Docking- and pharmacophore-based virtual screening for the identification of novel Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) inhibitor with a thiobarbiturate scaffold.

Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (MptpB) is an important virulence factor for Mtb that contributes to survival of the bacteria in macrophages. The absence of a human ortholog makes MptpB an attractive target for new therapeutics to treat tuberculosis. MptpB inhibitors could be an effective treatment to overcome emerging TB drug resistance. Adopting a structure-based virtual screening strategy, we successfully identified thiobarbiturate-based drug-like MptpB inhibitor 15 with an IC50 of 22.4 µM, and as a non-competitive inhibitor with a Ki of 24.7 µM. Importantly, not only did it exhibit moderate cell membrane permeability, compound 15 also displayed potent inhibition of intracellular TB growth in the macrophage, making it an excellent lead compound for anti-TB drug discovery. To the best of our knowledge, this novel thiobarbiturate is the first class of MptpB inhibitor reported so far that leveraged docking- and pharmacophore-based virtual screening approaches. The results of preliminary structure-activity relationship demonstrated that compound 15 identified herein was not a singleton and may inspire the design of novel selective and drug-like MptpB inhibitors.

Dietary supplementation of vitamin C: an effective measure for protection against UV-B irradiation using fish as a model organism.

The development of UV-B protective mechanisms in aquacultural species is essential for the sustainable production of healthy aqua crop. Freshwater carp Catla catla larvae (13.5 ± 1.12 mg) were fed with a diet containing 0.5% vitamin C (D1) and a control diet (D2) for 40 days. Each group was exposed to two doses of UV-B irradiation: 360 (5 min, D15 min and D25 min) and 720 mJ cm-2 (10 min, D110 min and D210 min) for 15 days. Significantly (p < 0.05) higher survival and average weight were recorded in D1 compared to D2 exposed to the same dose. Also, significantly (p < 0.001) higher nitric oxide synthase and lower thiobarbituric acid reactive substances and heat shock protein 70 levels were recorded in D15 min compared to the other groups. A direct relationship was found between the dose of UV-B and DNA fragmentation in muscles. DNA damage indices such as tail DNA, tail extent moment and olive tail moment were significantly (p < 0.01) lower in D15 min. Thus, supplementation of vitamin C in the diet provides UV-B protection to larvae.

Antidiabetic, Antihyperlipidemic, and Antioxidant Activities of Mulberry Lees Fermented Products in Diabetic Mice.

Mulberry lees are the sediment in the bottom of the barrel, which can be obtained from the processing of mulberry wine, and they are considered as low-value byproducts. In this study, mulberry lees were extracted with ethanol, and then fermented with Monascus pilosus to obtain fermented products (M × M). Male ICR mice were diabetes induced by STZ, and then oral administration of fermented products. The results showed that fermented products could reduce 31.9% to 47.9% plasma glucose, 25.8% to 48.2% total cholesterol, and 16.7% to 25% triglyceride levels in diabetic mice, and it can greatly lower the malondialdehyde (MDA) content by 26.4% to 59.7% but raise antioxidant enzyme activity in the liver of the mice. Moreover, fermented products not only could reduce AST and ALT activity of the diabetic mice, thereby alleviating liver inflammation, but also lowered the urea nitrogen and creatinine levels, improved glomerulus volume, and reduced swelling and inflammation in the kidneys. It was concluded that mulberry lees fermented products could be served as a value-added resource for human health.

Enzymatic System of Antioxidant Protection of Erythrocytes in Diabetic Rats Treated with Medicinal Mushrooms Agaricus brasiliensis and Ganoderma lucidum (Agaricomycetes).

Excessive glucose concentrations in blood and cells promote the intensification of auto-oxidation. This is one of the mechanisms through which free radicals form in hyperglycemia. As a result of hyperglycemia, oxidative stress develops and lipid peroxidation (LPO) is enhanced. Erythrocytes are particularly susceptible to reactive oxygen species and LPO, which can violate cell functions. This article describes the analysis of the influence of mycelia from the medicinal mushrooms Agaricus brasiliensis and Ganoderma lucidum on the enzymatic link of the antioxidant system in rat erythrocytes under streptozotocin-induced diabetes mellitus. Oxidative stress was strengthened in red blood cells of diabetic rats, as evidenced by decreased activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, and by increased amounts of thiobarbituric acid-positive products, which are markers of LPO. Administration of A. brasiliensis and G. lucidum submerged cultivated mycelial powder to animals with streptozotocin-induced diabetes restored superoxide dismutase, catalase, and glutathione peroxidase activity and reduced the amounts of thiobarbituric acid-positive products to control values, but did not affect the activity of glutathione reductase.

Cultivar and Metal-Specific Effects of Endophytic Bacteria in Helianthus tuberosus Exposed to Cd and Zn.

Plant growth promoting endophytic bacteria (PGPB) isolated from Brassica napus were inoculated in two cultivars of Helianthus tuberosus (VR and D19) growing on sand supplemented with 0.1 mM Cd or 1 mM Zn. Plant growth, concentrations of metals and thiobarbituric acid (TBA) reactive compounds were determined. Colonization of roots of H. tuberosus D19 by Pseudomonas sp. 262 was evaluated using confocal laser scanning microscopy. Pseudomonas sp. 228, Serratia sp. 246 and Pseudomonas sp. 262 significantly enhanced growth of H. tuberosus D19 exposed to Cd or Zn. Pseudomonas sp. 228 significantly increased Cd concentrations in roots. Serratia sp. 246, and Pseudomonas sp. 256 and 228 resulted in significantly decreased contents of TBA reactive compounds in roots of Zn exposed D19 plants. Growth improvement and decrease of metal-induced stress were more pronounced in D19 than in VR. Pseudomonas sp. 262-green fluorescent protein (GFP) colonized the root epidermis/exodermis and also inside root hairs, indicating that an endophytic interaction was established. H. tuberosus D19 inoculated with Pseudomonas sp. 228, Serratia sp. 246 and Pseudomonas sp. 262 holds promise for sustainable biomass production in combination with phytoremediation on Cd and Zn contaminated soils.

The effects of walnut supplementation on hippocampal NMDA receptor subunits NR2A and NR2B of rats.

OBJECTIVES: Walnuts contain numerous selected dietary factors that have an impact on brain functions, especially learning and memory formation in the hippocampus. Hippocampal N-methyl d-aspartate receptors (NMDARs) are involved in the formation of cognitive functions. In this study, we aimed to investigate the molecular effects of walnut supplementation on the hippocampal expressions of NMDARs involved in cognitive functions and lipid peroxidation levels in rats. METHODS: The male Sprague-Dawley rats (6 months old, n = 24) were fed with a walnut-supplemented diet (6% walnut diet, n = 12) and a control diet (rat food, n = 12) as ad libitum for 8 weeks. At the end of this period, NMDAR subunits NR2A and NR2B in the hippocampi were assayed by western blotting. Lipid peroxidation levels were measured using the thiobarbituric acid. RESULTS: The expression of NR2A and NR2B was elevated in the walnut-supplemented rats compared with the control group (P < 0.05). In addition, the levels of lipid peroxidation in the walnut-supplemented group were significantly decreased compared with the control group. DISCUSSION: We suggested that walnut supplementation may have protective effects against the decline of cognitive functions by regulating NMDAR and lipid peroxidation levels in the hippocampus. The study provides evidence that selected dietary factors (polyunsaturated fatty acids, melatonin, vitamin E, and flavonoids) within walnut may help to trigger hippocampal neuronal signal transduction for the formation of learning and memory.

Hepatic oxidative stress and metal subcellular partitioning are affected by selenium exposure in wild yellow perch (Perca flavescens).

Yellow perch (Perca flavescens) collected from 11 lakes in the Canadian mining regions of Sudbury (Ontario) and Rouyn-Noranda (Quebec) display wide ranges in the concentrations of cadmium (Cd), nickel (Ni), selenium (Se), and thallium (Tl) in their livers. To determine if these trace elements, as well as copper (Cu) and zinc (Zn), are causing oxidative stress in these fish, we measured three biochemical indicators (glutathione (GSH), glutathione disulfide (GSSG) and thiobarbituric acid-reactive substances (TBARS)) in their livers. We observed that 44% of the yellow perch that we collected were at risk of cellular oxidative stress and lipid peroxidation. Considering all fish from all lakes, higher liver Se concentrations were coincident with both lower proportions of GSSG compared to GSH and lower concentrations of TBARS, suggesting that the essential trace-element Se acts as an antioxidant. Furthermore, fish suffering oxidative stress had higher proportions of Cd, Cu and Zn in potentially sensitive subcellular fractions (organelles and heat-denatured proteins) than did fish not suffering from stress. This result suggests that reactive oxygen species may oxidize metal-binding proteins and thereby reduce the capacity of fish to safely bind trace metals. High Cd concentrations in metal-sensitive subcellular fractions likely further exacerbate the negative effects of lower Se exposure.

Effects of probiotic supplementation on systemic and intestinal oxidant-antioxidant events in splenectomized rats.

PURPOSE: The objective of this study was to show the effects of probiotic supplementation on systemic and intestinal oxidant-antioxidant events in splenectomized rats. METHODS: Male rats were divided into control (group 1) and splenectomized (group 2) groups, and after splenectomy, some rats were given Lactobacillus delbruckii subsp. bulgaricus (highest amount of extracellular polysaccharides, 211 mg/l) for 7 days (group 3) or were given the treatment for 7 days before and 7 days after splenectomy (group 4). The plasma and small intestine tissue thiobarbituric acid reactive substances (TBARS), sulfhydryl group, glutathione, ascorbic acid, and nitric oxide metabolites (NO x ) levels were determined by a spectrophotometer. RESULTS: We found increased TBARS levels in both the plasma and small intestine in the splenectomized rats compared to controls. L. delbruckii subsp. bulgaricus supplementation decreased the TBARS levels in the plasma in the splenectomized rats. In this study, the plasma TBARS and NO x levels were decreased by L. delbruckii subsp. bulgaricus supplementation after or both after and before splenectomy (groups 3 and 4). CONCLUSIONS: Together, these data suggest that. L. delbruckii subsp. bulgaricus supplementation is beneficial for decreasing lipid peroxidation and enhancing the antioxidant capacity of systemic and intestinal tissue in splenectomized rats.

In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects.

BACKGROUND: Berberis vulgaris is a well known plant with traditional herbal medical history. The aims of this study was to bioscreen and compare the in vitro biological activity (antioxidant, cholinergic, antidaibetic and the anticancer) of barberry crude extract and berberine active compound. METHODS: The effect of B. vulgaris extract and berberine chloride on cellular thiobarbituric acid reactive species (TBARS) formation, diphenyle-α-picrylhydrazyl (DPPH) oxidation, cellular nitric oxide (NO) radical scavenging capability, superoxide dismutase (SOD), glutathione peroxidase (GPx), acetylcholinesterase (AChE) and α-gulcosidase activities were spectrophotometrically determined. On the other hand, the effect of extract and berberine as anticancer was estimated on three different cell lines which were MCF-7, HepG-2, and Caco-2 cells by using neutral red uptake assay which compared with control normal cells (PBMC). RESULTS: Our results showed that barberry crude extract contains 0.6 mg berberine/mg crude extract. Barberry extract showed potent antioxidative capacity through decreasing TBARS, NO and the oxidation of DPPH that associated with GPx and SOD hyperactivation. Inhibitory effect of berberis crude extract on α-glucosidase was more potent than that of berberine chloride, while both had the same AChE inhibitory effect. Besides, different concentrations of both berberine chloride and barberry ethanolic extract showed to have no growth inhibitory effect on normal blood cells (PBMC). Otherwise, both berberine chloride and barberry ethanolic extract showed to have inhibitory effect on the growth of breast, liver and colon cancer cell lines (MCF7, HepG2 and CACO-2, respectively) at different incubation times starting from 24 hrs up to 72 hrs and the inhibitory effect increased with time in a dose dependent manner. CONCLUSION: This work demonstrates the potential of the barberry crude extract and its active alkaloid, berberine, on suppressing lipid peroxidation, suggesting a promising use in the treatment of hepatic oxidative stress, Alzheimer and idiopathic male factor infertility. Beside, berberis vulgaris ethanolic extract is safe non-toxic extract as it was not inhibit the growth of PBMC that can induce cancer cell death that could return to its powerful antioxidant activity.

Rokumi-jio-gan-containing prescriptions regulate oxidative stress through improving dyslipidemia in a subtotal nephrectomized rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Rokumi-jio-gan-containing prescriptions, traditional medicine, are widely used to treat renal dysfunction in Japan. AIM OF THE STUDY: The present study was conducted to examine whether two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) have an ameliorative effect on dyslipidemia in nephrectomized rats. MATERIALS AND METHODS: Each prescription was orally administered to nephrectomized rats at 150mg/kg body weight per day for 10 weeks, and its effect was compared with vehicle-treated nephrectomized rats. RESULTS: Rats given Hachimi-jio-gan and Bakumi-jio-gan showed an improvement of renal functional parameters such as serum urea nitrogen, creatinine, creatinine clearance, and urinary protein. The increased triglyceride, total cholesterol, non-esterified fatty acid, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol/low-density lipoprotein cholesterol levels in serum, and triglyceride and total cholesterol contents in the kidney of nephrectomized rats were significantly decreased by Hachimi-jio-gan and Bakumi-jio-gan administration. Furthermore, Hachimi-jio-gan acts as a regulator of peroxisome proliferator-activated receptor α, sterol regulatory element binding protein (SREBP)-1, and SREBP-2. On the contrary, the increased reactive oxygen species and thiobarbituric acid-reactive substance were decreased, while superoxide dismutase and the reduced glutathione/oxidized glutathione ratio were augmented by Hachimi-jio-gan rather than Bakumi-jio-gan. The improvement of nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, NF-E2-related factor 2, and heme oxygenase-1 was marked in the group administered Bakumi-jio-gan. However, oil red O staining showed that the increased lipid deposition in the kidney of nephrectomized rats improved on Hachimi-jio-gan and Bakumi-jio-gan administration. CONCLUSION: This study provides scientific evidence that two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) improve oxidative stress via dyslipidemia in the remnant kidney of nephrectomized rats.

The restriction of grazing duration does not compromise lamb meat colour and oxidative stability.

Over 72 days, 33 lambs were fed: concentrates in stall (S), grass at pasture for 8 hours (8 h), or grass at pasture for 4 hours in the afternoon (4h-PM). The 4h-PM treatment did not affect the carcass yield compared to the 8h treatment. Meat colour development after blooming was unaffected by the treatments. The 4 h-PM treatment increased the proportion of polyunsaturated fatty acids (PUFA; P<0.0005) and of the highly peroxidizable fatty acids (HP-PUFA; P<0.001) in meat compared to the 8h treatment. The S treatment increased lipid oxidation (higher TBARS values) and impaired colour stability (higher H* values) of meat over storage compared to the 8h and 4 h-PM treatments (P<0.0005 and P=0.003, respectively). No difference in meat oxidative stability was found between the 8h and the 4h-PM treatments. In conclusion, growing lambs can tolerate a restriction of grazing duration without detrimental effects on performances and meat oxidative stability.

Lipid and colour stability of M. longissimus muscle from lambs fed camelina or linseed as oil or seeds.

Colour and lipid stability of M. longissimus dorsi (LD) from sheep fed diets containing different lipid sources (Megalac (MG), camelina oil (CO), linseed oil (LO), NaOH-treated camelina seed (CS), NaOH-treated linseed (LS) or CO treated with ethanolamine (CA)) were examined. After 100 days on-feed, samples of LD were collected, fatty acid profile determined and colour and lipid oxidation (2-thiobarbituric acid reactive substances; TBARS) measured during retail display in high oxygen packaging. The LS ration was most effective in increasing the 18:3n-3 and conjugated linoleic acid (CLA) concentration in muscle. Within camelina, CA resulted in the highest 18:3n-3 and lowest CLA concentration in muscle. There was no difference in colour stability. Oil (seed) supplementation increased TBARS compared to MG in the early part of display while linseed-based rations tended to cause higher TBARS than camelina-based rations. Higher muscle 18:3n-3 concentration was associated with higher oxidation during early retail display but this was not reflected in a loss of colour stability.

Suitability of TBA method for the evaluation of the oxidative effect of non-water-soluble and water-soluble rosemary extracts.

The antioxidative effects of rosemary and grape-seed extracts spiked in human plasma were examined using the thiobarbituric acid (TBA) method. The TBA values of plasma spiked with reagents to generate reactive oxygen species, such as singlet oxygen ((1)O(2)), hydroxyl radicals ((·)OH), peroxynitrite (ONOO(-)), and superoxide anions (O(2)(·-)), were measured by a flow injection analysis method with fluorescence (FL) detection. TBA values obtained by the addition of 50 mg/mL of rosemary extracts for (1)O(2), (·)OH, ONOO(-), and O(2)(·-) increased to 964 ± 65%, 1063 ± 61%, 758 ± 78%, and 698 ± 41%, respectively (n = 3, P < 0.01), whereas the values with 1 mg/mL of grape-seed extracts or tocopherol decreased (40.2 - 66.3%). Furthermore, the antioxidative effects of rosemary extract in rat plasma, spiked with reagents to generate (·)OH, were examined by high-performance liquid chromatography with FL detection. No peak, other than TBA-malondialdehyde, could be detected using wavelengths of 532 (λ(ex)) and 553 nm (λ(em)).

Effects of oral supplementation with plant superoxide dismutase extract on selected redox parameters and an inflammatory marker in a 2,000-m rowing-ergometer test.

The aim of this study was to investigate the effect of plant superoxide dismutase extract (GliSODin) supplementation on the balance of oxidants and antioxidants in the serum and erythrocytes of competitive rowers. The double-blinded study included 19 members of the Polish rowing team who were participating in a preparatory camp. Subjects were randomly assigned to the supplemented group (n = 10), who received 2 capsules (500 mg) of GliSODin extract once daily for 6 weeks, or the placebo group (n = 9). At the beginning and end of the study, subjects performed a 2,000-m maximum-effort test on a rowing ergometer. Blood samples were taken from the antecubital vein before each exercise test, 1 min after completing the test, and after a 24-hr restitution period. The following redox parameters were assessed in erythrocytes: superoxide dismutase (SOD) activity, glutathione peroxidase activity, and concentrations of thiobarbituric-acid-reactive substances. In addition, creatine kinase activity and total antioxidant capacity were measured in plasma samples, lactate levels were determined in capillary blood samples, and C-reactive protein and lactate dehydrogenase concentrations were measured in serum. After supplementation, SOD activity was significantly higher (p = .0037) in the supplemented group than the placebo group, and C-reactive protein was significantly (p = .00001) lower in athletes receiving GliSODin than those in the placebo group. In conclusion, supplementation with an extract rich in SOD activity promoted antioxidant status and protected against increased inflammation in the serum of professional rowers but had no effect on oxidative damage induced by exhaustive exercise.

Morinda citrifolia Linn leaf extract possesses antioxidant activities and reduces nociceptive behavior and leukocyte migration.

Herbal drugs have been used since ancient times to treat a wide range of diseases. Morinda citrifolia Linn (popularly known as "Noni") has been used in folk medicine by Polynesians for over 2,000 years. It is reported to have a broad range of therapeutic effects, including effects against headache, fever, arthritis, gingivitis, respiratory disorders, infections, tuberculosis, and diabetes. The aim of this study was to investigate the antioxidant, anti-inflammatory, antinociceptive, and antibacterial properties of the aqueous extract from M. citrifolia leaves (AEMC). Antioxidant activity was observed against lipid peroxidation, nitric oxide, and hydroxyl radicals. The antinociceptive effect of AEMC was observed in the acetic acid-induced writhing test at the higher dose. Moreover, AEMC significantly reduced the leukocyte migration in doses of 200 and 400 mg/kg and showed mild antibacterial activity. Together, the results suggest that properties of M. citrifolia leaf extract should be explored further in order to achieve newer tools for managing painful and inflammation conditions, including those related to oxidant states.

A facilitated approach to evaluate the inhibitor mode and potency of compounds targeting microsomal prostaglandin e synthase-1.

Microsomal prostaglandin E(2) synthase-1 (MPGES1) catalyzes the formation of prostaglandin E(2) from the endoperoxide prostaglandin H(2). MPGES1 expression is induced in inflammatory diseases, and this enzyme is regarded as a potential drug target. To aid in the drug discovery effort, a simple method for determination of inhibition mechanism and potency toward both prostaglandin H(2) and glutathione (GSH) has been developed. Using an assay with thiobarbituric acid-based detection, the inhibitory effects of six MPGES1 inhibitors were evaluated. The IC(50) values obtained at three substrate (S) concentrations ([S]K(M)) were used to estimate inhibition modality and inhibition constant values. This facilitated strategy is a useful and general screening method to evaluate the inhibitory effects of new drug compounds.

In vitro and in vivo antioxidant properties of extracts from Coptis chinensis inflorescence.

The inflorescence of cultivated Coptis chinensis has been valued for tea production for many years in China. The antioxidant activities of C. chinensis inflorescence extracts prepared by various solvents were investigated by using several established in vitro systems: 2,2'-azinobis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS), α,α-diphenyl-ß-picrylhydrazyl (DPPH) and superoxide radical scavenging assays, reducing power assay, and ferrothiocyanate (FTC) and thiobarbituric acid (TBA) assays. The results showed that the 70% ethanol extract (EE) had the strongest antioxidant activity in vitro among the various extracts. Based on the in vitro results, EE was used to evaluate the antioxidant activity of C. chinensis inflorescence in vivo. The liver and kidney of intoxicated animals showed a significant decrease in superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels, while the malondialdehyde (MDA) level showed a significant increase. These changes were significantly reversed after treatment with EE and the standard vitamin E. Thus, the C. chinensis inflorescence may be a valuable natural source that can be applicable to food industries.

Antioxidant status in rats after long-term intake of anthocyanins and ellagitannins from blackberries.

BACKGROUND: This study reported the effects of the daily intake of anthocyanins and ellagitannins (ET) extracted from blackberries on the markers for oxidative status in healthy rats. RESULTS: The phenolic compounds were administered from three different extracts: an aqueous extract of blackberry (BJ) and its two derived fractions: anthocyanin-enriched (AF) and ET-enriched (EF) fractions. After 35 days' administration, the AF and EF extracts significantly reduced thiobarbituric acid reactive substance levels and increased glutathione levels in the liver,kidney and brain. Plasma antioxidant capacity increased only in the group that received AF. Antioxidant enzyme activity and expression did not follow a pattern of response varying according to the tissues and extracts. A significant increase in the catalase activity was observed only in the plasma of the groups administered anthocyanin-containing extracts,which were the BJ and AF groups. Glutathione peroxidase activity was significantly increased in the liver and brain after EF treatment, and the highest increase in its expression was observed in the livers and brains of rats that received AF and EF, respectively. CONCLUSION: The results demonstrate that long-term intake of anthocyanin and ET through diet affects antioxidant enzymeactivity and expression, and enhances oxidative markers in healthy rats.

Salvia leriifolia Benth (Lamiaceae) extract demonstrates in vitro antioxidant properties and cholinesterase inhibitory activity.

The object of the present study was to investigate the in vitro antioxidant properties and cholinesterase inhibitory activity of Salvia leriifolia Benth extracts and fractions. The functional role of herbs and spices and their constituents is a hot topic in food-related plant research. Salvia species have been used since ancient times in folk medicine for cognitive brain function and have been subjected to extensive research. Thus, we hypothesize that S leriifolia, because of its functional properties, would be a good candidate to use as a nutraceutical product for improving memory in the elderly or patients affected by Alzheimer disease (ad). To test this hypothesis, we examined the cholinesterase inhibitory activity using the modified colorimetric Ellman's method against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The n-hexane exhibited the highest activity, with inhibitory concentration 50% (IC(50)) values of 0.59 and 0.21 mg/mL, for AChE and BChE, respectively. This extract was fractionated, and 9 of these fractions (A-I) were obtained and tested. Fraction G, characterized by the presence of sesquiterpenes as major components, was the most active against AChE (IC(50) = 0.05 mg/mL). Because oxidative stress is a critical event in the pathogenesis of AD, we decided to screen the antioxidant activity (AA) using 2,2-diphenyl-1-picrylhydrazyl test, ß-carotene bleaching test, and bovine brain peroxidation (thiobarbituric acid) assay. The ethyl acetate extract showed the highest activity, with IC(50) values of 2 and 33 µg/mL on ß-carotene bleaching test and thiobarbituric acid test, respectively. These results suggest potential health benefits of S leriifolia extracts. However, this finding requires additional investigation in vivo.

Gastroprotective effect of barbatusin and 3-beta-hydroxy-3-deoxibarbatusin, quinonoid diterpenes isolated from Plectranthus grandis, in ethanol-induced gastric lesions in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Validate the popular use of Plectranthus grandis in gastric disorders through the active components. AIMS: Isolation of barbatusin (BB) and 3beta-hydroxy-3-deoxibarbatusin (BBOH), diterpenes from Plectranthus grandis, and evaluation of their gastroprotective effect and possible mechanisms of action. MATERIALS AND METHODS: Isolation and chemical characterization of diterpenes from Plectranthus grandis by chromatographic and spectroscopic methods and evaluation of gastroprotective action of the diterpenes through ethanol-induced gastric injury in mice model. It was evaluated the effect of capsazepine, indomethacin and the role of nitric oxide and K(ATP-) channels on the gastroprotective effect of BBOH and BB. Additionally it was measured the concentrations of gastric mucus, non-proteic-sulfhydryl groups and total thiobarbituric acid-reactive substances. RESULTS: Orally administered BBOH and BB at doses of 5 and 10mg/kg, markedly reduced the gastric lesions by 59 and 96%, and 32 and 76%, respectively, with superior results as compared to N-acetylcysteine (150 mg/kg, i.p.), reference compound that caused 85% lesion suppression. Although BBOH presented a higher gastroprotection than BB they act by similar mechanisms in relation to N-acetylcysteine, and prevent the depletion of gastric mucus, gastric mucosal non-proteic-sulfhydryl groups as well as the increase in thiobarbituric acid-reactive species. Moreover, the gastroprotective effect of BB was effectively blocked in mice pretreated with TRPV1 antagonist capsazepine, by the non-selective cyclooxygenase inhibitor indomethacin, or by the nitric oxide synthase inhibitor L-NAME but not by K(+)(ATP) channel inhibitor glibenclamide. In contrast, the gastroprotective effect of BBOH was blocked only by indomethacin and glibenclamide pretreatments. CONCLUSION: The protective role for BBOH and BB affording gastroprotection against gastric damage induced by ethanol indicates that these compounds contribute for the activity of Plectranthus species. The different modes of action are probably related to differences in their chemical structure.