AbstractIn this study, two ethanolic extracts, from Stokesia aster (Slae26) and Geranium pratense (Gpre36) respectively, were evaluated in order to assess the cytotoxic activity and potential antiproliferative activity upon the nontumorigenic human epithelial cell line derived from the mammary gland (MCF-12A) and the human breast tumor cell line (BT-20). The selection of the plant species was done on the basis of their chemical composition, specifically combinations of luteolin derivatives with caffeic and gallic acid derivatives. Therefore, the S. laevis ethanolic extract proved its capacity to inhibit the viability of both normal and tumor breast cell lines (i.e., up to 90% cell viability inhibition, IC50 = 42 µg/mL). On the contrary, the G. pratense ethanolic extract proved weak stimulatory effects on the viability of the two human breast cell lines studied. The obtained results were discussed in the contexts of computational studies and drug-likeness bioactivity of seven common luteolin derivatives: luteolin, luteolin-7-O-glucoside/cynaroside, luteolin-5-O-glucoside/galuteolin, luteolin-6-C-glucoside/isoorientin, luteolin-8-C-glucoside/orientin, luteolin-3′,4′-di-O-glucoside and luteolin-7,3′-di-O-glucoside. Computational studies have revealed that the hydrophilic behavior of luteolin derivatives (log P values) does not follow other tested parameters (e.g., polar surface area values), possibly explaining different efficacy concerning the biological properties in vitro. These predictions could be a starting point for studies on the biochemical mechanism by which luteolin derivatives induce biological effects.

This study is focused on the encapsulation of polyphenols from Lycium barbarum leaves into liposomes as a strategy to improve their delivery. Liposomes loaded with Lycium barbarum leaves extract were obtained and characterized for particle size, polydispersity, entrapment efficiency, and stability. Liposomes presented entrapment efficiency higher than 75%, nanometric particle size, narrow polydispersity, and good stability over three months at 4 °C. The liposomes containing Lycium barbarum offered a slower release of polyphenols with attenuated burst effect compared with the dissolution of free Lycium barbarum extract in phosphate buffer solution at pH 7.4. Moreover, an in vitro pretreatment of 24 h with loaded liposomes showed a cytoprotective effect against H2O2-induced cytotoxicity on L-929 mouse fibroblasts cells. These preliminary findings imply that liposomes could be successfully employed as carriers for polyphenols in pharmaceutical applications.

Stokesia laevis (common name Stokes aster) ethanolic extract (Slae26) containing 5 mg GAE/mL extract was investigated to establish cytotoxicity and anti-proliferative effects. The assays were performed on normal murine fibroblast cell line L929 and malignant murine melanoma cell line B16, respectively; for the first time in literature data, potential cytotoxic and anti-proliferative effects of the ethanolic extract from S. laevis on both, normal murine fibroblast cell line L929, and murine melanoma cell line B16 have been proved. The study is supplemented by molecular docking simulations of the major components of Slae26 against human tyrosinase receptor, to evaluate possible melanogenesis inhibition.

The paper deals with the preparation and characterisation of hydroalcoholic polyphenolic extract from Sambucus ebulus (SE) leaves that was further loaded into three-types of lipid vesicles: liposomes, transfersomes, and ethosomes, to improve its bioavailability and achieve an optimum pharmacological effect. For Sambucus ebulus L.-loaded lipid vesicles, the entrapment efficiency, particle size, polydispersity index and stability were determined. All prepared lipid vesicles showed a good entrapment efficiency, in the range of 75–85%, nanometric size, low polydispersity indexes, and good stability over three months at 4 °C. The in vitro polyphenols released from lipid vehicles demonstrated slower kinetics when compared to the free extract dissolution in phosphate buffer solution at pH 7.4. Either free SE extract or SE extract loaded into lipid vesicles demonstrated a cytoprotective effect, even at low concentration, 5 ug/mL, against hydrogen peroxide-induced toxicity on L-929 mouse fibroblasts’ cell lines. However, the cytoprotective effect depended on the time of the cells pre-treatment with SE extract before exposure to a hydrogen peroxide solution of 50 mM concentration, requiring at least 12 h of pre-treatment with polyphenols with radical scavenging capacity.

This study evaluates in vitro cytotoxic and antiproliferative activity on human colon tumor cell line Caco-2 (ATCC-HTB-37) of a standardized (5 mg GAE/mL) ethanolic extract from Stokesia laevis (Slae26), of five polyphenols compounds (reference substances, ref.), namely luteolin-7-O-glucoside, luteolin-8-C-glucoside, caffeic acid, gentisic acid, and p-aminobenzoic acid (PABA), as well as of Slae26 combinations with the five reference substances, 1:1 mass rate (GAE, ref.). Cell viability studies (MTS test) have revealed IC50 values of 36 μg GAE/mL in the case of Slae26 ethanolic extract, while Slae26 combinations with the five phenolics indicated IC50 values around 5 μg GAE/mL. In silico docking studies on the molecular targets human tankyrase 1 (TNKS1) and human tankyrase 2 (TNKS2) in complex with their native ligands, Co-crystallized 3J5A and Co-crystallized FLN, indicated score values of −104.15 and −76.97, respectively; in the series of the reference compounds studied, luteolin-7-O-glucoside was revealed with the best score values on both molecular targets (−80.49 and −85.17), together signifying real antiproliferative potential against human colon cancer of Slae26, of luteolin-7-O-glucoside, and of Slae26 combinations with all food-related bioactive compounds tested.

Aronia melanocarpa L. fruit (common black chokeberry) is one of the most abundant sources of antioxidant compounds in the plant world, superior to all edible fruits; chokeberry fruits contain up to 100 g total phenols per kg fresh material, predominantly (−)epicatechin, cyanidin-3-glycosides and procyanidins (60%), added to quercetin and caffeoyl quinic acid derivates.

This study aimed to compare in vitro cell cytotoxicity and antiproliferative potency of three standardized ethanolic extracts (5mg GAE/mL sample) from quince flower petals, leaves and fruit pellet on four cell lines (L-929, and HepG2, Caco-2 and BT-20 respectively). Comparative analytical qualitative studies (HPTLC) indicated that if quince leaf extracts (Col40) mainly contain quercetin and kaempferol derivates, the flower petal extracts (Cof40) contain caffeoylquinic acid derivates, while the fruit pellet extracts (Cop40) are comprised of quercetin and caffeoylquinic acid derivates. Pharmacological studies demonstrated the lack of toxicity of test extracts; the most important antiproliferative effects were observed on the hepatic cancer cell line HepG2 (up to 75%, 53% and 70% inhibition in the case of Col40, Cof40 and Cop40 test extracts), followed by the colon cancer cell line Caco-2 (up to 69%, 77% and 40% inhibition) and breast cancer cell line BT-20 (up to 54%, 61% and 19% inhibition). The docking simulations on hyperoside, isoquercitrin, astragalin, and quercetin and kaempferol compared to the synthetic co-crystallized LI0 A1000 ligand (a strong inhibitor of anti-apoptotic protein Bcl-2) indicated astragalin as the most feasible protein inhibitor, but quercetin and kaempferol respected all the parameters involved in the Lipinski rule, making them the most promising antiproliferative candidates.

The aim of this study was to develop a delivery system for polyphenols from an extract of Echinacea purpurea leaves, based on liposomes. Liposomes loaded with Echinacea purpurea were prepared and characterized in terms of entrapment efficiency, size, polydispersity index, stability and release behavior. Results showed good entrapment efficiency, small sizes, low polydispersity index and good stability over 90 days at 4oC. Also, the liposomal formulations presented reduced burst release and slow release of polyphenols compared with free extract. Therefore, liposomes offer a great potential in the development of drug delivery systems for polyphenols.