelah ikan berumur dua bulan.Ukuran fragmen DNA aromatase pada gonad betina sekitar 200 bp. Perendaman chrysin dan kalium meningkatkan persentase ikan jantan (p<0,1). Analisis RT-PCR menunjukkan bahwa madu, chrysin, dan kalium dapat menekan ekspresi gen aroma-g pada jam ke-12 pascaperendaman. Dengan demikian dapat disimpulkan bahwa madu, chrysin dan kalium dapat digunakan untuk pengarahan diferensiasi ikan nila, dan mekanis-menya seperti penghambat aromatase