Chemical Characterization, Antioxidant Capacity and Anti-Oxidative Stress Potential of South American Fabaceae Desmodium tortuosum.

It has been proposed that oxidative stress is a pathogenic mechanism to induce cytotoxicity and to cause cardiovascular and neuronal diseases. At present, natural compounds such as plant extracts have been used to reduce the cytotoxic effects produced by agents that induce oxidative stress. Our study aimed to evaluate the antioxidant and cytoprotective capacity of Desmodium tortuosum (D. tortuosum) extract in the co- and pre-treatment in EA.hy926 and SH-SY5Y cell lines subjected to oxidative stress induced by tert-butylhydroperoxide (t-BOOH). Cell viability, reactive oxygen species (ROS), nitric oxide (NO), caspase 3/7 activity, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and molecular expression of oxidative stress biomarkers (SOD2, NRF2 and NFκB1) and cell death (APAF1, BAX, Caspase3) were all evaluated. It was observed that the D. tortuosum extract, in a dose-dependent manner, was able to reduce the oxidative and cytotoxicity effects induced by t-BOOH, even normalized to a dose of 200 µg/mL, which would be due to the high content of phenolic compounds mainly phenolic acids, flavonoids, carotenoids and other antioxidant compounds. Finally, these results are indicators that the extract of D. tortuosum could be a natural alternative against the cytotoxic exposure to stressful and cytotoxic chemical agents.

Physiological Doses of Oleic and Palmitic Acids Protect Human Endothelial Cells from Oxidative Stress.

Oxidative stress has been proposed to be a pathogenic mechanism to induce endothelial dysfunction and the onset of cardiovascular disease. Elevated levels of free fatty acids can cause oxidative stress by increasing mitochondrial uncoupling but, at physiological concentrations, they are essential for cell and tissue function and olive oil free fatty acids have proved to exhibit beneficial effects on risk factors for cardiovascular disease. We hypothesize that realistic concentrations within the physiological range of oleic (OA) and palmitic (PA) acids could be beneficial in the prevention of oxidative stress in vascular endothelium. Hence, pre-treatment and co-treatment with realistic physiological doses of palmitic and oleic acids were tested on cultured endothelial cells submitted to a chemically induced oxidative stress to investigate their potential chemo-protective effect. Cell viability and markers of oxidative status: reactive oxygen species (ROS), reduced glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GPx) and glutathione reductase (GR) were evaluated. As a conclusion, the increased ROS generation induced by stress was significantly prevented by a pre- and co-treatment with PA or OA. Moreover, pre- and co-treatment of cells with FFAs recovered the stress-induced MDA concentration to control values and significantly recovered depleted GSH and normalized GPx and GR activities. Finally, pre- and co-treatment of cells with physiological concentrations of PA or OA in the low micromolar range conferred a substantial protection of cell viability against an oxidative insult.

Biological Actions and Molecular Mechanisms of Sambucus nigra L. in Neurodegeneration: A Cell Culture Approach.

Sambucus nigra flowers (elderflower) have been widely used in traditional medicine for the relief of early symptoms of common cold. Its chemical composition mainly consists of polyphenolic compounds such as flavonoids, hydroxycinnamic acids, and triterpenes. Although the antioxidant properties of polyphenols are well known, the aim of this study is to assess the antioxidant and protective potentials of Sambucus nigra flowers in the human neuroblastoma (SH-SY5Y) cell line using different in vitro approaches. The antioxidant capacity is first evaluated by the oxygen radical absorbance capacity (ORAC) and the free radical scavenging activity (DPPH) methods. Cell viability is assessed by the crystal violet method; furthermore, the intracellular ROS formation (DCFH-DA method) is determined, together with the effect on the cell antioxidant defenses: reduced glutathione (GSH) and antioxidant enzyme activities (GPx, GR). On the other hand, mTORC1 hyperactivation and autophagy blockage have been associated with an increase in the formation of protein aggregates, this promoting the transference and expansion of neurodegenerative diseases. Then, the ability of Sambucus nigra flowers in the regulation of mTORC1 signaling activity and the reduction in oxidative stress through the activation of autophagy/mitophagy flux is also examined. In this regard, search for different molecules with a potential inhibitory effect on mTORC1 activation could have multiple positive effects either in the molecular pathogenic events and/or in the progression of several diseases including neurodegenerative ones.

Dietary Polyphenols in Metabolic and Neurodegenerative Diseases: Molecular Targets in Autophagy and Biological Effects.

Polyphenols represent a group of secondary metabolites of plants which have been analyzed as potent regulators of multiple biological processes, including cell proliferation, apoptosis, and autophagy, among others. These natural compounds exhibit beneficial effects and protection against inflammation, oxidative stress, and related injuries including metabolic diseases, such as cardiovascular damage, obesity and diabetes, and neurodegeneration. This review aims to summarize the mechanisms of action of polyphenols in relation to the activation of autophagy, stimulation of mitochondrial function and antioxidant defenses, attenuation of oxidative stress, and reduction in cell apoptosis, which may be responsible of the health promoting properties of these compounds.

Cocoa Flavanols Protect Human Endothelial Cells from Oxidative Stress.

Oxidative stress may cause functional disorders of vascular endothelia which can lead to endothelial apoptosis and thus alter the function and structure of the vascular tissues. Plant antioxidants protect the endothelium against oxidative stress and then become an effective option to treat vascular diseases. Cocoa flavanols have been proven to protect against oxidative stress in cell culture and animal models. In addition, epidemiological and interventional studies strongly suggest that cocoa consumption has numerous beneficial effects on cardiovascular health. The objective of this study was to test the chemo-protective effect of realistic concentrations of a cocoa phenolic extract and its main monomeric flavanol epicatechin on cultured human endothelial cells submitted to an oxidative challenge. Both products efficiently restrained stress-induced reactive oxygen species and biomarkers of oxidative stress such as carbonyl groups and malondialdehyde, and recovered depleted glutathione, antioxidant defences and cell viability. Our results demonstrate for the first time that a polyphenolic extract from cocoa and its main flavonoid protect human endothelial cells against an oxidative insult by modulating oxygen radical generation and antioxidant enzyme and non-enzyme defences.

Molecular Targets Involved in the Neuroprotection Mediated by Terpenoids.

Natural products and their derivatives represent the most consistently successful source of drug leads. Terpenoids, a structurally diverse group, are secondary metabolites widely distributed in nature, endowed with a wide range of biological activities such as antibacterial, anti-inflammatory, antitumoral, or neuroprotective effects, which consolidate their therapeutic value. During the last decades, and taking into consideration the prevalence of aging-related diseases, research activity into the neuroprotective effects of these types of compounds has increased enormously. Several signaling pathways involved in neuroprotection are targets of their mechanism of action and mediate their pleiotropic protective activity in neuronal cell damage. In the present review, molecular basis of the neuroprotection exerted by terpenoids is presented, focusing on preclinical evidence of the therapeutic potential of diterpenoids and triterpenoids on neurodegenerative disorders. By acting on diverse mechanisms simultaneously, terpenoids have been emphasized as promising multitarget agents.

Protective Effect of Silybum marianum and Silibinin on Endothelial Cells Submitted to High Glucose Concentration.

Silybum marianum Gaertn. (Milk thistle) has been used since ancient times for the relief of liver diseases characterized by intense oxidative stress such as inflammatory liver disease and cirrhosis. As oxidative stress by hyperglycemia is involved in micro- and macrovascular complications of type 2 diabetes, our aim was to assess the protective effect of milk thistle seed extract against oxidative stress induced by a high glucose concentration on endothelial cells (EA.hy926 cells). High-performance liquid chromatographic analysis shows flavonolignans silychristin and silibinin A and B as major components. No cell toxicity was observed for concentrations up to 100 µg/mL of milk thistle extract for 24 h. Concentrations of 5-25 µg/mL of the extract were used to assess the protective effect on EA.hy926 cells treated with 30 mM glucose for 24 h. Oxidative damage by 30 mM glucose was shown as a significant decrease in reduced glutathione and a significant increase in protein carbonyls and antioxidant enzyme activities. S. marianum extract recovered reduced glutathione and balanced the elevated carbonyls and enzyme activity. Silibinin alone also recovered reduced glutathione and antioxidant enzymes. S. marianum protects endothelial cell against oxidative damage by modulating antioxidant enzyme activity, reduced glutathione, and protein carbonyl levels.

Current knowledge in Polypodium leucotomos effect on skin protection.

This article provides an overview of pharmacology, toxicity, pharmacokinetics and clinical data of Polypodium leucotomos L. (PL). PL aerial part has proven to exert antioxidant, photoprotective and immunomodulatory activities; its mechanism of action is complex and includes several activities: (1) PL diminishes the production of reactive oxygen and nitrogen species (ROS, RNS); (2) PL inhibits the photoisomerization of trans-urocanic acid (t-UCA); (3) PL inhibits apoptosis induced by ultraviolet radiation; (4) PL prevents damage to genetic material and (5) PL enhances DNA repair. PL is not mutagenic and does not induce acute or chronic toxicity. Its biological effects have been proved in cell cultures, animal models, murine models and in human beings. Photoprotective activity has been assessed in healthy volunteers as well as in patients suffering from several cutaneous diseases such as vitiligo, psoriasis, idiopathic photodermatosis or melasma. PL results to be an efficient treatment especially for sensitive cutaneous phototypes and adds extra protection when ultraviolet radiation (UVR) exposure cannot be avoided, such as wide or narrow band UVB phototherapy or treatment with psoralens plus UVA exposure radiation.

Effect of cooking and germination on phenolic composition and biological properties of dark beans (Phaseolus vulgaris L.).

Legumes are the basés diet in several countries. They hold a high nutritional value, but other properties related to human health are nowadays being studied. The aim of this work was to study the influence of processes (boiling or germination) on the phenolic composition of dark beans (Phaseolus vulgaris L. c.v. Tolosana) and their effect on their antioxidant, neuroprotective and anticancer ability. Phenolic composition of raw and processed dark beans was analysed by HPLC-PAD and HPLC-ESI/MS. The antioxidant activity was evaluated by ORAC. Astrocytes cultures (U-373) have been used to test their neuroprotective effect. Anticancer activities were evaluated on three different cell lines (renal adenocarcinoma (TK-10), breast adenocarcinoma (MCF-7) and melanoma (UACC-62)) by sulphorhodamine B method. Qualitative and quantitative differences in phenolic composition have been observed between raw and processed dark beans that influence the antioxidant activity, mainly for germinated samples which show a decrease of antioxidant capacity. Although every assayed extracts decreased reactive oxygen species release and exhibited cytotoxicity activities on cancer cell lines, raw beans proved to be the most active in neuroprotective and antitumoral effects; this sample is especially rich in phenolic compounds, mainly anthocyanins. This study further demonstrated that phenolic composition of dark beans is related with cooking process and so with their neuroprotective and anticancer activity; cooking of dark beans improves their digestion and absorption at intestinal level, while maintaining its protective ability on oxidative process at cellular level.

Study of red wine neuroprotection on astrocytes.

Phenolic composition of wine depends not only on the grape variety from which it is made, but on some external factors such as winemaking technology. Red wine possesses the most antioxidant effect because of its high polyphenolic content. The aim of this work is to study for the first time, the neuroprotective activity of four monovarietal Spanish red wines (Merlot (ME), Tempranillo (T), Garnacha (G) and Cabernet-Sauvignon (CS)) through its antioxidant ability, and to relate this neuroprotection to its polyphenolic composition, if possible. The wine effect on neuroprotection was studied through its effect as free radical scavenger against FeSO4, H2O2 and FeSO4 + H2O2. Effect on cell survival was determined by 3(4,5-dimethyltiazol-2-il)-2,5-diphenyltetrazolium reduction assay (MTT) and lactate dehydrogenase (LDH) release assay on astrocytes cultures. Results showed that most of the studied wine varieties induced neuroprotection through their antioxidant ability in astrocytes, Merlot being the most active; this variety is especially rich in phenolic compounds, mainly catechins and oligomeric proanthocyanidins. Our results show that red wine exerts a protection against oxidative stress generated by different toxic agents and that the observed neuroprotective activity is related to their polyphenolic content.