An ancient remedial repurposing: synthesis of new pinocembrin fatty acid acyl derivatives as potential antimicrobial/anti-inflammatory agents.

Five new pinocembrin derivatives (MC1-MC5) were synthesized by Steglich reaction, and investigated for their antimicrobial, antioxidant, and anti-inflammatory activity. MC2 (oleoyl derivative) and MC3 (linoleoyl derivative) have shown the highest inhibitory effects on bacterial proliferation, with MIC values of 32 µg/mL against Staphylococcus aureus. The docosahexaenoyl derivative MC5 displayed the highest anti-inflammatory activity, decreasing NO production in LPS-stimulated macrophages with an IC50 value of 15.51 µg/mL higher than the positive control diclofenac (IC50 of 39.71 µg/mL). All new synthesized compounds showed no anti-proliferative effects on RAW 264.7 cells. Results demonstrated as the introduction of fatty acid substituents improved the biological profile of pinocembrin. Moreover, the chemical nature of substituents significantly affects the bioactivity. These preliminary results outline the importance to investigate the synthesis of pinocembrin fatty acids derivatives as new and safe anti-microbial/anti-inflammatory agents.

Ruta chalepensis L. (Rutaceae) leaf extract: chemical composition, antioxidant and hypoglicaemic activities.

Ruta chalepensis L. (Rutaceae) leaf extract was investigated for its chemical profile and antioxidant and hypoglycaemic properties. The antioxidant effects were investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ß-carotene bleaching, and metal chelating activity assays. The carbohydrate-hydrolysing enzymes inhibition assay was used to test the hypoglycaemic potential. R. chalepensis showed a high content of hesperidin and rutin with values of 591.9 and 266.7 mg/g dry extract, respectively. The extract exhibited a promising protection of lipid peroxidation (IC50 value of 16.9 µg/mL) and inhibited both α-amylase and α-glucosidase enzymes in a concentration-dependent manner. The highest activity was found against α-amylase (IC50 value of 69.0 µg/mL). The obtained results support the use of R. chalepensis leaves as healthy food ingredients.

Assessment of antioxidant, antitumor and pro-apoptotic effects of Salvia fruticosa Mill. subsp. thomasii (Lacaita) Brullo, Guglielmo, Pavone & Terrasi (Lamiaceae).

The aim of the present study was to investigate the in vitro antioxidant and antitumor effects of Salvia fruticosa Mill subsp. thomasii (Lacaita) Brullo, Guglielmo, Pavone & Terrasi (Lamiaceae). The aerial parts were extracted by maceration with methanol. This extract was partitioned with methanol and n-hexane. Luteolin, luteolin 7-O-glucoside, rutin and salvigenin were isolated from the methanol-soluble fraction. n-Hexane fraction showed viridiflorol, ß-pinene, 1,8-cineole, as main components. The methanol-soluble fraction exerted antitumor activity against human breast cancer (MCF-7 and MDA-MB-231) and human colorectal carcinoma (RKO and Caco-2) cells. TUNEL test revealed that S. fruticosa subsp. thomasii leads to cells death by apoptosis, with low cytotoxic effects on non-tumoral 3T3-L1 cells. Moreover, it exerted the highest protection of lipid peroxidation and reduced the oxidative stress induced by menadione treatment in 3T3-L1 murine fibroblasts. S. fruticosa subsp. thomasii bioactivity could promote its use not only as food but also in nutraceutical/pharmaceutical industries.

Potential role of natural compounds against skin aging.

Skin aging is an inevitable biological phenomenon of human life. Advancing age brings changes to all components of the integumentary system with consequent signs on the skin. Skin aging is mainly due to intrinsic (chronologic) and extrinsic aging (photo-aging). Photo-aging is a consequence of exposure to ultraviolet radiations. Despite variable economic conditions, the skin care market based on natural products continues to see strong growth. In this context, the research of naturally occurring anti-aging agents is greatly expanding and in recent years numerous plant-derived products have been investigated. This review article focuses on highlighting recent advances in current knowledge on anti-aging natural products grouped and presented according to their family origin. Plants from 35 families were reviewed. A variety of phytomolecules, derived in particular from polyphenols, triterpenes and sterols classes, demonstrated a promising activity. Among them carnosic acid, curculigoside, curcumin, glycyrrhizic acid, mangiferin, mirkoin, asiaticoside, rosmarinic acid, tectorigenin, tyrosol etc., able to inhibit tyrosinase, hyaluronidase, elastase, and collagenase, to scavenge free radicals from skin cells, to prevent trans-epidermal water loss, and to contribute to protect skin from wrinkles, were largely investigated and herein discussed. Extracts and pure compounds from Fabaceae, Asperaceae and Zingiberaceae families have shown particular interest and appear most promising in the development of anti-aging products.

Evaluation of phototoxic potential of aerial components of the fig tree against human melanoma.

OBJECTIVES: To date, Ficus carica L. cultivar Dottato (F. carica) has not been studied from a phototoxic point of view. In the present work, aerial components of F. carica from Italy, were examined to assess their antioxidant and phototoxic activity on human melanoma cells. A relationship between antioxidant, phototoxic activities and chemical composition has also been investigated. MATERIALS AND METHODS: Coumarin and fatty acid content in F. carica leaves, bark and woody parts were examined and compared by capillary GC and GC/MS. Polyphenolic content was also determined. Linoleic acid peroxidation and DPPH test were used to assess antioxidant activities, and MTT assay was used to evaluate anti-proliferative activity, on C32 human melanoma cells, after irradiation with a UVA dose of 1.08 J/cm(2). RESULTS: Leaves demonstrated the best antioxidant and anti-proliferative activity in comparison to bark and wood. In particular, leaves were shown to possess the highest anti-radical activity and inhibition of peroxidation, with IC(50) values of 64 and 1.48 µg/ml respectively. The leaves had highest anti-proliferative activity with IC(50) value of 3.92 µg/ml. The phytochemical investigation revealed different composition between the coumarins, psoralen and bergapten, fatty acids, polyphenols and flavonoid content among plant parts. CONCLUSIONS: Data obtained indicate that this type of fig tree may constitute an excellent source of bioactive compounds, such as phenolics, coumarins and fatty acids. This study offers a new perspective in developing others formulations potentially useful in photodynamic therapy for treatment of non-melanoma skin cancers.

Antioxidant and antibacterial activities on foodborne pathogens of Artocarpus heterophyllus Lam. (Moraceae) leaves extracts.

Total water extract, ethyl acetate, and aqueous fractions from the leaves of Artocarpus heterophyllus were evaluated for phenolic content, antioxidant, and antibacterial activities against some foodborne pathogens such as E. coli, Listeria monocytogenes, Salmonella typhimurium, Salmonella enterica, Bacillus cereus, Enterococcus faecalis, and Staphylococcus aureus. The minimum inhibitory concentration (MICs) of extract and fractions determined by the agar dilution method were ranged from 221.9 microg/mL for ethyl acetate fraction to 488.1 microg/mL for total extract. In the agar diffusion method the diameters of inhibition were 12.2 for the total extract, 10.7 and 11.5 for ethyl acetate and aqueous fractions, respectively. A. heterophyllus showed significant antioxidant activity tested in different in vitro systems (DPPH, ABTS, FRAP, and Fe(2+) chelating activity assay). In particular, in DPPH assay A. heterophyllus total extract exhibited a strong antiradical activity with an IC(50) value of 73.5 microg/mL while aqueous fraction exerted the highest activity in FRAP assay (IC(50) value of 72.0 microg/mL). The total phenols content by Folin-Ciocalteau method was determined with the purpose of testing its relationship with the antioxidant and antibacterial activities.

Natural products as alpha-amylase and alpha-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: an update.

The inhibition of alpha-glucosidase and alpha-amylase, enzymes involved in the digestion of carbohydrates, can significantly reduce the post-prandial increase of blood glucose and therefore can be an important strategy in the management of blood glucose level in type 2 diabetic and borderline patients. Currently, there is renewed interest in plant-based medicines and functional foods modulating physiological effects in the prevention and cure of diabetes and obesity. The plant kingdom is a wide field to search for natural effective oral hypoglycaemic agents that have slight or no side effects. More than ca. 1200 plant species have been recorded to be used empirically worldwide for their alleged hypoglycaemic activity. Therefore, natural alpha-glucosidase and alpha-amylase inhibitors from plant sources offer an attractive strategy for the control of hyperglycaemia. This article reviews recent data on plant extracts and isolated natural compounds that are being tested for their hypglycaemic activity, highlights ongoing research and considers the future persepctives.

Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells.

OBJECTIVES: The purpose of this study was to evaluate cytotoxic activity of Platycladus orientalis, Prangos asperula and Cupressus sempervirens ssp. pyramidalis essential oils and to identify active components involved in inhibition of population growth of human cancer cell lines. MATERIALS AND METHODS: Essential oils were obtained by hydrodistillation and were analysed by gas chromatography and gas chromatography coupled to mass spectrometry. Antiproliferative activity was tested on amelanotic melanoma C32 cells and on renal cell adenocarcinoma cells, using the sulphorhodamine B assay. RESULTS: Cupressus sempervirens ssp. pyramidalis leaf oil exerted the highest cytotoxic activity with an IC(50)value of 104.90 microg/mL against C32, followed by activity of P. orientalis and P. asperula on the renal adenocarcinoma cell line (IC(50) of 121.93 and 139.17 microg/mL, respectively). P. orientalis essential oil was also active against amelanotic melanoma with an IC(50) of 330.04 microg/mL. Three identified terpenes, linalool, beta-caryophyllene and alpha-cedrol, were found to be active on both cell lines tested. CONCLUSIONS: Our findings provide novel insights into the field of cytotoxic properties of essential oils. This study provided evidence on how cytotoxic activity of the oils is not always related to their major constituents, except for lower activity found in both cell lines for alpha-cedrol. Interestingly, beta-caryophyllene and linalool exhibited comparable IC(50) values to the commercial drug vinblastine on the ACHN cell line. This opens a new field of investigation to discover mechanisms responsible for the observed activity.

Inhibitory effects on the digestive enzyme alpha-amylase of three Salsola species (Chenopodiaceae) in vitro.

Hypoglycaemic effects of Salsola kali, S. soda, and S. oppositifolia (Chenopodiaceae) aerial parts were examined using in vitro assay based on the inhibition of a-amylase. The S. kali ethyl acetate fraction was the most active with a C1050 value 0.022 mg/ml. Through bioassay-guided fractionation processes two flavonol glycosides, isorhamnetin-3-O-glucoside and isorhamnetin-3-O-rutinoside, were isolated by silica gel column chromatography and characterized by spectroscopic methods. Isorhamnetin-3-O-rutinoside showed an interesting activity (IC50 0.129 mM).

In vitro hypoglycemic and antimicrobial activities of Senecio leucanthemifolius Poiret.

This study reports on the alpha-amylase inhibitory and antimicrobial activities of Senecio leucanthemifolius Poiret. Extracts of S. leucanthemifolius were tested for their antimicrobial and antifungal activities against seven different pathogenic microorganisms using the microdilution technique. The ethyl acetate extract exhibited a strong antibiotic activity against Staphylococcus aureus with a MIC value of 31.25 microg mL(-1), while the n-hexane extract showed a significant activity against dermatophytic fungi. S. leucanthemifolius extracts were tested also for their potential hypoglycemic activity through the in vitro inhibition of alpha-amylase. The dichloromethane extract inhibited alpha-amylase with a value of 56.6% at 0.05 mg mL(-1) and the n-butanol extract showed a value of 89.2% at 1 mg mL(-1).

Bioactive extracts from Senecio samnitum Huet.

The antimicrobial and cytotoxic activities of extracts from Senecio samnitum Huet are reported. Extracts from S. samnitum were able to inhibit the in vitro proliferation of four human tumor cell lines. The dichloromethane extract demonstrated effective cytotoxic activity with IC50 of 22.89 microg mL(-1) on the Caco-2 cell line and the EtOAc extract had IC50 value of 11.91 microg mL(-1) against the COR-L23 cell line. The n-hexane extract displayed the best antibacterial activity against Gram positive bacteria, particularly Staphylococcus aureus. The antifungal activity of all extracts was also seen, particularly against the dermatophytes Trichophyton tonsurans and Microsporum gypseum for the methanol and n-hexane extracts.

In-vitro antiproliferative effects on human tumour cell lines of extracts and jacaranone from Senecio leucanthemifolius Poiret.

We have studied the cytotoxic activity of extracts and jacaranone from Senecio leucanthemifolius Poiret. Extracts from S. leucanthemifolius were able to inhibit the in-vitro proliferation of a series of human tumour cell lines. The dichloromethane extract demonstrated effective cytotoxic activity with an IC50 of 20.1 microg mL(-1) on the large cell carcinoma cell line COR-L23. The ethyl acetate extract showed an IC50 value of 5.0 microg mL(-1) and the butanol extract an IC50 value of 6.4 microg mL(-1) on the same cell line. A major active constituent of the dichloromethane extract was shown to be jacaranone, which was demonstrated to have a very strong activity against all of the tumour cell lines with IC50 values between 2.86 and 3.85 microg mL(-1), although it did not account for all the activity observed. Constituents of S. leucanthemifolius extracts were identified by GC/MS analysis and NMR.

Influence of environmental factors on composition of volatile constituents and biological activity of Helichrysum italicum (Roth) Don (Asteraceae).

The biovariability of Helichrysum italicum (Roth) Don grown wild in Calabria and Sardinia (Italy) was reported. This species has been characterized through the detection, isolation and quantitative evaluation of chemical markers (alpha-terpinolene, trans-cariophyllene and neryl acetate) by GC and GC-MS. Antioxidant activity of the methanolic H. italicum extracts using DPPH and beta-carotene bleaching test showed that the Calabrian samples were more active than those from Sardinia. The antibacterial activity of all extracts evidenced the best performance on the Gram positive bacteria particularly on Micrococcus luteus. Moreover, antifungal activity of all extracts was also tested evidencing important results particularly on the phytopathogene fungus Pythium ultimum. In general, as regards the antifungal activity, the extracts from Sardinia were more active than those from Calabria. The phytochemical analysis and the biological activity data suggested a possible use of these plant matrices in alimentary, cosmetic and pharmaceutical fields.

Comparative chemical composition and variability of biological activity of methanolic extracts from Hypericum perforatum L.

The biovariability of Hypericum perforatum L. (St. John's Wort) grown wild in Calabria and Sardinia (Italy) was reported with the aim to characterize the species through the isolation, detection, and quantitative evaluations of chemical markers (hypericin, quercetin, rutin) by HPLC analysis. Antioxidant activity of the methanolic H. perforatum extracts showed that the Calabrian samples were more active than those from Sardinia. The antibacterial activity evidenced the best performance on the gram positive bacteria with a MIC value of 50 microg/mL. Moreover, antifungal activity of all the extracts was also tested which showed interesting results particularly on the phytopathogene fungus P. ultimum. The variability shown by the samples could be attributed to environmental factors such as chemical-physical properties, composition of the soil, geographical coordinate, altitude, and solar exposure. The phytochemical analysis and the biological activity data suggested a possible use of H. perforatum extracts in the alimentary, cosmetic, and pharmaceutical fields.

Antioxidant and cytotoxic activities of Retama raetam subsp. Gussonei.

The aim of this study was to evaluate the in vitro antioxidant and cytotoxic activities of the methanol extracts of Retama raetam subsp. gussonei leaves and seeds. The antioxidant activity of the extracts was assessed by means of two different tests: (1) bleaching of the stable 2,2-diphenyl-1-picrylhydrazil (DPPH) radical; and (2) lipid peroxidation of liposomes which were prepared from bovine brain extract. In both tests used leaves extract showed a significant antioxidant effect. The extract of leaves also demonstrated a good cytotoxic activity against COR-L23 (large cell carcinoma) cell line.

Arctiin and onopordopicrin from Carduus micropterus ssp. perspinosus.

The isolation of (-)-arctiin (1), arctigenin (2), onopordopicrin (3), kaempferide, eriodictyol, luteolin and stigmasterol from the aerial parts of Carduus micropterus ssp. perspinosus, is reported.