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Mitochondria as pharmacological targets in Down syndrome.

Mitochondria play a pivotal role in cellular energy-generating processes and are considered master regulators of cell life and death fate. Mitochondrial function integrates signalling networks in several metabolic pathways controlling neurogenesis and neuroplasticity. Indeed, dysfunctional mitochondria and mitochondrial-dependent activation of intracellular stress cascades are critical initiating events in many human neurodegenerative or neurodevelopmental diseases including Down syndrome (DS). It is well established that trisomy of human chromosome 21 can cause DS. DS is associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, molecular mechanisms responsible for mitochondrial damage and energy deficits have been identified and characterized in several DS-derived human cells and animal models of DS. Therefore, therapeutic strategies targeting mitochondria could have great potential for new treatment regimens in DS. The purpose of this review is to highlight recent studies concerning mitochondrial impairment in DS, focusing on alterations of the molecular pathways controlling mitochondrial function. We will also discuss the effects and molecular mechanisms of naturally occurring and chemically synthetized drugs that exert neuroprotective effects through modulation of mitochondrial function and attenuation of oxidative stress. These compounds might represent novel therapeutic tools for the modulation of energy deficits in DS.

In vitro antioxidant and antihemolytic effects of the essential oil and methanolic extract of Allium rotundum L.

OBJECTIVE: A plethora of scientific evidence showed that several plant species from the genus Allium (Alliaceae) possess multiple therapeutic effects. Present paper aimed to examine the antioxidant and antihemolytic activities of the essential oil and methanol extract Allium rotundum L. through different in vitro assays. MATERIALS AND METHODS: 1,1-diphenyl-2-picryl hydroxyl radical (DPPH), nitric oxide as well as hydrogen peroxide scavenging, Fe2+ chelating, reducing power and also hemoglobin-induced linoleic acid peroxidation assay systems have been utilized to examine antioxidant effects of these samples. Total amounts of phenolic and flavonoid contents were calculated. The antihemolytic effect was investigated against hemolysis induced by hydrogen peroxide in rat erythrocytes. Also, mineral contents of plant were evaluated by atomic absorption spectroscopy. RESULTS: IC50 for DPPH radical-scavenging activity were 284 ± 11.64 for methanol extract and 1264 ± 45.60 µg ml-1 for essential oil, respectively. The extract has shown better reducing effects versus essential oil. The extract also demonstrated better activity in nitric oxide-scavenging activity. IC50 were 464 ± 19.68 for extract and 1093 ± 38.25 µg ml-1 for essential oil. The extract shows better activity than essential oil in Fe2+ chelating system. IC50 were 100 ± 3.75 for extract and 1223 ± 36.25 µg ml-1 for essential oil. The A. rotundum extract and essential oil showed significant H2O2 scavenging effects at dose-dependent manners. IC50 was 786 ± 29.08 mg ml-1 for essential oil. The amounts of eight elements were determined. The concentrations of elements were in the order: Mn> Fe> Zn> Cu> Ni> Cd. CONCLUSIONS: The extract showed a higher antioxidant effect in all tested models including DPPH, nitric oxide, reducing power as well as iron chelating and antihemolytic activities than essential oil. The latter showed more potent antioxidant activity in scavenging H2O2 and lipid peroxidation model. Antioxidant activities of extract may be attributed at least in part, due to its phenolic and flavonoid contents.

The Role of Hesperidin in Cell Signal Transduction Pathway for the Prevention or Treatment of Cancer.

During past two decades, plant-derived bioactive compounds have been reported as novel therapeutic agents for prevention and/or mitigation of different human diseases such as cancer, inflammation, cardiovascular and neurodegenerative diseases. Hesperidin is known as one of the most common and bioactive constituents of Citrus (C) species which possesses multiple health-promotion effects. A plethora of scientific literature reported that hesperidin possesses in-vitro and in-vivo anticancer activities. In addition, there are numerous scientific evidences regarding the molecular mechanisms of anticancer activities of hesperidin and its aglycone, hesperetin. However, in this case, the number of comprehensive reviews on molecular mechanisms underlying the anticancer effects of hesperidin is sparse. Therefore, in this work we present a critical review of the available literature regarding the molecular mechanisms of the anticancer effects of hesperidin and its aglycone, hesperetin.

Molecular Targets of Omega-3 Fatty Acids for Cancer Therapy.

Nowadays, dietary guidelines acknowledge the therapeutic role of omega-3 polyunsaturated fatty acids, as the most important class of fatty acids, against different human diseases. During the last two decades, the average level of consumption of omega-3 polyunsaturated fatty acids has increased from 0.1 to 0.2 g per day. Omega-3 polyunsaturated fatty acids are a group of long-chain polyunsaturated fatty acids which are identified in different foods such as fatty fish, shellfish, and vegetable oils. A growing body of epidemiological and experimental evidence supports the anticancer effects of omega-3 polyunsaturated fatty acids, which led to the identification of their molecular targets in several cancer models. The present review focuses on the basic evidence supporting the potential applications of omega-3 polyunsaturated fatty acids in cancer therapy.

Anthocyanins as a potential therapy for diabetic retinopathy.

Diabetic retinopathy is one of the most common complications of diabetes. A plethora of literature indicates that oxidative stress may play a central role in the pathogenesis of diabetic retinopathy. One could thus hypothesise that antioxidant therapies may be protective for diabetic retinopathy. Anthocyanins are important natural bioactive pigments responsible for red-blue colour of fruits, leaves, seeds, stems and flowers in a variety of plant species. Apart from their colours, anthocyanins are known to be health-promoting phytochemicals with potential properties useful to protect against oxidative stress in some degenerative diseases. They also have a variety of biological properties including anti-inflammatory, antibacterial, anticancer, and cardio-protective properties. Some reports further suggest a therapeutic role of anthocyanins to prevent and/or protect against ocular diseases but more studies are needed to examine their potential as alternative therapy to diabetic retinopathy. The present article reviews the available literature concerning the beneficial role of anthocyanins in diabetic retinopathy.

Flavonoids and dementia: an update.

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

Antidepressant and antihemolytic activities of Vicia sojakii.

OBJECTIVES: Many pharmacological activities have been reported in Vicia (V.) genus. The aim of present study was to investigate antidepressant and antihemolytic activities of aerial parts of V. sojakii. MATERIALS AND METHODS: Antidepressant activity of methanolic extract was evaluated by forced swimming test (FST) and tail suspension tests (TST) in male Swiss albino mice. Antihemolytic effect of extract was also determined. RESULTS: Extract showed good antidepressant activity in both FST and TST. It shortened remarkably the immobility period in FST and TST and exhibited a dose dependent activity. Extract in 125 mg kg(-1) showed significant activity as compared to control (p < 0.05) in both test. Extract at 1500 mg kg(-1) showed the same activity of imipramine 15 mg kg(-1) (p > 0.05) in FST. Extract show good antihemolytic activity against H2O2 induced hemolysis. CONCLUSIONS: Our report indicated the V. sojakii aerial parts extract was safe and showed remarkable antidepressant activity in FST and TST in mice. It also exhibited good antihemolytic activity. These results introduced V. sojakii as an easily accessible source of natural antidepressant.

Antidepressant activity of Hibiscus esculentus L.

OBJECTIVES: Hibiscus (H.) esculentus L. (Okra) is distributed from Africa to Asia, Southern European and America and widely used as food. The aim of present study was to investigate antidepressant activity of Okra seeds and leaves. MATERIALS AND METHODS: Antidepressant activity of methanolic extracts were evaluated by forced swimming test (FST) and tail suspension tests (TST). Also, total phenol and flavonoid contents were measured by Folin Ciocalteau and AlCl3 assays, respectively. RESULTS: Phenol and flavonoid contents of extracts were determined as gallic acid and quercetin equivalents from a calibration curve, respectively. Extracts showed good antidepressant activity in both FST and TST. The extracts shortened remarkably the immobility period in FST and TST and exhibited a dose dependent activity. Seeds extract in 250, 500 and 750 mg kg-1 showed significant activity as compared to control (p < 0.001). Both extracts at 750 mg kg-1 showed similar activity as imipramine 15 mg kg-1 (p > 0.05) in TST. Extracts contained high amount of phenol and flavonoids. No mortality has been observed up to 2 g kg-1 for seeds and 2.5 g kg-1 for leaves. CONCLUSIONS: These results introduced H. esculentus seeds and leaves as an easily accessible and edible source of natural antidepressant.

Anticonvulsant activity of Hypericum scabrum L.; possible mechanism involved.

OBJECTIVES: Hypericum (H.) spp. has been used in traditional medicine for their anticonvulsant effect for many years. In spite of many works on this genus, little is known about H. scabrum. In this work, anticonvulsant activity of H. scabrum was investigated. MATERIALS AND METHODS: Anticonvulsant activity of aqueous extract was evaluated by pentylenetetrazole (PTZ) induced convulsion and picrotoxin induced convulsion. Also, nitric oxide radical scavenging was investigated as a possible mechanism involved. RESULTS: Extract (125-500 mg kg-1, i.p.) significantly delayed the onset of PTZ induced convulsion. At 500 mg kg-1, 100% protection against mortality was observed. At this dose, it significantly prolonged the onset of picrotoxin induced convulsion in mice, too. It showed significant nitric oxide radical scavenging activity. CONCLUSIONS: Mechanism of anticonvulsant activity may be through GABA and/or nitric oxide pathway.

Antihemolytic activity and mineral contents of Juglans regia L. flowers.

OBJECTIVES: Juglans (J.) regia L. is known to possess many biological properties. In this study, antihemolytic activity of methanol extract of Juglans regia L. flower were investigated. MATERIALS AND METHODS: Antihemolytic activities of Juglans regia L. flowers were evaluated by various in vitro assays. In addition, scavenging of hydrogen peroxide and mineral contents of flowers were determined using atomic absorption spectroscopy. RESULTS: Extract showed good antihemolytic activity against H2O2 and CuOOH induced hemolysis in comparison with control. Extract was capable of scavenging H2O2 in a concentration dependent manner. IC50 for H2O2 scavenging activity was 311±12.8 µg ml-1. The amount of eight elements was determined and was in the order: Mn > Cu > Fe > Zn. CONCLUSIONS: Our study indicate that J. regia flower has remarkable antihemolytic activity, which maybe result of its high phenol and flavonoid contents, especially quercetin.

Hepatoprotective activity of Allium paradoxum.

OBJECTIVE: Recent studies show that free radicals are important mediators of hepatic injury induced by carbon tetrachloride. Allium (A.) paradoxum showed antioxidant and antihemolytic activities. This work was conduct to determine the possible protective effect of this plant against hepatotoxicity. MATERIALS AND METHODS: Subcutaneous injection of 3 ml/kg carbon tetrachloride diluted in olive oil (1:1 dilution) was employed for inducing acute liver toxicity. The protective effect of aerial parts and bulbs of A. paradoxum at flowering stage were determined. RESULTS: Both aerial parts and bulbs extracts at the doses 500 and 750 mg/kg, i.p. offered significant hepatoprotective effect by reducing the serum marker enzymes, serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Histopathological studies further confirmed the hepatoprotective activity of aerial parts and bulbs extracts when compared with the CCl4 treated groups. CONCLUSION: Extracts of A. paradoxum showed significant hepatoprotective activity compared with control group.

Biological activities of flavonoid-rich fraction of Eryngium caucasicum Trautv.

OBJECTIVES: Eryngium (E.) caucasicum was found as a new cultivated vegetable plant in northern Iran and used in several local foods. Little information is available on biological properties of E. caucasicum. In this work antioxidant activity of flavonoid-rich fraction of this plant was investigated by eight in vitro assay systems. MATERIALS AND METHODS: 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), nitric oxide and hydrogen peroxide scavenging activities, Fe2+ chelating ability, reducing power and hemoglobin-induced linoleic acid peroxidation were used to evaluate antioxidant activities. Antihemolytic activities were evaluated against CuOOH and H2O2 induced hemolysis in rat erythrocyte. RESULTS: IC50 for DPPH scavenging activity was 391.2 +/- 14.9, 706.6 +/- 22.3 and 779.7 +/- 16.7 microg ml(-1) for aqueous (AQ), ethyl acetate (EA) and n-hexane (HE) fractions, respectively. There was no difference between reducing power of AQ fraction activity and vitamin C (p > 0.05). IC50 for NO radical-scavenging activity was in order of AQ (133.5 +/- 6.2 microg ml(-1)) > EA (350.1 +/- 14.8 microg ml(-1)) > and HE (639.9 +/- 21.7 microg ml(-1)) fractions, respectively. Extracts showed weak Fe2+ chelating ability. HE fraction showed better activity (173.5 +/- 9.6 microg ml(-1)). Extracts exhibited weak hydrogen peroxide scavenging activity but exhibited very good antioxidant activity against the hemoglobin-induced linoleic acid peroxidation. There was no significant difference between AQ fraction and vitamin C (p > 0.01). Fractions delayed the onset of the CuOOH induced hemolysis. AQ fraction showed very high total phenol and flavonoid contents which was higher than other fractions. High phenol and flavonoid content of AQ fraction may lead to its better antioxidant activity. CONCLUSIONS: E. caucasicum fractions exhibited different levels of antioxidant and antihemolytic activities in all tested models. These results can be useful as a starting point of view for further applications of E. caucasicum aerial parts or its constituents in pharmaceutical preparations.

Antioxidant and antihemolytic activities of flavonoid rich fractions of Artemisia tschernieviana Besser.

OBJECTIVES: Artemisia (Asteraceae) contains more than 400 species. Many of the plants belonging to this genus are known to possess biological properties. In this study, antioxidant and antihemolytic activities of flavonoid rich fractions of A. tschernieviana Besser were evaluated. MATERIAL AND METHODS: Plant aerial parts were extracted with 60% acetone. Extract was fractionated sequentially with hexane (HE), ethyl acetate (EA) and water (AQ). Antioxidant and antihemolytic activities of these fractions were assessed. Their antihemolytic activity was determined by H2O2 and cumene hydroperoxide induced hemolysis models. RESULTS: AQ fraction showed very powerful activity in 1,1-disphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity with IC50 = 0.12 +/- 0.01 microg ml(-1) that was better than controls (vitamin C, quercetin and butylated hydroxyanisole (BHA)). This fraction showed very powerful reducing power assay that was better than vitamin C (p < 0.01). EA fraction showed higher activity in scavenging nitric oxide with IC50 = 0.14 +/- 0.04 microg ml(-1). In iron chelating activity HE fraction showed the best activity (IC50 = 162.2 +/- 8.7 microg ml(-1)). In scavenging of hydrogen peroxide, AQ fraction showed better activity than control group. This fraction had higher phenol and flavonoid contents. EA fraction showed higher antihemolytic activity with IC50 = 728.8 +/- 29 microg ml(-1). CONCLUSIONS: The fractions show very good activities in studied models. Aqueous fractions showed better activity than the others in nearly all tested models. These results can be useful as a starting point of view for further applications of A. tschernieviana aerial parts or its constituents in pharmaceutical preparations after performing clinical in vivo researches.

Antioxidant activity of polyphenol and ultrasonic extracts from fruits of Crataegus pentagyna subsp. elburensis.

The effects of two extracting methods on the total phenolic and total flavonoid contents of Crataegus pentagyna subsp. elburensis Waldst. & Kit. ex Willd fruit extracts were investigated. Antioxidant activities of polyphenol (PP) fraction and ultrasonic (US) extraction were evaluated with four different in vitro antioxidant tests. IC(50) for DPPH radical-scavenging activity was 32.2 ± 1.6 for PP fraction and 36.7 ± 1.5 µg mL(-1) for US extract. Reducing powers of extracts increased with the increase of their concentrations. PP fraction exhibited high reducing power at 2-32 µg mL(-1). Extracts exhibited good H(2)O(2) radical scavenging and Fe(2+) chelating ability. Their high phenolic and flavonoid contents could be responsible for their antioxidant activity and pharmacologic actions.

Antioxidant activity of hydroalcholic extract of Ferula gummosa Boiss roots.

OBJECTIVES: Ferula gummosa Boiss is native to central Asia. This plant has traditionally been used in the treatment of many diseases. The antihypoxic and antioxidant activities of Ferula gummosa roots were investigated. MATERIAL AND METHODS: 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), nitric oxide and hydrogen peroxide scavenging activities, Fe2+ chelating ability, reducing power and hemoglobin-induced linoleic acid peroxidation were used to evaluate antioxidant activities. Antihemolytic activity was evaluated by H2O2 induced hemolysis in rat erythrocytes. The total amount of phenolic compounds was determined as gallic acid equivalents and total flavonoid contents were calculated as quercetin equivalents from a calibration curve. RESULTS: The extracts showed moderate antioxidant activity in some models. IC50 for DPPH radical-scavenging activity was 579.6 +/- 19.4 microg/ml. The extracts showed weak nitric oxide-scavenging activity between 0.1 and 1.6 mg ml(-1) but showed good Fe2+ chelating ability. IC50 was 895.5 +/- 24.1 microg/ml. The extract also exhibited low antioxidant activity in the linoleic acid model but were capable of scavenging hydrogen peroxide in a concentration dependent manner. Tested extract show moderate activity in H2O2 induced hemolysis in rat erythrocytes which was not comparable with vitamin C. CONCLUSIONS: F. gummosa Boiss root showed different level antioxidant and antihemolytic activities. Biological effects may be attributed, at least in part, to the presence of phenols and flavonoids in the extract.

In vitro antioxidant activity of flower, seed and leaves of Alcea hyrcana Grossh.

OBJECTIVES: Alcea hyrcana Grossh (A. hyrcana Grossh) (malvacea), is native to northern of Iran. Many of the plants belonging to the genus Alcea are known to possess ethnomedical and biological properties. In this study, antioxidant activities of methanolic extracts of flower, seed and leaves of Alcea hyrcana Grossh were evaluated by various antioxidant assays. MATERIAL AND METHODS: 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), nitric oxide and hydrogen peroxide scavenging activities, Fe2+ chelating ability, reducing power and hemoglobin-induced linoleic acid peroxidation test were used to evaluate antioxidant activities. The total amount of phenolic compounds was determined as gallic acid equivalents and total flavonoid contents were calculated as quercetin equivalents from a calibration curve. Total phenolic and flavonoid contents also have been determined. RESULTS: All extracts showed good antioxidant activities. The A. hyrcana Grossh leaves extract exhibited strong ferrous chelating activity with IC50 = 0.11 +/- 0.01 mg ml(-1), nitric oxide radical scavenging with IC50 = 0.45 +/- 0.01 mg ml(-1) and better reducing power activity than other extracts. The seeds extract showed high scavenging activity against free radicals, including both the hydrogen peroxide and DPPH radicals. Only leaves extract had good activity in linoleic acid model. Seeds extract had significant higher total phenol (68.9 +/- 3.7 mg gallic acid equivalent/g of extract powder) and leaves had higher flavonoids contents (28.3 +/- 2.6 mg quercetin equivalent/g of extract powder) than other parts. CONCLUSIONS: The leaves, seed and flower extracts of A. hyrcana Grossh exhibited good but different levels of antioxidant activity in all the models studied. The extracts had good iron chelation, H2O2 and nitric oxide scavenging activities. Antioxidant activities may be attributed, at least in part, to the presence of phenols and flavonoids.

Antioxidant and antihaemolytic activities of Ferula foetida regel (Umbelliferae).

OBJECTIVES: The Ferula genus (Umbelliferae) is a rich source of gum-resin and is much utilized in folklore medicine. This study is designed to examine antioxidant and antihaemolytic activities of Ferula foetida regel flower, stem and leaf extracts. MATERIALS AND METHODS: 1,1-Diphenyl-2-picryl hydrazyl radical (DPPH), nitric oxide and H2O2 scavenging activities, Fe2+ chelating ability, reducing power and hemoglobin-induced linoleic acid peroxidation were used to evaluate antioxidant activities. Antihaemolytic activity was evaluated by H2O2 induced hemolysis in rat erythrocyte. Total phenolic compounds were determined as gallic acid equivalents and total flavonoid contents were calculated as quercetin equivalents from a calibration curve. RESULTS: The leaf aqueous-ethanol extract showed the highest activity in DPPH radical scavenging activity. All extracts showed weak nitric oxide scavenging activity. The stem extract had better activity in nitric oxide scavenging model than the other extracts (IC50 = 896.9 +/- 21.9 microg ml(-1)), but it was not comparable to quercetin (p < 0.001). The leaf extract exhibited better H2O2 scavenging and Fe2+ chelating activity than the other parts. The extracts exhibited good antioxidant activity in linoleic acid peroxidation test but were not comparable to vitamin C (p < 0.001). Extracts showed weak reducing power activity. The stem extract showed better antihaemolytic activity than the flower and leaf. The flower extract had higher phenolic contents. The extracts exhibited different levels of antioxidant and antihaemolytic activities in all tested models. CONCLUSIONS: This study showed remarkable antioxidant and antihemolytic activities in Feruia foetida. Biological effects may be attributed to the presence of phenols and flavonoids in the extract. It is very promising for further biochemical experiments.

Antiinflammatory and antioxidant activities of gum mastic.

OBJECTIVES: Pistacia lentiscus has traditionally been used in the treatment of many diseases. Its resin was investigated for its mineral contents, anti-inflammatory and antioxidant activities in rats. MATERIAL AND METHODS: Inhibition of carrageenan induced edema was used to evaluate anti-inflammatory activity. Fe2+ chelating ability, 1,1-diphenyl-2-picryl hydrazyl radical (DPPH) and nitric oxide scavenging activities were used to evaluate antioxidant activities and mineral contents were determined by atomic absorption spectroscopy. Gallic acid content was determined by HPLC. RESULTS: Resin produced statistically significant inhibition of edema at all doses when compared to the control groups. A 100% inhibition of inflammation was observed at 800 mg/kg i.p. Resin exhibit no toxicity up to 3 g/kg body weights i.p. in mice. Weak DPPH and nitric oxide scavenging activities were observed but showed good Fe2+ chelating ability (IC50 = 162 microg ml(-1)). The amount of elements was decreased in the order: Cu > Fe, Zn > Mn > Ni, Cd. Gallic acid content was 0.1 mg/g resin. CONCLUSIONS: These experimental data support the use of Pistacia lentiscus resin as an antiinflammatory and antioxidant agent.