Hypericum foliosum Quality Botanical and Chemical Markers and In Vitro Antioxidant and Anticancer Activities.

Hypericum foliosum Aiton is an endemic Azorean Hypericum species. Even though the aerial parts of Hypericum foliosum are not described in any official pharmacopoeia, they are utilized in local traditional medicine due to their diuretic, hepatoprotective, and antihypertensive properties. This plant has previously been the subject of phytochemical characterization and has been studied for its antidepressant activity, showing significant results in animal models. The lack of a description of the main characteristics of the aerial parts, which would be necessary to properly identify this medicinal plant species, contributes to the possibility of misidentification events. We performed macroscopic and microscopic analyses that identified specific differential characteristics, such as the absence of dark glands, the dimensions of the secretory pockets in the leaf, and the presence of translucent glands in the powder. To continue our previous work on the biological activity of Hypericum foliosum, ethanol, dichloromethane/ethanol, and water extracts were prepared and studied for their antioxidant and cytotoxic activity. Extracts showed in vitro selective cytotoxic activity in human lung cancer cell line A549, colon cancer cell line HCT 8, and breast cancer cell line MDA-MB-231, with dichloromethane/ethanol showing higher activity against all cell lines (IC50 values of 71.49, 27.31, and 9.51 µg/mL, respectively). All extracts also showed significant antioxidant activity.

Hypericum Genus as a Natural Source for Biologically Active Compounds.

Hypericum L. genus plants are distributed worldwide, with numerous species identified throughout all continents, except Antarctica. These plant species are currently used in various systems of traditional medicine to treat mild depression, wounds and burns, diarrhea, pain, fevers, and their secondary metabolites previously shown, and the in vitro and/or in vivo cytotoxic, antimicrobial, anti-inflammatory, antioxidant, antihyperglycemic, and hepatoprotective activities, as well as the acetylcholinesterase and monoamine oxidase inhibitory activities. We conducted a systematic bibliographic search according to the Cochrane Collaboration guidelines to answer the question: "What is known about plants of Hypericum genus as a source of natural products with potential clinical biological activity?" We documented 414 different natural products with confirmed in vitro/in vivo biological activities, and 58 different Hypericum plant species as sources for these natural products. Phloroglucinols, acylphloroglucinols, xanthones, and benzophenones were the main chemical classes identified. The selective cytotoxicity against tumor cells, cell protection, anti-inflammatory, antimicrobial, antidepressant, anti-Alzheimer's, and adipogenesis-inhibition biological activities are described. Acylphloroglucinols were the most frequent compounds with anticancer and cell-protection mechanisms. To date, no work has been published with a full descriptive list directly relating secondary metabolites to their species of origin, plant parts used, extraction methodologies, mechanisms of action, and biological activities.

Minimizing the Silver Free Ion Content in Starch Coated Silver Nanoparticle Suspensions with Exchange Cationic Resins.

This work describes the optimization of a methodology for the reduction of silver ions from silver nanoparticle suspensions obtained from low-yield laboratory procedures. The laboratory synthesis of silver nanoparticles following a bottom-up approach starting from silver nitrate, originates silver ions that were not reduced to their fundamental state for nanoparticles creation at the end of the process. However, it is well known that silver ions can easily influence chemical assays due to their chemical reactivity properties and can limit biological assays since they interfere with several biological processes, namely intracellular ones, leading to the death of living cells or organisms. As such, the presence of silver ions is highly undesirable when conducting biological assays to evaluate the influence of silver nanoparticles. We report the development of an easy, low-cost, and rapid methodology that is based on cation exchange resins to minimize the silver ion content in a raw suspension of silver nanoparticles while preserving the integrity of the nanomaterials. This procedure preserves the physical-chemical properties of the nanoparticles, thus allowing the purified nanoparticulate systems to be biologically tested. Different types of cationic resins were tested, and the developed methodology was optimized by changing several parameters. A reduction from 92% to 10% of free silver/total silver ratio was achieved when using the Bio-Rad 50W-X8 100-200 mesh resin and a contact time of 15 min. Filtration by vacuum was used to separate the used resin from the nanoparticles suspension, allowing it to be further reused, as well as the purified AgNPs suspension.

Fluorescent CSC models evidence that targeted nanomedicines improve treatment sensitivity of breast and colon cancer stem cells.

To be able to study the efficacy of targeted nanomedicines in marginal population of highly aggressive cancer stem cells (CSC), we have developed a novel in vitro fluorescent CSC model that allows us to visualize these cells in heterogeneous population and to monitor CSC biological performance after therapy. In this model tdTomato reporter gene is driven by CSC specific (ALDH1A1) promoter and contrary to other similar models, CSC differentiation and un-differentiation processes are not restrained and longitudinal studies are feasible. We used this model for preclinical validation of poly[(d,l-lactide-co-glycolide)-co-PEG] (PLGA-co-PEG) micelles loaded with paclitaxel. Further, active targeting against CD44 and EGFR receptors was validated in breast and colon cancer cell lines. Accordingly, specific active targeting toward surface receptors enhances the performance of nanomedicines and sensitizes CSC to paclitaxel based chemotherapy. FROM THE CLINICAL EDITOR: Many current cancer therapies fail because of the failure to target cancer stem cells. This surviving population soon proliferates and differentiates into more cancer cells. In this interesting article, the authors designed an in vitro cancer stem cell model to study the effects of active targeting using antibody-labeled micelles containing chemotherapeutic agent. This new model should allow future testing of various drug/carrier platforms before the clinical phase.