Ioana Pavel

A biomaterial must be biologically compatible, mechanical, functional, corrosion resistant and easily adapt to clinical and laboratory technologies. Dental biomaterials are materials used to replace a part of a living system or to work closely with living tissue. Many scientific articles present different polymeric biocomposites with possible application in dentistry and this is a proof of the opportunity of a research in a field in full ascent and with great availability in the promotion of materials destined to �work under biological constraint� and which must also meet the functional requirements of a dental implant. The objectives of this research were to obtain and to comparatively evaluate different polymeric microparticles that can be used in dentistry. The samples based on poly(lactic-co-glycolic acid) and respectively polyurethane microparticles were characterized by pH and Zetasizer measurements, and in vitro cytotoxicity assays. The results indicate the obtaining of parti...

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...

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 reduce...

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 an...

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.

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 bee...

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 detec...

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 benefi...

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 t...

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 aspect...

Maslinic acid is a pentacyclic triterpene with a plethora of biological activities, including anti-inflammatory, antioxidant, antimicrobial, cardioprotective, and antitumor effects. New derivatives with improved properties and broad-spectrum activity can be obtained following structural changes of the compound. The present study was aimed to characterize a benzylamide derivative of maslinic acid—benzyl (2α, 3β) 2,3-diacetoxy-olean−12-en-28-amide (EM2)—with respect to the anti-angiogenic and anti-inflammatory effects in two in vivo experimental models. Consequently, the compound showed good tolerability and lack of irritation in the chorioallantoic membrane assay with no impairment of the normal angiogenic process during the tested stages of development. In the acute ear inflammation murine model, application of EM2 induced a mild anti-inflammatory effect that was potentiated by the association with zinc chloride (ZnCl2). A decrease in dermal thickness of mice ears was observed when ...

Apigenin (4′,5,7-trihydroxyflavone) (Api) is an important component of the human diet, being distributed in a wide number of fruits, vegetables and herbs with the most important sources being represented by chamomile, celery, celeriac and parsley. This study was designed for a comprehensive evaluation of Api as an antiproliferative, proapoptotic, antiangiogenic and immunomodulatory phytocompound. In the set experimental conditions, Api presents antiproliferative activity against the A375 human melanoma cell line, a G2/M arrest of the cell cycle and cytotoxic events as revealed by the lactate dehydrogenase release. Caspase 3 activity was inversely proportional to the Api tested doses, namely 30 μM and 60 μM. Phenomena of early apoptosis, late apoptosis and necrosis following incubation with Api were detected by Annexin V-PI double staining. The flavone interfered with the mitochondrial respiration by modulating both glycolytic and mitochondrial pathways for ATP production. The metabo...

The purpose of the present study was to determine the antioxidant capacity, the total phenol content, tannins, the cytotoxic and antiproliferative activity of some aqueous extracts obtained from spruce bark (Picea abies L.) and beech bark (Fagus sylvatica L.). In this regard, two types of extracts were obtained from both species using different methods of extraction: classical water bath extraction and ultrasound-assisted extraction. The antioxidant activity (AOA) was determined by means of DPPH assay and the cytotoxic and antiproliferative effects were determined using Alamar Blue technique and scratch assay. The total phenol content was determined colorimetrically by means of the Folin–Ciocalteu method. In vitro antitumor activity was tested on two different cell lines: A375 (human melanoma) and A549 (lung carcinoma) because of their different origin and metastatic potential. In addition, a non-tumor cell line (HaCaT human keratinocytes) was used in order to evaluate the samples selectivity. The results indicated that the aqueous extracts obtained by classical extraction had a higher antioxidant activity compared to the extracts obtained by ultrasound-assisted extraction. Moreover, the AOA of Picea abies L. bark extracts proved to be superior to those obtained from Fagus sylvatica L. bark extracts. Regarding the effect on cancer cells, the samples elicited a dose-dependent cytotoxic effect on A375 human melanoma cells, while on A549 lung carcinoma cells, the extractive solutions stimulated tumor cells viability, an effect that was reduced by increasing the concentration of the samples. Furthermore, the extractive solutions proved to possess antiproliferative properties when tested at the highest concentration; results that could be correlated with the antioxidant effects. In the case of the non-tumor cell line, the samples did not display a cytotoxic activity and stimulated cells proliferation.

Gold nanoparticles are currently investigated as theranostics tools in cancer therapy due to their proper biocompatibility and increased efficacy related to the ease to customize the surface properties and to conjugate other molecules. Betulin, [lup-20(29)-ene-3β, 28-diol], is a pentacyclic triterpene that has raised scientific interest due to its antiproliferative effect on several cancer types. Herein we described the synthesis of surface modified betulin-conjugated gold nanoparticles using a slightly modified Turkevich method. Transmission electron microscopy (TEM) imaging, dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used for the characterization of obtained gold nanoparticles. Cytotoxic activity and apoptosis assessment were carried out using the MTT and Annexin V/PI apoptosis assays. The results showed that betulin coated gold nanoparticles presented a dose-dependent cytotoxic effect and induced apoptosi...

Modulation of mitochondrial bioenergetics and glycolysis in malignancies has recently emerged a potential chemotherapeutic strategy since numerous malignant cells have overcome inhibition of the glycolytic pathway by increasing mitochondrial ATP production. Quercetin is a flavonoid with antioxidant, antiangiogenic, and chemoprotective properties but the mitochondrial effects are less characterized. The present study was purported to assess the effects of quercetin on the bioenergetic profile of B164A5 murine melanoma cell line. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured at 24, 48, and 72 h of treatment of B164A5 murine melanoma cells with increasing concentrations (25, 50, 100, and 150 µM) of quercetin using the extracellular flux analyzer Seahorse XF24e (Seahorse Agilent). Analysis of mitochondrial function was performed in the presence of the classic modulators of the electron transport chain: oligomycin, FCCP, and rotenone. 72-h tr...

Isoflavones are natural compounds belonging to the class of isoflavonoids, molecules with a chemical structure based on the 3-phenyl chromen-4-one backbone. As a particular element, the isoflavones are called also phytoestrogens, due to the structural similarity with 17-β estradiol, the primary female sex hormone, presenting both estrogen-agonist and estrogen-antagonist properties. This class of secondary plant metabolites has been extensively reported in the literature for a wide range of therapeutic activities including antioxidant, chemopreventive, anti-inflammatory, anti-allergic, antibacterial, cardio preventive effects. To sum up the latest information regarding the main isoflavones found in dietary sources as natural anti-inflammatory agents. The review updates with the recent research about genistein, daidzein, glycitein, biochanin A, formononetin and equol as anti-inflammatory phytocompounds. As a particular element the implications of this isoflavones in the link between i...

Malignant melanoma is a very aggressive form of skin cancer, with increasing rates every year, with an etiology that derives from the transformation and uncontrolled growth of melanocytes. There are several treatment options which can be used as unique treatment or combined, depending upon the stage of melanoma including surgical excision, chemotherapy, immunotherapy, targeted therapy. Plant Kingdom displays an unequalled potential for the synthesis of highly diversified chemical structures. Although natural compounds are synthesized in order to help the plant to interact with the environment, a large number of phytochemicals act as drugs within the human or animal body by activating various biochemical pathways. The study aims to review another approach in the management of this highly aggressive form of skin cancer, namely the effect of natural compounds in the chemoprevention of malignant melanoma.

Lupinus spp. are herbaceous perennial flowering plants included in the Fabaceae family. Among the approximately 200 species belonging to this genre, Lupinus albus L., also known as white lupin, Lupinus angustifolius L., and narrow-leafed lupin or blue lupin, represent two of the most studied species due to their intense culinary use and potential biological activity. The intention of the study was to characterize total phenolic content, perform FTIR analysis, and antiproliferative effects against A375 human melanoma cells extracts obtained from germinated and ungerminated seeds from Lupinus albus L. and Lupinus angustifolius L. Total phenolic content was assessed using the Folin-Ciocalteu colorimetric method. FTIR spectra were carried out by a Shimadzu Prestige-21 spectrometer in the range 400-4000 cm-1, using KBr pellets and resolution of 4 cm-1. Antiproliferative capacity was screened by employing the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and scratch a...

Despite tremendous research efforts for effective therapies, cancer remains the plague of the century and its burden is expected to increase worldwide in the near future. Metabolic reprogramming is a firmly established hallmark of all cancers, regardless their cellular or tissue origin, being a prerequisite for both tumor growth and invasion. Functional dependence of tumors on glycolysis and glutaminolysis and the crucial contribution of mitochondria to the tumor bioenergetic versatility are well recognized features and established therapeutic targets. The complex landscape of tumor metabolism in the context of the dynamic, bidirectional cross-talk with its stromal environment is a rapidly evolving field that increasingly supports the view of cancer both as metabolic disease and a disease of impaired cellular 'communication'. Many of the approved anticancer drugs are derived from natural sources and the search of novel drug candidates is still a priority view the rapid devel...

Drotaverine (also known as dihydroperparine or No-Spa(®) ) is an antispasmodic drug closely related to papaverin. Drotaverin also acts as a cytostatic compound for several human tumor cell lines and nonmalignant mouse fibroblasts, and EC50 values as low as 3.0 μM were observed in SRB assays for HT-29 human colorectal carcinoma cells. Small structural changes (e.g., aromatization, benzylic oxidation) led to a reduced activity or a complete loss of cytotoxicity. Staining of the cells with acridine orange showed the cell membrane of the dead cells to be still intact, and a slight G1/G0 arrest in the treated cells was observed after 24 h. Extra annexin V-FITC/PI assays and flow cytometry revealed drotaverine mainly to act as a cytostatic and only to a minor extent as cytotoxic agent.

Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low μM range for several human tumor cell lines. Low EC50 values were obtained especially for the picolinylamides 14-16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis.

Oleanolic and ursolic acids (OA and UA) are two pentacyclic triterpenes, ubiquitously spread in plants, previously known for their chemopreventive capacity on different types of cancer. The major pharmacological disadvantage of these phytocompounds is their poor water solubility, which often limits their applicability. Using the interfacial polycondensation combined with spontaneous emulsification technique, polyurethane nanostructures (PU) were synthetized in order to improve this problem. In order to test the in vivo chemopreventive potential of the two pure compounds, as well as the encapsulated compounds in PU used as drug carriers, a chemically-induced skin carcinogenesis model was constructed. UA and OA have a moderate chemopreventive activity against tumors induced by 7,12-dimethylbenzantracene (DMBA) and 12-O-tetradecanoilphorbol-13-acetate (TPA) application. Incorporation of active agents in PU did not lead to increased chemopreventive effect. PU is not a suitable formulati...

Skin injuries, and especially wounds of chronic nature, can cause a major negative impact on the quality of life. New efficient alternatives are needed for wound healing therapy and herbal products are being investigated due to a high content of natural compounds with promising healing activity. For this purpose, we investigated three Artemisia species, Artemisia absinthium L. (AAb), Artemisia dracunculus L. (ADr) and Artemisia annua L. (AAn). Ethanolic extracts, containing different polyphenolic compounds, elicited strong antioxidant activities in the DPPH assay, comparable to ascorbic acid. Human ketratinocyte proliferation was stimulated and wound closure was enhanced by all three extracts at concentrations of 100 µg/mL. The Artemisia extracts modulated angiogenesis by increasing vessel formation, especially following treatment with A. annua and A. dracunculus, extracts with a significantly higher content of chlorogenic acid. Good tolerability and anti-irritative effects were als...