Valproic acid inhibits cell growth in both MCF-7 and MDA-MB231 cells by triggering different responses in a cell type-specific manner.

BACKGROUND: Breast cancer is the second leading cause of death among women after lung cancer. Despite the improvement in prevention and in therapy, breast cancer still remains a threat, both for pre- and postmenopausal women, due to the development of drug resistance. To counteract that, novel agents regulating gene expression have been studied in both hematologic and solid tumors. The Histone Deacetylase (HDAC) inhibitor Valproic Acid (VA), used for epilepsy and other neuropsychiatric diseases, has been demonstrated a strong antitumoral and cytostatic activity. In this study, we tested the effects of Valproic Acid on the signaling pathways involved in breast cancer cells viability, apoptosis and in Reactive Oxygen Species (ROS) production using ER-α positive MCF-7 and triple negative MDA-MB-231 cells. METHODS: Cell proliferation assay was performed by MTT Cell cycle, ROS levels and apoptosis were analyzed by flow cytometry, protein levels were detected by Western Blotting. RESULTS: Cell treatment with Valproic Acid reduced cell proliferation and induced G0/G1 cell cycle arrest in MCF-7 and G2/M block in MDA-MB-231 cells. In addition, in both cells the drug enhanced the generation of ROS by the mitochondria. In MCF-7 treated cells, it has been observed a reduction in mitochondrial membrane potential, a down regulation of the anti-apoptotic marker Bcl-2 and an increase of Bax and Bad, leading to release of cytochrome C and PARP cleavage. Less consistent effects are recorded in MDA-MB-231 cells, in which the greater production of ROS, compared to MCF-7cells, involves an inflammatory response (activation of p-STAT3, increased levels of COX2). CONCLUSIONS: Our results have demonstrated that in MCF-7 cells the Valproic Acid is a suitable drug to arrest cell growth, to address apoptosis and mitochondrial perturbations, all factors that are important in determining cell fate and health. In a triple negative MDA-MB 231 cells, valproate directs the cells towards the inflammatory response with a sustained expression of antioxidant enzymes. Overall, the not always unequivocal data between the two cellular phenotypes indicate that further studies are needed to better define the use of the drug, also in combination with other chemotherapy, in the treatment of breast tumors.

Centranthus ruber (L.) DC. and Tropaeolum majus L.: Phytochemical Profile, In Vitro Anti-Denaturation Effects and Lipase Inhibitory Activity of Two Ornamental Plants Traditionally Used as Herbal Remedies.

Ornamental plants often gain relevance not only for their decorative use, but also as a source of phytochemicals with interesting healing properties. Herein, spontaneous Centranthus ruber (L.) DC. and Tropaeolum majus L., mainly used as ornamental species but also traditionally consumed and used in popular medicine, were investigated. The aerial parts were extracted with methanol trough maceration, and resultant crude extracts were partitioned using solvents with increasing polarity. As previous studies mostly dealt with the phenolic content of these species, the phytochemical investigation mainly focused on nonpolar constituents, detected with GC-MS. The total phenolic and flavonoid content was also verified, and HPTLC analyses were performed. In order to explore the potential antiarthritic and anti-obesity properties, extracts and their fractions were evaluated for their anti-denaturation effects, with the use of the BSA assay, and for their ability to inhibit pancreatic lipase. The antioxidant properties and the inhibitory activity on the NO production were verified, as well. Almost all the extracts and fractions demonstrated good inhibitory effects on NO production. The n-hexane and dichloromethane fractions from T. majus, as well as the n-hexane fraction from C. ruber, were effective in protecting the protein from heat-induced denaturation (IC50 = 154.0 ± 1.9, 270.8 ± 2.3 and 450.1 ± 15.5 µg/mL, respectively). The dichloromethane fractions from both raw extracts were also effective in inhibiting pancreatic lipase, with IC50 values equal to 2.23 ± 0.02 mg/mL (for C. ruber sample), and 2.05 ± 0.02 mg/mL (T. majus). Obtained results support the traditional use of these species for their beneficial health properties and suggest that investigated plant species could be potential sources of novel antiarthritic and anti-obesity agents.

Essential Oils of Foeniculum vulgare subsp. piperitum and Their in Vitro Anti-Arthritic Potential.

Wild Foeniculum vulgare subsp. piperitum (C.Presl) Bég. flowers, fruits and leaves were extracted with steam distillation and obtained essential oils (EOs) were characterized using GC/MS. The study was designed to verify the potential effectiveness of fennel EOs in the treatment of inflammation and arthritis. Since tissue proteins denaturation is a major cause of arthritic diseases, fennel EOs and their main constituents were evaluated for their ability to inhibit the heat-induced proteins degradation using bovine serum albumin as a protein model. Moreover, the in vitro inhibitory effects of the three EOs on the pro-inflammatory mediator nitric oxide (NO) production were verified in LPS-stimulated RAW 264.7 cells. Estragole (28.81-33.40 %), anethole (24.16-27.40 %), fenchone (9.76-18.48 %), α-phellandrene (1.63-8.37 %) and limonene (5.54-6.05 %) were the major constituents. All the EOs showed a concentration-dependent biological activity, being the flower EO the most effective in inhibiting NO production (IC50 =232.2±11.3 µg/mL). The leaf EO showed a very good bovine serum albumin (BSA) anti-denaturation activity (IC50 =95.9±2.4 µg/mL). Moreover, four components were proved to be effective in protecting protein from heat-induced degradation, being α-phellandrene the most active compound (IC50 =73.2±1.9 µg/mL).

A Review of Biologically Active Natural Products from Mediterranean Wild Edible Plants: Benefits in the Treatment of Obesity and Its Related Disorders.

Wild foods constitute an essential component of people's diets around the world. According to the Food and Agriculture Organization (FAO), over 100 million people in the EU consume wild foods, while 65 million collect some form of wild food themselves. The Mediterranean basin is a biodiversity hotspot of wild edible species. Nowadays, due to the renewed interest in alimurgic plants and the recent findings on the beneficial role of their phytochemical constituents, these species have been defined as "new functional foods". Research on natural products has recently regained importance with the growing understanding of their biological significance. Botanical food supplements marketed for weight and fat loss in obese subjects will be one of the most important items in marketed nutraceuticals. The aim of this report was to review the phytochemical compounds of Mediterranean wild edible species and their therapeutic potential against obesity and its related disorders. Results on the in vitro and in vivo activity of the most interesting plant extracts and their bioactive components are presented and discussed. The most interesting discoveries on their mechanisms of action are reported as well. Overall, this contribution highlights the importance and beneficial health roles of wild edible species.

Viscosified Solid Lipidic Nanoparticles Based on Naringenin and Linolenic Acid for the Release of Cyclosporine A on the Skin.

Psoriasis is one of the most common human skin disorders. Although its pathogenesis is complex and not completely know, the hyperactivation of the immune system seem to have a key role. In this regard, among the most effective systemic therapeutics used in psoriasis, we find cyclosporine, an immunosuppressive medication. However, one of the major problems associated with the use of cyclosporine is the occurrence of systemic side effects such as nephrotoxicity, hypertension, etc. The present work fits in this context and its aim is the design of suitable platforms for cyclosporine topical release in psoriasis treatment. The main objective is to achieve local administration of cyclosporine in order to reduce its systemic absorption and, consequently, its side effects. In order to improve dermal penetration, solid lipid nanoparticles (SLNs) are used as carriers, due to their lipophilicity and occlusive properties, and naringenin and linolenic acid are chosen, due to their properties, as starting materials for SLNs design. In order to have dermatological formulations and further modulate drug release, SLNs are incorporated in several topical vehicles obtaining gels with different degree of lipophilicity. Potential applications for psoriasis treatment were evaluated by considering the encapsulation efficiency, release profiles, in vitro skin permeation, and anti-inflammatory effects.

Biological Properties and Bioactive Components of Allium cepa L.: Focus on Potential Benefits in the Treatment of Obesity and Related Comorbidities.

Common onion (Allium cepa L.) is one of the oldest cultivated plants, utilized worldwide as both vegetable and flavouring. This species is known to contain sulphur amino acids together with many vitamins and minerals. A variety of secondary metabolites, including flavonoids, phytosterols and saponins, have also been identified. Despite the predominant use of this plant as food, a wide range of beneficial effects have also been proved. Different biological properties, such as antioxidant, antimicrobial and antidiabetic, have been reported. The aim of this review is to provide an overview of the studies concerning the beneficial effects of this species against obesity and its related comorbidities, such as hyperlipidaemia, hypertension and diabetes. Both in vitro and in vivo results about onion dietary supplementation have been taken into account. Furthermore, this review examines the possible role of onion bioactive components in modulating or preventing weight-gain or related diseases, as well as the possible mechanisms behind their activity.

Phytochemical and Biological Profile of Moricandia arvensis (L.) DC.: An Inhibitor of Pancreatic Lipase.

Pancreatic lipase, a key enzyme for lipid absorption, is one of the most important targets for the treatment of obesity, while natural compounds have recently attracted much interest as potential inhibitors of this enzyme. Here, in an attempt to find new effective agents, the methanolic extract from Moricandia arvensis (L.) DC. and its sub-extracts were investigated for their potential inhibitory activity. The ability to inhibit pancreatic lipase was verified through the in vitro evaluation of the prevention of p-nitrophenyl caprylate hydrolysis. The antioxidant activity was also verified by means of DPPH and ß-carotene bleaching tests. Compositional profiling revealed that flavonoid glycosides were the main specialized metabolites present in the methanolic extract from the aerial parts of the plant with kaempferol and quercetin representing the two O-glycosylated aglycones. Kaempferol-3-O-ß-(2″-O-glucosyl)-rutinoside and kaempferol-3-O-a-arabinosyl-7-O-rhamnoside were the most abundant flavonols. The crude methanolic extract and the dichloromethane and ethyl acetate sub-extracts showed a strong lipase inhibitory activity, with IC50 values of 2.06 ± 0.02, 1.52 ± 0.02 and 1.31 ± 0.02 mg/mL, respectively. The best capacity to scavenge DPPH radical was detected for the ethyl acetate sub-extract (IC50 = 171.9 ± 1.0 µg/mL), which was also effective in protecting linoleic acid from peroxidation (IC50 = 35.69 ± 2.30 µg/mL). Obtained results support the hypothesis that M. arvensis can be a source of bioactive phytochemicals for the pharmacological inhibition of dietary lipids absorption.

Investigation of the Potential Health Benefits as Lipase Inhibitor and Antioxidant of Leopoldia comosa (L.) Parl.: Variability of Chemical Composition of Wild and Cultivated Bulbs.

There is a great interest in the nutritional value of vegetables and fruits and how the habitat affects nutritive and biological properties. In vitro studies here reported were performed to evaluate the inhibitory activity of formulations from edible plant on pancreatic lipase. The aim of this study was also to evaluate the biovariability of L. comosa (L.) Parl. bulbs from Italy. The wild bulbs were compared with the same cultivated species that are commonly commercialized to identify samples with the best quality for a potential therapeutic application. Hydroalcoholic extract and polar fraction of wild bulbs showed a very important pancreatic lipase inhibitory activity, with IC50 values of 0.166 ± 0.005 and 0.153 ± 0.005 mg/mL, respectively. In order to characterize the extracts, gas chromatography associated with mass spectrometry (GC/MS) analysis was performed, revealing the predominance of palmitic acid. Phenolic and flavonoid composition was also evaluated. L. comosa extract obtained from wild bulbs demonstrated both antioxidant and anti-obesity activities that might be attributed to a wide range of present phenolic compounds.

Crocus cancellatus subsp. damascenus stigmas: chemical profile, and inhibition of α-amylase, α-glucosidase and lipase, key enzymes related to type 2 diabetes and obesity.

Spices are appreciated for their medicinal properties besides their use as food adjuncts to enhance the sensory quality of food. In this study, Crocus cancellatus subsp. damascenus was investigated for its antioxidant activities employing different in vitro systems. Stigma extract demonstrated a radical scavenging activity against both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals with IC50 values of 34.6 and 21.6 µg/mL and a good ferric reducing ability (53.9 µM Fe(II)/g). In order to clarify the potential functional properties of this spice, the carbohydrate-hydrolysing enzymes and pancreatic lipase inhibitory properties were investigated. Crocus cancellatus subsp. damascenus extract inhibited α-amylase and α-glucosidase with IC50 values of 57.1 and 68.6 µg/mL, respectively. The bioactivity was discussed in terms of phytochemicals content. The obtained results may be of interest from a functional point of view or as food additive and to promote the revalorization of this species.

Inhibitory Effect on Lipid Absorption and Variability of Chemical Constituents from Capparis sicula subsp. sicula and Capparis orientalis.

In continuation of our research program on Mediterranean dietary plants, a bioassay-guided fractionation of extracts from several accessions of Capparis sicula subsp. sicula and Capparis orientalis aerial parts was carried out. Antilipidemic activity of samples was assayed using inhibition of pancreatic lipase. To study the metabolic variability in Capparis species, HPTLC analyses were performed in order to characterize the species through the detection, isolation, and quantitative evaluation of rutin taken as significant chemical marker. The best activity was exerted by C. orientalis accession no. C10 and C. sicula subsp. sicula accession no. C6. The bioactivity evaluation of specific chemical markers, rutin and glucocapparin, led to the identification of a potent antilipidemic compound rutin. The HPTLC analysis showed large variation among the different analyzed samples with respect to rutin concentration. The chemical investigation showed a different composition between the species and between the collection zones. The variations showed by the studied accessions of caper could be attributed to exogenous factors. Capparis species contained predominantly quercetin rutinoside (rutin), accompanied by other constituents such as the glucosinolate glucocapparin. These rutin-rich extracts exhibited pronounced dose-dependent enzyme inhibitory activities toward pancreatic lipase.

Effects of Saponins on Lipid Metabolism: A Review of Potential Health Benefits in the Treatment of Obesity.

Obesity is one of the greatest public health problems. This complex condition has reached epidemic proportions in many parts of the world, and it constitutes a risk factor for several chronic disorders, such as hypertension, cardiovascular diseases and type 2 diabetes. In the last few decades, several studies dealt with the potential effects of natural products as new safe and effective tools for body weight control. Saponins are naturally-occurring surface-active glycosides, mainly produced by plants, whose structure consists of a sugar moiety linked to a hydrophobic aglycone (a steroid or a triterpene). Many pharmacological properties have been reported for these compounds, such as anti-inflammatory, immunostimulant, hypocholesterolemic, hypoglycemic, antifungal and cytotoxic activities. The aim of this review is to provide an overview of recent studies about the anti-obesity therapeutic potential of saponins isolated from medicinal plants. Results on the in vitro and in vivo activity of this class of phytochemicals are here presented and discussed. The most interesting findings about their possible mechanism of action and their potential health benefits in the treatment of obesity are reported, as well.

Hypolipidemic and Antioxidant Properties of Hot Pepper Flower (Capsicum annuum L.).

At present, the various medical treatments of obesity involve side effects. The aim of the research is therefore to find natural compounds that have anti-obesity activity with minimum disadvantages. In this study, the hypolipidemic effect of hydroalcoholic extract of flowers from Capsicum annuum L. was examined through the evaluation of inhibition of pancreatic lipase. Antioxidant activity was assessed using different tests: 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (˙NO) and lipid peroxidation inhibition assays. Phytochemical analysis indicated that total phenolic and flavonoid content in the extract was 128.7 ± 4.5 mg chlorogenic acid equivalent/g of crude extract and 17.66 ± 0.11 mg of quercetin equivalent/g of crude extract, respectively. The extract inhibited pancreatic lipase with IC50 value equal to 3.54 ± 0.18 mg/ml. It also inhibited lipid peroxidation with IC50 value of 27.61 ± 2.25 µg/ml after 30 min of incubation and 41.69 ± 1.13 µg/ml after 60 min of incubation. The IC50 value of radical scavenging activity was 51.90 ± 2.03 µg/ml. The extract was also able to inhibit NO production (IC50 = of 264.3 ± 7.98 µg/ml) without showing any cytotoxic effect.

Inhibition of Cancer Cell Proliferation and Antiradical Effects of Decoction, Hydroalcoholic Extract, and Principal Constituents of Hemidesmus indicus R. Br.

Indian Sarsaparilla (Hemidesmus indicus R. Br.) is widely used in Indian traditional medicine. In the present work, we explored the effects of decoction, traditional Ayurvedic preparation, and hydroalcoholic extract, a phytocomplex more traditionally studied and commercialized as food supplement in western medicine, from the roots as possible source of chemicals with new functional potential linked to their nutritional uses. The antiproliferative and antioxidant properties were assayed. To test antiproliferative affects, different cancer cell lines, growing both as monolayers (CaCo2, MCF-7, A549, K562, MDA-MB-231, Jurkat, HepG2, and LoVo) and in suspension (K562 and Jurkat) were used. The decoction showed strong activity on HepG2 cells, while the hydroalcoholic extracts were active on HepG2, LoVo, MCF-7, K562, and Jurkat cell lines. Weak inhibition of cancer cell proliferation was observed for the principal constituents of the preparations: 2-hydroxy-4-methoxybenzaldehyde, 2-hydroxy-4-methoxybenzoic acid, and 3-hydroxy-4-methoxybenzaldehyde that were tested alone. The antiradical activity was tested with 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt tests and inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. Interesting result has also been obtained for hydroalcoholic extract regarding genoprotective potential (58.79% of inhibition at 37.5 µg/mL).

In vitro investigation of the potential health benefits of wild Mediterranean dietary plants as anti-obesity agents with α-amylase and pancreatic lipase inhibitory activities.

BACKGROUND: Inhibition of digestive enzymes is one of the most widely studied mechanisms used to determine the potential efficacy of natural products as anti-obesity agents. In vitro studies reported here were performed to evaluate the inhibitory activity of formulations of edible plants from Italy on amylase and lipase by monitoring the hydrolysis of nitrophenyl caprilate and the hydrolysis of glycoside bonds in digestible carbohydrate foods. RESULTS: The formulation obtained from Capparis sicula exhibited the strongest inhibitory effect on pancreatic lipase (IC50 = 0.53 mg mL(-1) ) while the Borago officinalis formulation exhibited the strongest inhibitory effect on α-amylase (IC50 = 31.61 µg mL(-1) ). In order to characterise the extracts, high-performance thin-layer chromatography analysis of the formulations was performed, revealing the predominance of (±)-catechin in Mentha aquatica formulation, rutin in C. sicula, and caffeic acid and chlorogenic acid in Echium vulgare. CONCLUSION: The results obtained indicated that the extracts of C. sicula and B. officinalis could be good candidates for further studies to isolate pancreatic lipase and α-amylase inhibitors, respectively.

Hypericum perforatum: Influences of the habitat on chemical composition, photo-induced cytotoxicity, and antiradical activity.

CONTEXT: Hypericin, isolated from Hypericum perforatum L. and about another 300 Hypericum species (Guttiferae), is one of the most powerful photosensitizers found in nature. OBJECTIVE: The aim of this study was to assess the variability of chemical composition and biological activities of four H. perforatum samples, collected at different altitudes in the South Apennine of Italy. MATERIALS AND METHODS: MTT assay was used to evaluate the antiproliferative activity of different samples concentrations (0.6-100 µg/mL) after irradiation at 365 nm. The inhibition of nitric oxide production was evaluated after 24 h of incubation using the macrophage cell line RAW 264.7 and sample solutions ranging from 12.5 to 1000 µg/mL. Antioxidant activities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and ß-carotene bleaching test (ranges were 12.5-1000 and 1-400 µg/mL, respectively). Chemical composition was evaluated through HPTLC, and different contents of hypericin and rutin have been observed. RESULTS: The most phototoxic sample was collected from Zumpano (no. 1 at 370 m), with IC50 values of 24.61 ± 0.02 µg/mL. Sample no. 1 showed also the best radical scavenging activity (IC50 value of 9.18 ± 0.03 µg/mL) and the best antioxidant activity (IC50 value of 10.04 ± 0.03 µg/mL after 30 min of incubation). Best activity of extract no. 1 was well in accordance with chemical data, including the phenolic total content and particular metabolome profile. DISCUSSION AND CONCLUSION: This paper confirms the usefulness in maintaining the exploration of H. perforatum activities, in order to confirm its potentiality as a multipurpose plant.

Molecular Docking Studies and In Vitro Activity of Paliurus spina-christi Mill Extracts as Pancreatic Lipase Inhibitors.

Obesity is a risk factor for the onset of chronic diseases. One of the most promising approaches to treating obesity consists of reducing dietary fat absorption using extracts from plants because they contain phenolic compounds, especially flavonoids. Paliurus spina-christi, belonging to the Rhamnaceae family, is one of the five species belonging to the Paliurus genus. Herein, the aerial parts of the plant were extracted with methanol through the pressurized cyclic solid-liquid extraction using the Naviglio extractor®. The extracts were analyzed with High Performance Thin Layer Chromatography and investigated for their in vitro biological potential. The phytochemical analysis revealed that rutin has been shown to be the most abundant flavonoid component. The best antiradical activity was observed for the fruit extract with an IC50 value of 53.41 ± 1.24 µg/mL. This extract also has a better inhibitory capacity on lipid peroxidation evaluated at a different time of incubation. Potent lipase inhibitor activity of the extract from fruits was also demonstrated with in vitro experiments. This property can be attributed to a direct interaction of main components of P. spina-christi extract with the human pancreatic enzyme as demonstrated by the results of molecular docking experiments conducted on the crystallographic structures of lipase.

Use of Essential Oils to Counteract the Phenomena of Antimicrobial Resistance in Livestock Species.

Antimicrobial resistance is an increasingly widespread phenomenon that is of particular concern because of the possible consequences in the years to come. The dynamics leading to the resistance of microbial strains are diverse, but certainly include the incorrect use of veterinary drugs both in terms of dosage and timing of administration. Moreover, the drug is often administered in the absence of a diagnosis. Many active ingredients in pharmaceutical formulations are, therefore, losing their efficacy. In this situation, it is imperative to seek alternative treatment solutions. Essential oils are mixtures of compounds with different pharmacological properties. They have been shown to possess the antibacterial, anti-parasitic, antiviral, and regulatory properties of numerous metabolic processes. The abundance of molecules they contain makes it difficult for treated microbial species to develop pharmacological resistance. Given their natural origin, they are environmentally friendly and show little or no toxicity to higher animals. There are several published studies on the use of essential oils as antimicrobials, but the present literature has not been adequately summarized in a manuscript. This review aims to shed light on the results achieved by the scientific community regarding the use of essential oils to treat the main agents of bacterial infection of veterinary interest in livestock. The Google Scholar, PubMed, SciELO, and SCOPUS databases were used for the search and selection of studies. The manuscript aims to lay the foundations for a new strategy of veterinary drug use that is more environmentally friendly and less prone to the emergence of drug resistance phenomena.

Enhancing the nitric oxide inhibitory activity using a combination of plant essential oils and mixture design approach.

The synergistic effects of essential oils (EOs) from three aromatic plant species, Foeniculum vulgare subsp. piperitum (C.Presl) Bég. (FV), Origanum heracleoticum L. (OH) and Lavandula austroapennina N.G.Passal., Tundis & Upson. (LA), were evaluated for their inhibitory properties on nitric oxide production in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). We utilized a Design of Experiments (DoE) methodology to optimize a formulation by combining three Essential Oils (EOs), while simultaneously taking into account two response variables, maximization of NO inhibition with minimum cytotoxicity. The optimal blend of components was predicted, and the statistical outcome's efficacy was experimentally verified. The combination corresponding to 87.7 % FV, 12.3 % LA and 0.0 % OH showed high inhibitory effect (76.3 %) with negligible cytotoxicity (4.5 %). This research provides new information on the interactions among fennel, oregano and lavender essential oils and shows how they can synergistically inhibit in vitro LPS-induced NO production.

Conjugation of l-NAME to prenyloxycinnamic acids improves its inhibitory effects on nitric oxide production.

A series of 10 compounds resulting from the conjugation of O-prenylated naturally occurring benzoic and cinnamic acids to l-NAME were synthesized and tested together with the corresponding unprenylated parent molecule as anti-inflammatory agents for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophages. Results indicated that the coupling between O-geranyl and O-isopentenylcinnamic acids and l-NAME led to products with an enhanced activity when compared to the parent compounds.

Rapid solid-liquid dynamic extraction of Cachrys pungens Jan ex Guss. aerial parts: influence on the photobiological and antioxidant properties.

Cachrys pungens Jan ex Guss. (Apiaceae) is a perennial plant native to Italy and Northwestern Africa. This species is known for its content in furanocoumarins, and the methanolic extract obtained with maceration previously demonstrated significant phototoxicity on 375 melanoma cells. Here, in order to better explain the biological effects, the apoptotic responses on melanoma cancer cell line were verified. The aerial parts were extracted with methanol through an innovative solid-liquid extraction technology, the Naviglio extractor®, and the raw extract was tested for its photobiological properties on human melanoma C32 cells irradiated with UVA light. The in vitro antioxidant potential was assessed as well. The sample exerted a concentration-dependent photocytotoxic activity (IC50 value = 3.00 ± 0.16 µg/mL). In line with these evidences, in C32-treated cells subjected to UV irradiation, further data have reported an up-regulation of p53 and PARP, both proteins involved in apoptotic response and DNA repair.