Iridoid- and flavonoid-enriched fractions of Cornus sanguinea and Cornus mas exert antioxidant and anti-inflammatory effects and inhibit key enzymes in the treatment of metabolic disorders.

Background: Berry fruits are recognized as a "superfood" due to their high content of bioactive compounds and health benefits. Scope and approach: Herein, extracts of Cornus sanguinea and Cornus mas fresh and dried fruits obtained by different extraction procedures (ethanolic and hydroalcoholic maceration, ultrasound-assisted extraction, and Soxhlet apparatus) were analysed using liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS) and compared to identify the main healthy compounds and their impact on the inhibition of key enzymes (pancreatic lipase, α-glucosidase, and α-amylase) associated with metabolic disorders. The antioxidant activity and inhibition of nitric oxide (NO) and NF-κB pathway were also investigated. Key findings and conclusions: Flavonoids, iridoids, and phenolic acids were the main classes of identified compounds. Herein, kaempferol 3-O-galactoside, kaempferol 3-O-glucoside, quercetin, quercetin 3-O-xyloside, and myricetin 3-O-galactoside were detected for the first time in C. sanguinea. Remarkable antioxidant effects and promising α-glucosidase and lipase inhibitory activity were observed with extracts obtained by hydroalcoholic maceration of both Cornus dried fruits. Consequently, these extracts were subjected to fractionation using Amberlite XAD-16 resin. The most promising biological activities, which are attributed to the presence of some flavonoids and iridoids, were detected with the C. sanguinea fractions, in particular SD2(II). The results of this study offer new insights into the potential development of functional foods, nutraceuticals, and food supplements using the Cornus species.

Biological Investigation and Chemical Study of Brassica villosa subsp. drepanensis (Brassicaeae) Leaves.

Brassica villosa subsp. drepanensis (Caruel) Raimondo & Mazzola, belonging to the Brassica oleracea complex, is a wild edible plant endemic to western Sicily and a relative of modern cultivated Brassica crops. In this study, the antioxidant properties, anti-inflammatory activities, enzymatic inhibition, and cytotoxicity in cancer cells of B. villosa subsp. drepanensis leaf ethanolic extract were analysed for the first time. In addition, its chemical profile was investigated partitioning the total 70% ethanol extract among ethyl acetate, n-butanol, and water to obtain three residues that were subjected to chromatographic separation. Two flavonol glycosides, a phenol glucoside, two amino acids, and purine/pyrimidine bases were obtained. The presence of the glucosinolate glucoiberin was detected in the water extract by UHPLC-MS analysis. The total polyphenol and flavonoid content of the 70% ethanol extract showed good antioxidant capacities and anti-inflammatory properties by reducing nitric oxide release and reactive oxygen species levels and increasing glutathione in lipopolysaccharide-stimulated RAW 264.7 cells. The extract inhibited the enzymatic activity of α-amylase, α-glucosidase, and, significantly, of lipase. The MTT assay showed that the extract did not affect the viability of normal HFF-1 and RAW 264.7 cells. Among the cancer cell lines tested, an antiproliferative action was only observed in CaCo-2. The cytotoxicity of the extract was further confirmed by LDH release assay and by the destabilization of the oxidative balance. Results confirmed the antioxidant properties of the crude extract responsible for the anti-inflammatory effect on healthy cells and cytotoxicity in cancer cells.

Carbon Source Influences Antioxidant, Antiglycemic, and Antilipidemic Activities of Haloferax mediterranei Carotenoid Extracts.

Haloarchaeal carotenoids have attracted attention lately due to their potential antioxidant activity. This work studies the effect of different concentrations of carbon sources on cell growth and carotenoid production. Carotenoid extract composition was characterized by HPLC-MS. Antioxidant activity of carotenoid extracts obtained from cell cultures grown under different nutritional conditions was determined by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Ability Power (FRAP) and ß-carotene bleaching assays. The ability of these carotenoid extracts to inhibit α-glucosidase, α-amylase, and lipase enzymes was also assessed to determine if they could be used to reduce blood glucose and lipid absorption. The maximum production of carotenoids (92.2 µg/mL) was observed combining 12.5% inorganic salts and 2.5% of glucose/starch. Antioxidant, hypoglycemic, and antilipidemic studies showed that higher carbon availability in the culture media leads to changes in the extract composition, resulting in more active haloarchaeal carotenoid extracts. Carotenoid extracts obtained from high-carbon-availability cell cultures presented higher proportions of all-trans-bacterioruberin, 5-cis-bacterioruberin, and a double isomeric bacterioruberin, whereas the presence 9-cis-bacterioruberin and 13-cis-bacterioruberin decreased. The production of haloarchaeal carotenoids can be successfully optimized by changing nutritional conditions. Furthermore, carotenoid composition can be altered by modifying carbon source concentration. These natural compounds are very promising in food and nutraceutical industries.

Santolina pinnata Viv. Exerts Promising Antitumor Activity against Breast Cancer Cells and Anti-Inflammatory Effects in LPS-Stimulated RAW 264.7 Cells.

Cancer is one of the largest causes of mortality in the world, and due to its incidence, the discovery of novel anticancer drugs is of great importance. Many successful anticancer drugs used in clinical practices are derived from natural products. The genus Santolina is a group of species distributed in the Mediterranean area and used in traditional medicine for their biological properties. The aim of this work was to investigate, for the first time, the multi-target biological potential of Italian Santolina pinnata in relation to their chemical profile, by which an interesting natural source of valuable phytochemicals endowed with anticancer and anti-inflammatory features could be assessed. n-Hexane (EHSP) and methanol (EMSP) extracts were investigated by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography (UHPLC), respectively. Anti-proliferative activity was analyzed on MCF-7 and MDA-MB-231 breast cancer cells, as well as on non-tumorigenic MCF-10A cells, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptotic death was assessed by comet assay. Cell motility and invasive features were examined in highly invasive MDA-MB-231 by wound-healing scratches, while, in both breast cancer cell lines, by gel-zymography experiments. The anti-inflammatory potential was analyzed by nitric oxide (NO) production and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) staining experiments in bacterial lipopolysaccharides (LPS) which stimulated RAW 264.7 cells. EHSP and EMSP extracts exhibited anticancer activity against breast cancer cells, promoting apoptotic death, as well as decreasing cell migration and invasive behaviours. The highest activity (IC50 of 15.91 µg/mL) was detected against MDA-MB-231 cells, a highly invasive breast cancer cell line. Both extracts were also able to promote anti-inflammatory effects (IC50 values ranging from 27.5 to 61.14 µg/mL), as well as to reduce NO levels by inducing inhibitory effects on NF-κB nuclear translocation in LPS-stimulated RAW 264.7 cells. The different biological behaviours found between the extracts could be related to their different chemical compositions. Herein, the multi-target biological potential of S. pinnata in inducing antitumor and anti-inflammatory effects was comprehensively demonstrated. These findings will provide important stepping-stones for further investigations and may lead to the development of highly effective S. pinnata extract-based treatments for breast cancer and inflammatory processes.

The potential of pumpkin seed oil as a functional food-A comprehensive review of chemical composition, health benefits, and safety.

The growing interest in foods that can be beneficial to human health is bringing into focus some products that have been used locally for centuries but have recently gained worldwide attention. One of these foods is pumpkin seed oil, which has been used in culinary and traditional medicine, but recent data also show its use in the pharmaceutical and cosmetic industries. In addition, some sources refer to it as a potential functional food, mainly because it is obtained from pumpkin seeds, which contain many functional components. However, the production process of the oil may affect the content of these components and consequently the biological activity of the oil. In this review, we have focused on summarizing scientific data that explore the potential of pumpkin seed oil as a functional food ingredient. We provide a comprehensive overview of pumpkin seed oil chemical composition, phytochemical content, biological activity, and safety, as well as the overview of production processes and contemporary use. The main phytochemicals in pumpkin seed oil with health-related properties are polyphenols, phytoestrogens, and fatty acids, but carotenoids, squalene, tocopherols, and minerals may also contribute to health benefits. Most studies have been conducted in vitro and support the claim that pumpkin seed oil has antioxidant and antimicrobial activities. Clinical studies have shown that pumpkin seed oil may be beneficial in the treatment of cardiovascular problems of menopausal women and ailments associated with imbalance of sex hormones.

Bioavailability Study of Isothiocyanates and Other Bioactive Compounds of Brassica oleracea L. var. Italica Boiled or Steamed: Functional Food or Dietary Supplement?

The levels of bioactive compounds in broccoli and their bioavailability following broccoli intake can be affected by the cooking procedures used for vegetable preparation. In the present pilot study, we compared the human plasma bioavailability of antioxidant compounds (ß-carotene, lutein and isothiocyanate) and of phylloquinone (vitamin K) on seven volunteers before and after the administration of boiled and steamed broccoli. Moreover, plasma isothiocyanate (ITCs) levels were also evaluated after the administration of a single dose of BroccoMax®, a dietary supplement containing GLSs with active myrosinase. Steam-cooking has been demonstrated to promote higher plasma bioavailability in ITCs than boiling (AUCSTEAMED = 417.4; AUCBOILED = 175.3) and is comparable to that reached following the intake of BroccoMax®, a supplement containing glucoraphanin and active myrosinase (AUC = 450.1). However, the impact of boiling and steaming treatment on plasma bioavailability of lipophilic antioxidants (lutein and ß-carotene) and of phylloquinone was comparable. The lutein and ß-carotene plasma levels did not change after administration of steamed or boiled broccoli. Conversely, both treatments led to a similar increase of phylloquinone plasma levels. Considering the antioxidant action and the potential chemopreventive activity of ITCs, steaming treatments can be considered the most suitable cooking method to promote the health benefits of broccoli in the diet.

Mechanistic aspects of carotenoid health benefits - where are we now?

Dietary intake and tissue levels of carotenoids have been associated with a reduced risk of several chronic diseases, including cardiovascular diseases, type 2 diabetes, obesity, brain-related diseases and some types of cancer. However, intervention trials with isolated carotenoid supplements have mostly failed to confirm the postulated health benefits. It has thereby been speculated that dosing, matrix and synergistic effects, as well as underlying health and the individual nutritional status plus genetic background do play a role. It appears that our knowledge on carotenoid-mediated health benefits may still be incomplete, as the underlying mechanisms of action are poorly understood in relation to human relevance. Antioxidant mechanisms - direct or via transcription factors such as NRF2 and NF-κB - and activation of nuclear hormone receptor pathways such as of RAR, RXR or also PPARs, via carotenoid metabolites, are the basic principles which we try to connect with carotenoid-transmitted health benefits as exemplified with described common diseases including obesity/diabetes and cancer. Depending on the targeted diseases, single or multiple mechanisms of actions may play a role. In this review and position paper, we try to highlight our present knowledge on carotenoid metabolism and mechanisms translatable into health benefits related to several chronic diseases.

Carotenoids: Considerations for Their Use in Functional Foods, Nutraceuticals, Nutricosmetics, Supplements, Botanicals, and Novel Foods in the Context of Sustainability, Circular Economy, and Climate Change.

Carotenoids are versatile isoprenoids that are important in food quality and health promotion. There is a need to establish recommended dietary intakes/nutritional reference values for carotenoids. Research on carotenoids in agro-food and health is being propelled by the two multidisciplinary international networks, the Ibero-American Network for the Study of Carotenoids as Functional Foods Ingredients (IBERCAROT; http://www.cyted.org) and the European Network to Advance Carotenoid Research and Applications in Agro-Food and Health (EUROCAROTEN; http://www.eurocaroten.eu). In this review, considerations for their safe and sustainable use in products mostly intended for health promotion are provided. Specifically, information about sources, intakes, and factors affecting bioavailability is summarized. Furthermore, their health-promoting actions and importance in public health in relation to the contribution of reducing the risk of diverse ailments are synthesized. Definitions and regulatory and safety information for carotenoid-containing products are provided. Lastly, recent trends in research in the context of sustainable healthy diets are summarized.

Impact of extraction processes on phytochemicals content and biological activity of Citrus × clementina Hort. Ex Tan. leaves: New opportunity for under-utilized food by-products.

Plants are a rich source of natural bioactive compounds with a wide range of applications in the food and pharmaceutical industries. Citrus × clementina leaves extracts and essential oils may be a potential candidate for formulation of products characterized by hypoglycaemic, antioxidant and anti-browning properties. C. × clementina leaves collected in three different areas in Calabria (South Italy) were extracted by Soxhlet apparatus, maceration, Ultrasound assisted maceration, and hydrodistillation. Hesperidin, tangeritin, and sinensetin were identified by HPLC-DAD analysis as dominant constituents of the extracts. The absence of coumarins and furanocoumarins was demonstrated. GC-MS analyses of essential oils evidenced the presence of sabinene, linalool, and (E)-ß-ocimene as main compounds. Based on RACI and GAS values calculated by the integration of data obtained by DPPH, ABTS, FRAP and ß-carotene bleaching methods, hydroalcoholic extract obtained by Ultrasound assisted maceration of the leaves collected in Corigliano Calabro showed the highest antioxidant activity. Ultrasound assisted hydroalcoholic extract of Cetraro leaves revealed the highest α-amylase inhibitory activity (IC50 of 64.37 µg/ml). Promising results of C. × clementina extracts as tyrosinase inhibitors were also obtained. To evaluate the relationship between identified compounds and bioactivity PCA was performed. Taking into account results obtained by this study, C. × clementina leaves that were considered Citrus-by-products could be utilized for formulation of food additives, nutraceuticals and functional foods.

Anchusa azurea Mill. (Boraginaceae) aerial parts methanol extract interfering with cytoskeleton organization induces programmed cancer cells death.

The present study aimed to determine the chemical composition, antioxidant effects and antitumor properties of a methanol extract of Anchusa azurea Mill. (Boraginaceae) aerial parts against four tumour cell lines (MCF-7, MDA-MB-231, RKO, and R2C). The antioxidant effects were assessed by using ß-carotene bleaching, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing ability power (FRAP) tests. HPLC analyses revealed chlorogenic acid, catechin, caffeic acid, and astragalin as the most abundant compounds. Interesting results were obtained in the ß-carotene bleaching test with IC50 values of 7.6 and 27.5 µg mL-1 after 30 and 60 min of incubation, respectively. Furthermore, the A. azurea extract protects 3T3-L1 mouse cells from oxidative stress induced by menadione and exhibits good antitumor activity, with very low toxicity. Our data indicate that the antitumor properties are due to the ability to induce programmed cancer cell death through caspase 3/7 and 9 activation and interference with the cytoskeleton dynamics.

Fixed oil from seeds of narrow-leaved ash (F. angustifolia subsp. angustifolia): Chemical profile, antioxidant and antiproliferative activities.

Fraxinus angustifolia subsp. angustifolia is a plant with an age-old use for the production of manna. However, it is also a valuable source of fixed oil rich-seeds. In the present study we examined the chemical and biological properties of this oil in order to support a possible application in foodstuffs, nutraceuticals and cosmetics. Fatty acid composition, volatile and phenolic substances were evaluated. Oleic and linoleic acid represented 45.5% and 50.0%, respectively, of the total fatty acid composition. Among polar phenolic substances identified (secoiridoids, phenylethanoid glycosides, phenolic acids and alcohols, flavonoids, coumarins) isoverbascoside is for the first time reported in this species. Volatiles were mainly characterized by sesquiterpenes. The oil showed good antioxidant activity, in terms of ABTS radical scavenging activity, with an IC50 value of 28.2 µg/mL. The antiproliferative activity was also investigated: amelanotic melanoma (C32) and lung carcinoma (A549) cells were the most sensitive with IC50 values comparable to that of the positive control vinblastine. These findings shed light on the potential use of F. angustifolia subsp. angustifolia fixed oil in nutraceutics and cosmetics.

Comparative analysis of chemical composition, antioxidant and anti-proliferative activities of Italian Vitis vinifera by-products for a sustainable agro-industry.

Vitis vinifera leaves are wine industry wastes. In this study, the chemical composition, antioxidant and anti-proliferative activity of six Italian grapevine leaves extracts (Arvino, Gaglioppo, Greco Nero, Magliocco Canino, Magliocco Dolce, and Nocera) were evaluated. HPLC analyses revealed quercetin as dominant constituent (127.52-187.33 mg/kg) followed by rutin (55.99-143.67 mg/kg). The antioxidant activity was determined using DPPH, ABTS, FRAP and ß-carotene bleaching tests. Gaglioppo showed the highest radical scavenging ability with IC50 of 7.2 and 19.1 µg/mL, for DPPH and ABTS, respectively. Magliocco Dolce showed a 1.6-times higher FRAP activity than that of the positive control BHT. The anti-proliferative activity was determined by SRB assay against MCF-7, MDA-MB-231, A549 and COR-L23 human tumor cells. Greco Nero showed the highest anti-proliferative activity against MDA-MB-231 with IC50 of 28.4 µg/mL. Based on the obtained results grape leaves should be considered an interesting ingredient for the development of functional food products.

Arbutus species (Ericaceae) as source of valuable bioactive products.

In addition to nutrients, plant foods contain compounds that may provide additional health benefits improving the quality of life. Species from Arbutus genus (Ericaceae) represent a promising source of healthy phytochemicals. Bioactive compounds including such as anthocyanins, iridoids, phenols, triterpenes, sterols, and fatty acids are reported from Arbutus species. Some Arbutus species revealed promising biological activities including antioxidant, anti-inflammatory, anti-proliferative, anti-diabetic, and antimicrobial activities, and deserve for that reason further consideration for new drug discovery. However, only few species are investigated scientifically for their chemical profile and biological activities. The aim of this article is to summarize the current knowledge of the components and biological properties of Arbutus species common in Mediterranean area, as well as the future prospects on their applications as potentially valuable products.

A Review of the Traditional Uses, Phytochemistry and Biological Activities of the Genus Santolina.

The genus Santolina is a taxonomically complex group of plant species widely distributed in the Mediterranean flora and used in traditional medicine since ancient times for their biological properties, including antimicrobial, anti-inflammatory, antispasmodic, digestive, and analgesic activities. Phytochemical investigations of Santolina species have revealed the presence of terpenoids as the main bioactive constituents of the genus. Coumarins and flavonoids were also identified. This review deals, for the first time, with information on the traditional uses, chemical profile, and biological properties of plants of the genus Santolina in order to provide input for future research prospects.

From Vegetable Waste to New Agents for Potential Health Applications: Antioxidant Properties and Effects of Extracts, Fractions and Pinocembrin from Glycyrrhiza glabra L. Aerial Parts on Viability of Five Human Cancer Cell Lines.

Glycyrrhiza glabra cultivation and harvesting produces substantial quantities of aerial parts as waste. With the aim to prospect an innovative valorization of these byproducts, the aerial parts were harvested in May and October and analyzed for their chemical profile, antioxidant properties, and effects on viability of five cancer cell lines. Pinocembrin was the main constituent. A significant protection of lipid peroxidation was observed with the May total extract (IC50 of 4.2 ± 0.4 µg/mL at 30 min of incubation). The effects on viability of HeLa, MCF-7, MDA-MB-231, Caco-2, and PC3 human cancer cells were investigated. All samples shown a remarkable activity with IC50 values below 25 µg/mL. Samples from plants harvested in May exhibited greater activity than those harvested in October. MCF-7 and HeLa were the most sensitive cells with IC50 in the range 2.73-3.01 and 3.28-5.53 µg/mL, respectively. G. glabra aerial parts represent a good source of valuable products.

Antioxidant and Carbohydrate-Hydrolysing Enzymes Potential of Sechium edule (Jacq.) Swartz (Cucurbitaceae) Peel, Leaves and Pulp Fresh and Processed.

Sechum edule peel, leaves and pulp were investigated for their chemical composition (total phenol, flavonoid, carotenoid and vitamin C content), and for antioxidant activity and carbohydrate-hydrolysing enzymes (α-amylase and α-glucosidase) inhibition. In order to evaluate the incidence of cooking process on retention of healthy phytochemicals, the pulp was subjected to different treatments (grill roasting, domestic oven baking, microwave cooking, blanching and steaming). Cooking processes reduced the total phenol content (58.5 mg/g extract for fresh pulp vs 26.3 and 29.3 mg/g extract for roasted and steamed samples, respectively). Pulp was found to be the most active in 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) (IC50 of 0.1 mg/mL), whereas peel showed the highest activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) test (IC50 of 0.4 mg/mL). Moreover, peel exhibited the highest inhibitory activity against α-amylase with an IC50 of 0.2 mg/mL, except for steamed cooking process, which drastically influenced the bioactivity against both enzymes.

Chemical Profile and Antioxidant Properties of Extracts and Essential Oils from Citrus × limon (L.) Burm. cv. Femminello Comune.

Citrus × limon cv. Femminello Comune (Rutaceae) from Rocca Imperiale (Italy), one of the six Protected Geographical Indication (PGI) Italian lemon crops, has been recently received renewed interest. In this work, fresh and dried peels and leaves were extracted by hydrodistillation, supercritical fluid extraction (SFE), and Soxhlet apparatus. Chemical profile was assessed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). Except for leaves extracts obtained by Soxhlet apparatus, the monoterpene hydrocarbons fraction dominated. Limonene, γ-terpinene, and ß-pinene were the main identified compounds. The antioxidant activity was investigated using different in vitro assays namely 2,2-diphenyl-1-picrylhydrazyl (DPPH), ABTS, ferric reducing ability power (FRAP), and ß-carotene bleaching test. In DPPH test, the essential oil obtained by hydrodistillation of fresh peel exhibited the highest activity (IC50 of 1.17 mg/ml). Leaves extracted by SFE showed a good activity in both DPPH and ß-carotene bleaching test with IC50 values of 2.20 and 6.66 mg/ml, respectively. Monoterpene hydrocarbons fraction exhibited a positive Pearson's correlation coefficient with all antioxidant assays. Leaves, often considered waste material, should be considered from a different point because they represent a matrix of indisputable interest.

Edible Flowers: A Rich Source of Phytochemicals with Antioxidant and Hypoglycemic Properties.

Edible flowers are receiving renewed interest as rich sources of bioactive compounds. Ethanol extracts of eight edible flowers were phytochemically characterized and investigated for their bioactivity. Rutin, quercetin, luteolin, kaempferol, and myricetin were selected as standards and quantified by HPLC. The fatty acid profile was analyzed by GC and GC-MS. Antioxidant properties were evaluated by using different in vitro tests. The hypoglycemic effects were investigated via the inhibition of α-amylase and α-glucosidase. Sambucus nigra exhibited the highest radical-scavenging activity (IC50 of 1.4 µg/mL), followed by Hedysarum coronarium (IC50 of 1.6 µg/mL). Both species contained high quercetin and rutin contents. S. nigra extract exerted the highest activity in preventing lipid oxidation. Malva sylvestris extract inhibited both α-amylase and α-glucosidase with IC50 values of 7.8 and 11.3 µg/mL, respectively. These findings support the consumption of edible flowers as functional foods and their use as sources of natural antioxidants by the food industry.

Omega-3 polyunsaturated fatty acids and cancer: lessons learned from clinical trials.

Over the past decades, extensive studies have addressed the therapeutic effects of omega-3 polyunsaturated fatty acids (omega-3 FAs) against different human diseases such as cardiovascular and neurodegenerative diseases, cancer, etc. A growing body of scientific research shows the pharmacokinetic information and safety of these natural occurring substances. Moreover, during recent years, a plethora of studies has demonstrated that omega-3 FAs possess therapeutic role against certain types of cancer. It is also known that omega-3 FAs can improve efficacy and tolerability of chemotherapy. Previous reports showed that suppression of nuclear factor-κB, activation of AMPK/SIRT1, modulation of cyclooxygenase (COX) activity, and up-regulation of novel anti-inflammatory lipid mediators such as protectins, maresins, and resolvins, are the main mechanisms of antineoplastic effect of omega-3 FAs. In this review, we have collected the available clinical data on the therapeutic role of omega-3 FAs against breast cancer, colorectal cancer, leukemia, gastric cancer, pancreatic cancer, esophageal cancer, prostate cancer, lung cancer, head and neck cancer, as well as cancer cachexia. We also discussed the chemistry, dietary source, and bioavailability of omega-3 FAs, and the potential molecular mechanisms of anticancer and adverse effects.

The cellular protective effects of rosmarinic acid: from bench to bedside.

Rosemary (Rosmarinus officinalis L.) is one of the most common household herbs, used as spices in a variety of foods, and employed in traditional medicine for its healing properties. Rosemary is a rich source of active antioxidant constituents such as phenolic diterpenes, flavonoids and phenolic acids. Caffeic acid and rosmarinic acid are the most important bioactive constituents. Rosmarinic acid is the ester of caffeic acid and 3,4-dihydroxyphenyllactic acid and is widely identified in different plant species. Chemical structure of rosmarinic acid contains two phenolic rings: one of them is derived from phenylalanine via caffeic acid and the other from tyrosine via dihydroxyphenyl-lactic acid. Its large-scale production is obtained from plant cell cultures of Coleus blumei Benth. It is easily absorbed through gastrointestinal tract as well as the skin. Rosmarinic acid is one of the most important and well known natural antioxidant compounds, which possesses neuroprotective effects in different models of neuroinflammation, neurodegeneration, as well as chemicalinduced neurotoxicity and oxidative stress. Therefore, in present review, we aim to discuss about chemistry, sources, biotechnological production and neuroprotective actions of rosmarinic acid with emphasis on its possible molecular mechanisms of neuroprotection.