Online Questionnaire with Fibromyalgia Patients Shows Negative Correlations between Disease Severity and Adherence to Mediterranean Diet.

Fibromyalgia (FM) is a multidimensional disorder in which intense chronic pain is accompanied by a variety of psychophysical symptoms that impose a burden on the patients' quality of life. Despite the efforts and the recent advancement in research, FM pathogenesis and effective treatment remain unknown. Recently, the possible role of dietary patterns and/or components has been gaining attention. The current study aimed to investigate a potential correlation between adherence to the Mediterranean diet (MedDiet) and FM severity in a sample of Italian FM patients. An online survey was designed, composed of customized questions and validated questionnaires with the aim of investigating the intensity and type of pain, the presence of other psychophysical symptoms, the overall impact of FM, general food and lifestyle habits, and adherence to the MedDiet. The collected responses were analyzed for descriptive statistics, linear regression, and propensity score analyses. The results show that, despite considerable use of pharmaceuticals and supplements, FM participants suffered from a high-severity grade disease. However, those with good adherence to the MedDiet experienced a lower pain intensity and overall FM impact. A propensity score analysis indicates a positive influence of the MedDiet against FM severity, thus unveiling the need for well-designed intervention studies to evaluate the therapeutic potential of different dietary patterns.

The Essential Oil of Citrus lumia Risso and Poit. 'Pyriformis' Shows Promising Antioxidant, Anti-Inflammatory, and Neuromodulatory Effects.

Citrus lumia Risso and Poit. 'Pyriformis' are horticultural varieties of Citrus lumia Risso. The fruit is very fragrant and pear-shaped, with a bitter juice, a floral flavor, and a very thick rind. The flavedo shows enlarged (0.74 × 1.16 mm), spherical and ellipsoidal secretory cavities containing the essential oil (EO), visible using light microscopy, and more evident using scanning electron microscopy. The GC-FID and GC-MS analyses of the EO showed a phytochemical profile characterized by the predominance of D-limonene (93.67%). The EO showed interesting antioxidant and anti-inflammatory activities (IC50 0.07-2.06 mg/mL), as evaluated by the in vitro cell-free enzymatic and non-enzymatic assays. To evaluate the effect on the neuronal functional activity, the embryonic cortical neuronal networks grown on multi-electrode array chips were exposed to non-cytotoxic concentrations of the EO (5-200 µg/mL). The spontaneous neuronal activity was recorded and the mean firing rate, mean burst rate, percentage of spikes in a burst, mean burst durations and inter-spike intervals within a burst parameter were calculated. The EO induced strong and concentration-dependent neuroinhibitory effects, with IC50 ranging between 11.4-31.1 µg/mL. Furthermore, it showed an acetylcholinesterase inhibitory activity (IC50 0.19 mg/mL), which is promising for controlling some of the key symptoms of neurodegenerative diseases such as memory and cognitive concerns.

Fibromyalgia in Pregnancy: Neuro-Endocrine Fluctuations Provide Insight into Pathophysiology and Neuromodulation Treatment.

Fibromyalgia (FM) is a chronic pain disorder with unclear pathophysiological mechanisms, which leads to challenges in patient management. In addition to pain, the disorder presents with a broad range of symptoms, such as sleep disruption, chronic fatigue, brain fog, depression, muscle stiffness, and migraine. FM has a considerable female prevalence, and it has been shown that symptoms are influenced by the menstrual cycle and periods of significant hormonal and immunological changes. There is increasing evidence that females with FM experience an aggravation of symptoms in pregnancy, particularly during the third trimester and after childbirth. In this perspective paper, we focus on the neuro-endocrine interactions that occur between progesterone, allopregnanolone, and cortisol during pregnancy, and propose that they align with our previously proposed model of FM pathogenesis based on GABAergic "weakening" in a thalamocortical neural loop system. Based on our hypothesis, we introduce the possibility of utilizing transcranial direct current stimulation (tDCS) as a non-invasive treatment potentially capable of exerting sex-specific effects on FM patients.

Nutraceutical Potential of High-latitude and High-altitude Berries Rich in Ellagitannins.

INTRODUCTION: This review concerns three species of berries, namely the high- -latitude cloudberry (Rubus chamaemorus) and arctic bramble (Rubus arcticus), and the high-altitude yellow raspberry (Rubus ellipticus). These plants are mostly exploited on a local basis as food or traditional remedies but could have a wider usage as nutraceuticals due to their richness in ellagitannins (ETs) and other phenolic compounds. ETs are hexahydroxydiphenoyl esters of carbohydrates and the largest group of hydrolysable tannins. They are distinctly antioxidant and bioactive compounds, and therefore, are considered as majorly responsible for the biological properties of ET-rich berries. The health benefits of ETs are mainly due to the release of ellagic acid and to their metabolic transformation by the gut microbiota into urolithins, and include, among others, anti-inflammatory, antiviral, anti-bacterial, and anticancer actions. METHODS: Based on the literature searches in the Web of Science, Scopus, and PubMed databases, ethnobotanical, pharmaceutical, medicinal, and nutritional knowledge concerning the three berry species was covered. This includes empirical use of traditional preparations and experimental studies with various extracts and fractions from fruits and other plant portions, covering in vitro, preclinical, and clinical research. RESULTS: The data reveal a wide spectrum of potential uses in health care, providing in some cases an experimental confirmation of traditional uses. CONCLUSION: The examined berry species can act as nutraceutical foods, having positive effects on regular consumers but could also be exploited in more technological ways to produce food complements from ET-rich extracts.

Online Questionnaire with Fibromyalgia Patients Reveals Correlations among Type of Pain, Psychological Alterations, and Effectiveness of Non-Pharmacological Therapies.

Fibromyalgia (FM) is a chronic pain syndrome with an unclear etiology. In addition to pain, FM patients suffer from a diverse array of symptoms and comorbidities, encompassing fatigue, cognitive dysfunction, mood disorders, sleep deprivation, and dizziness. Due to the complexity of FM, the diagnosis and treatment of it are highly challenging. The aim of the present work was to investigate some clinical and psychological characteristics of FM patients, and to uncover possible correlations with pharmacological and non-pharmacological therapies. We conducted a cross-sectional, questionnaire-based study aimed at evaluating pain, psychological traits, and the self-perceived effectiveness of pharmacological and non-pharmacological treatments in an Italian population of FM patients. Descriptive statistics, correlation, and inference analyses were performed. We found a prevalence of a neuropathic/nociplastic type of pain, which correlated with psychological traits such as anxiety, low mood, psychophysical discomfort, and the inability to relax. The pain type and psychological traits proved to play a role in determining the self-perceived effectiveness of therapeutic interventions. Patients revealed a better response to non-pharmacological therapies, particularly dietary interventions, relaxation techniques, and psychotherapy rather than pharmacological interventions. The sum of our data indicates that for better outcomes, the type of pain and psychological traits should be considered for tailor-made treatments considering non-pharmacological protocols as a complement to the use of drugs.

Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey.

Fibromyalgia (FM) is an unsolved central pain processing disturbance. We aim to provide a unifying model for FM pathogenesis based on a loop network involving thalamocortical regions, i.e., the ventroposterior lateral thalamus (VPL), the somatosensory cortex (SC), and the thalamic reticular nucleus (TRN). The dynamics of the loop have been described by three differential equations having neuron mean firing rates as variables and containing Hill functions to model mutual interactions among the loop elements. A computational analysis conducted with MATLAB has shown a transition from monostability to bistability of the loop behavior for a weakening of GABAergic transmission between TRN and VPL. This involves the appearance of a high-firing-rate steady state, which becomes dominant and is assumed to represent pathogenic pain processing giving rise to chronic pain. Our model is consistent with a bulk of literature evidence, such as neuroimaging and pharmacological data collected on FM patients, and with correlations between FM and immunoendocrine conditions, such as stress, perimenopause, chronic inflammation, obesity, and chronic dizziness. The model suggests that critical targets for FM treatment are to be found among immunoendocrine pathways leading to GABA/glutamate imbalance having an impact on the thalamocortical system.

Vestibular Disability/Handicap in Fibromyalgia: A Questionnaire Study.

Fibromyalgia (FM) is a poorly understood, central pain processing disorder characterized by a broad range of symptoms, such as chronic pain, sleep disruption, chronic fatigue, and psychosomatic symptoms. In addition, recent studies have shown that FM patients also experience dizziness. We aimed to establish a prevalence rate of vestibular symptoms in a population of FM patients through a battery of questionnaires investigating socio-demographic, clinical and psychological characteristics, combined with the Dizziness Handicap Inventory (DHI) and the Situational Vertigo Questionnaire (SVQ). A total of 277 respondents, officially diagnosed with FM, completed the full study, while 80 controls were also included for DHI and SVQ questionnaires. We found that FM participants were significantly affected by vestibular symptoms, which correlated with FM-associated pain and non-pain symptoms. The dizziness reported by FM participants showed peculiar features suggesting an FM-intrinsic mechanism of vestibular dysfunction, possibly linked to migraine and dysautonomia conditions. Correlations between dizziness and depressive mood (or neuroticism), revealed an impact of dizziness on psychological status, leading to depressive reactions and interpersonal difficulties, and possibly involving a noxious, self-sustained stress condition. In conclusion, data showed a manifesting dizziness condition in FM patients that warrants careful clinical attention due to its possible inherent role in the syndrome.

Anti-Inflammatory and Wound Healing Properties of Leaf and Rhizome Extracts from the Medicinal Plant Peucedanum ostruthium (L.) W. D. J. Koch

Peucedanum ostruthium (L.) W. D. J. Koch (Apiaceae) is a worldwide perennial herb native to the mountains of central Southern Europe. The rhizome has a long tradition in popular medicine, while ethnobotanical surveys have revealed local uses of leaves for superficial injuries. To experimentally validate these uses, plant material was collected in the Gran Paradiso National Park, Aosta Valley, Italy, and the rhizome and leaves were micromorphologically and phytochemically characterized. Polyphenol-enriched hydroalcoholic rhizome and leaf extracts, used in cell-free assays, showed strong and concentration-dependent antioxidant and anti-inflammatory activities. In vitro tests revealed cyclooxygenase and lipoxygenase inhibition by the leaf extract, while the rhizome extract induced only lipoxygenase inhibition. MTT assays on HaCaT keratinocytes and L929 fibroblasts showed low cytotoxicity of extracts. In vitro scratch wound test on HaCaT resulted in a strong induction of wound closure with the leaf extract, while the effect of the rhizome extract was lower. The same test on L929 cells showed similar wound closure induction with both extracts. The results confirmed the traditional medicinal uses of the rhizome as an anti-inflammatory and wound healing remedy for superficial injuries but also highlighted that the leaves can be exploited for these purposes with equal or superior effectiveness.

Carpobrotus edulis (L.) N.E.Br. extract as a skin preserving agent: From traditional medicine to scientific validation.

OBJECTIVE: Carpobrotus edulis (L.) N.E.Br. is a succulent perennial plant native to South Africa and grows invasively in the Mediterranean basin. It is commonly used for the treatment of various diseases, including skin wound healing and regeneration, for which experimental validation is lacking. We therefore evaluated the skin healing properties by testing a C. edulis aqueous leaf extract (CAE) on cell cultures and in enzymatic assays. METHODS: Micro-morphological analysis of leaves was carried out using scanning electron microscopy and light microscopy. Phytochemical features and antioxidant activity of CAE were evaluated by reversed-phase liquid chromatography coupled with diode array detection and electrospray ion trap mass spectrometry (RP-LC-DAD-ESI-MS), and in vitro cell-free assays. Biological activities were evaluated using keratinocytes and fibroblasts, as well as elastase, collagenase, and hyaluronidase. RESULTS: CAE showed high carbohydrates (28.59% ± 0.68%), total phenols ([101.9 ± 6.0] g gallic acid equivalents/kg dry extract [DE]), and flavonoids ([545.9 ± 26.0] g rutin equivalents/kg DE). RP-LC-DAD-ESI-MS revealed the predominant presence of hydroxycinnamic acids (51.96%), followed by tannins (14.82%) and flavonols (11.32%). The extract was not cytotoxic, had a strong and dose-dependent antioxidant activity, and inhibited collagenase (> 90% at 500 µg/mL) and hyaluronidase (100% at 1000 µg/mL). In cell culture experiments, CAE increased wound closure and collagen production, which was consistent with its high polyphenol content. CONCLUSION: Our data support the use of the C. edulis for skin care and the treatment of skin problems. Moreover, use of C. edulis for skin care purposes could be an eco-friendly solution to reduce its invasiveness in the environment.

Epigallocatechin-3-gallate mobilizes intracellular Ca2+ in prostate cancer cells through combined Ca2+ entry and Ca2+-induced Ca2+ release.

AIMS: To elucidate the mechanism by which (-)-epigallocatechin-3-gallate (EGCG) mediates intracellular Ca2+ increase in androgen-independent prostate cancer (PCa) cells. MAIN METHODS: Following exposure to different doses of EGCG, viability of DU145 and PC3 PCa cells was evaluated by MTT assay and the intracellular Ca2+ dynamics by the fluorescent Ca2+ chelator Fura-2. The expression of different channels was investigated by qPCR analysis and sulfhydryl bonds by Ellman's assay. KEY FINDINGS: EGCG inhibited DU145 and PC3 proliferation with IC50 = 46 and 56 µM, respectively, and induced dose-dependent peaks of internal Ca2+ that were dependent on extracellular Ca2+. The expression of TRPC4 and TRPC6 channels was revealed by qPCR in PC3 cells, but lack of effect by modulators and blockers ruled out an exclusive role for these, as well as for voltage-dependent T-type Ca2+ channels. Application of dithiothreitol and catalase and sulfhydryl (SH) measurements showed that EGCG-induced Ca2+ rise depends on SH oxidation, while the effect of EGTA, dantrolene, and the PLC inhibitor U73122 suggested that EGCG-induced Ca2+ influx acts as a trigger for Ca2+-induced Ca2+ release, involving both ryanodine and IP3 receptors. Different from EGCG, ATP caused a rapid Ca2+ increase, which was independent of external Ca2+, but sensitive to U73122. SIGNIFICANCE: EGCG induces an internal Ca2+ increase in PCa cells by a multi-step mechanism. As dysregulation of cytosolic Ca2+ is directly linked to apoptosis in PCa cells, these data confirm the possibility of using EGCG as a synergistic adjuvant in combined therapies for recalcitrant malignancies like androgen-independent PCa.

Depigmenting potential of lichen extracts evaluated by in vitro and in vivo tests.

Melanin is the main pigment of human skin, playing the primary role of protection from ultraviolet radiation. Alteration of the melanin production may lead to hyperpigmentation diseases, with both aesthetic and health consequences. Thus, suppressors of melanogenesis are considered useful tools for medical and cosmetic treatments. A great interest is focused on natural sources, aimed at finding safe and quantitatively available depigmenting substances. Lichens are thought to be possible sources of this kind of compounds, as the occurrence of many phenolic molecules suggests possible effects on phenolase enzymes involved in melanin synthesis, like tyrosinase. In this work, we used four lichen species, Cetraria islandica Ach., Flavoparmelia caperata Hale, Letharia vulpina (L.) Hue, and Parmotrema perlatum (Hudson) M. Choisy, to obtain extracts in solvents of increasing polarity, viz. chloroform, chloroform-methanol, methanol, and water. Cell-free, tyrosinase inhibition experiments showed highest inhibition for L. vulpina methanol extract, followed by C. islandica chloroform-methanol one. Comparable results for depigmenting activities were observed by means of in vitro and in vivo systems, such as MeWo melanoma cells and zebrafish larvae. Our study provides first evidence of depigmenting effects of lichen extracts, from tyrosinase inhibition to cell and in vivo models, suggesting that L. vulpina and C. islandica extracts deserve to be further studied for developing skin-whitening products.

Polyphenol Characterization and Skin-Preserving Properties of Hydroalcoholic Flower Extract from Himantoglossum robertianum (Orchidaceae).

Himantoglossum robertianum (Loisel.) P. Delforge is a Mediterranean orchid whose propagation in vitro has been achieved, making it eligible as a source of bioactive substances. Flowers were analyzed by light and SEM microscopy and used to obtain a polyphenol-rich, hydroalcoholic flower extract (HFE). HFE was characterized for total phenols, flavonoids and proanthocyanidins, and for polyphenol profile by RP-LC-DAD. Antioxidant assays, in vitro collagenase and elastase inhibition, and MTT and cell motility assays on HaCaT keratinocytes were done. Microscopy showed epidermal cells containing anthocyanins in the flower labellum. Flavonoids (flavones and flavan-3-ols) represented the most abundant compounds (42.91%), followed by scopoletin (33.79%), and phenolic acids (23.3%). Antioxidant assays showed strong activities, rating ORAC > FRAP > TEAC > ß-carotene bleaching > DPPH > iron-chelation. Biological assays showed elastase and collagenase inhibition (up to 42% and 78%, respectively), improvement of HaCaT cell viability after treatment with 500 µM H2O2 (from 30% to 84% of control), and stimulation of cell migration rate up to 210% of control. In summary, HFE counteracted different free radicals, while protective properties were shown by cell-free and cell-based bioassays, suggesting the possible use of H. robertianum flowers for skin-preserving, repair, and anti-aging applications.

Nutritional and medicinal properties of underexploited legume trees from West Africa.

This review concerns three legume trees (family Fabaceae, subfamily Caesalpinioideae) from West Africa, namely Detarium microcarpum, Parkia biglobosa and Dialium guineense, and illustrates their nutritional value and therapeutic properties. These species are an important source of nutrition for West African populations, but their agricultural exploitation is still incomplete. The survey was conducted on Scopus, Web of Science, and Medline, using scientific and common English names of the species as keywords and then selecting papers related to nutritional and medicinal properties. Main food products are fruit pulp and seeds, though leaves can also be used. Most relevant dietary features are high protein, vitamin, and micronutrient contents. Various therapeutic and nutritional benefits of these plants have been documented by ethnobotanical and experimental studies, stimulating an interest for their possible use as functional food or drug sources. Most studied medicinal properties include antidiabetic and antimicrobial activities of D. microcarpum, cardiovascular protective and antidiabetic activities of P. biglobosa, and bilharzia-preventing molluscicidal activity of D. guineense. Phytochemical characterizations have revealed potential sources of active drugs, such as D. guineense saponins and D. microcarpum diterpenes. Scientific results support popular uses of these legume trees, indicating a prominent nutritional and health value.

Antioxidant and cytoprotective activities of an ancient Mediterranean citrus (Citrus lumia Risso) albedo extract: Microscopic observations and polyphenol characterization.

Citrus fruits are a rich source of bio-functional compounds with various and well-proven health properties. We focused our attention on an ancient Mediterranean species, Citrus lumia Risso. The aim of this work was to investigate the polyphenol content and biological activities of C. lumia albedo extract by cell-free and cell-based assays. Fifteen polyphenols were quantified by LC-DAD-FLD analysis (flavonoids 89.34% and phenolic acids 10.66%) with eriocitrin and hesperidin as major components (52.81% and 31.31%, respectively). These results were corroborated also by micromorphological observations, which showed clusters of needle-shaped crystals of hesperidin highlighted by TBO staining. C. lumia albedo extract revealed marked antioxidant and free radical scavenging properties, and a significant cytoprotective activity on t-BOOH-treated lymphocytes. Results indicate that C. lumia albedo extract could be exploited as an antioxidant source, suggesting the use of albedo, currently considered a by-product, as a valuable raw material for nutraceutical employments.

(-)- Epigallocatechin-3-gallate induces GRP78 accumulation in the ER and shifts mesothelioma constitutive UPR into proapoptotic ER stress.

GRP78 is a molecular chaperone of the endoplasmic reticulum (ER) that aids proper folding of nascent polypeptides. When unfolded proteins accumulate, GRP78 triggers unfolded protein response (UPR), involving activation of transcription factors like XBP1 and CHOP that may restore cell homeostasis. Increased expression of GRP78 and mild UPR can be constitutive in cancer cells, hindering apoptosis, and promoting cell survival, for example, by GRP78 relocation to the plasma membrane that activates MAPK and PI3 K/AKT pathways. These processes are thought to favor the insurgence of chemoresistance and worsen patient outcome. We have previously shown that (-)-epigallocatechin-3-gallate (EGCG) enhances ROS production and alters Ca2+ homeostasis in cell lines deriving from therapy-recalcitrant malignant mesothelioma (MMe). We consider here the EGCG impact on GRP78 and downstream factors by using qRT-PCR, Western blot, immunofluorescence, caspase assays, GRP78 siRNA silencing, and cell surface ELISA. MMe cells were found to display mild constitutive UPR, as shown by increased levels of GRP78, and presence of the protein at the cell surface, linked to AKT activation. Exposure to EGCG further increased GRP78 in the ER, and induced ATF4, spliced XBP1, CHOP, and EDEM expressions, combined with a reduction of cell surface GRP78 and a rise in caspase 3 and 8 activities. We propose that GRP78 accumulation in the ER, caused by EGCG, converts constitutive UPR of MMe cells into proapoptotic ER stress. This argues for a possible therapeutic use of EGCG in the treatment of MMe as a co-drug able to abolish chemoresistance to conventional drugs at tolerable doses.

Posidonia oceanica (L.) Delile Ethanolic Extract Modulates Cell Activities with Skin Health Applications.

Seagrasses are high plants sharing adaptive metabolic features with both terrestrial plants and marine algae, resulting in a phytocomplex possibly endowed with interesting biological properties. The aim of this study is to evaluate the in vitro activities on skin cells of an ethanolic extract obtained from the leaves of Posidonia oceanica (L.) Delile, family Potamogetonaceae, herein named Posidonia ethanolic extract (PEE). PEE showed high radical scavenging activity, high phenolic content, and resulted rich in chicoric acid, as determined through HPLC-MS analysis. The use of MTT assay on fibroblasts showed a PEE cytotoxicity threshold (IC05) of 50 µg/mL at 48 h, while a sub-toxic dose of 20 µg/mL induced a significant increase of fibroblast growth rate after 10 days. In addition, an ELISA assay revealed that PEE doses of 5 and 10 µg/mL induced collagen production in fibroblasts. PEE induced dose-dependent mushroom tyrosinase inhibition, up to about 45% inhibition at 1000 µg/mL, while 50% reduction of melanin was observed in melanoma cells exposed to 50 µg/mL PEE. Finally, PEE lipolytic activity was assessed by measuring glycerol release from adipocytes following triglyceride degradation. In conclusion, we have collected new data about the biological activities of the phytocomplex of P. oceanica seagrass on skin cells. Our findings indicate that PEE could be profitably used in the development of products for skin aging, undesired hyperpigmentation, and cellulite.

Therapeutic Properties of Bioactive Compounds from Different Honeybee Products.

Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA), with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities. Propolis contains caffeic acid phenethyl ester and artepillin C, specific of Brazilian propolis, with antiviral, immunomodulatory, anti-inflammatory and anticancer effects. Bee venom consists of toxic peptides like pain-inducing melittin, SK channel blocking apamin, and allergenic phospholipase A2. Bee pollen is vitaminic, contains antioxidant and anti-inflammatory plant phenolics, as well as antiatherosclerotic, antidiabetic, and hypoglycemic flavonoids, unsaturated fatty acids, and sterols. Beeswax is widely used in cosmetics and makeup. Given the importance of drug discovery from natural sources, this review is aimed at providing an exhaustive screening of the bioactive compounds detected in honeybee products and of their curative or adverse biological effects.

Antiproliferative hydroxy-fatty acids from the fodder legume Stylosanthes guianensis.

Stylosanthes guianensis is a fodder legume native from South America and widely grown worldwide. Dried plant material was purchased on the web and taxonomically identified by light and SEM microscopy, and morphological analysis of plants germinated from seeds. The plant was extracted with dichloromethane:2-propanol (9:1). Bioguided fractionation using calcein-AM cytotoxicity assay on HeLa and A431 tumor cells allowed to isolate a lipophilic fraction, endowed with strong cytotoxicity. By means of 1- and 2-D NMR, HPLC-MS, and HR-ESIMS it could be seen that the fraction was an inseparable mixture of complex lipids, mainly consisting of esterified 3-hydroxy fatty acids. Acidic methanolysis of the mixture yielded 3-OH C10 and C12 carboxylic acids, together with palmitic, stearic, and arachidonic acids. Mass values indicate the presence of dimeric and trimeric combinations of 3-hydroxy, C10/C12 acids, and C16/C18/C20 acids, linked via ester bond. Monomeric hydroxyl-fatty acids were also observed, in particular derivatives of mono-hydroxy and di-hydroxy linolenic, linoleic, and oleic acids. 3-O-acylated, esterified fatty acids are unusual in higher plants, and recall motifs of Gram-negative endotoxin lipid A. These oxylipins are likely to be responsible for the antiproliferative activity of S. guianensis, suggesting possible use of the plant in the development of antitumor drugs.

Moraceae Plants with Tyrosinase Inhibitory Activity: A Review.

Hyperpigmentation is an abnormal darkening of the skin mostly derived from excessive melanin production. It is typical of skin disorders including melasma associated to pregnancy or age, freckles, sun freckles and photoaging, age spots, and actinic keratosis. These conditions can be uncomfortable for aesthetic reasons and specific depigmenting treatment is frequently requested. Tyrosinase (EC 1.14.18.1) is the rate-limiting enzyme of melanin synthesis and the main target of antihyperpigmentation remedies. Much interest is focused on compounds able to inhibit tyrosinase activity, particularly natural products, for which there is an increasing demand in the fields of cosmetics and pharmaceutical applications. This review concerns plants from the Moraceae family that have shown tyrosinase inhibition in vitro, including species from the genera Morus, Artocarpus, Maclura (Cudrania), Broussonetia, Milicia (Chlorophora), and Ficus. Compounds with remarkable tyrosinase inhibitory properties have been isolated from the wood and bark of different species, such as calchones, stilbenoids, flavonoids and diterpenes. Studies of structure-activity relationships have suggested that an unsubstituted resorcinol moiety is important for the acquirement of strong tyrosinase inhibition, but various exceptions have been reported. A few species, such as M. alba, A. heterophyllus, A. incisus, Maclura tricuspidata, and C. excelsa, have also shown inhibition of melanin biosynthesis on cultured melanoma cells. In addition, wood extract and the stilbene artocarpin from A. incisus have induced whitening effects on guinea pig skin, while an extract from A. lakoocha has hindered melanin formation in human volunteers. The complex of data indicates that Moraceae plants deserve attention for the development of natural and semi-synthetic tyrosinase inhibitors able to compete with, or outclass, currently available skin whitening drugs.

Resveratrol induces intracellular Ca(2+) rise via T-type Ca(2+) channels in a mesothelioma cell line.

AIMS: Intracellular calcium (Ca(2+)) is known to play an important role in cancer development and growth. Resveratrol (Res) is a stilbene polyphenol occurring in several plant species and known for various possible beneficial effects, including its ability to inhibit proliferation and to induce apoptosis in cancer cells. This study was designed to determine whether Res affects Ca(2+) signaling in cancer cells. MAIN METHODS: We used the REN human mesothelioma cell line, as an in vitro cancer cell model, and the non-malignant human mesothelial MeT5A cell line, as normal cell model. Cytosolic Ca(2+) concentration was measured by the fluorescent indicator Fura-2. Immunofluorescence, Western blot, and siRNA technique were employed to assess the involvement of T-type Ca(2+) channels. Cell viability was determined by the calcein assay. KEY FINDINGS: REN cells transiently exposed to 1-10µM Res showed increasing peaks of Ca(2+) that were absent in Ca(2+)-free medium and were reduced by non-selective (Ni(2+)), and highly selective (NNC 55-0396) T-type Ca(2+) channels antagonist, and by siRNA knockout of Cav3.2T-type Ca(2+) channel gene. Dose-dependent curve of Res-induced Ca(2+) peaks showed a rightward shift in normal MeT-5A mesothelial cells (EC50=4.9µM) with respect to REN cells (EC50=2.7µM). Moreover, incubation with 3 and 10µM Res for 7days resulted in cell growth inhibition for REN, but not for MeT-5A cells. SIGNIFICANCE: Res induces Ca(2+) influx, possibly mediated through T-type Ca(2+) channels, with significant selectivity towards mesothelioma cells, suggesting a possible use as an adjuvant to chemotherapy drugs for mesothelioma clinical treatment.