Junipers of Various Origins as Potential Sources of the Anticancer Drug Precursor Podophyllotoxin.

Juniper representatives are natural sources of plenty of bioactive metabolites and have been used since ancient times as folk remedies against tapeworms, warts, cancer, etc. The antiproliferative activities of junipers are attributed to podophyllotoxin (PPT), which is a precursor for the synthesis of efficient anticancer drugs. However, the natural sources of PPT, Sinopodophyllum hexandrum (Royle) T. S. Ying and Podophyllum peltatum L., are already endangered species because of their intensive industrial exploitation. Therefore, identification of other sources of PPT is necessary. This study is a broad comparative investigation of junipers, for which original sources have been accessed from different continents of the world. The present research is aimed at the identification of species, producing PPT and other lignans at concentrations that are sufficient for the high antiproliferative activity of the corresponding extracts. Cytotoxic juniper leaf extracts demonstrated a broad spectrum of activity on a panel of cancer cell lines. The antiproliferative properties of junipers were attributed to the combined activity of great diversity of lignans (podophyllotoxin, deoxypodophyllotoxin, ß-peltatin, yatein, matairesinol, anhydropodorhizol, etc.), detected by UHPLC-HRMS and LC-ESI-MS/MS in the corresponding extracts. Several species of the genus Juniperus L. were outlined as perspective sources of drug precursors with potential pharmaceutical applications.

Cytotoxicity and Microbicidal Activity of Commonly Used Organic Solvents: A Comparative Study and Application to a Standardized Extract from Vaccinium macrocarpon.

The cytotoxicity and microbicidal capacity of seven organic solvents commonly applied for studying plant extracts and bioactive compounds were systematically investigated based on international standards. Four cell lines of normal (CCL-1, HaCaT) or tumor (A-375, A-431) tissue origin, seven bacterial and one fungal strain were used. The impact of the least toxic solvents in the determination of in vitro cytotoxicity was evaluated using a standardized extract from Vaccinium macrocarpon containing 54.2% v/v proanthocyanidins (CystiCran®). The solvents ethanol, methoxyethanol and polyethylene glycol were the least cytotoxic to all cell lines, with a maximum tolerated concentration (MTC) between 1 and 2% v/v. Ethanol, methanol and polyethylene glycol were mostly suitable for antimicrobial susceptibility testing, with minimum inhibitory concentrations (MICs) ≥ 25% v/v. The MTC values of the solvents dimethyl sulfoxide, dimethoxyethane and dimethylformamide varied from 0.03% to 1.09% v/v. The MICs of dimethyl sulfoxide, methoxyethanol and dimethoxyethane were in the range of 3.125-25% v/v. The cytotoxic effects of CystiCran® on eukaryotic cell lines were directly proportional to the superimposed effect of the solvents used. The results of this study can be useful for selecting the appropriate solvents for in vitro estimation of the cytotoxic and growth inhibitory effects of bioactive molecules in eukaryotic and prokaryotic cells.

Rose Flowers-A Delicate Perfume or a Natural Healer?

Plants from the Rosacea family are rich in natural molecules with beneficial biological properties, and they are widely appreciated and used in the food industry, perfumery, and cosmetics. In this review, we are considering Rosa damascena Mill., Rosa alba L., Rosa centifolia L., and Rosa gallica L. as raw materials important for producing commercial products, analyzing and comparing the main biological activities of their essential oils, hydrolates, and extracts. A literature search was performed to find materials describing (i) botanical characteristics; (ii) the phytochemical profile; and (iii) biological properties of the essential oil sand extracts of these so called "old roses" that are cultivated in Bulgaria, Turkey, India, and the Middle East. The information used is from databases PubMed, Science Direct, and Google Scholar. Roses have beneficial healing properties due to their richness of beneficial components, the secondary metabolites as flavonoids (e.g., flavones, flavonols, anthocyanins), fragrant components (essential oils, e.g., monoterpenes, sesquiterpenes), and hydrolysable and condensed tannins. Rose essential oils and extracts with their therapeutic properties-as respiratory antiseptics, anti-inflammatories, mucolytics, expectorants, decongestants, and antioxidants-are able to act as symptomatic prophylactics and drugs, and in this way alleviate dramatic sufferings during severe diseases.

Extracts of medicinal plants with natural deep eutectic solvents: enhanced antimicrobial activity and low genotoxicity.

Natural deep eutectic solvents (NADES) are a new alternative to toxic organic solvents. Their constituents are primary metabolites, non-toxic, biocompatible and sustainable. In this study four selected NADES were applied for the extraction of two medicinal plants: Sideritis scardica, and Plantago major as an alternative to water-alcohol mixtures, and the antimicrobial and genotoxic potential of the extracts were studied. The extraction efficiency was evaluated by measuring the extracted total phenolics, and total flavonoids. Best extraction results for total phenolics for the studied plants were obtained with choline chloride-glucose 5:2 plus 30% water; but surprisingly these extracts were inactive against all tested microorganisms. Extracts with citric acid-1,2-propanediol 1:4 and choline chloride-glycerol 1:2 showed good activity against S. pyogenes, E. coli, S. aureus, and C. albicans. Low genotoxicity and cytotoxicity were observed for all four NADES and the extracts with antimicrobial activity. Our results confirm the potential of NADESs for extraction of bioactive constituents of medicinal plants and further suggest that NADES can improve the effects of bioactive extracts. Further studies are needed to clarify the influence of the studied NADES on the bioactivity of dissolved substances, and the possibility to use such extracts in the pharmaceutical and food industry.

Three new prenyloxy chromanones from aerial parts of Hypericum aucheri.

Three new prenyloxy chromanone derivatives, aucherine A-C (6, 7 and 9) as well as six known prenylated phloroglucinols (1-5 and 8) were isolated from the aerial parts of Hypericum aucheri Jaub. Et Spach. The structures of the isolated compounds were established by means of spectral techniques (HRESIMS, 1D and 2D NMR). The new compounds were tested on а panel of human tumor cell line using MTT assay. All tested compounds exerted moderate cytotoxicity with IC50 values ranging from 19.6 to 57.8 µM. The influence of the new compounds on some key signaling molecules (procaspase-9 and Bcl-xL), implicated in the regulation of programmed cell death was assessed by Western blot analysis.

Cytotoxic prenylated acylphloroglucinols from Hypericum annulatum.

A phytochemical investigation of the aerial parts of Hypericum annulatum Moris led to the isolation of five new prenylated acylphloroglucinol derivatives hyperannulatins A-E (1-3, 5 and 7) in addition to the known hypercalyxone A (4) and 3-geranyl-1-(2'-methylpropanoyl)phloroglucinol (6). The structures were determined by 1D and 2D NMR and MS spectroscopic techniques. Compounds 1 and 2 have in their structure evgenyl group, a rare hydrocarbon side chain. The cytotoxicity of isolated compounds was established on a panel of tumor cell lines (HL-60, HL-60/DOX, MDA-MB, SKW-3 and K-562) and was determined using MTT based assays. The compounds 1 and 2 showed to be the most potent cytotoxic agents, whose IC50 values against the chemosensitive cell lines ranged 3.42-5.87 µM and 1.48-8.21 µM, respectively. Noteworthy, albeit all tested compounds were less potent than podophyllotoxin their IC50 values were comparable to that of the other reference drug etoposide. In some of the cell lines compounds 1 and 2 even outclassed the cytotoxicity of etoposide.