Elena González-Burgos

Sideritis spp.: Uses, chemical composition and pharmacological activities—A review

The genus Sideritis (Lamiaceae) comprises more than 150 perennial and annual vegetal species widely distributed in the Mediterranean area, together with Canary and Madeira islands. It is a controversial botanic genus, with a complex taxonomical classification due to the high number of hybridizations that occur between species; their study requires a deep research experience. Sideritis species have been traditionally used as teas for feeding, flavoring agents and in folk medicine as antiinflammatory, antiulcerative, antimicrobial, vulnerary, antioxidant, antispasmodic, anticonvulsant, analgesic and carminative agents. The chemical components found in Sideritis genus include terpenes, flavonoids, essential oil, iridoids, coumarins, lignanes and sterols, among others. Diterpenes, flavonoids and essential oil occur in almost every species and are the main compounds responsible for the observed in vivo and in vitro pharmacological activities. The aim of this review is to provide a comprehensive overview on the botanical, phytochemical and pharmacological aspects from the genus Sideritis, with the objective of establishing scientific basis that explains its ethnopharmacological use.

Terpene Compounds in Nature: A Review of Their Potential Antioxidant Activity

Reactive Oxygen Species are involved in the pathological development of many important human diseases such as neurodegenerative diseases, cardiovascular processes, diabetes and many others. The most promising strategy to prevent from the oxidative damage caused by these reactive species is the use of antioxidant molecules. These compounds can act as direct antioxidants through free radical scavenging mechanisms and/or as indirect antioxidants by enhancing the antioxidant status (enzymatic and non-enzymatic). Terpenes, one of the most extensive and varied structural compounds occurring in nature, display a wide range of biological and pharmacological activities. Here we highlight their antioxidant properties. Due to their antioxidant behaviour terpenes have been shown to provide relevant protection under oxidative stress conditions in different diseases including liver, renal, neurodegenerative and cardiovascular diseases, cancer, diabetes as well as in ageing processes. Evidence for this comes from the increasing number of publications on this issue in recent years. This review provides a complete overview of the natural terpenes with potential antioxidant properties, focusing on their source, structures, antioxidant mechanisms through which they exert their pharmacological and possible therapeutic activities.

Mitochondria-Targeted Protective Compounds in Parkinson's and Alzheimer's Diseases

Mitochondria are cytoplasmic organelles that regulate both metabolic and apoptotic signaling pathways; their most highlighted functions include cellular energy generation in the form of adenosine triphosphate (ATP), regulation of cellular calcium homeostasis, balance between ROS production and detoxification, mediation of apoptosis cell death, and synthesis and metabolism of various key molecules. Consistent evidence suggests that mitochondrial failure is associated with early events in the pathogenesis of ageing-related neurodegenerative disorders including Parkinsons disease and Alzheimers disease. Mitochondria-targeted protective compounds that prevent or minimize mitochondrial dysfunction constitute potential therapeutic strategies in the prevention and treatment of these central nervous system diseases. This paper provides an overview of the involvement of mitochondrial dysfunction in Parkinsons and Alzheimers diseases, with particular attention to in vitro and in vivo studies on promising endogenous and exogenous mitochondria-targeted protective compounds.

Neuroprotective properties of Spanish red wine and its isolated polyphenols on astrocytes

The neuroprotective effect of Merlot red wine and its isolated polyphenols was evaluated in an oxidative stress model induced by Fenton reaction and hydrogen peroxide in the human astrocytoma U373 MG cell line. Compared with cells treated only with oxidative stress inductors, the pre-incubation with Merlot red wine for 24h caused a significant increase in cell viability for all concentrations assayed. The most abundant polyphenols found in Merlot red wine were the flavonoids catechin (37.8mg/l), epicatechin (52.3mg/l), quercetin (5.89mg/l) and procyanidins (15.2mg/l), the hydroxybenzoic acid gallic acid (16.7mg/l), and the phenolic alcohol tyrosol (31.4mg/l). The potential protective role of these polyphenols when isolated was then assessed in treated Fenton reaction U373 MG cells. Polyphenols decreased reactive oxygen species generation and increased the activity and the protein expression of the antioxidant enzymes catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase. Of the polyphenols, quercetin and procyanidins showed the highest neuroprotective effect.

Major selected monoterpenes α-pinene and 1,8-cineole found in Salvia lavandulifolia (Spanish sage) essential oil as regulators of cellular redox balance.

Abstract Context: Salvia lavandulifolia has been employed in folk medicine for the treatment of memory and dementia problems. This specie contains numerous bioactive terpenes which may contribute to its effectiveness. Objective: To analyze the composition of essential oil of S. lavandulifolia and to investigate the potential in vitro cytoprotective and antioxidant activities of its major compounds, α-pinene and 1,8-cineole, against H2O2-induced oxidative stress in the U373-MG cell line. Materials and methods: Chemical composition was analyzed by gas chromatography; antioxidant capacity was measured using the ORAC assay, and cytoprotective activity was evaluated using the MTT assay (for cell viability) (range of concentrations: 10–400 μM), DCFH-DA assay (for intracellular ROS generation), thiobarbituric acid reactive substances (TBARS) method (for lipid peroxidation), and spectrofometric techniques and Western blot (for enzymatic activity and protein expression, respectively) at 10 and 25 µM. Results: α-Pinene (18.39%) and 1,8-cineole (19.57%) were identified as major compounds in S. lavandulifolia essential oil. Pretreatments with these monoterpenes protected U373-MG cells against H2O2-induced oxidative injury by attenuating the loss of cell viability (IC50 : 79.70 µM to α-pinene and 66.23 µM to 1,8-cineole) and cell morphology, inhibiting ROS production (the most active compound was 1,8-cineole by decreasing the ROS production over 30–45% at 10 and 25 μM) and lipid peroxidation and increasing the endogenous antioxidant status (glutathione levels and CAT, SOD, GR, GPx, and HO-1 activity and protein expression). Conclusions: These findings demonstrate for the first time the effects of the monoterpenes 1,8-cineole and α-pinene identified in S. lavandulifolia essential oil as regulators of cellular redox balance in astrocytes.

Parmeliaceae family: phytochemistry, pharmacological potential and phylogenetic features

Parmeliaceae is the largest family of lichenized fungi comprising about 2700 species distributed in about 80 genera. A wide array of secondary metabolites including depsides, depsidones, aliphatic acids, triterpenes, anthraquinones, secalonic acids, pulvinic acid derivatives and xanthones have been identified within this family. Many of these bioactive compounds such as usnic acid and atranorin are exclusively found in this family, being of great relevance for the systematics and phylogeny. Moreover, these compounds exert different biological roles including antimicrobial, antioxidant, cytotoxic, anti-inflammatory, analgesic and enzyme inhibitory actions. The current review focuses on the phytochemistry and main phylogenetic aspects of Parmeliaceae, and it discusses the pharmacological findings and mechanisms of action of their extracts and isolated compounds. The present work actually collects information related to more than 65 lichen species (from 21 different genuses and heterogeneous distribution) and 75 isolated metabolites. As reported, the best studied genus from a pharmacological point of view is Parmelia, followed by Usnea. At the species level, Cetraria islandica and Evernia prunastri attract remarkable interest in their bioactive activities and metabolite content. The major pharmacological activities investigated on extracts and compounds from Parmeliaceae spp. have been antimicrobial, anticancer and antioxidant potentials; and regarding isolated compounds, the aforementioned usnic acid and atranorin are among the most studied metabolites. Reviewed data suggest that some of these lichens and natural compounds are worthy of further investigation.

Protective effects of Merlot red wine extract and its major polyphenols in PC12 cells under oxidative stress conditions.

UNLABELLED The potential effect of the extracts from free-run and pressed Merlot red wine has been evaluated in PC12 cells under oxidative stress situation. Comparing both vinification process, pressed Merlot red wine extract possessed higher neuroprotective activity than the free run wine, possibly attributed to the major content in all global polyphenolic families. High performance liquid chromatography determination of individual polyphenols showed that the major compounds found in Merlot red wine extract were quercetin, catechin, epicatechin, tyrosol, gallic acid, and procyanidins. Pretreatments with these polyphenolic compounds (0.25 mM and 0.1 mM, 24 h) significantly increased cell viability of H(2)O(2) and Fenton reaction treated cells. Moreover, these polyphenols attenuated ROS production and decreased the Redox Index of glutathione (RI = GSSG/GSH + GSSG) in cells treated only with Fenton reaction. Furthermore, some polyphenols induced antioxidant enzymes activity and protein expression. Quercetin was the most active. These results support the beneficial effects of red wine extracts and some of its polyphenols under oxidative stress conditions. PRACTICAL APPLICATION This research provides evidences of the preventive properties of wine extracts and its major polyphenols under oxidative stress conditions.

Kaurane diterpenes from Sideritis spp. exert a cytoprotective effect against oxidative injury that is associated with modulation of the Nrf2 system

Kaurane diterpenes have been shown to possess antioxidant properties. As a part of our ongoing studies on the identification of biologically active diterpenes from Sideritis spp., we have previously isolated and structurally elucidated the major kaurane diterpenes foliol, linearol and sidol, in a previous study from the aerial parts of Sideritis linearifolia and Sideritis leucantha. We have now examined the ability of these compounds to protect PC12 cells in an H2O2-induced oxidative stress model. Linearol and sidol (5 and 10 μM, 24 h) significantly attenuated loss of mitochondrial function (MTT assay) and membrane integrity (LDH assay) and morphological changes associated with H2O2-mediated cytotoxicity. Moreover, pretreatments with linearol and sidol effectively reduced intracellular ROS production, decreased MDA levels (lipid peroxidation product) and restored GSH/GSSG ratio. Furthermore, analysis of the effect of diterpenes on antioxidant enzymes showed that linearol and sidol induced the upregulation and protein expression of the main antioxidant enzymes CAT, SOD, GPx, GR and HO-1. Considering molecular mechanisms for maintaining cellular redox homeostasis by linearol and sidol, it would appear that the Nrf2 transcription factor seems to be involved. These results indicate that linearol and sidol are potential cytoprotective compounds, through antioxidant mechanisms, under H2O2-induced oxidative stress.

Nrf2-dependent neuroprotective activity of diterpenoids isolated from Sideritis spp

ETHNOPHARMACOLOGICAL RELEVANCE The species of the genus Sideritis are extensively used in the Mediterranean area in folk medicine for their digestive, antimicrobial, anti-inflammatory and antioxidant properties, among others. Moreover, Sideritis species as tea infusions are popularly known for improving memory function and cognitive ability. Diterpenoids are one of the most abundant and important pharmacological interest of the classes of natural products presented in these medicinal plants. AIM OF THE STUDY To determine for the first time the neuroprotective effects, based on their antioxidant properties, of the three isolated major diterpenoids andalusol, conchitriol and lagascatriol in an oxidative stress model. MATERIALS AND METHODS H2O2 was used as oxidant inductor and rat adrenal pheochromocytoma PC12 cells as cellular model. Cell viability was measured using MTT and LDH assays, lipid peroxidation was determined by HPLC, GSH and GSSG levels assessed by fluorometric techniques, enzymatic activity and protein expression were determined by spectrofometric techniques and Western blot, respectively. RESULTS Pretreatments with the three diterpenoids significantly attenuated H2O2-induced changes in mitochondrial integrity and activity (MTT assay), in cell membrane integrity (LDH assay) and in cell morphology. Moreover, these diterpenoids inhibited intracellular ROS production H2O2-induced, reduced lipid peroxidation and counteracted GSH/GSSG changes. Furthermore, both activities and protein expression of the endogenous antioxidant enzymes (CAT, SOD, GR, GPx and HO-1) were increased. The Nrf2 pathway was involved, at least in part, in the protective effects of these diterpenoids. CONCLUSION These findings suggest that these natural compounds provide significant antioxidant effects in PC12 under for counteracting the oxidative damage H2O2-induced and their potential role as useful agents for the prevention of those oxidative stress-mediated dementia disorders. Andalusol was the most active compound among the studied diterpenoids.

In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells

Abstract Oxidative stress is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Natural products are considered as therapeutically useful antioxidant agents against reactive oxygen species (ROS). We have evaluated the antioxidant and protective potential of the monoterpenes 1,8-cineole and α-pinene against H2O2-induced oxidative stress in PC12 (rat pheochromocytoma) cells. Pretreatment with these monoterpenes was found to attenuate the loss of cell viability and the changes in cell morphology. Moreover, they inhibited the intracellular ROS production and markedly enhanced the expression of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and heme-oxygenase 1 (HO-1). In addition, they were able to decrease apoptosis as is evident from reduced capase-3 activity. The mechanisms of their antioxidant action appear to involve ROS scavenging and induction of the nuclear Nrf2 factor. This study demonstrates the potential beneficial therapeutic effect of these common monoterpenes on the oxidant/antioxidant balance in diseases of the nervous system.