Effects of Novel Chalcone Derivatives upon H9c2 and MDCK Cell Viability

Many compounds with potential anti-cancer activity fail to reach the latter stages of clinical trials due to adverse effects, often causing cardiac and renal toxicity. Here, we synthesised a group of novel chalcone compounds, thought to have potential anti-cancer activity4 and assessed their effects upon cardiac and renal cell viability. Data revealed that all compounds produced minimal short term toxicity. Further work will be performed to assess the long term effects of these compounds on cell viability, leading to mechanistic studies and structure activity relationship analyses

Petals of Crocus sativus L. as a potential source of the antioxidants crocin and kaempferol.

Collaboration between Leicester School of Pharmacy - De Montfort Universit, Department of Life, Health and Environmental Sciences - University of L'Aquila, and Department of Biochemistry and Biotechnology - University of Thessaly The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Saffron fromthe province of L'Aquila, in the Abruzzo region of Italy, is highly prized and has been awarded a formal recognition by the European Union with EU Protected Designation of Origin (PDO) status. Despite this, the saffron regions are abandoned by the younger generations because the traditional cultivation of saffron (Crocus sativus L.) is labour intensive and yields only one crop of valuable saffron stamens per year. Petals of the saffron Crocus have had additional uses in traditional medicine and may add value to the crops for local farmers. This is especially important because the plant only flowers between October andNovember, and farmers will need to make the best use of the flowers harvested in this period. Recently, the petals of C. sativus L., which are considered a wastematerial in the production of saffron spice,were identified as a potential source of natural antioxidants. The antioxidants crocin and kaempferol were purified by flash column chromatography, and identified by thin layer chromatography (TLC), HPLC–DAD, infrared (IR), and nuclear magnetic resonance (1H & 13C NMR) spectroscopy. The antioxidant activity was determined with the ABTS and DPPH tests. The antioxidant activities are mainly attributed to carotenoid and flavonoid compounds, notably glycosides of crocin and kaempferol. We found in dried petals 0.6% (w/w) and 12.6 (w/w) of crocin and kaempferol, respectively. Petals of C. sativus L. have commercial potential as a source for kaempferol and crocetin glycosides, natural compounds with antioxidant activity that are considered to be the active ingredients in saffron-based herbal medicine

Polymer-drug nanoconjugate – an innovative nanomedicine: challenges and recent advancements in rational formulation design for effective delivery of poorly soluble drugs.

The published manuscript is available at EurekaSelect via - See more at: http://dx.doi.org/10.2174/2211738504666160213001714Abstract Background: Over the last four decades, the use of water soluble polymers in rational formulation design has rapidly evolved into valuable drug delivery strategies to enhance the safety and therapeutic effectiveness of poorly soluble drugs, particularly anticancer drugs. Novel advances in polymer chemistry have provided new generations of well defined polymeric architectures for specific applications in polymer-drug conjugate design. However, total control of crucial parameters such as particle size, molecular weight distribution, polydispersity, localization of charges, hydrophilic-lipophilic balance and non site-specific coupling reactions during conjugation has been a serious challenge. Objective: This review briefly describes the current advances in polymer-drug nanoconjugate design and various challenges hindering their transformation into clinically useful medicines. Method: Existing literature was reviewed. Results: This review provides insights into the significant impact of covalent and non-covalent interactions between drug and polymer on drug loading [or conjugation] efficiency, conjugate stability, mechanism of drug release from the conjugate and biopharmaceutical properties of poorly soluble drugs. The utility values and application of Quality by Design principles in rational design, optimization and control of the Critical Quality Attributes [CQA] and Critical Process Parameters [CPP] that underpin the safety, quality and efficacy of the nanoconjugates are also presented. Conclusion: It was apparent that better understanding of the physicochemical properties of the nanoconjugates as well as the drug-polymer interaction during conjugation process is essential to be able to control the biodistribution, pharmacokinetics, therapeutic activity and toxicity of the nanoconjugates which will in turn enhance the prospect of successful transformation of these promising nanoconjugates into clinically useful nanomedicines

In vitro biocompatibility of a new hydrogel with Crocin, powerful antioxidant found in Crocus Sativus L. flowers

Recently, attention has been paid to the identification of natural antioxidants from the petals of Crocus S. flowers that are normally considered waste[1]. The antioxidant activities are mainly attributed to carotenoid compounds, like crocin. Scientific evidences demonstrate that this kind of compounds are among the most important natural plant sources of antioxidant activity in the human diet, protecting the body against damages caused by reactive oxygen species (ROS). This antioxidant was extracted using methanol and ethanol. In this experiment, it was used a new hydrogel consisting of three polymers - Polyvinyl pyrrolidone (PVP), Agar and Polyethylene glycol (PEG) – and Crocin, mixed, reticulated and then sterilized by gamma irradiation at 25 kGy. For the in vitro experimental protocol, it was used a primary culture of fibroblasts taken from the subcutaneous tissue of a newborn mice, seeding the cells on a little square (1cm2 area) of both kinds of hydrogel. As the ISO protocol prescribes, the experiments were repeated 3 times for each kind of hydrogel, stopping the culture at the 3rd, 7th and 14th day after the seeding. For all steps, 3 Petri dishes were used as controls without biomaterials. At fixed deadline, all Petri dishes were stained, using the Wright method for cell counting and morphological evaluations. The microscopic analysis revealed the complete biocompatibility of the hydrogel. The Petri dishes with this kind of new hydrogel has an overproduction of collagen from the fibroblasts. The presence of this natural important compound in saffron petals, now offers new possibilities for the best use of the hole flower. This study is still in progress.http://www.fupress.net/index.php/ijae/article/view/1495

Activity of Antioxidants from Crocus sativus L. Petals: Potential Preventive Effects towards Cardiovascular System

The petals of the saffron crocus (Crocus sativus L.) are considered a waste material in saffron production, but may be a sustainable source of natural biologically active substances of nutraceutical interest. The aim of this work was to study the cardiovascular effects of kaempferol and crocin extracted from saffron petals. The antiarrhythmic, inotropic, and chronotropic effects of saffron petal extract (SPE), kaempferol, and crocin were evaluated through in vitro biological assays. The antioxidant activity of kaempferol and crocin was investigated through the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay using rat cardiomyoblast cell line H9c2. The MTT assay was applied to assess the effects of kaempferol and crocin on cell viability. SPE showed weak negative inotropic and chronotropic intrinsic activities but a significant intrinsic activity on smooth muscle with a potency on the ileum greater than on the aorta: EC50 = 0.66 mg/mL versus EC50 = 1.45 mg/mL. Kaempferol and crocin showed a selective negative inotropic activity. In addition, kaempferol decreased the contraction induced by KCl (80 mM) in guinea pig aortic and ileal strips, while crocin had no effect. Furthermore, following oxidative stress, both crocin and kaempferol decreased intracellular ROS formation and increased cell viability in a concentration-dependent manner. The results indicate that SPE, a by-product of saffron cultivation, may represent a good source of phytochemicals with a potential application in the prevention of cardiovascular diseases

Nobiletin bioactivation in MDA-MB-468 breast cancer cells by cytochrome P450 CYP1 enzymes.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linkNobiletin is a fully methoxylated flavone that has demonstrated anticancer activity via multiple modes of action. In the present study, the metabolism and further antiproliferative activity of nobiletin was evaluated in the CYP1 expressing human breast cancer cell line MDA–MB–468 and the normal breast cell line MCF10A. Nobiletin was metabolized in MDA–MB–468 cells to a single-demethylated derivative assigned NP1. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Nobiletin exhibited submicromolar IC50 (0.1±0.04 μM) in MDA–MB–468 cells, whereas it was considerably less active in MCF10A cells (40 μM). In the presence of the CYP1 inhibitor acacetin, the conversion of nobiletin to NP1 was significantly reduced in MDA–MB–468 cells. Furthermore, a significant increase was noted in the population of the cells at the G1 phase, following treatment with nobiletin (10 μM) for 24 h compared with the control cells treated with DMSO (0.1%) alone (55.9±0.14 vs. 45.6±1.96), whereas the cell cycle of MCF10A cells was not significantly altered under the same treatment conditions. Taken collectively, the results suggest that nobiletin is selectively bioactivated in MDA–MB–468 breast cancer cells via metabolism by the CYP1 family of enzymes

Pyrogallol is the main antibacterial compound in the aqueous extract of Boswellia dalzielii bark

Plants belonging to the genus Boswellia (Burseraceae) have long been appreciated for their pharmacological properties such as anti-inflammatory, antioxidative and anticancer activities1. In the Northern part of Nigeria, the bark of B. dalzielii Hutch. is an important ingredient for the treatment of infections2. To identify water-soluble antibacterial compounds, powdered bark was macerated in water for 6 to 24h at a range of temperatures. The aqueous extracts were subsequently fractionated by column chromatography, and the fractions were initially screened against wild type and methicillin resistant strains of Staphylococcus aureus. Then, minimum inhibitory concentrations of purified fractions were determined using series of concentrations from 2 mg/mL to 8 μg/mL. Results showed that longer maceration resulted in stronger antibacterial activity. With the aid of NMR and accurate mass analysis, pyrogallol was identified as the main antibacterial agent, with MIC values ranging from 24-28 μg/mL for MRSA to 34-36 μg/mL for wild-type S. aureus. Gallic acid was found to play a lesser role (MIC >200 μg/mL). Pyrogallol was found not to be a plant secondary metabolite, but a metabolic product from microbial degradation of gallic acid from the bark. Only two bacterial species could be isolated from the plant material, which were identified as Raoultella planticola and Enterobacter cloacae. Of these two micro-organisms, R. planticola was shown to be responsible for the production of pyrogallol. This is an example of bacterial allelopathy, which results in an increased efficacy of the aqueous extract