Evaluation of the use of chamomile in isolation and in association with laser photobiomodulation in the healing of rats oral mucosa.

Laser photobiomodulation (LPBM) has been shown to be one of the possible modulating agents of inflammation. Similarly, medicinal plants, such as chamomile (Matricaria recutita) are also used with the same purpose. To evaluate tissue repair in the dorsum of the tongue of rats under topical use of chamomile alone and in association with LPBM. Seventy-five male Wistar rats received a standardized wound on the dorsum of the tongue and were allocated into experimental groups: Control (G1), Chamomile Fluid extract (G2), Chamomile Infusion (G3), Laser (G4), Chamomile Infusion + Laser (G5). Euthanasia was done on days 3, 7, and 14 after surgery. Ulcers were evaluated and measured with a caliper. Sections stained with hematoxylin and eosin and Picrosirius Red allowed evaluation of edema, inflammatory infiltrate, cellularity, and re-epithelialization and characterization of total collagen. Histomorphometric analysis of the percentage of total collagen, the distance from the basal layer to the epithelial surface, and the thickness of the stratum corneum were performed. The G2 and G4 groups modulated the exudative and proliferative phases of inflammation, both clinically and histologically. The G3 and G5 groups did not show significant differences in relation to the G1 group in most of the evaluated parameters. Chamomile fluid extract and LPBM alone showed better clinical and histological responses for tissue repair than the association between these therapeutic modalities. There were differences in the parameters of clinical, histological, and histomorphometric patterns between the experimental groups of the present investigation. The LPBM proved to be superior in the performed analysis.

Ayahuasca and its major component harmine promote antinociceptive effects in mouse models of acute and chronic pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayahuasca (AYA) is a psychedelic brew used in religious ceremonies. It is broadly used as a sacred medicine for treating several ailments, including pain of various origins. AIM OF THE STUDY: To investigate the antinociceptive effects of AYA and its mechanisms in preclinical models of acute and chronic pain in mice, in particular during experimental neuropathy. MATERIALS AND METHODS: The antinociceptive effects of AYA administered orally were assessed in the following models of pain: formalin test, Complete Freund's Adjuvant (CFA)-induced inflammation, tail flick test, and partial sciatic nerve ligation model of neuropathic pain. Antagonism assays and Fos immunohistochemistry in the brain were performed. AYA-induced toxicity was investigated. AYA was chemically characterized. The antinociceptive effect of harmine, the major component present in AYA, was investigated. RESULTS: AYA (24-3000 µL/kg) dose-dependently reduced formalin-induced pain-like behaviors and CFA-induced mechanical allodynia but did not affect CFA-induced paw edema or tail flick latency. During experimental neuropathy, single treatments with AYA (24-3000 µL/kg) reduced mechanical allodynia; daily treatments once or twice a day for 14 days promoted consistent and sustained antinociception. The antinociceptive effect of AYA (600 µL/kg) was reverted by bicuculline (1 mg/kg) and methysergide (5 mg/kg), but not by naloxone (5 mg/kg), phaclofen (2 mg/kg), and rimonabant (10 mg/kg), suggesting the roles of GABAA and serotonergic receptors. AYA increased Fos expression in the ventrolateral periaqueductal gray and nucleus raphe magnus after 1 h, but not after 6 h or 14 days of daily treatments. AYA (600 µL/kg) twice a day for 14 days did not alter mice's motor function, spontaneous locomotion, body weight, food and water intake, hematological, biochemical, and histopathological parameters. Harmine (3.5 mg/kg) promoted consistent antinociception during experimental neuropathy. CONCLUSIONS: AYA promotes consistent antinociceptive effects in different mouse models of pain without inducing detectable toxic effects. Harmine is at least partially accountable for the antinociceptive properties of AYA.

Evaluation of the effect of Matricaria recutita monotherapy or in combination with photodynamic therapy on tissue repair in the dorsum of the tongue of rats.

OBJECTIVE: The search for treatments that accelerate the healing of lesions is of constant interest. Matricaria recutita (chamomile) is a plant with antimicrobial, anti-inflammatory, and healing properties, and antimicrobial Photodynamic Therapy (aPDT) eradicates microorganisms, which favors tissue repair. This study aimed to evaluate the effect of the topical use of chamomile with or without aPDT on tissue repair in rats' tongues. METHODOLOGY: A total of 75 male Wistar rats underwent standardized ulceration on the dorsum of the tongue using a punch of 5 mm diameter and were randomly allocated into the following groups: control (G1), chamomile fluid extract (G2), chamomile infusion (G3), aPDT (G4), and chamomile infusion + aPDT (G5). On the 3rd, 7th, and 14th days postoperatively, euthanasia was performed, and the ulcers were measured using calipers. The presence of edema, inflammatory infiltrate, cellularity, re-epithelialization, and characterization of total collagen were evaluated using sections stained with Hematoxylin and Eosin and Red Sirius. Histomorphometry analyses of the percentage of total collagen, the distance from the basal layer to the epithelial surface, and the thickness of the stratum corneum were performed. Descriptive (absolute/relative frequencies and modes) and exploratory analyses were performed. The associations between the groups and the presence of ulcers were analyzed with Fisher's exact test. All analyses were performed using the R program and statistical significance was set at p=0.05. RESULTS: The G2 positively modulated the exudative and proliferative phases of repair, both clinically (p<0.0001) and histologically, whether in descriptive or inferential analyses (p<0.05). The G3 showed a significant difference in clinical parameters compared with G1 (p<0.0001). The G4 and G5 did not positively modulate tissue repair. CONCLUSION: The chamomile fluid extract showed better outcomes for tissue repair in the rat tongue.

JM-20 protects against 6-hydroxydopamine-induced neurotoxicity in models of Parkinson's disease: Mitochondrial protection and antioxidant properties.

We have previously shown that JM-20, a new chemical entity consisting of 1,5-benzodiazepine fused to a dihydropyridine moiety, protects against rotenone-induced neurotoxicity in an experimental model of Parkinson's disease (PD). The aim of this study was to investigate the effect of a novel hybrid molecule, named JM-20, in in vitro and in vivo models of PD induced by 6-hydroxydopamine (6-OHDA). PC-12 cells were exposed to 6-OHDA and treated with JM-20. Protection against mitochondrial damage induced by 6-OHDA was also investigated using isolated rat brain mitochondria. We found that JM-20 protected PC-12 cells against cytotoxicity induced by 6-OHDA and inhibited hydrogen peroxide generation, mitochondrial swelling and membrane potential dissipation. For in vivo experiments, adult male Wistar rats were lesioned in the substantia nigra pars compacta (SNpc) by 6-OHDA administration. JM-20 was orally administered (10, 20 or 40 mg/kg), intragastric via gavage, 24 h after surgery and daily for seven days. Treatment with JM-20 significantly reduced the percentage of motor asymmetry and increased vertical exploration. It improved the redox state of the SNpc and the striatal tissue of these animals. Also, JM-20 reduced glial fibrillary acidic protein overexpression and increased tyrosine hydroxylase-positive cell number, both in SNpc. Altogether, these results demonstrate that JM-20 is a potential neuroprotective agent against 6-OHDA-induced damage in both in vitro and in vivo models. The mechanism underlying JM-20 neuroprotection against 6-OHDA appears to be associated with the control of oxidative injury and mitochondrial impairment.

Inhibition of salt appetite in sodium-depleted rats by carvacrol: Involvement of noradrenergic and serotonergic pathways.

Carvacrol, a monoterpene phenol present in the essential oil of oregano, possesses several biological properties, such as antioxidant, anti-inflammatory, anxiolytic, anticonvulsive and antinociceptive. In vitro studies have shown that carvacrol inhibits serotonin, noradrenaline and dopamine transporters and the enzymes monoamine oxidase-A and B. Different brain functions are controlled by monoamines, including cardiovascular control, thirst and sodium appetite. In the present study we investigated the effects of intracerebroventricular (i.c.v.) injection of carvacrol on sodium appetite, and the participation of brain serotonergic and noradrenergic pathways on carvacrol effects. Neuronal activation in homeostasis-related brain areas induced by i.c.v. injection of carvacrol was also evaluated. Carvacrol dose-dependently inhibited hypertonic saline intake (1.5%) in sodium-depleted rats, and this antinatriorexigenic effect was reduced by brain serotonergic depletion and by alpha-adrenergic blockade. Furthermore, i.c.v. injections of carvacrol significantly increased the neuronal activation in brain areas involved in the control of salt appetite, such as MnPO, OVLT, PVN, SON, CeA and MeA. Taken together, our data show that carvacrol presents antinatriorexigenic activity through serotonin and noradrenaline pathways within brain circuits involved in the modulation of the body fluid homeostasis.

Evaluation of the effect of Matricaria recutita monotherapy or in combination with photodynamic therapy on tissue repair in the dorsum of the tongue of rats*

Abstract The search for treatments that accelerate the healing of lesions is of constant interest. Matricaria recutita (chamomile) is a plant with antimicrobial, anti-inflammatory, and healing properties, and antimicrobial Photodynamic Therapy (aPDT) eradicates microorganisms, which favors tissue repair. Objective This study aimed to evaluate the effect of the topical use of chamomile with or without aPDT on tissue repair in rats' tongues. Methodology A total of 75 male Wistar rats underwent standardized ulceration on the dorsum of the tongue using a punch of 5 mm diameter and were randomly allocated into the following groups: control (G1), chamomile fluid extract (G2), chamomile infusion (G3), aPDT (G4), and chamomile infusion + aPDT (G5). On the 3rd, 7th, and 14th days postoperatively, euthanasia was performed, and the ulcers were measured using calipers. The presence of edema, inflammatory infiltrate, cellularity, re-epithelialization, and characterization of total collagen were evaluated using sections stained with Hematoxylin and Eosin and Red Sirius. Histomorphometry analyses of the percentage of total collagen, the distance from the basal layer to the epithelial surface, and the thickness of the stratum corneum were performed. Descriptive (absolute/relative frequencies and modes) and exploratory analyses were performed. The associations between the groups and the presence of ulcers were analyzed with Fisher's exact test. All analyses were performed using the R program and statistical significance was set at p=0.05. Results The G2 positively modulated the exudative and proliferative phases of repair, both clinically (p<0.0001) and histologically, whether in descriptive or inferential analyses (p<0.05). The G3 showed a significant difference in clinical parameters compared with G1 (p<0.0001). The G4 and G5 did not positively modulate tissue repair. Conclusion The chamomile fluid extract showed better outcomes for tissue repair in the rat tongue.

Impulsivity is relevant for trauma exposure and PTSD symptoms in a non-clinical population.

Impulsivity is a relevant construct for explaining both normal individual differences in personality and more extreme personality disorder, and is often investigated within clinical populations. This study aims to explore the college students' impulsivity patterns and to investigate the association across levels of impulsivity with trauma exposure and PTSD development in a non-clinical population. A one-phase census survey of seven college institutions assessed 2213 students in three metropolitan regions of Northeastern Brazil. All subjects anonymously completed a self-applied protocol consisting of: a socio-demographic questionnaire, Trauma History Questionnaire (THQ), PTSD Checklist (PCL-C), and Barratt Impulsiveness Scale (BIS-11). The median for frequency of trauma exposure was 4 events for people with low and normal impulsivity, and 6 for highly impulsive ones. Individuals with higher impulsivity presented earlier exposition than non-impulsive ones, and worst outcome: 12.4% with PTSD, against 8.4% and 2.3% (normal and low impulsivity). Of the three factors of impulsivity, the Attentional factor conferred the strongest association with PTSD development. Results suggest that impulsivity is also a relevant trait in a non-clinical population and is associated with trauma exposure and PTSD. Strategies to promote mental health in adolescents may be pertinent, especially with the aim of managing impulsivity.

Blockade of 5-Ht3 receptors in the septal area increases Fos expression in selected brain areas.

Serotonin is widely distributed throughout the brain and is involved in a multiplicity of visceral, cognitive and behavioral responses. It has been previously shown that injections of different doses of ondansetron, a 5-HT3 receptor antagonist, into the medial septum/vertical limb of the diagonal band complex (MS/vDB) induce a hypertensive response in rats. On the other hand, administration of m-CPBG, a 5-HT3 agonist, into the MS/vDB inhibits the increase of blood pressure during restraint stress. However, it is unclear which neuronal circuitry is involved in these responses. The present study investigated Fos immunoreactive nuclei (Fos-IR) in different brain areas following the blockade of 5-HT3 receptors located in the MS/vDB in sham and in sinoaortic denervated (SAD) rats. Ondansetron injection into the MS/vDB increases Fos-IR in different brain areas including the limbic system (central amygdala and ventral part of the bed nucleus of the stria terminalis), hypothalamus (medial parvocellular parts of the paraventricular nucleus, anterodorsal preoptic area, dorsomedial hypothalamic nucleus), mesencephalon (ventrolateral periaqueductal gray region) and rhombencephalon (lateral parabrachial nucleus) in sham rats. Barodenervation results in higher Fos expression at the parvocellular and magnocellular part of the paraventricular nucleus, the lateral parabrachial nucleus, the central nucleus of amygdala, the locus coeruleus, the medial part of the nucleus of the solitary tract, the rostral ventrolateral medulla and the caudal ventrolateral medulla following 5-HT3receptor blockade in the MS/vDB. Based on the present results and previous data showing a hypertensive response to ondansetron injected into the MS/vDB, it is reasonable to suggest that 5-HT3receptors in the MS/vDB exert an inhibitory drive that may oscillate as a functional regulatory part of the complex central neuronal network participating in the control of blood pressure.

Estudo do tratamento agudo e crônico com os antidepressivos nortriptilina e desipramina na expressão cerebral de C-Fos e nas respostas comportamentais no nado forçado em ratos

Muitos estudos têm sido realizados com o objetivo de esclarecer os mecanismos fisiopatogênicos da depressão, no entanto, o processo neurobiológico exato que leva a depressão e os mecanismos responsáveis pelo efeito terapêutico de drogas antidepressivas não foram completamente elucidados. Dessa forma, os objetivos do presente trabalho foram: 1) Comparar o perfil da expressão de c-Fos no cérebro de ratos sob tratamento agudo e crônico com antidepressivos tricíclicos, especialmente no que diz respeito ao fenômeno da janela terapêutica; 2) Comparar as respostas comportamentais (imobilidade, nado e escalada) no teste do nado forçado em ratos sob tratamento agudo com nortriptilina e desipramina; 3) Investigar se o padrão de resposta comportamental observado em ratos submetidos ao teste do nado forçado pode confirmar a ocorrência de janela terapêutica para o antidepressivo nortriptilina. Foram utilizados ratos adultos Wistar com 8 semanas de idade. Para o estudo do efeito da administração aguda na expressão de c-Fos e teste do nado forçado, foram utilizados desipramina e (5, 10,25 e 50 mg/kg), nortriptilina (5, 10,25 e 50 mg/kg) ou soro fisiológico 0,9% (controles) via intraperitonial. No estudo do efeito da administração crônica de nortriptilina e desipramina, foram utilizadas as doses de 5, 10, 15 e 20 mg/kg de desipramina e nortriptilina via intraperitonial durante 14 dias. O grupo controle recebeu soro fisiológico 0,9% nas mesmas condições. O presente estudo mostra que, no tratamento agudo com os antidepressivos tricíclicos nortriptilina e desipramina, em diferentes doses, há aumento da expressão de c-Fos de forma dose-dependente nas seguintes áreas: MPOL, PVN, SCh, hipocampo (CAI), CeA e MeA. Enquanto a desipramina apresentou uma curva linear crescente, a nortriptilina mostrou curva em forma de U invertido, sendo que tanto a menor quanto a maior dose se diferenciam do grupo controle. O mesmo padrão de resposta foi observado com a administração crônica destes antidepressivos. Além disso, verificou-se no teste do nado forçado que a desipramina diminui o tempo de imobilidade de forma dose dependente linear crescente, enquanto a nortriptilina reduziu o tempo de imobilidade de forma dose-dependente em forma de U, sendo que a menor e a maior dose apresentaram menor efeito no tempo de imobilidade. Em suma, nossos dados mostram que as áreas estudadas podem estar implicadas na atividade dos antidepressivos nortriptilina e desipramina.

Efeito do estresse térmico agudo na expressão de C-Fos em cérebro de ratos

Diferentes grupos de pesquisa têm se dedicado à investigação dos mecanismos cerebrais de controle cardiovascular, do balanço hidrossalino e da termorregulação. Entretanto, informações detalhadas sobre aspectos anatômicos, funcionais e neuroquímicos da rede neuronal responsável pela termorregulação são escassas. Objetivos desse trabalho foram: 1. Verificar a ativação de diferentes áreas cerebrais durante o estresse térmico agudo em ratos sob diferentes condições de hidratação (animais normoidratados, desidratados e hiperosmóticos); 2. Mensurar a concentração plasmática de Na+, K+ e da osmolaridade plasmática, assim como a temperatura corporal de animais normoidratados, desidratados e hiperosmóticos. No estudo da expressão de c-Fos, foram utilizados três grupos experimentais com 16 ratos cada (Wistar, machos, 250-320g), sendo um grupo de normoidratados, um grupo de desidratados e um grupo de animais hiperosmóticos. Cada grupo foi subdividido em dois grupos com 8 ratos em cada, sendo o grupo controle mantido em condições normais de Ta (23 ± 2°C) e outro grupo exposto a Ta elevada (máximo 34°C) durante 45min. Em outro grupo experimental, as mesmas condições foram repetidas e foram feitas as determinações da temperatura corporal, das concentrações plasmáticas de Na + e K+ e, da osmolaridade plasmática. Os resultados do presente estudo demonstraram que, ratos submetidos ao estresse térmico agudo durante 45 minutos, sob diferentes condições de hidratação (normoidratado, desidratado e hiperosmótico), apresentam mudanças nas concentrações plasmáticas de Na+ e K+, osmolaridade plasmática, da temperatura corporal, assim como apresentaram aumento na expressão de c-Fos no núcleo neuronal de diferentes estruturas hipotalâmicas e extrahipotalâmicas conhecidas por estarem envolvidas no controle da temperatura corporal e do balanço hidrossalino. O aumento da expressão de c-Fos nas áreas: septallateral (LSV) e área preóptica, em resposta ao estresse térmico e à desidratação sugere um papel integrado r destas áreas para o controle homeostático e termorregulatório.

Efeito do estresse térmico agudo na expressão de c-Fos em cérebros de ratos / Acute heat stress induces c-fos in the rat forebrain

Diferentes grupos de pesquisa tem se dedicado à investigação dos mecanismos cerebrais de controle cardiovascular, do balanço hidrossalino e da termorregulação. Entretanto, informações detalhadas sobre aspectos anatômicos, funcionais e neuroquímicos da rede neuronal responsável pela termorregulação são escassas. Objetivos desse trabalho foram: 1. Verificar a ativação de diferentes áreas cerebrais durante o estresse térmico agudo em ratos sob diferentes condições de hidratação (animais normoidratados, desidratados e hiperosmóticos); 2. Mensurar a concentração plasmática de Na+, K+ e da osmolaridade plasmática, assim como a temperatura corporal de animais normoidratados, desidratados e hiperosmóticos. No estudo da expressão de c-Fos, foram utilizados três grupos experimentais com 16 ratos cada (Wistar, machos, 250-320g), sendo um grupo de normoidratados, um grupo de desidratados e um grupo de animais hiperosmóticos. Cada grupo foi subdividido em dois grupos com 8 ratos em cada, sendo o grupo controle mantido em condições normais de Ta (23+ ou 2C) e outro grupo exposto a Ta elevada (máximo 34C) durante 45 min. Em outro grupo experimental, as mesmas condições foram repetidas e foram feitas as determinações da temperatura corporal, das concentrações plasmáticas de Na+ e K+, osmolaridade plasmática. Os resultados do presente estudo demonstraram que, ratos submetidos ao estresse térmico agudo durante 45 minutos, sob diferentes condições de hidratação (normoidratado, desidratado e hiperosmótico), apresentam mudanças nas concentrações plasmáticas de Na+ e K+, osmolaridade plasmática, da temperatura corporal, assim como apresentaram aumento na expressão de Cfos no núcleo neuronal de diferentes estruturas hipotalâmicas e extrahipotalâmicas conhecidas por estarem envolvidas no controle da temperatura corporal e do balanço hidrossalino. O aumento da expressão de Cfos nas área: septal lateral (LSV) e área preóptica, em resposta ao estresse térmico e à desidratação sugere um papel integrador destas áreas para o controle homeostáticos e termoregulatório

Efeito do estresse térmico agudo na expressão de c-Fos em cérebros de ratos / Acute heat stress induces c-fos in the rat forebrain

Diferentes grupos de pesquisa tem se dedicado à investigação dos mecanismos cerebrais de controle cardiovascular, do balanço hidrossalino e da termorregulação. Entretanto, informações detalhadas sobre aspectos anatômicos, funcionais e neuroquímicos da rede neuronal responsável pela termorregulação são escassas. Objetivos desse trabalho foram: 1. Verificar a ativação de diferentes áreas cerebrais durante o estresse térmico agudo em ratos sob diferentes condições de hidratação (animais normoidratados, desidratados e hiperosmóticos); 2. Mensurar a concentração plasmática de Na+, K+ e da osmolaridade plasmática, assim como a temperatura corporal de animais normoidratados, desidratados e hiperosmóticos. No estudo da expressão de c-Fos, foram utilizados três grupos experimentais com 16 ratos cada (Wistar, machos, 250-320g), sendo um grupo de normoidratados, um grupo de desidratados e um grupo de animais hiperosmóticos. Cada grupo foi subdividido em dois grupos com 8 ratos em cada, sendo o grupo controle mantido em condições normais de Ta (23+ ou 2C) e outro grupo exposto a Ta elevada (máximo 34C) durante 45 min. Em outro grupo experimental, as mesmas condições foram repetidas e foram feitas as determinações da temperatura corporal, das concentrações plasmáticas de Na+ e K+, osmolaridade plasmática. Os resultados do presente estudo demonstraram que, ratos submetidos ao estresse térmico agudo durante 45 minutos, sob diferentes condições de hidratação (normoidratado, desidratado e hiperosmótico), apresentam mudanças nas concentrações plasmáticas de Na+ e K+, osmolaridade plasmática, da temperatura corporal, assim como apresentaram aumento na expressão de Cfos no núcleo neuronal de diferentes estruturas hipotalâmicas e extrahipotalâmicas conhecidas por estarem envolvidas no controle da temperatura corporal e do balanço hidrossalino. O aumento da expressão de Cfos nas área: septal lateral (LSV) e área preóptica, em resposta ao estresse térmico e à desidratação sugere um papel integrador destas áreas para o controle homeostáticos e termoregulatório