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.

The impact of cultivar on polyphenol and biogenic amine profiles in Calabrian red grapes during winemaking.

In this study, during winemaking, was evaluated the influence of cultivar on bioactive compounds (organic acids, d-(+)-glucose, d-(-)-fructose, biogenic amines (BAs), anthocyanins, polyphenols and flavonoids) and antioxidant activity of Calabrian (Southern Italy) autochthonous grapes (Arvino, Gaglioppo, Greco Nero, Magliocco Canino, Magliocco Dolce and Nocera). Phenolic compounds increased from grapes to wine for all varieties. Arvino grapevine showed the highest DPPH radical scavenging activity, while a promising inhibition of the lipid peroxidation was observed with Greco Nero grapes. BAs were mostly formed during alcoholic fermentation and Arvino always showed the lowest BAs amounts, while Magliocco Canino generally exhibited the highest. Collectively, the results demonstrated that Calabrian autochthonous grapevines were rich in sugars, organic acids and phenolic compounds thus allowing the production of high quality wines.

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.

Flavonoids and dementia: an update.

Dementia is a strongly age-related syndrome due to cognitive decline that can be considered a typical example of the combination of physiological and pathological aging-associated changes occurring in old people; it ranges from intact cognition to mild cognitive impairment, which is an intermediate stage of cognitive deterioration, and dementia. The spread of this syndrome has induced to study and try to reduce dementia modifiable risk factors. They include insulin resistance and hyperinsulinaemia, high blood pressure, obesity, smoking, depression, cognitive inactivity or low educational attainment as well as physical inactivity and incorrect diet, which can be considered one of the most important factors. One emerging strategy to decrease the prevalence of mild cognitive impairment and dementia may be the use of nutritional interventions. In the last decade, prospective data have suggested that high fruit and vegetable intakes are related to improved cognitive functions and reduced risks of developing a neurodegenerative process. The protective effects against neurodegeneration could be in part due to the intake of flavonoids that have been associated with several health benefits such as antioxidant and anti-inflammatory activities, increased neuronal signaling, and improved metabolic functions. The present article is aimed at reviewing scientific studies that show the protective effects of flavonoid intake against mild cognitive impairment and dementia.

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.

Effects on free radicals and inhibition of alpha-amylase of Cardamine battagliae (Cruciferae), an apoendemic Calabrian (southern Italy) plant.

The present study showed for the first time the biological properties of different fractions from Cardamine battagliae Cesca & Peruzzi, an apoendemic Calabrian (southern Italy) plant that belongs to the Cruciferae family. The antioxidant activities of the different fractions of C. battagliae were carried out using two different in vitro assays (beta-carotene bleaching test and lipid peroxidation of liposomes assay) while radical scavenging activity was carried out using DPPH test. AcOEt fraction showed the highest activity on DPPH inhibition (IC50 of 0.162 mg mL(-1)) while dichloromethane fraction showed the highest activity on beta-carotene bleaching (IC(50) of 0.004 mg mL(-1)). The assay for alpha-amylase inhibition showed that n-hexane fraction showed the highest activity with an IC50 of 0.055 mg mL(-1).

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).

Composition and alpha-amylase inhibitory effect of essential oils from Cedrus libani.

The inhibitory activity of alpha-amylase and the phytochemical composition of Cedrus libani essential oils obtained from wood, leaves and cones were investigated. The C. libani woods oil exhibit an IC(50) value of 0.14 mg/ml, whereas the leaves and cones oils were devoid of any significant activity.

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).

Cytotoxic activity of antioxidant constituents from Hypericum triquetrifolium Turra.

The Sulforodamine B (SRB) assay was used to test cytotoxicity against four human cancer cell lines and one normal cell line of antioxidant constituents isolated from Hypericum triquetrifolium Turra. Methanolic extract and pure compounds were tested against the large cell lung carcinoma cell line COR-L23, the hepatocellular carcinoma cell line HepG-2, renal cell adenocarcinoma ACHN, the amelanotic melanoma cell line C32 and normal human foetal lung MRC5. The results showed that I3-II8-biapigenin exhibited strong cytotoxic activity (IC50 = 5.73 micro g mL(-1)) showing a certain degree of selectivity against the different cell types.

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.

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.

Analgesic properties of electromagnetic field therapy in patients with chronic pelvic pain.

AIM: Demonstration of analgesic effects of electromagnetic field treatment in cases of chronic refractory pelvic pain. STUDY DESIGN: Prospective non-controlled trial, 64 women complaining about pelvic pain of at least 6 months duration, resistant to standard therapies, submitted to electromagnetic field applications on both iliac regions by Thelf Systems apparatus by two applications daily lasting 2 hours each for 20-40 days. Control visit after 3 months. RESULTS: Complete subsidence of pain in 39 cases (61%), in 15 patients (23%) relief during treatment, then mild endopelvic tension after a 3-month control; in 10 cases (16%) symptoms reduced only during application hours, unchanged at follow-up. Outcome of treatment appears to be independent of pre-existent psychosocial variables. CONCLUSION: Magnetic therapy shows a real analgesic effect on pelvic pain, and seems to contribute to resolution of complex interactions between somatic nociceptive stimuli and psychosocial implications affecting pain perception in these patients.

Secondary tumors of the ovary. III. Tumors of the gastrointestinal tract and other sites.

16 cases of secondary ovarian tumors observed from 1977 to 1986, and in which the primary neoplasms involved other organs outside the genital tract or the breast, are studied. The observations concerned 13 metastases of the gastro-intestinal tract cancer (6 typical Krukenberg tumors, 3 "tubular" Krukenberg tumors, and 4 non-Krukenberg tumors), 1 urinary bladder cancer, 1 pancreatic cancer, and 1 tumor of unknown origin (probably an amelanotic melanoma). The histological diagnosis was very difficult in patients with no evidence of the primary malignancy, or in patients in whom the metastases simulate a concomitant primary ovarian tumor. The characteristic histological findings, histochemistry, and immuno histochemistry may suggest a correct diagnosis in most of situations.

Hyperparathyroidism in a pregnant woman with previous thyroid carcinoma. Case report and review of the literature.

A 29 year old woman, primipara, at 26 weeks' gestation had been undergone, five years before, a total thyroidectomy owing to a mixed papillary-follicular carcinoma of thyroid. After thyroidectomy the patient was placed on suppressive thyroxine treatment. Since she was 22 years old she suffered from recurrent renal colics and cholelithiasis. For these reasons she underwent, at the age of 27, an operation to remove bilateral renal calculi and a cholecystectomy owing to gall-stones. During her pregnancy biochemical determinations revealed slight and persistent hypercalcemia, hypophosphatemia, elevated urine calcium besides elevated serum parathyroid hormone (PTH) levels. Thus a diagnosis of primary hyperparathyroidism was taken into consideration. It was considered, but temporarily delayed, the surgical exploration of the neck. A strict clinic overseeing of the patient, which allowed her to carry out the pregnancy happily, was undertaken. Any thyroid carcinoma repercussion on pregnancy was not noted. A left inferior parathyroid adenoma was removed five months after the woman's delivery. The child psychosomatic development, at one year of age, was absolutely normal. A review of the literature indicates that when a pregnancy is complicated by hyperparathyroidism its prognosis is improved by parathyroidectomy, if possible during the second trimester. In patients with asymptomatic hypercalcemia and/or in late pregnancy surgical treatment may be postponed until after delivery. It is also demonstrated that thyroid carcinoma is not aggravated by pregnancy and that the latter can develop without any worry for mother and fetus.