Neuroinflammation and hypersensitivity evidenced by the acute and 28-day repeated dose toxicity tests of ostrich oil in mice.

The ostrich oil (OO) has been topically used for decades to treat skin diseases. Its oral use has been encouraged through e-commerce advertising several health benefits to OO without scientific evidence on its safety or effectiveness. This study presents the chromatographic profile of a commercially available OO and its acute and 28-day repeated dose in vivo toxicological profiles. OO anti-inflammatory and antinociceptive effects were also investigated. Omega-9 (ω-9; oleic acid; 34.6%) and -6 (linoleic acid; 14.9%) were detected as OO main constituents. A high single dose of the OO (2 g/kg of ω-9) demonstrated no or low acute toxicity. However, when orally treated with OO (30-300 mg/kg of ω-9) for 28 consecutive days, mice exhibited altered locomotor and exploratory activities, hepatic damage, and increased hindpaw sensitivity accompanied by increased levels of cytokine and brain-derived neurotrophic factor in their spinal cords and brains. Lack of anti-inflammatory or antinociceptive activities was also evidenced in 15-day-OO treated mice. These results indicate that chronic consumption of OO induces hepatic injury, in addition to neuroinflammation and subsequent hypersensitivity and behavioural changes. Thus, there is no evidence to support OO use to treating illness in humans.

Gastroprotective effect of Artemisia absinthium L.: A medicinal plant used in the treatment of digestive disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Wormwood (Artemisia absinthium L.) is traditionally used for stomach pain and gastric relief. However, its possible gastroprotective effect has not yet been experimentally evaluated. AIM OF THE STUDY: This study evaluated the gastroprotective effect of aqueous extracts obtained through hot and room temperature maceration of A. absinthium aerial parts in rats. MATERIALS AND METHODS: The gastroprotective effect of hot aqueous extract (HAE) and room temperature aqueous extract (RTAE) from A. absinthium aerial parts were evaluated in rats using a model of acute gastric ulcer induced by ethanol p.a. The stomachs were collected to measure the gastric lesion area and histological and biochemical analysis. UHPLC-HRMS/MS analysis was used to determine the chemical profile of the extracts. RESULTS: Eight main peaks in the UHPLC chromatogram were identified in both HAE and RTAE extracts: tuberonic acid glycoside (1), rupicolin (2), 2-hydroxyeupatolide (3), yangabin (4), sesartemin (5), artemetin (6), isoalantodiene (7), and dehydroartemorin (8). For RTAE, a higher diversity of sesquiterpene lactones was observed. The groups treated with RTAE at 3%, 10%, and 30% presented a gastroprotective effect, reducing the lesion area by 64.68%, 53.71%, and 90.04%, respectively, when compared with the vehicle (VEH)-treated group. On the other hand, the groups treated with HAE at 3%, 10%, and 30% presented values of lesion areas higher than those of the VEH group. Changes in the submucosa layer, inflammatory process with edema, cellular infiltration, and mucin depletion were detected in the gastric mucosa exposed to ethanol, which was fully prevented by RTAE treatment. Neither HAE nor RTAE could increase the reduced glutathione levels in the injured gastric tissue, but RTAE (30%) reduced the formation of lipid hydroperoxides. When the rats were pre-treated with NEM (a chelator of non-protein thiols) or L-NAME (non-selective nitric oxide synthase inhibitor), the RTAE lost the ability to protect the gastric mucosa. CONCLUSIONS: This study corroborates the ethnopharmacological use of this specie to treat gastric disorders revealing the gastroprotective effect of the room-temperature aqueous extract of A. absinthium aerial parts. Its mode of action may involve the ability of the infusion to maintain the gastric mucosal barrier integrity.

Two morphotypes versus two chemotypes of Psidium cattleyanum: Chemical and pharmacological comparison and a rational approach for marker selection.

Psidium cattleyanum has two morphotypes: one with yellow fruits and other with red fruits. The leaves are popularly used as anti-inflammatory. However, no distinction is made between the types. Therefore, this study compared chemical and pharmacological data of both morphotypes to select proper biomarkers to ensure P. cattleyanum leaves quality. After extraction optimization by experimental design, 28 samples were analyzed by HPLC. Using Principal Component Analysis, it was possible to detect two chemotypes, unrelated to the color of the fruits. However, the extracts obtained from both chemotypes seemed to play similar anti-inflammatory effect, demonstrated by anti-chemotactic activity. The compounds common to both chemotypes were isolated and identified as hyperoside, miquelianin and quercitrin; these compounds also demonstrated anti-inflammatory potential. Since both chemotypes played similar activity, along with the isolated flavonoids, these flavonoids were selected as biomarkers for quality control of P. cattleyanum leaves. Following ICH guidelines, a HPLC method was validated. In summary, this study demonstrated that hyperoside, miquelianin and quercitrin can be used as biomarkers for quality control of P. cattleyanum leaves and a method was developed and validated to be used interchangeably for both morpho- and chemotypes.

Usnic acid enantiomers restore cognitive deficits and neurochemical alterations induced by Aß1-42 in mice.

Alzheimer's disease (AD) is the most prevalent form of dementia with a complex pathophysiology not fully elucidated but with limited pharmacological treatment. The Usnic acid (UA) is a lichen secondary metabolite found in two enantiomeric forms: (R)-(+)-UA or (S)-(-)-UA, with antioxidant and anti-inflammatory potential. Thus, given the role of neuroinflammation and oxidative injury in the AD, this study aimed to investigate experimentally the cognitive enhancing and anti-neuroinflammatory effects of UA enantiomers. First, the interactions of UA on acetylcholinesterase (AChE) was assessed by molecular docking and its inhibitory capability on AChE was assessed in vitro. In vivo trials investigated the effects of UA enantiomers in mice exposed to Aß1-42 peptide (400 pmol/mice) intracerebroventricularly (i.c.v.). For this, mice were treated orally during 24 days with (R)-(+)-UA or (S)-(-)-UA at 25, 50, or 100 mg/kg, vehicle, or donepezil (2 mg/kg). Animals were submitted to the novel object recognized, Morris water maze, and inhibitory-avoidance task to assess the cognitive deficits. Additionally, UA antioxidant capacity and neuroinflammatory biomarkers were measured at the cortex and hippocampus from mice. Our results indicated that UA enantiomers evoked complex-receptor interaction with AChE like galantamine in silico. Also, UA enantiomers improved the learning and memory of the animals and in parallel decreased the myeloperoxidase activity and the lipid hydroperoxides (LOOH) on the cortex and hippocampus and reduced the IL-1ß levels on the hippocampus. In summary, UA restored the cognitive deficits, as well as the signs of LOOH and neuroinflammation induced by Aß1-42 administration in mice.

Phenolic profile by HPLC-ESI-MS/MS of six Brazilian Eugenia species and their potential as cholinesterase inhibitors.

Eugenia genus is known for its phenolic metabolites, which may influence the progression of the Alzheimer Disease. This study aimed to evaluate the anticholinesterase effects of six Eugenia species from Brazil. Leaves and stems were submitted to maceration (methanol) and partitioned with dichloromethane and ethyl acetate (EtOAc). Samples were screened (200 µg mL-1) for the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). HPLC-ESI-MS/MS analysis allowed the identification of twenty-eight phenolic compounds. Regarding the enzymatic activity, EtOAc fraction of E. mattosii exhibited the best results. Chemical and pharmacological aspects of seasonal E. mattosii extracts were evaluated. The extract from leaves collected in the winter was the most effective for AChE, and the extract from leaves collected in the spring was the most effective for BuChE. Correlating the enzymatic results with the chemical data, it was possible to associate these effects to isoquercitrin, quercetin, catechin, epicatechin, procatecuic acid and myricitrin content.

Açaí berries (Euterpe oleracea Mart.) dried extract improves ethanol-induced ulcer in rats.

OBJECTIVES: Açaí (Euterpe oleracea) is widely consumed in Brazil and known for its numerous health-beneficial properties. This study investigated the gastroprotective potential of the dried açaí berries extract (DAE). METHODS: Dried açaí berries extract effect was evaluated against ethanol-induced gastric ulcer in rats. Its ability to regulate antioxidant defenses and reduce inflammatory parameters was evaluated in the ulcerated tissues. The scavenger capability of DAE was assessed by DPPH assay, and phytochemical composition was accessed by UHPLC. KEY FINDINGS: The extract showed radical scavenger activity in vitro (IC50  = 210 µg/ml) and gastroprotective effect in vivo, reducing the ulcerated area by 83%, 67% and 48% at doses of 30 and 100 mg/kg (p.o) and 3 mg/kg (i.p), respectively, compared with vehicle group. Besides, DAE (100 mg/kg, p.o) increased the GSH content and GST activity in ulcerated mucosa. Animals treated with DAE showed normalized levels of SOD activity, elevated CAT activity and decreased MPO activity, as well as reduced TNF-α levels, compared with vehicle group. Peonidin-3-glucoside, peonidin-3-rutinoside, cyanidin-3,5-hexoside-pentoside, cyaniding-3-glucoside, pelargonidin-3-glucoside and pelargonidin-3-rutinoside were identified in DAE. CONCLUSIONS: Our findings suggest that DAE reduces the inflammation and maintains the oxidative balance of gastric mucosa, therefore being a promising natural resource or useful nutraceutical to protect gastric mucosa.

Experimental Design Methodologies for the Optimization of Chiral Separations: An Overview.

In this chapter, the application of design of experiments (DoE) for chiral separation optimization using supercritical fluid chromatography (SFC), liquid chromatography (LC), capillary electrophoresis (CE), and capillary electrochromatography (CEC) methods is reviewed. Both screening and optimization steps are covered, including a discussion of each aspect, such as factor-, level-, and response selection. Different designs are also presented, highlighting their applications.

Hydroalcoholic extract of Tagetes erecta L. flowers, rich in the carotenoid lutein, attenuates inflammatory cytokine secretion and improves the oxidative stress in an animal model of ulcerative colitis.

Given the role of oxidative stress in ulcerative colitis (UC) etiology, and the amount of lutein (a carotenoid with antioxidant properties) in the dry hydroalcoholic extract of Tagetes erecta flowers (DHETE), this study investigated the intestinal anti-inflammatory properties of DHETE in an animal model of UC. The amount of lutein in the extract was determined by 1H-nuclear magnetic resonance spectroscopy, and total phenols, radical scavenger capability, cytotoxicity, and effects on reactive oxygen species and nitric oxide production were evaluated in vitro. Experimental UC was established by adding 5% dextran sulfate sodium (DSS) to drinking water, with the effects of DHETE (30-300 mg/kg, once a day for 7 days) on the morphological (colon length and weight), clinical (disease activity index and body weight loss), microscopic (histological score and mucin levels), and biochemical parameters analyzed. The lutein concentration found in DHETE was 8.2%, and DHETE scavenged 2,2-diphenyl-1-picrylhydrazyl radicals at 1000 µg/mL The exposure of intestinal epithelial cells to DHETE did not change its viability but reduced reactive oxygen species and nitric oxide production after lipopolysaccharide stimulation. In vivo, DHETE (300 mg/kg) attenuated weight loss, disease activity index, colon shortening, and histopathological changes promoted by DSS intake. Moreover, DHETE increased mucin colonic staining. The treatment with DHETE decreased myeloperoxidase activity as well as tumor necrosis factor and interleukin-6 levels. The extract also increased reduced glutathione levels and catalase activity and normalized superoxide dismutase and glutathione-S-transferase activities. In conclusion, DHETE reduced colitis severity by attenuating inflammatory cytokine secretion and improved the endogenous antioxidant defense in DSS-induced UC in mice.

All that glitters is not gold: Panning cytotoxic natural products and derivatives with a fused tricyclic backbone by the estimation of their leadlikeness for cancer treatment.

Tricyclic compounds call the attention because of their pharmacological properties, and are considered a preferred platform for the development of drugs. Especially, in cancer treatment, these planar compounds are known for their ability to stack with DNA base pairs, acting as intercalators. In this sense, natural products (NPs) are a prodigal source of polycyclic compounds, comprising classes, such as carbolines, anthraquinones and xanthones. However, most of these compounds lack suitable physico-chemical properties, compatible to oral bioaviability. In this perspective, this paper aims to overview the role of tricyclic cores in the development of cytotoxic compounds, focusing on the leadlikeness estimation of the most prominent NP classes and their synthetic derivatives.

Toxicological profile and acetylcholinesterase inhibitory potential of Palicourea deflexa, a source of ß-carboline alkaloids.

Palicourea genus is chemically and taxonomically close to Psychotria genus, a well-known source of neuroactive alkaloids. It has been previously reported the pharmacological potential of these alkaloids in some targets related to the neurodegenerative process. In this context, this study was carried out in order to evaluate the toxic effects and acetylcholinesterase (AChE) inhibitory potential of Palicourea deflexa fraction of total alkaloids (FTA). P. deflexa FTA was analyzed by means of HPLC-DAD and HRMS-ESI. We performed toxicological screening through Fish Embryo Toxicity (FET) test using zebrafish embryo and abnormal developmental phenotypes were recorded daily. For AChE inhibition, zebrafish brains were used as enzymatic source and formation of thiolate dianion of 5,5'-Dithiobis(2-nitrobenzoic acid) (DTNB) was used to monitor acetylthiocholine hydrolysis. Lineaweaver-Burk double reciprocal plots were used to indicate mode of inhibition. Chemical analysis of the P. deflexa FTA allowed the identification of the main compound as harman-3-carboxylic acid. This fraction was evaluated in vivo for its toxicological effect. The zebrafish embryo test indicated that the FTA has a lethal concentration of 50% (LC50)=72.18µg/mL. Further, the FTA was evaluated for its AChE inhibitory profile, demonstrating an inhibitory concentration of 50% (IC50) of 50.65µg/mL. Lineaweaver-Burk double reciprocal plots indicated a mixed mode of inhibition. It is reported for the first time the toxicological and pharmacological profile of the alkaloid fraction of Palicourea deflexa in zebrafish models.

The validation of Calophyllum brasiliense ("guanandi") uses in Brazilian traditional medicine as analgesic by in vivo antinociceptive evaluation and its chemical analysis.

Calophyllum brasiliense is used as anti-inflammatory and analgesic in Brazilian traditional medicine. Thus, the main purpose of this study is to evaluate the antinociceptive effect of the chloroform fraction of C. brasiliense (CFCB) roots and to investigate its main mechanism of action. The antinociceptive effect of CFCB was evaluated in mice using acetic acid-induced writhing, formalin-induced paw licking, and hot-plate tests and capsaicin- and glutamate-induced nociception. Brasiliensic acid and 1,2-dimethoxyxanthone were isolated and evaluated in writhing test. The amount of 1,2-dimethoxyxanthone was determined in the fraction by UPLC-DAD. CFCB inhibited abdominal constrictions induced by acetic acid up to 97%, with an ID50 of 9.4 mg/kg (i.p.) and 131.8 mg/kg (p.o.). In the formalin test, CFCB impaired paw licking with an ID50 of 26.3 mg/kg for the first phase and 27.5 mg/kg for the second phase (i.p.). The painful response evoked by capsaicin and glutamate was significantly reduced (ID50 26.7 and 47.9 mg/kg, i.p.). The latency time was increased up to 76% at 60 mg/kg (i.p.) in the hot-plate test. 1,2-Dimethoxyxanthone was almost three times more potent (ID50 27.6 µmol/kg, i.p.) than brasiliensic acid (72.0 µmol/kg) in acetic acid-induced writhing test. The amount of the xanthone was estimated as 92.5 mg/g in the extract. CFCB inhibited the nociceptive response associated to several agents. TRPV1 channels play an important role in the mechanism of action of the fraction. In addition, 1,2-dimethoxyxanthone largely contributes to the antinociceptive effect of CFCB.

Monoamine Oxidase Inhibitory Activity of Biflavonoids from Branches of Garcinia gardneriana (Clusiaceae).

Garcinia gardneriana is chemically characterized by the presence of biflavonoids. Taking into account that flavonoids are able to inhibit monoamine oxidase (MAO) activity, in the present study, the chemical composition of the branches' extract of the plant is described for the first time and the MAO inhibitory . activity of the isolated biflavonoids was evaluated. Based on spectroscopic and spectrometric data, it was possible to identify volkesiflavone, morelloflavone (1), Gb-2a (2) and Gb-2a-7-Ο-glucoside (3) in the ethyl acetate fraction from ethanol extract of the branches. Compounds 1-3 were evaluated in vitro and demonstrated the capacity to inhibit MAO-A activity with an IC50 ranging from 5.05 to 10.7 µM, and from 20.7 to 66.2 µM for MAO-B. These inhibitions corroborate with previous IC50 obtained for monomeric flavonoids, with a higher selectivity for MAO-A isoform. The obtained results indicate that biflavonoids might be promising structures for the identification of new MAO inhibitory compounds.

Origanum majorana Essential Oil Lacks Mutagenic Activity in the Salmonella/Microsome and Micronucleus Assays.

The present study aimed to investigate the in vitro mutagenic activity of Origanum majorana essential oil. The most abundant compounds identified by GC-MS were γ-terpinene (25.73%), α-terpinene (17.35%), terpinen-4-ol (17.24%), and sabinene (10.8%). Mutagenicity was evaluated by the Salmonella/microsome test using the preincubation procedure on TA98, TA97a, TA100, TA102, and TA1535 Salmonella typhimurium strains, in the absence or in the presence of metabolic activation. Cytotoxicity was detected at concentrations higher than 0.04 µL/plate in the absence of S9 mix and higher than 0.08 µL/plate in the presence of S9 mix and no gene mutation increase was observed. For the in vitro mammalian cell micronucleus test, V79 Chinese hamster lung fibroblasts were used. Cytotoxicity was only observed at concentrations higher than or equal to 0.05 µg/mL. Moreover, when tested in noncytotoxic concentrations, O. majorana essential oil was not able to induce chromosome mutation. The results from this study therefore suggest that O. majorana essential oil is not mutagenic at the concentrations tested in the Salmonella/microsome and micronucleus assays.

The monoamine oxidase inhibitory activity of essential oils obtained from Eryngium species and their chemical composition.

CONTEXT: Monoamine oxidase (MAO) inhibitors are used in the treatment of depression, anxiety disorders, and the symptomatic treatment of Parkinson's disease. Eryngium, the most representative of the Apiaceae family, is well known for the presence of essential oils (EOs), which have already demonstrated MAO inhibitory potential. OBJECTIVE: The objective of this study is to evaluate the MAO inhibitory capacity of the EOs obtained from Eryngium floribundum Cham. & Schlecht. (EF), E. eriophorum Cham. & Schlecht. (EE), E. nudicaule Lam. (EN), E. horridum Malme (EH), and E. pandanifolium Cham. & Schlecht. (EP). MATERIALS AND METHODS: EOs were obtained from fresh whole plants by hydrodistillation (3 h). Chemical analyses were performed by GC/MS using apolar and polar columns, with oven temperature from 60 to 300 °C at 3 °C/min. The MAO-A and -B activities were evaluated in vitro by an end-point method using kynuramine as the substrate and mitochondrial suspension or human recombinant enzymes as the enzymatic source. DMSO 2%, clorgyline 10(-7) M, and pargyline 10(-6) M were used as controls. RESULTS AND DISCUSSION: EFEO, EEEO, ENEO, EHEO, and EPEO GC/MS analysis showed (E)-caryophyllene (4.9-10.8%), germacrene D (0.6-35.1%), bicyclogermacrene (10.4-17.2), spathulenol (0.4-36.0%), and globulol (1.4-18.6%) as main constituents. None of the EOs inhibited MAO-A activity (4 and 40 µg/mL). However, EHEO inhibited MAO-B activity with an IC50 value of 5.65 µg/mL (1-200 µg/mL). Pentadecane (10 µM), its major constituent (53.5%), did not display significant MAO-B inhibition. CONCLUSION: The study demonstrates the promising application of Eryngium species as a source of potential central nervous system bioactive secondary metabolites, specially related to neurodegenerative disorders.

Multifunctional Monoamine Oxidases and Cholinesterases Inhibitory Effects, as well as UPLC-DAD-MS Chemical Profile of Alkaloid Fractions Obtained from Species of the Palicoureeae Tribe.

In the present study, the effects were evaluated of alkaloid fractions (AFs) from Psychotria species and correlated genera, Palicourea and Rudgea, on monoamine oxidases (MAOs) and cholinesterases (ChEs). By HPLC-DAD and UPLC-DAD-MS analyses, indole alkaloids (IA) were detected in all AFs. For the Psychotria and Palicourea species, these IA corresponded to tetrahydro-p-carboline alkaloids (THPCA). On the other hand, pyrrolidinoindoline core compounds were observed for Rudgea species. Regarding their pharmacological activities, none of the AFs was able to inhibit AChE. However, the BChE activity was impaired by the Psychotria and Palicourea AFs. In addition, MAO-A was inhibited by both AFs, but only Psychotria nemorosa AF was able to inhibit significantly MAO-B. Rudgea AFs demonstrated a poor inhibitory profile on MAO-A. Taken together, our results highlighted the Psychotria and Palicourea genera as important sources of scaffolds for the development of MAO-A and BChE inhibitors aiming at the treatment of neurodegenerative and neuropsychiatric diseases.

The catechol-O-methyltransferase inhibitory potential of Z-vallesiachotamine by in silicoand in vitro approaches

AbstractZ-Vallesiachotamine is a monoterpene indole alkaloid that has a β-N-acrylate group in its structure. This class of compounds has already been described in different Psychotriaspecies. Our research group observed that E/Z-vallesiachotamine exhibits a multifunctional feature, being able to inhibit targets related to neurodegeneration, such as monoamine oxidase A, sirtuins 1 and 2, and butyrylcholinesterase enzymes. Aiming at better characterizing the multifunctional profile of this compound, its effect on cathecol-O-methyltransferase activity was investigated. The cathecol-O-methyltransferase activity was evaluated in vitro by a fluorescence-based method, using S-(5′-adenosyl)-l-methionine as methyl donor and aesculetin as substrate. The assay optimization was performed varying the concentrations of methyl donor (S-(5′-adenosyl)-l-methionine) and enzyme. It was observed that the highest concentrations of both factors (2.25 U of the enzyme and 100 µM of S-(5′-adenosyl)-l-methionine) afforded the more reproducible results. The in vitro assay demonstrated that Z-vallesiachotamine was able to inhibit the cathecol-O-methyltransferase activity with an IC50 close to 200 µM. Molecular docking studies indicated that Z-vallesiachotamine can bind the catechol pocket of catechol-O-methyltransferase enzyme. The present work demonstrated for the first time the inhibitory properties of Z-vallesiachotamine on cathecol-O-methyltransferase enzyme, affording additional evidence regarding its multifunctional effects in targets related to neurodegenerative diseases.

Beyond organoleptic characteristics: the pharmacological potential of flavonoids and their role in leukocyte migration and in L-selectin and ß2-integrin expression during inflammation.

Flavonoids are compounds responsible for several organoleptic characteristics of plant-derived foods. They are also bioactive compounds with antiinflammatory role. Different mechanisms for this activity have been reported, but their effects on cell migration are not fully understood. In the present study, the role of flavonoids on leukocyte migration in vivo was investigated, using the carrageenan-induced pleurisy model and intravital microscopy in rats. It was found that quercetin (1), rutin (2), flavone (5), apigenin (6) and flavonol (7) reduced cell migration to the pleural cavity and inhibited rolling, adhesion and transmigration. Additionally, flow cytometry assays showed that the in vitro treatment with all compounds (15-60 µM) did not cause cell death and 1 inhibited the cleavage of L-selectin and the ß2-integrin expression, whereas 2 and 7 only inhibited the ß2-integrin expression. Together, data herein presented clearly show the ability of flavonoids to inhibit in vivo neutrophil influx into inflamed tissue, by acting in different mechanisms of neutrophil migration.

Role of gastric mucus secretion, oxinitrergic system and sulfhydryl groups on the gastroprotection elicited by Polygala cyparissias (Polygalaceae) in mice.

OBJECTIVES: This study has aimed to assess the mechanisms of action for the gastroprotective effect of the acetone extract (PCAE) and methanol fraction (PCMF) of Polygala cyparissias, as well as to evaluate the activity of 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (1), 1,7-dihydroxy-2,3-dimethoxyxanthone (2) and astragalin (3). METHODS: Gastric secretion and mucus content were determined by pylorus ligation in mice. Nitric oxide (NO) and sulfhydryl group participation were observed by the pretreatment of mice with L-NAME or NEM. Acute ulcer was induced by ethanol/HCl and chronic ulcer by acetic acid. Anti-Helicobacter pylori activity was evaluated by the agar solid dilution assay. KEY FINDINGS: Neither PCAE nor PCMF had the ability to reduce H(+) concentration. However, both of them enhanced mucus secretion. PCAE demonstrated its gastroprotection in a NO-dependent manner, while PCMF exerted the activity depending on the sulfhydryl group. In chronic ulcer, the curative ratios for the PCAE and PCMF were 67.5 and 58.4%, respectively. No effect over H. pylori was detected. Compounds 1, 2 and 3 were able to reduce lesions in the order of 79.6, 73.8 and 67.6%, respectively. CONCLUSIONS: The data suggested that PCAE and PCMF displayed antiulcer activity due to different mechanisms and with the participation of phenolic compounds obtained from the plant.

Anti-hyperalgesic activity of corilagin, a tannin isolated from Phyllanthus niruri L. (Euphorbiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Corilagin (ß-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-D-glucose) is a tannin isolated from Phyllanthus niruri (Euphorbiaceae). This plant is well known for their therapeutic purposes to treat several diseases associated with dolorous process and are used in several ethno-medicines in tropical and subtropical countries. AIM OF THE STUDY: This study was designed to evaluate the anti-hyperalgesic activity of corilagin using chemically and thermally based nociception models in mice. MATERIALS AND METHODS: Corilagin was isolated from Phyllanthus niruri (Euphorbiaceae) by extraction and chromatographic procedures and the anti-hyperalgesic activity was evaluated by using writhing, formalin, capsaicin, glutamate and hot plate tests in mice. RESULTS: Corilagin presented activity in acetic acid model with the ID50 calculated value of 6.46 (3.09-13.51) being about 20.6 fold more potent than acetylsalicylic acid. It also exhibited activity against the first phase of formalin test with ID50 value of 18.38 (15.15-22.59) µmol/kg. In the capsaicin and glutamate models, corilagin demonstrated significant activity at the 3 mg/kg. CONCLUSION: The experimental data demonstrated that corilagin exhibits anti-hyperalgesic activity that may be due to interaction with the glutamatergic system.

Gastroprotective activity of methanol extract and marrubiin obtained from leaves of Marrubium vulgare L. (Lamiaceae).

OBJECTIVES: The purpose of this study was to assess the gastroprotective properties of the methanol extract and the diterpene marrubiin obtained from the leaves of M. vulgare. METHODS: Assays were performed using different protocols in mice. Studies focusing on mechanisms of gastroprotection were also undertaken. KEY FINDINGS: In the model of ethanol-induced ulcers, we observed a significant reduction in all the parameters analysed; the curative ratios obtained were 49.31±0.57, 74.31±0.91 and 79.86±0.59 for the groups treated with 50 and 100mg/kg of extract of M. vulgare and omeprazole (30mg/kg), respectively. For indomethacin-induced ulcers, the percentages of ulcer inhibition were 50.32±5.60, 66.24±4.30, 82.17±04.09 and 67.52±4.38, for the groups treated with 25, 50 and 100mg/kg M. vulgare and positive control (cimetidine), respectively. In both models, the marrubiin (25mg/kg) produced a significant reduction in all the parameters when compared with the control group (P<0.01). There was also a significant increase in pH and mucus production in the groups treated with M. vulgare extract and marubiin. The results also demonstrated that the gastroprotection induced by the extract and marubiin is related to the activity of nitric oxide and endogenous sulfhydryls, which are important gastroprotective factors. CONCLUSIONS: The results of this study show that the extract of M. vulgare and marrubiin displays antiulcer activity and that this effect can be partly attributed to the isolated diterpene.