In vivo/in vitro studies of the effects of the type II arabinogalactan isolated from Maytenus ilicifolia Mart. ex Reissek on the gastrointestinal tract of rats.

Type II arabinogalactan (AG) is a polysaccharide found in Maytenus ilicifolia (Celastraceae), a plant reputed as gastroprotective. Oral and intraperitoneal administration of the AG protected rats from gastric ulcers induced by ethanol. No alteration of mechanisms related to acid gastric secretion and gastrointestinal motility were observed. In vitro, the AG showed a potent scavenging activity against the radical of DPPH (2,2-diphenyl-1-picrylhydrazyl) with an IC50 value of 9.3 microM. However, the mechanism of the gastroprotective action remains to be identified.

Gastroprotective activity of the chloroform extract of the roots from Arctium lappa L.

Arctium lappa L. is used in folk medicine as a diuretic, depurative and digestive stimulant and in dermatological conditions. The objective of this study was to evaluate the effect and the possible mechanisms involved in the gastroprotective effects of a chloroform extract (CE) of the roots from A. lappa and its fractions. Oral pretreatment with CE (10, 30 and 100 mg kg(-1)) significantly reduced gastric lesions induced by ethanol by 61%, 70% and 76%, respectively. Oral administration of CE (100 mg kg(-1) per day for 7 days) reduced the chronic gastric ulceration induced by acetic acid by 52%. Intraduodenal CE (100, 300 and 600 mg kg(-1)) reduced the total acidity of gastric secretion by 22%, 22% and 33%, respectively, while i.p. administration (10, 30 and 100 mg kg(-1)) inhibited total acidity by 50%, 60% and 67%, respectively. In-vitro, CE inhibited H+, K+ -ATPase activity with an EC50 of 53 microgmL(-1) and fraction A (30 and 100 microgmL(-1)) reduced this by 48% and 89%, respectively. CE had no effect on gastrointestinal motility. CE (250 microgmL(-1)) and fraction B (100 and 250 microgmL(-1)) had free-radical scavenging ability, inhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical activity by 50%, 20% and 55%, respectively. Collectively, the results show that the CE protects animals from gastric lesions by reducing gastric acid secretion via inhibition of gastric H+, K+ -ATPase.

Antiulcerogenic activity of bark extract of Tabebuia avellanedae, Lorentz ex Griseb.

Tabebuia avellanedae is commonly used for the treatment of peptic ulcers. We carried out this study with the ethanolic extract of bark from Tabebuia avellanedae (EET) (30-1000 mg/kg) to determine its gastroprotective activity and to clarify the pathways involved in this effect. Acute gastric ulceration in rats was produced by oral administration of ethanol and ibuprofen. After ethanol administration, the gastric wall mucus was examined. Chronic gastric ulceration was produced by injection of acetic acid in rat gastric subserosa. Anti-secretory studies were undertaken using Shay rat pylorus ligature technique and measurement of enzymatic activity of H+, K+-ATPase in vitro. Administration of EET p.o. or i.p. significantly inhibited gastric mucosa damage induced by ethanol and ibuprofen. The anti-ulcer effect was further confirmed by enhanced gastric mucus production. In pylorus ligature rats, EET significantly reduced the basal gastric acid secretion and total acidity; moreover, it inhibited the increase in total acidity induced by histamine. In addition, EET reduced the activity of H+, K+, ATPase. The results obtained in the present pharmacological assay indicate that this plant has a protective action against gastric lesions, involving the maintenance of protective factors, such as mucus and prostaglandin, besides the reduction of gastric total acidity.

Trigeminal sensory neuropathy and facial contact dermatitis due to Anthurium sp.

BACKGROUND: Trigeminal sensory neuropathy (TSN) describes a heterogeneous group of disorders manifesting as facial numbness. OBJECTIVE: We report the case of a patient who had TSN associated with contact dermatitis due to Anthurium sp. METHOD/RESULTS: A 21-year-old female patient developed left hemifacial contact dermatitis after exposure to the anthurium plant. The patient had paresthesias and pain in the V2 and V3 divisions of the left trigeminal nerve. Eight days after its onset the dermatitis resolved, but numbness developed in the V2 and V3 divisions of the left trigeminal nerve. Cranial CT scan and MRI, as well as CSF and extensive work-up exams, were normal. After one month the symptoms disappeared completely. CONCLUSION: Anthurium sp, an indoor ornamental plant that contains calcium oxalate crystals, and can causes contact dermatitis. To our knowledge, this is the first report associating TSN with contact dermatitis due to Anthurium sp.

µ- and κ-Opioid receptor activation in the dorsal periaqueductal grey matter differentially modulates panic-like behaviours induced by electrical and chemical stimulation of the inferior colliculus.

It has been shown that electrical stimulation of the mesencephalic tectum (MT) provokes defensive responses in both humans and rodents. During an emotional aversive state, some convergent studies have also demonstrated the existence of a complex interaction between endogenous opioid peptide- and γ-aminobutyric acid (GABA)-containing connections during fear-induced responses. It has been proposed that opioid neurons exert an influence on GABAergic interneurons, which, in turn, exert inhibitory tonic control on the mesencephalic excitatory pathways. Thus, opioid peptides can disinhibit neurons that are tonically inhibited by GABA, therefore, modulating the expression of defensive behavioural reactions. In the present work, we used both electric stimulation and microinjections of the GABAA receptor antagonist bicuculline in the inferior colliculus (IC) of Wistar rats in combination with microinjections of µ- and κ-opioid receptor selective agonists into the dorsal columns of periaqueductal grey matter (dPAG) to evaluate the effects on panic-like behaviours elicited by IC electrical and chemical stimulation. The present results showed that neurochemical lesions of the dPAG caused a significant impairment in the organisation of defensive responses by IC neurons, reducing the duration [t(14)=3.0; p<0.01] of defensive immobility and the duration [t(14)=2.8; p<0.05] and frequency [t(14)=2.5; p<0.05] of escape. Paradoxically, treating the dPAG with the µ-opioid receptor agonist met-enkephalin caused a significant reduction of panic-like behaviours induced by both electrical and chemical stimulation of the IC, increasing the escape behaviour threshold [F(2,23)=13.5; p<0.001] and decreasing the frequency [F(3,36)=11.7; p<0.001] and duration [F(3,36)=11.6; p<0.001] of escape and the duration of defensive immobility [F(3,36)=16.1; p<0.05]. In contrast, treating the dPAG with the κ-opioid receptor agonist salvinorin-A increased the frequency [F(3,36)=12.4; p<0.01] and duration [F(3,34)=16.1; p<0.01] of defensive immobility induced by GABAA receptor blockade in the IC. The present results suggest the existence of a complex neuronal network in the MT in which endogenous opioid peptides and GABAergic pathways interact in the control of fear-related behavioural responses.

Neuroanatomical and neuropharmacological approaches to postictal antinociception-related prosencephalic neurons: the role of muscarinic and nicotinic cholinergic receptors.

Several studies have suggested the involvement of the hippocampus in the elaboration of epilepsy. There is evidence that suggests the hippocampus plays an important role in the affective and motivational components of nociceptive perception. However, the exact nature of this involvement remains unclear. Therefore, the aim of this study was to determine the role of muscarinic and nicotinic cholinergic receptors in the dorsal hippocampus (dH) in the organization of postictal analgesia. In a neuroanatomical study, afferent connections were found from the somatosensory cortex, the medial septal area, the lateral septal area, the diagonal band of Broca, and the dentate gyrus to the dH; all these areas have been suggested to modulate convulsive activity. Outputs to the dH were also identified from the linear raphe nucleus, the median raphe nucleus (MdRN), the dorsal raphe nucleus, and the locus coeruleus. All these structures comprise the endogenous pain modulatory system and may be involved either in postictal pronociception or antinociception that is commonly reported by epileptic patients. dH-pretreatment with cobalt chloride (1.0 mmol/L CoCl2/0.2 µL) to transiently inhibit local synapses decreased postictal analgesia 10 min after the end of seizures. Pretreatment of the dH with either atropine or mecamylamine (1.0 µg/0.2 µL) attenuated the postictal antinociception 30 min after seizures, while the higher dose (5.0 µg/0.2 µL) decreased postictal analgesia immediately after the end of seizures. These findings suggest that the dH exerts a critical role in the organization of postictal analgesia and that muscarinic and nicotinic cholinergic receptor-mediated mechanisms in the dH are involved in the elaboration of antinociceptive processes induced by generalized tonic-clonic seizures.

The role of 5-HT1A receptors in the anti-aversive effects of cannabidiol on panic attack-like behaviors evoked in the presence of the wild snake Epicrates cenchria crassus (Reptilia, Boidae).

The potential anxiolytic and antipanic properties of cannabidiol have been shown; however, its mechanism of action seems to recruit other receptors than those involved in the endocannabinoid-mediated system. It was recently shown that the model of panic-like behaviors elicited by the encounters between mice and snakes is a good tool to investigate innate fear-related responses, and cannabidiol causes a panicolytic-like effect in this model. The aim of the present study was to investigate the 5-hydroxytryptamine (5-HT) co-participation in the panicolytic-like effects of cannabidiol on the innate fear-related behaviors evoked by a prey versus predator interaction-based paradigm. Male Swiss mice were treated with intraperitoneal (i.p.) administrations of cannabidiol (3 mg/kg, i.p.) and its vehicle and the effects of the peripheral pre-treatment with increasing doses of the 5-HT1A receptor antagonist WAY-100635 (0.1, 0.3 and 0.9 mg/kg, i.p.) on instinctive fear-induced responses evoked by the presence of a wild snake were evaluated. The present results showed that the panicolytic-like effects of cannabidiol were blocked by the pre-treatment with WAY-100635 at different doses. These findings demonstrate that cannabidiol modulates the defensive behaviors evoked by the presence of threatening stimuli, and the effects of cannabidiol are at least partially dependent on the recruitment of 5-HT1A receptors.

Anti-aversive effects of cannabidiol on innate fear-induced behaviors evoked by an ethological model of panic attacks based on a prey vs the wild snake Epicrates cenchria crassus confrontation paradigm.

Several pharmacological targets have been proposed as modulators of panic-like reactions. However, interest should be given to other potential therapeutic neurochemical agents. Recent attention has been given to the potential anxiolytic properties of cannabidiol, because of its complex actions on the endocannabinoid system together with its effects on other neurotransmitter systems. The aim of this study was to investigate the effects of cannabidiol on innate fear-related behaviors evoked by a prey vs predator paradigm. Male Swiss mice were submitted to habituation in an arena containing a burrow and subsequently pre-treated with intraperitoneal administrations of vehicle or cannabidiol. A constrictor snake was placed inside the arena, and defensive and non-defensive behaviors were recorded. Cannabidiol caused a clear anti-aversive effect, decreasing explosive escape and defensive immobility behaviors outside and inside the burrow. These results show that cannabidiol modulates defensive behaviors evoked by the presence of threatening stimuli, even in a potentially safe environment following a fear response, suggesting a panicolytic effect.

Inhibition of gastric H+, K(+)-ATPase activity by compounds from medicinal plants.

H+, K(+)-ATPase enzyme is a therapeutic target for the treatment of gastric disturbances. Several medicinal plants and isolated compounds inhibit the acid gastric secretion through interaction with the proton pump. In order to add new properties to some natural constituents, five compounds, a benzylated derivative of vincoside, a diterpene (abietic acid) and three alkaloids (cephaeline, vinblastine and vindoline), were tested for their activities on gastric H+, K(+)-ATPase isolated from rabbit stomach. All the compounds inhibited H+, K(+)-ATPase activity with varied potency. The IC50 value for benzylvincoside was 121 (50-293) microM, and for abietic acid 177 (148-211) microM. The alkaloids cephaeline, vinblastine and vindoline inhibited the H+, K(+)-ATPase activity with IC50 values of 194, 761 and 846 microM, respectively. The results suggest that benzylvincoside, abietic acid and cephaeline can be important sources for the development of anti-secretor agents.

Involvement of glutamate and cytokine pathways on antinociceptive effect of Pfaffia glomerata in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Pfaffia glomerata (Spreng) Pedersen (Amaranthaceae) is a medicinal plant known in Brazil as "Paratudo" and "Brazilian ginseng" and is commonly used as tonic, antidiabetic and to treat gastric disorders. AIM OF THE STUDY: This study evaluates the possible mechanism by which hydroalcoholic extract (HE) of Pfaffia glomerata exerts its antinociceptive effect. MATERIALS AND METHODS: The HE was evaluated in acetic acid and glutamate models of pain or by biting behavior following intrathecal (i.t.) administration of agonists of excitatory aminoacids (EAA) receptors glutamate and pro-inflammatory cytokines, IL-1beta and TNF-alpha in mice. RESULTS: Oral administration of HE produced dose-dependent inhibition of acetic acid-induced visceral pain and glutamate-induced pain, with ID(50) of 64.6 (47.7-87.5)mg/kg and ID(50) of 370.8 (253.4-542.7)mg/kg, respectively. The HE (300 mg/kg, p.o.) antinociception, in the acetic acid test, was not affected by i.p. treatment of animals with naloxone. In addition, HE (300 mg/kg, p.o.) inhibited the pain-related behaviors induced by i.t. injection of trans-ACPD and TNF-alpha, but not by NMDA, AMPA, kainate or IL-1beta. CONCLUSIONS: Our results suggest that inhibition of glutamatergic metabotropic receptors and TNF-alpha may account for the antinociceptive action reported for the HE in models of chemical pain used in this study.

Antinociceptive properties of the hydroalcoholic extract, fractions and compounds obtained from the aerial parts of Baccharis illinita DC in mice.

The present study assessed the possible antinociceptive action of the hydroalcoholic extract, fractions and pure compounds obtained from the aerial parts of Baccharis illinita DC (Asteraceae) in behavioural models of chemical nociception in mice. The hydroalcoholic extract and fractions (hexane and aqueous but not EtOAc fraction) obtained from B. illinita (30-1000 mg/kg orally) produced a dose-related inhibition of the acetic acid-induced nociceptive response. However, the hexane fraction was more potent than the hydroalcoholic extract and the aqueous fraction. The hexane fraction derivatives baurenol, alpha-spinasterol and oleanolic acid (0.00001-10 mg/kg intraperitoneally) also caused potent inhibition of acetic acid-induced pain. The hexane fraction (300-1000 mg/kg orally) produced inhibition of both phases of formalin-induced pain. Moreover, the hexane fraction (30-600 mg/kg orally) also caused a dose-dependent inhibition of glutamate-induced pain. Nevertheless, the hexane fraction only at the dose of 300 mg/kg orally, produced partial inhibition of the paw oedema caused by carrageenan. Furthermore, the hexane fraction (300 mg/kg orally) caused inhibition of the nociceptive response induced by intrathecal injection of N-methyl-d-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, tumour necrosis factor-alpha and interleukin-1beta. In contrast, the hexane fraction did not affect the biting response induced by the metabotropic or ionotropic glutamatergic receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid and kainate, respectively. In addition, the antinociception caused by the hexane fraction (300 mg/kg orally) in the acetic acid test was not affected by intraperitoneal treatment of mice with naloxone (a non-selective opioid receptor antagonist). The precise mechanism responsible for the antinociceptive effect of the hexane fraction remains unclear, but appears to be partly associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, baurenol, alpha-spinasterol and oleanolic acid have an important role in the antinociceptive effects of the hexane fraction. Moreover, the antinociceptive action demonstrated in the present study supports the ethnomedical uses of this plant.

Gastroprotective constituents of Salvia officinalis L.

The gastrointestinal activity of hydroalcoholic extract (HE) of Salvia officinalis was evaluated in a model of ethanol-induced gastric lesion. HE showed excellent activity, with ID(50) 84.0 (54.8-128.9) mg/kg. The acetic acid-induced ulcer and the total acidity of the gastric secretion were also reduced by HE, and, in vitro experiments, the H(+),K(+)-ATPase activity was inhibited. Carnosol was identified as a possible active constituent for the gastroprotective effect of HE.

Muscarinic-dependent inhibition of gastric emptying and intestinal motility by fractions of Maytenus ilicifolia Mart ex. Reissek.

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex. Reissek (Celastraceae) is widely used in Brazilian folk medicine to treat gastric disturbances. AIM OF THE STUDY: This work intended to characterize the effects of Maytenus ilicifolia on gastrointestinal motility. MATERIALS AND METHODS: Gastric emptying and intestinal transit were measured in the same animal. Mice received a semisolid marked with phenol red, half an hour after treatment with extracts. The amount of marker in the stomach and the distance reached in the intestine after 15 min were measured as index of gastrointestinal emptying and intestinal transit, respectively. RESULTS: Intraperitoneal administration of a flavonoid-rich extract potently reduced the gastric emptying (ED(50)=89 mg/kg) and the intestinal transit (ED(50)=31 mg/kg) of mice. Bio-guided purification of the flavonoid-rich extract by chemical partition with solvents of decreasing polarity yielded fraction insF with about 12-14 times higher activity than the initial flavonoid extract in both the gastric emptying and the intestinal transit. The inhibitory effects of the insF (9.7 mg/kg, i.p.) on gastric emptying and intestinal transit were reversed by co-administration of bethanechol (10 mg/kg, s.c.) but not by co-administration of metoclopramide (30 mg/kg, p.o.) indicating muscarinic but not dopaminergic interaction of the compounds of Maytenus. Chemical investigation of the insF fraction by HPLC-MS allowed the identification of 4 free flavonoids (catechin, epicatechin, quercetin and kaempferol), 29 flavonol glycosides and 8 tannins. The flavonol glycosides ranged from 1 to 4 monosaccharide units, having mainly quercetin and kaempferol as aglycone moieties, and the tannins were composed by catechin/epicatechin and/or afzelechin/epiafzelechin. CONCLUSIONS: Overall, the results indicate that the components of Maytenus ilicifolia have a potential use in the treatment of gastrointestinal motility disturbances such as diarrhea.

Trigeminal sensory neuropathy and facial contact dermatitis due to Anthurium sp

BACKGROUND: Trigeminal sensory neuropathy (TSN) describes a heterogeneous group of disorders manifesting as facial numbness. OBJECTIVE: We report the case of a patient who had TSN associated with contact dermatitis due to Anthurium sp. METHOD/RESULTS: A 21-year-old female patient developed left hemifacial contact dermatitis after exposure to the anthurium plant. The patient had paresthesias and pain in the V2 and V3 divisions of the left trigeminal nerve. Eight days after its onset the dermatitis resolved, but numbness developed in the V2 and V3 divisions of the left trigeminal nerve. Cranial CT scan and MRI, as well as CSF and extensive work-up exams, were normal. After one month the symptoms disappeared completely. CONCLUSION: Anthurium sp, an indoor ornamental plant that contains calcium oxalate crystals, and can causes contact dermatitis. To our knowledge, this is the first report associating TSN with contact dermatitis due to Anthurium sp.

INTRODUÇÃO: A neuropatia trigeminal sensitiva (NTS) representa um grupo heterogêneo de doenças, cuja manifestação clínica é a presença de dormência na região facial. OBJETIVO: Relatamos o caso de paciente que apresenta NTS associada com dermatite de contato (DC) devido à planta Anthurium sp. MÉTODO/RESULTADOS: Uma paciente com 21 anos desenvolveu DC na região hemi-facial esquerda, após exposição à planta Anthurium sp. Após a resolução do quadro de dermatite, a referida paciente apresentou dormência e parestesias no território do segundo e terceiro ramos do nervo trigêmeo esquerdo. Um mês após o início do quadro houve resolução completa dos sintomas. CONCLUSÃO: O Anthurium é uma planta ornamental que contém cristas de oxalato de cálcio, que podem causar DC. Para o nosso conhecimento este é o primeiro relato associando NTS e dermatite de contato devido à exposição ao Anthurium sp.