Cutaneous Polymeric-Micelles-Based Hydrogel Containing Origanum vulgare L. Essential Oil: In Vitro Release and Permeation, Angiogenesis, and Safety Profile In Ovo.

Origanum vulgare var. vulgare essential oil (OEO) is known as a natural product with multiple beneficial effects with application in dermatology. Oregano essential oil represents a potential natural therapeutic alternative for fibroepithelial polyps (FPs), commonly known as skin tags. Innovative formulations have been developed to improve the bioavailability and stability of essential oils. In this study, we aimed to evaluate the morphology of a polymeric-micelles-based hydrogel (OEO-PbH), the release and permeation profile of oregano essential oil, as well as to assess in vivo the potential effects on the degree of biocompatibility and the impact on angiogenesis in ovo, using a chick chorioallantoic membrane (CAM). Scanning electron microscopy (SEM) analysis indicated a regular aspect after the encapsulation process, while in vitro release studies showed a sustained release of the essential oil. None of the tested samples induced any irritation on the CAM and the limitation of the angiogenic process was noted. OEO-PbH, with a sustained release of OEO, potentially enhances the anti-angiogenic effect while being well tolerated and non-irritative by the vascularized CAM, especially on the blood vessels (BVs) in the presence of leptin treatment. This is the first evidence of in vivo antiangiogenic effects of a polymeric-micelle-loaded oregano essential oil, with further mechanistic insights for OEO-PbH formulation, involving leptin as a possible target. The findings suggest that the OEO-containing polymeric micelle hydrogel represents a potential future approach in the pathology of cutaneous FP and other angiogenesis-related conditions.

Comparison of In Vitro Antimelanoma and Antimicrobial Activity of 2,3-Indolo-betulinic Acid and Its Glycine Conjugates.

Malignant melanoma is one of the most pressing problems in the developing world. New therapeutic agents that might be effective in treating malignancies that have developed resistance to conventional medications are urgently required. Semisynthesis is an essential method for improving the biological activity and the therapeutic efficacy of natural product precursors. Semisynthetic derivatives of natural compounds are valuable sources of new drug candidates with a variety of pharmacological actions, including anticancer ones. Two novel semisynthetic derivatives of betulinic acid-N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) and N-(2,3-indolo-betulinoyl)glycylglycine (BA2)-were designed and their antiproliferative, cytotoxic, and anti-migratory activity against A375 human melanoma cells was determined in comparison with known N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic acid (BA4) and naturally occurring betulinic acid (BI). A dose-dependent antiproliferative effect with IC50 values that ranged from 5.7 to 19.6 µM was observed in the series of all five compounds including betulinic acid. The novel compounds BA1 (IC50 = 5.7 µM) and BA2 (IC50 = 10.0 µM) were three times and two times more active than the parent cyclic structure B4 and natural BI. Additionally, compounds BA2, BA3, and BA4 possess antibacterial activity against Streptococcus pyogenes ATCC 19615 and Staphylococcus aureus ATCC 25923 with MIC values in the range of 13-16 µg/mL and 26-32 µg/mL, respectively. On the other hand, antifungal activity toward Candida albicans ATCC 10231 and Candida parapsilosis ATCC 22019 was found for compound BA3 with MIC 29 µg/mL. This is the first report of antibacterial and antifungal activity of 2,3-indolo-betulinic acid derivatives and also the first extended report on their anti-melanoma activity, which among others includes data on anti-migratory activity and shows the significance of amino acid side chain on the observed activity. The obtained data justify further research on the anti-melanoma and antimicrobial activity of 2,3-indolo-betulinic acid derivatives.

Phytochemical Characterization and Biological Evaluation of Origanum vulgare L. Essential Oil Formulated as Polymeric Micelles Drug Delivery Systems.

This study presents phytochemical characterization and biological evaluation of Origanum vulgare L. essential oil (OEO) formulated as polymeric micelles drug delivery systems as a possible non-invasive approach for the management of skin tags. GC-MS analysis of Romanian OEO revealed the identification and quantification of 43 volatile compounds (thymol and carvacrol being the main ones). The antioxidant activity was shown by four consecrated methods: CUPRAC, ABTS, ORAC and DPPH. OEO was incorporated by micellar solubilization into a binary hydrogel based on a Pluronic F 127/L 31 block-copolymers mixture. The pH, consistency, spreadability, particle size, polydispersity index and zeta potential of the OEO-loaded poloxamer-based binary hydrogel (OEO-PbH) were investigated. OEO-PbH was skin compatible in terms of pH and exhibited adequate spreadability and consistency. The minimal inhibitory concentrations of the tested OEO were similar to those obtained for the formulation, lower (2.5 µg/mL) for yeast and higher (40-80 µg/mL) for Gram-negative bacilli. As keratinocytes are among main components of skin tags, an in vitro evaluation was conducted in order to see the effect of the formulation against HaCaT human keratinocytes. OEO-PbH decreased HaCaT cells migration and proliferation and elicited a cytotoxic and pro-apoptotic effect in a dose- and time-dependent manner. No harmful effect on the viability of dendritic cells (DCs) was detected following the incubation with different concentrations (0-200 µg/mL) of the 5% formulation. Treatment in inflammatory DCs (+LPS) indicated a decrease in cytokine production of IL-6, TNF-α and IL-23 but no significant effect on IL-10 in any of the tested concentrations.

Oxidative Stability and Protective Effect of the Mixture between Helianthus annuus L. and Oenothera biennis L. Oils on 3D Tissue Models of Skin Irritation and Phototoxicity.

The present study was aimed to evaluate the oxidative stability as well as to assess the protective effect of the mixture of Helianthus annuus L. (HAO) and Oenothera biennis L. (OBO) oils on 3D tissue models of skin irritation and phototoxicity. The following methods were used: GS analysis (fatty acids composition), thiobarbituric acid-reactive substances assay (TBA) (lipid oxidation degree of tested samples), 3D EpiDerm models (skin irritation and phototoxicity). For HAO the detected saturated fatty acids (SFA) were palmitic acid (7.179%), stearic acid (3.586%), eicosanoic (0.138%) and docosanoic acid (0.548%) The monounsaturated acids (MUFA) were palmitoleic acid (0.158%) and oleic acid (28.249%) and the polyunsaturated acids (PUFA) were linoleic acid (59.941%) and linolenic acid (0.208%). For OBO the detected SFA were myristic acid (0.325%), pentadecylic acid (0.281%), palmitic (7.2%), stearic (2.88%), and arachidic acid (0.275%). Regarding MUFA, even a lower proportion (8.196%) was observed, predominantly being oleic acid, cis form (7.175%), oleic (n10) (0.558%) and 11-eicosenoic (0.210%) acids. The higher content was found for PUFA (82.247%), the most significant proportions being linoleic acid (72.093%), arachidonic acid (9.812%) and linolenic (0.233%). Obtained data indicate a good oxidative stability and biocompatibility of the mixture on the 3D EpiDerm models with no irritant and no phototoxic effects. Oenothera biennis L. oil may be an excellent natural choice in order to delay or prevent oxidative damage of Helianthus annuus L. oil.

Green Synthesis of Silver Nanoparticles Using Populi gemmae Extract: Preparation, Physicochemical Characterization, Antimicrobial Potential and In Vitro Antiproliferative Assessment.

Green route is an economic, facile and eco-friendly method, employed for the synthesis of various types of nanoparticles, having it as a starting point biological entity, especially as a plant extract. The present study aims to obtain silver nanoparticles (AgNPs) starting from an ethanolic extract of Populi gemmae (Pg), by adjusting the reaction parameters. The morphological and structural characterization exhibited that both the reaction temperature and the concentration of metal salt, contributes to the obtaining of Pg-AgNPs with adjustable size and shape. The newly synthesized nanoparticles exhibited a good antibacterial activity on Gram-positive bacteria as well as antifungal activity. The in vitro antiproliferative activity of Pg-AgNPs was assessed on two different cancer cell lines (breast cancer cells-MCF7 and lung carcinoma epithelial cells-A549). Results have shown that the green-synthetized Pg-AgNPs_S2 (obtained at 60 °C, using AgNO3 of 5 M) induced a substantial decrease in tumor cell viability in a dose-dependent manner with an IC50 ranging from 5.03 to 5.07 µg/mL on A549 cell line and 3.24 to 4.93 µg/mL on MCF7 cell line.

An Up-To-Date Review Regarding Cutaneous Benefits of Origanum vulgare L. Essential Oil.

Due to the plethora of pharmacological activities reported in the literature, Origanum vulgare L. is a valuable aromatic plant for the medicine of the XXI century. Recent studies highlight that Origanum vulgare L. essential oil (OvEo) has gained attention in the dermatological field due to the cosmeceutical potential correlated with the presence of thymol and carvacrol. As a result of the fulminant expansion of bacterial resistance to antibiotics and the aggressiveness of skin infections, OvEo was extensively studied for its antimicrobial activity against Staphyloccocus spp. and Pseudomonas aeruginosa. Moreover, researchers have also assessed the anti-inflammatory activity of OvEo, suggesting its tissue remodeling and wound healing potential. Whereas OvEo comprises important biological activities that are used in a wide range of pathologies, recently, essential oils have shown great potential in the development of new therapeutic alternatives for skin disorders, such as acne, wounds or aging. Furthermore, substantial efforts have been committed to the development of modern formulations, such as microemulsions and nanoemulsions, in order to create the possibility for topical application. The review brings to the fore the most recent findings in the dermatological field regarding potential plant-based therapies involving OvEo, emphasizing the modern pharmaceutical formulation approaches and the cutaneous benefits in skin disorders.

Antimicrobial activity, in vitro anticancer effect (MCF-7 breast cancer cell line), antiangiogenic and immunomodulatory potentials of Populus nigra L. buds extract.

PURPOSE: The aim of this study was to evaluate the antioxidant potential, antimicrobial activity, the in vitro anticancer effect (tested on MCF-7 breast cancer cell line), as well as the antiangiogenic and immunomodulatory potential of Populus nigra L. bud (Pg) extract collected from the western part of Romania. RESULTS: Populus nigra L. bud extract presents an important antioxidant activity, due to the rich phytochemical composition. Regarding the biological activity, results have shown that poplar bud extract presents a significant inhibitory activity against Gram-positive bacteria and a dose-dependent decrease of MCF-7 tumor cell viability with an IC50 of 66.26 µg/mL, while not affecting healthy cells. Phenomena of early apoptotic events at the maximum concentration tested (150 µg/mL) were detected by Annexin V-PI double staining. The extract induced G0/G1 phase cell cycle arrest. In addition, Pg extract showed antiangiogenic potential on the chorioallantoic membrane. Also, at the highest concentration (150 µg/mL), good tolerability and no signs of toxicity upon vascular plexus were observed. Moreover, in low concentrations, the Pg extract had immunomodulatory activity on primary human dendritic cells by upregulating IL-12 and IL-23 subunits. CONCLUSION: The study concludes that poplar bud extract elicited antioxidant activity, antitumor properties on the breast cancer cell line, followed by an antiangiogenic effect and an immunomodulatory potential on human primary dendritic cells. The biological activity of Populus nigra L. buds extract may open new directions of research on the topic addressed.

Inorganic Element Determination of Romanian Populus nigra L. Buds Extract and In Vitro Antiproliferative and Pro-Apoptotic Evaluation on A549 Human Lung Cancer Cell Line.

Populus nigra L. is a plant from Salicaceae family, native in Europe. Many parts of this tree can be used as active ingredients, but the most valuable are the buds. In recent years, a growing number of studies reported their activity in the development of a wide range of pharmacological activities including diabetes, cardiovascular diseases, and cancer. The aim of this study was to determine the phytochemical composition and to evaluate the inorganic elements' concentration as well as the in vitro antiproliferative and pro-apoptotic potential of a Populus nigra L. buds extract collected from Timișoara (Romania) against A549 human lung cancer cell line. Populus nigra L. bud extract was found to contain twelve different phenolic compounds. The inorganic elements concentrations were below the limit of detection for Co, Pb, and As, whereas Cu = 6.66 µg/g; Cr = 0.79 µg/g; Ni = 3.28 µg/g; Fe = 39.00 µg/g; Zn = 14.84 µg/g; Mn = 0.59 µg/g; Al = 2109.87 µg/g; and Cd = 0.019 µg/g. The extract was tested for the in vitro antiproliferative and pro-apoptotic potential on A549 human lung cancer cell line using different concentrations, namely 10, 25, 50, 75, 100, and 150 µg/mL. Results have shown that poplar bud extract induced a significant decrease of tumor cell viability in a dose-dependent manner with an IC50 = 72.49 µg/mL and blocked the cells in the G0/G1 phase of the cell cycle. Phenomena of early apoptosis (from 1.34 ± 0.33% control cells to 2.68 ± 0.62% at 150 µg/mL) and late apoptosis (from 1.43 ± 0.14% control cells to 5.15 ± 1.02% at 150 µg/mL) were detected by Annexin V-PI double staining. Poplar bud extract can be regarded as a promising candidate for future studies involving lung cancer.

An In Vitro-In Vivo Evaluation of the Antiproliferative and Antiangiogenic Effect of Flavone Apigenin against SK-MEL-24 Human Melanoma Cell Line.

One of the most important class of natural compounds with successful preclinical results in the management of cancer is the flavonoids. Due to the plethora of biological activities, apigenin (4',5,7 trihydroxyflavone) is a main representant of the flavone subclass. Although the antiproliferative and antiangiogenic effects of apigenin were studied on a significant number of human and murine melanoma cell lines, in order to complete the data existing in the literature, the aim of this study is to evaluate the in vitro effect of apigenin on SK-MEL-24 human melanoma cell line as well as in vivo on tumor angiogenesis using the aforementioned cell line on the chorioallantoic membrane assay. Results have shown that in the range of tested doses, the phytocompound presents significant antiproliferative, cytotoxic, and antimigratory potential at 30 µM, respectively, 60 µM. Moreover, the phytocompound in both tested concentrations limited melanoma cell growth and migration and induced a reduced angiogenic reaction limiting melanoma cell development.

Melissa officinalis L. Aqueous Extract Exerts Antioxidant and Antiangiogenic Effects and Improves Physiological Skin Parameters.

Melissa officinalis (MO) is a medicinal plant well-known for its multiple pharmacological effects, including anti-inflammatory, anticancer and beneficial effects on skin recovery. In this context, the present study was aimed to investigate the in vitro and in vivo safety profile of an MO aqueous extract by assessing cell viability on normal (HaCaT-human keratinocytes) and tumor (A375-human melanoma) cells and its impact on physiological skin parameters by a non-invasive method. In addition, the antioxidant activity and the antiangiogenic potential of the extract were verified. A selective cytotoxic effect was noted in A375 cells, while no toxicity was noticed in healthy cells. The MO aqueous extract safety profile after topical application was investigated on SKH-1 mice, and an enhanced skin hydration and decreased erythema and transepidermal water loss levels were observed. The in ovo CAM assay, performed to investigate the potential modulating effect on the angiogenesis process and the blood vessels impact, indicated that at concentrations of 100 and 500 µg/mL, MO aqueous extract induced a reduction of thin capillaries. No signs of vascular toxicity were recorded at concentrations as high as 1000 µg/mL. The aqueous extract of MO leaves can be considered a promising candidate for skin disorders with impaired physiological skin parameters.

Anticancer Potential of Betulonic Acid Derivatives.

Clinical trials have evidenced that several natural compounds, belonging to the phytochemical classes of alkaloids, terpenes, phenols and flavonoids, are effective for the management of various types of cancer. Latest research has proven that natural products and their semisynthetic variants may serve as a starting point for new drug candidates with a diversity of biological and pharmacological activities, designed to improve bioavailability, overcome cellular resistance, and enhance therapeutic efficacy. This review was designed to bring an update regarding the anticancer potential of betulonic acid and its semisynthetic derivatives. Chemical derivative structures of betulonic acid including amide, thiol, and piperidine groups, exert an amplification of the in vitro anticancer potential of betulonic acid. With the need for more mechanistic and in vivo data, some derivatives of betulonic acids may represent promising anticancer agents.

[Corrigendum] Mechanistic investigations of antitumor activity of a Rhodamine B­oleanolic acid derivative bioconjugate.

Subsequently to the publication of the above paper, the authors have realized that they should have credited a Professor René Csuk [Martin­Luther­Universität Halle­Wittenberg, Halle (Saale), Germany] for the use of a compound that his group synthesized in the study. Therefore, the authors wish to include the following text in the Acknowledgements' section of the Declarations: 'The authors are grateful to Professor Rene Csuk, Department of Organic Chemistry, Martin­Luther University Halle­Wittenberg, for providing us with the rhodamine B­conjugated oleanolic acid derivative (RhodOA)'. All the named authors agree to this Corrigendum, and apologize to Professor Csuk for the upset and inconvenience caused. [the original article was published in Oncology Reports 44: 1169­1183, 2020; DOI: 10.3892/or.2020.7666].

A Recent Insight Regarding the Phytochemistry and Bioactivity of Origanum vulgare L. Essential Oil.

Origanum vulgare L. is a widely used aromatic plant, especially due to its content in essential oil, mainly rich in carvacrol and thymol. The ethnopharmacological uses of Origanum vulgare L. essential oil (OEO) comprise digestive, respiratory, or dermatological disorders. The review focuses on the increasing number of recent studies investigating several biological activities of OEO. The bioactivities are in tight relation to the phytochemical profile of the essential oil, and also depend on taxonomic, climatic, and geographical characteristics of the plant material. The antibacterial, antifungal, antiparasitic, antioxidant, anti-inflammatory, antitumor, skin disorders beneficial effects, next to antihyperglycemic and anti-Alzheimer activities were reported and confirmed in multiple studies. Moreover, recent studies indicate a positive impact on skin disorders of OEO formulated as nanocarrier systems in order to improve its bioavailability and, thus, enhancing its therapeutic benefits. The review brings an up to date regarding the phytochemistry and bioactivity of Origanum vulgare L. essential oil, underlining also the most successful pharmaceutical formulation used for skin disorders.

Recent Advances Regarding the Phytochemical and Therapeutic Uses of Populus nigra L. Buds.

Populus nigra L. (Salicaceae family) is one of the most popular trees that can be found in deciduous forests. Some particularities that characterize the Populus genus refer to the fact that it includes more than 40 species, being widespread especially in Europe and Asia. Many residues, parts of this tree can be used as a bioresource for different extracts as active ingredients in pharmaceuticals next to multiple benefits in many areas of medicine. The present review discusses the latest findings regarding the phytochemical composition and the therapeutic properties of Populus nigra L. buds. The vegetal product has been described mainly to contain phenolic compounds (phenols, phenolic acids and phenylpropanoids), terpenoids (mono and sesquiterpenoids), flavones (e.g., apigenol and crysin), flavanones (e.g., pinocembrin and pinostrombin), caffeic/ferulic acids and their derivates, and more than 48 phytocompounds in the essential oils. The resinous exudates present on the buds have been the major plant source used by bees to form propolis. Several studies depicted its antioxidant, anti-inflammatory, antibacterial, antifungal, antidiabetic, antitumor, hepatoprotective, hypouricemic properties and its effects on melanin production. All these lead to the conclusion that black poplar buds are a valuable and important source of bioactive compounds responsible for a wide range of therapeutic uses, being a promising candidate as a complementary and/or alternative source for a large number of health problems. The aim of the review is to gather the existing information and to bring an up to date regarding the phytochemical and therapeutic uses of Populus nigra L. buds.

Biological Evaluation of Black Chokeberry Extract Free and Embedded in Two Mesoporous Silica-Type Matrices.

Black chokeberry fruits possess a wide range of biological activities, among which the most important that are frequently mentioned in the literature are their antioxidant, anti-inflammatory, anti-proliferative, and antimicrobial properties. The present paper reports, for the first time, the encapsulation of the ethanolic extract of Aronia melanocarpa L. fruits into two mesoporous silica-type matrices (i.e., pristine MCM-41 and MCM-41 silica decorated with zinc oxide nanoparticles). The aim of this work was to evaluate the antiradicalic capacity, the antimicrobial potential, and the effects on the cell viability on a cancer cell line (i.e., A375 human melanoma cell line) versus normal cells (i.e., HaCaT human keratinocytes) of black chokeberry extract loaded on silica-type matrices in comparison to that of the extract alone. The ethanolic polyphenolic extract obtained by conventional extraction was characterized by high-performance liquid chromatography with a photodiode array detector (HPLC-PDA) and spectrophotometric methods. The extract was found to contain high amounts of polyphenols and flavonoids, as well as good radical scavenging activity. The extract-loaded materials were investigated by Fourier transform infrared spectroscopy, N2 adsorption-desorption isotherms, thermal analysis, and radical scavenger activity on solid samples. The black chokeberry extract, both free and loaded onto mesoporous silica-type matrices, exhibited a significant antioxidant capacity. Antibacterial activity was recorded only for Gram-positive bacteria, with a more potent antibacterial effect being observed for the extract loaded onto the ZnO-modified MCM-41 silica-type support than for the free extract, probably due to the synergistic effect of the ZnO nanoparticles that decorate the pore walls of silica. The cellular viability test (i.e., MTT assay) showed dose- and time-dependent activity regarding the melanoma cell line. The healthy cells were less affected than the cancer cells, with all tested samples showing good cytocompatibility at doses of up to 100 µg/mL. Improved in vitro antiproliferative and antimigratory (i.e., scratch assay) potential was demonstrated through the loading of black chokeberry extract into mesoporous silica-type matrices, and the screened samples exhibited low selectivity against the tested non-tumor cell line. Based on presented results, one can conclude that mesoporous silica-type matrices are good hosts for black chokeberry extract, increasing its antioxidant, antibacterial (on the screened strains), and in vitro antitumor (on the screened cell line) properties.

Mechanistic investigations of antitumor activity of a Rhodamine B­oleanolic acid derivative bioconjugate.

Cancer remains a major health problem worldwide due to its high mortality rate. New therapeutic options highlight the importance of discovering new compounds that target the tumor microenvironment, interrupt angiogenesis and act selectively. The present study assessed the antitumor effect and investigated the mechanism of action of a rhodamine B­conjugated oleanolic acid derivative (RhodOA). Consequently, the compound was tested on different human tumor cell lines (A375 melanoma, A549 lung adenocarcinoma and MDA­MB­231 breast adenocarcinoma) and on a non­tumor cell line HaCaT human keratinocyte. RhodOA produced a dose­dependent decrease in tumor cell viability especially in the melanoma cells while affecting the keratinocytes less. In melanoma cells, RhodOA reduced cell migration and produced condensation of cell nuclei and of actin fibers. Furthermore, an impairment in melanoma cell mitochondrial function was observed, while the mitochondrial function of keratinocytes was left intact. In the in ovo chorioallantoic membrane model, RhodOA elicited antiangiogenic effect, without showing irritation effect on the membrane. The study provides information on the selective antitumor effect of the derivative and its ability to inhibit cellular respiration, therefore RhodOA can be classified as 'MITOCAN'.

Lemon Balm Extracts Prevent Breast Cancer Progression In Vitro and In Ovo on Chorioallantoic Membrane Assay.

Breast cancer is the most frequently diagnosed malignant pathology, representing the primary cause of cancer death in women. Natural products are an appealing strategy to limit the progression of the disease. Targeting angiogenesis in breast cancer may positively impact on poor prognosis of breast cancer. As source of natural compounds, we investigated the leaves of Melissa officinalis L. (MO), known as lemon balm, an aromatic plant that spontaneously grows in the South and Western areas of Romania, being traditionally recommended as anxiolytic, antispasmodic, or as digestive remedy. Our aim was to investigate the phytochemical profiling and the antiangiogenic and chemopreventive bioactivity of MO from Banat region, on breast cancer. Two ethanolic extracts of MO (MOE96 and MOE70) and one methanolic extract (MOM80) were subjected to polyphenol and triterpene profiling by HPLC-MS, and the antioxidant capacity was evaluated. The antiangiogenic potential was investigated using the chorioallantoic membrane assay (CAM). The MTT(3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide) assay was used to investigate the cytotoxic effects on MCF-7 and MDA-MB-231breast cancer cells, as well as on MCF-10A normal breast epithelial cells, while apoptosis was performed by DAPI staining. Rosmarinic acid (RA) and ursolic acid (UA) were revealed as dominant phytocompounds. The highest concentration in phytochemicals were found in MOM80; MOE96 was more concentrated in UA, while MOE70 extracted more RA. MOE96 inhibited cancer progression and angiogenesis in the in ovo CAM model using MDA-MB-231 cells, inhibiting breast cancer progression and angiogenesis for the MDA-MB-231 breast cancer cell line; no secondary tumoral areas were registered, indicative for a preventive effect against breast tumor cell invasiveness. The highest cell inhibitory activity was also exhibited by MOE96, in particular against the estrogen receptor positive MCF7 breast cancer cell line, with no cytotoxic effect on healthy cells. The estrogen receptor positive MCF7 cell line proved to be more sensitive to the extract antiproliferative activity than the triple negative MDA-MB-231 breast cancer cell line. Nevertheless, the chemopreventive potential of MOE96 extract is phenotype-dependent and is rather related to the apoptosis and antiangiogenic effects suggesting a multitargeted mechanism of action due to its multiple compound composition next to a concentration ratio of RA : UA in favor of UA.

Phytochemical and Biological Screening of Oenothera Biennis L. Hydroalcoholic Extract.

Oenothera biennis L. (OB), also commonly known as evening primrose, belongs to the Onagraceae family and has the best studied biological activity of all the members in the family. In therapy, the most frequently used type of extracts are from the aerial part, which are the fatty oils obtained from the seeds and have a wide range of medicinal properties. The aim of this study was to evaluate the phytochemical composition and biological activity of OB hydroalcoholic extract and to provide directions for the antimicrobial effect, antiproliferative and pro-apoptotic potential against A375 melanoma cell line, and anti-angiogenic and anti-inflammatory capacity. The main polyphenols and flavonoids identified were gallic acid, caffeic acid, epicatechin, coumaric acid, ferulic acid, rutin and rosmarinic acid. The total phenolic content was 631.496 µgGAE/mL of extract and the antioxidant activity was 7258.67 µmolTrolox/g of extract. The tested extract had a mild bacteriostatic effect on the tested bacterial strains. It was bactericidal only against Candida spp. and S. aureus. In the set of experimental conditions, the OB extract only manifested significant antiproliferative and pro-apoptotic activity against the A375 human melanoma cell line at the highest tested concentration, namely 60 µg/mL. The migration potential of A375 cells was hampered by the OB extract in a concentration-dependent manner. Furthermore, at the highest tested concentration, the OB extract altered the mitochondrial function in vitro, while reducing the angiogenic reaction, hindering compact tumor formation in the chorioallantoic membrane assay. Moreover, the OB extract elicited an anti-inflammatory effect on the experimental animal model of ear inflammation.

Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer.

Cannabis sativa L. is a plant long used for its textile fibers, seed oil, and oleoresin with medicinal and psychoactive properties. It is the main source of phytocannabinoids, with over 100 compounds detected so far. In recent years, a lot of attention has been given to the main phytochemicals present in Cannabis sativa L., namely, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Compared to THC, CBD has non-psychoactive effects, an advantage for clinical applications of anti-tumor benefits. The review is designed to provide an update regarding the multi-target effects of CBD in different types of cancer. The main focus is on the latest in vitro and in vivo studies that present data regarding the anti-proliferative, pro-apoptotic, cytotoxic, anti-invasive, anti-antiangiogenic, anti-inflammatory, and immunomodulatory properties of CBD together with their mechanisms of action. The latest clinical evidence of the anticancer effects of CBD is also outlined. Moreover, the main aspects of the pharmacological and toxicological profiles are given.

Romanian Wormwood (Artemisia absinthium L.): Physicochemical and Nutraceutical Screening.

Artemisia species are used worldwide for their antioxidant, antimicrobial and anti-inflammatory properties. This research was designed to investigate the phytochemical profile of two ethanolic extracts obtained from leaves and stems of A. absinthium L. as well as the biological potential (antioxidant activity, cytotoxic, anti-migratory and anti-inflammatory properties). Both plant materials showed quite similar thermogravimetric, FT-IR phenolic profile (high chlorogenic acid) with mild antioxidant capacity [ascorbic acid (0.02-0.1) > leaves (0.1-2.0) > stem (0.1-2.0)]. Alcoholic extracts from these plant materials showed a cytotoxic effect against A375 (melanoma) and MCF7 (breast adenocarcinoma) and affected less the non-malignant HaCaT cells (human keratinocytes) at 72 h post-stimulation and this same trend was observed in the anti-migratory (A375, MCF7 > HaCat) assay. Lastly, extracts ameliorated the pro-inflammatory effect of TPA (12-o-tetradecanoylphorbol-13-acetate) in mice ears, characterized by a diffuse neutrophil distribution with no exocytosis or micro-abscesses.