Comparative efficacy and toxic effects of carvacryl acetate and carvacrol on sheep gastrointestinal nematodes and mice.

Carvacrol is a compound isolated from some essential oils. It has been reported to possess anthelmintic activity. Acetylation of this monoterpene has been proposed as a potential way to reduce the toxicity and enhance the pharmacological effects of carvacrol. This study aimed to evaluate the effect of carvacryl acetate (CA) using in vitro and in vivo assays with gastrointestinal nematodes of small ruminants. The egg hatching test (EHT), larval development test (LDT) and adult worm motility (AWM) assessment were conducted to evaluate the effect of the acetylated product and pure carvacrol on Haemonchus contortus eggs, larvae and adults. The structural changes induced in adult H. contortus were assessed using scanning electron microscopy (SEM). CA and carvacrol acute toxicity was evaluated in mice. Finally, the efficacy of 250 mg/kg CA and 2.5mg/kg monepantel (positive control) were evaluated in 30 sheep naturally infected with gastrointestinal nematodes by the fecal egg count reduction test (FECRT). In vitro tests were analyzed by analysis of variance (ANOVA) followed by comparison with Tukey's test. The efficacy was calculated by the Boot Street program using the arithmetic average. The number of eggs in feces (epg) of the groups were transformed to log (x+1) and subjected to ANOVA to compare differences among the groups by Tukey's test. The level of significance was P<0.05. CA and carvacrol inhibited larval hatching by 89.3 and 97.7% at doses of 8.0 and 1.0mg/ml, respectively. At the concentration of 2mg/ml, CA and carvacrol inhibited 100% of larval development. At a concentration of 200 µg/ml, CA and carvacrol inhibited the motility of adult worms by 100% and 58.3% at 24h post-exposure, respectively. CA caused cuticle and vulvar flap wrinkling and bubbles to emerge from the tegument. Carvacrol caused more discreet effects on the cuticle and vulvar flap. The LD10 and LD50 of CA were 566.7 mg/kg and 1544.5mg/kg, respectively. The LD10 and LD50 of carvacrol were 546.8 mg/kg and 919 mg/kg, respectively. CA and monepantel reduced the epg of sheep by 65.9 and 96.4%, respectively, at 16 days post-treatment. CA showed in vitro and in vivo anthelmintic activity and was less toxic than carvacrol.

Evaluation of toxic, cytotoxic, mutagenic, and antimutagenic activities of natural and technical cashew nut shell liquids using the Allium cepa and Artemia salina bioassays.

The cashew nut releases a substance that is known as cashew nut shell liquid (CNSL). There are both natural (iCNSL) and technical (tCNSL) cashew nut shell liquids. This study used an Artemia salina bioassay to evaluate the toxic effects of iCNSL and tCNSL cashew nut shell liquids. It also evaluated the toxicity, cytotoxicity, and mutagenicity of CNSL and its effects on the damage induced by copper sulfate (CuSO4·5H2O) on the meristems' root of Allium cepa. Effects of the damage induced by CuSO4·5H2O were evaluated before (pre-), during (co-), and after (post-) treatments. The iCNSL contained 94.5% anacardic acid, and the tCNSL contained 91.3% cardanol. The liquids were toxic to A. salina. Toxicity, cytotoxicity, and mutagenicity were observed with iCNSL compared with the negative control. Similarly, iCNSL failed to inhibit the toxicity and cytotoxicity of CuSO4·5H2O. The tCNSL was not toxic, cytotoxic, or mutagenic in any of the concentrations. However, the lowest iCNSL concentrations and all of the tCNSL concentrations had preventive, antimutagenic, and reparative effects on micronuclei and on chromosomal aberrations in the A. cepa. Therefore, protective, modulating, and reparative effects may be observed in the A. cepa, depending on the concentration and type of CNSL used.

In vitro effects of arylhydrocoumarin on free radicals and oxidative stress in erythrocytes and Saccharomyces cerevisiae.

Neoflavonoids comprise a group of natural compounds with varied chemical structures and promising pharmacological properties, including antioxidant capacity. This work describes an evaluation of the in vitro antioxidant capacity of a new coumarin derivative, i.e., 7-acetoxy-4-aryl-3,4-dihydrocoumarin, in terms of its ability to quench the 2,2- diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), hydroxyl (OH•) and superoxide anion (O2(•-)) radicals, as well as its capacity to initiate electron transfer by reducing potential and inhibit lipid peroxidation by TBARS (thiobarbituric acid reactive substances) method. In addition, the antioxidant capacity of 7-acetoxy-4-aryl-3,4-dihydrocoumarin was evaluated against oxidative damage induced by hydrogen peroxide in erythrocyte suspensions and S. cerevisiae strains. In all methodologies investigated, high antioxidant capacities above 65% were demonstrated by 7-acetoxy-4-aryl-3,4-dihydrocoumarin against the DPPH(•), ABTS(•+), OH(•) and O2(•-) radicals. The ability of 7-acetoxy-4-aryl-3,4-dihydrocoumarin to inhibit oxidative damage induced by hydrogen peroxide in erythrocytes and S. cerevisiae strains demonstrates the importance of this compound in the protection against oxidative stress at the cellular level. Thus, the results obtained in this study suggest that 7-acetoxy-4-aryl-3,4-dihydrocoumarin can assist the development of new antioxidant products for possible use in the prevention or reduction of diseases related to oxidative stress.

Mikania glomerata: Phytochemical, Pharmacological, and Neurochemical Study.

The present study primarily aims to identify the relative density and the fatty acids (methyl esters) content present in the standardized ethanol extract of leaves of M. glomerata (EPMG). Meanwhile, in a second moment, this study evaluated the effects of the EPMG on the levels of amino acids in the hippocampus, and the mechanism of sedative and anxiolytic action. Adult mice were treated with doses of 200, 300, and 400 mg/kg and evaluated in open field, elevated plus-maze, light dark, and rotarod tests. Moreover, in the behavioral tests diazepam (GABAergic anxiolytic, 2 mg/kg) as positive control and flumazenil (GABA antagonist, 2.5 mg/kg) were used to identify mechanism of sedative and anxiolytic action produced by EPMG. The EPMG is constituted by the following compounds: methyl cinnamate, 2H-1-benzopyran-2-one, (2-hydroxyphenyl)methyl propionate, (Z)-methyl-hexadec-7-enoate, methyl hexadecanoate, hexadecanoic acid, (Z)-methyl-octadec-9-enoate, octadecanoic acid, and squalene. This extract demonstrated anxiolytic effects, which may be mediated by GABAergic system, and was able to increase GABA levels and reduce of glutamate and aspartate concentrations in mice hippocampus, which can directly and/or indirectly assist in their anxiolytic effect. Although more studies are needed, the EPMG could represent an interesting therapeutical strategy in the treatment of anxiety.

Behavioral and neurochemical studies in mice pretreated with garcinielliptone FC in pilocarpine-induced seizures.

Garcinielliptone FC (GFC) isolated from hexanic fraction seed extract of species Platonia insignis Mart. It is widely used in folk medicine to treat skin diseases in both humans and animals as well as the seed decoction has been used to treat diarrheas and inflammatory diseases. However, there is no research on GFC effects in the central nervous system of rodents. The present study aimed to evaluate the GFC effects at doses of 25, 50 or 75 mg/kg on seizure parameters to determine their anticonvulsant activity and its effects on amino acid (γ-aminobutyric acid (GABA), glutamine, aspartate and glutathione) levels as well as on acetylcholinesterase (AChE) activity in mice hippocampus after seizures. GFC produced an increased latency to first seizure, at doses 25mg/kg (20.12 ± 2.20 min), 50mg/kg (20.95 ± 2.21 min) or 75 mg/kg (23.43 ± 1.99 min) when compared with seized mice. In addition, GABA content of mice hippocampus treated with GFC75 plus P400 showed an increase of 46.90% when compared with seized mice. In aspartate, glutamine and glutamate levels detected a decrease of 5.21%, 13.55% and 21.80%, respectively in mice hippocampus treated with GFC75 plus P400 when compared with seized mice. Hippocampus mice treated with GFC75 plus P400 showed an increase in AChE activity (63.30%) when compared with seized mice. The results indicate that GFC can exert anticonvulsant activity and reduce the frequency of installation of pilocarpine-induced status epilepticus, as demonstrated by increase in latency to first seizure and decrease in mortality rate of animals. In conclusion, our data suggest that GFC may influence in epileptogenesis and promote anticonvulsant actions in pilocarpine model by modulating the GABA and glutamate contents and of AChE activity in seized mice hippocampus. This compound may be useful to produce neuronal protection and it can be considered as an anticonvulsant agent.

In vitro antioxidant and cytotoxic activity of some synthetic riparin-derived compounds.

This study aimed to study the in vitro antioxidant activity and cytotoxicity on tumor cells lines of six synthetic substances derived from riparins. All the substances showed antioxidant activity and riparins C, D, E, F presented cell growth inhibition rates greater than 70%, suggesting that these molecules have antitumor properties. These substances also caused greater than 80% releases of cytoplasmic lactate dehydrogenase enzyme (LDH). Although the antioxidant and antitumor properties presented herein require further assessment, the outcomes indicate that these novel riparins are promising biologically active compounds.

Phytochemical profile and qualification of biological activity of an isolated fraction of Bellis perennis.

This study describes the isolation and identification of apigenin-7-O-ghicopyranoside, a flavonoid isolated from the flowers of Bellis perennis L., Asteraceae, an species with a broad spectrum of biological activities. The in vitro antioxidant activity and the inhibition of the enzyme acetylcholinesterase were evaluated. The flavonoid showed strong in vitro antioxidant potential, because of the capacity of removal of hydroxyl radicals and nitric oxide, and also prevented the formation of thiobarbituric acid-reactive substances. These parameters were inhibited at the highest concentration of ApG at rates of 77.7%, 72% and 73.4%, respectively, in addition to inhibiting acetylcholinesterase, suggesting potential use in the treatment of neurodegenerative diseases.

Phytochemical Profile and Qualification of Biological Activity of an Isolated Fraction of Bellis perennis

This study describes the isolation and identification of apigenin-7-O-ghicopyranoside, a flavonoid isolated from the flowers of Bellis perennis L., Asteraceae, an species with a broad spectrum of biological activities. The in vitro antioxidant activity and the inhibition of the enzyme acetylcholinesterase were evaluated. The flavonoid showed strong in vitro antioxidant potential, because of the capacity of removal of hydroxyl radicals and nitric oxide, and also prevented the formation of thiobarbituric acid-reactive substances. These parameters were inhibited at the highest concentration of ApG at rates of 77.7%, 72% and 73.4%, respectively, in addition to inhibiting acetylcholinesterase, suggesting potential use in the treatment of neurodegenerative diseases.

Neuropharmacological effects of lipoic acid and ubiquinone on the mRNA level of interleukin-1ß and acetylcholinesterase activity in rat hippocampus after seizures.

The purpose of this study was to investigate the neuroprotective effects of lipoic acid and ubiquinone on interleukin-1ß (IL-1ß) mRNA levels and acetylcholinesterase (AChE) activities in rat hippocampus after pilocarpine-induced seizures. Wistar rats were intraperitoneally administered with either 0.9% saline (icontrol group), LA (10 or 20 mg/kg, LA10 or LA20 groups), UQ (20 or 40 mg/kg, UQ20 and UQ40 groups), pilocarpine (400 mg/kg, P400 group), or co-administration of pilocarpine with LA or UQ groups 30 min prior to LA or UQ administration. After the treatments, all groups were observed for 1 h. IL-1ß mRNA and AChE activity in rat hippocampus at 1 h after SE onset was determined. Results showed that rats pretreated with LA or UQ developed less seizures and SE more slowly and has less number than animals treated with pilocarpine alone. Reduced IL-1ß mRNA and marked AChE activities in the hippocampus were significantly higher in rats pretreated with LA or UQ in comparison with the values of the control and seized groups. Our findings strongly support the hypothesis that an increase on IL-1ß mRNA levels in hippocampus occurs during seizures induced by pilocarpine, which indicates that inflammatory process plays a crucial role in seizures pathogenic consequences. Our result also suggests that LA or UQ can exert significant neuroprotective effects, at least in part, because of the increase in the AChE activities in rat hippocampus that will be useful in the treatment of neurodegenerative diseases.