Evidências clínicas do uso de plantas medicinais e fitoterápicos na cicatrização de feridas cutâneas: uma revisão integrativa / Evidencia clínica sobre el uso de plantas medicinales y medicinas a base de hierbas en la curación de heridas en la piel: una revisión integrativa / Clinical evidence on the use of medicinal plants and herbal medicine in healing skin wounds: an integrative review

Introdução: Plantas medicinais e fitoterápicos são tradicionalmente utilizados na cicatrização de diversos tipos de feridas. Muitas plantas contêm compostos bioativos com propriedades anti-inflamatórias, antimicrobianas e cicatrizantes. Objetivo: Reunir evidências clínicas do uso de plantas medicinais e fitoterápicos na cicatrização de feridas cutâneas. Metodologia: Trata-se de uma revisão integrativa da literatura. Os estudos foram coletados das bases de dados MEDLINE/PubMed e LILACS, utilizando como estratégia de busca os termos ((WoundHealing) ou (Inflammation)) e ((MedicinalPlants) ou (Phytotherapy)) com recorte temporal de 2011 a 2021. Resultados: 15 estudos foram incluídos na revisão. A maioria dos estudos foram do tipo ensaio clínico controlado randomizado. Foi investigada a eficácia de 15 espécies medicinais para o tratamento de feridas agudas e crônicas, sendo as mais recorrentes queimaduras de segundo grau, úlceras crônicas e feridas cirúrgicas. As espécies medicinais que apresentaram melhores resultados foram babosa (Aloevera), centela (Centellaasiatica),beldroega (Portulacaoleraceae), Arnebia euchroma, hipérico (Hypericum perforatum) emil-folhas (Achilleamillefolium), melhorando critérios como eritema, edema, tempodere-epitelização, tempo de cicatrização e a aparência geral da ferida. Conclusões: Plantas medicinais e fitoterápicos apresentam eficácia no processo de cicatrização, sendo, portanto, alternativa terapêutica para o tratamento de feridas cutâneas (AU).

Introduction: Medicinal plants and herbal medicines are traditionally used to heal various types of wounds. Many plants contain bioactive compounds with anti-inflammatory, antimicrobial, and wound-healing properties. Objective: Gathering clinical evidence on the use of medicinal plants and herbal medicine in the healing of skin wounds. Methodology:Thisisan integrative review of the literature. The studies were collected from the MEDLINE/PubMed and LILACS data bases, using the terms ((WoundHealing) or (Inflammation)) and ((MedicinalPlants) or (Phytotherapy)) as a search strategy, from 2011 to 2021. Results: Fifteen studies were included in the review. Most of them were of the randomized controlled clinical trial type. The effectiveness of 15 medicinal species was investigated for the treatment of acute and chronic wounds, the most common of which were second-degree burns, chronic ulcers,and surgical wounds. The species with the best results were Aloe vera, Centella asiatica, Portulaca oleraceae, Arnebia euchroma, Hypericum perforatum, and Achillea millefolium, improving criteria such as erythema, edema, re-epithelialization time, healing time, and the general appearance of the wound. Conclusions: Medicinalplants and herbal medicine are effective in the healing process, therefore being a therapeutic alternative for treating skin wounds (AU).

Introducción: Las plantas medicinales y las medicinas a base de hierbas se utilizan tradicionalmente para curar diversos tipos de heridas. Muchas plantas contienen compuestos bioactivos con propiedades antiinflamatorias, antimicrobianas y cicatrizantes. Objetivo: Recopilar evidencia clínica sobre el uso de plantas medicinales y medicinas a base de hierbas en la curación de heridas cutáneas. Metodología: Se trata de una revisión integradora de la literatura. Los estudios fueron obtenidos de las bases de datos MEDLINE/PubMed y LILACS, utilizando como estrategia de búsqueda los términos ((WoundHealing) o (Inflammation)) y ((MedicinalPlants) o (Phytotherapy)) con un marco temporal de 2011 a 2021. Resultados: Se incluyeron 15 estudios en la revisión. La mayoría de los estudios fueron del tipo ensayo clínico controlado aleatorio. Se investigó la eficacia de 15 especies medicinales para el tratamiento de heridas agudas y crónicas, las más comunes fueron quemaduras de segundo grado, úlceras crónicas y heridas quirúrgicas. Las especies medicinales con mejoresr esultados fueron Aloe vera, Centella asiatica, Portulaca oleraceae, Arnebia euchroma, Hypericum perforatum y Achillea millefolium, mejorando criterios como eritema, edema, tiempo de reepitelización, tiempo de cicatrización y aspecto general de la herida. Conclusiones: Plantas medicinales y medicinas a base de hierbas son efectivas en el proceso de cicatrización, siendo portanto un aalternativa terapéutica para el tratamiento de heridas en la piel (AU).

Práticas integrativas e complementares em saúde na atenção primária à saúde de mossoró ­ rn / Integrative and Complementary Health Practices in Primary Health Care in Mossoró ­RN / Prácticas Integradoras y Complementarias de Salud en Atención Primaria de la Salud en Mossoró ­RN

Introdução:As Práticas Integrativas e Complementares em Saúde integram práticas e saberes milenares aos conhecimentos biomédicos ocidentais atuais. Dentro do Sistema Único de Saúde, especificamentena Atenção Primária, o principal local de atuação das referidas práticasé nas Unidades Básicas de Saúde.Objetivo:Avaliaro uso destas práticas nas Unidades Básicas do município de Mossoró/Rio Grande do Norte.Metodologia:Realizou-se um estudo descritivo transversal com abordagem quantitativa com gerentes de Unidades Básicas de Saúdede Mossoró. Foram utilizadosdoisquestionários: um para avaliar o conhecimento dos gerentes das Unidades Básicas acerca daspráticas integrativase outro para avaliar o seu usoe processo deimplementação. Os dados foram coletados através da aplicação dequestionários de forma online por meio da ferramenta Google Forms.Resultados:Vinte e três gerentesque,no estudo totalizou um percentual de 48,9%,responderamos questionários. A maioria dos entrevistados demonstrouconhecimentos sobreas Práticas,dasquaispodemos citar como sendoas mais conhecidas:acupuntura, meditação e fitoterapia. Apenas 17,4% das Unidades Básicas de Saúdeofertamas mesmas, sendo a fitoterapia a principal. A aplicação destasé realizada, majoritariamente,por enfermeiros, sendo saúde mental e dores musculares as indicações mais comuns. A falha na tentativa de implantação destas práticasfoi atribuídaà falta de capacitação profissional e recursos, enquanto a sua interrupçãose deudevidoà escassez de material e à pandemia da COVID-19. Conclusões:Este estudo encontrou uma baixa prevalência nas referidas práticasna cidade deMossoró. Destaca-se a necessidade de qualificação e capacitação dos profissionais da Atenção Primária à Saúdeem Práticas Integrativas e Complementares, bem como melhor gestão dos recursos para efetiva implementação no município, vistosua importância nos cuidados de saúde integral e prevenção de doenças (AU).

Introduction:Integrative and Complementary Health Practices integrate ancient practices and wisdom with current western biomedical knowledge. Within theUnified Health System, specifically in Primary Health Care, the main place where these practicesare applied is in Basic Health Units.Objective:To evaluate the use of these practicesin the Basic Units from the municipality of Mossoró/Rio Grande do Norte.Methodology:A cross-sectional and descriptive study with a quantitative approach was carried out with Basic Health Unit managers from Mossoró. Two questionnaires were used: one to assess the Basic Unit managers' knowledge aboutintegrative practices; and the other to evaluate their use and implementation process. The data were collected by applying questionnaires online using the Google Forms tool. Results:Twenty-three managers, who totaled a percentage of 48.9% in the study, answered the questionnaires. Most of the participants showed knowledge about the Practices, among which wecan mention the following as the best known: Acupuncture, Meditation and Herbal Medicine. Only 17.4% of the Basic Health Units offerthese practices, with Phytotherapy as the main one. Their application of these is mostly in charge of nurses, with mental health and muscle pain as the most common indications. Failure in the attempt to implement these practices was attributed to lack of professional training and resources, whereas their interruption was due to shortage of materials and to the COVID-19 pandemic.Conclusions:This study found a low prevalence of these practicesin the city of Mossoró. The need for qualification and training of thePrimary Health Care professionals inIntegrative and Complementary Practicesis highlighted, as well as better management of resources for effective implementation in the municipality, given their importance in terms of comprehensive health care and disease prevention (AU).

Introducción: Las Prácticas Integradoras y Complementarias de Salud integran prácticas y saberes milenarios con conocimientos biomédicos occidentales actuales. En el ámbito del Sistema Único de Salud, específicamente en Atención Primaria, el principal lugar en el que seaplican estas prácticasson las Unidades Básicas de Salud. Objetivo: Evaluar el uso de estas prácticas en Unidades Básicas delmunicipio de Mossoró/Rio Grande do Norte. Metodología: Se realizó un estudio descriptivo y transversal con enfoque cuantitativo con los gerentes de Unidades Básicas de Mossoró. Se utilizaron dos cuestionarios: uno para evaluar el conocimiento de los gerentesde Unidades Básicas sobre prácticas integradoras; y otro para evaluar su uso y proceso de implementación. Los datos se recopilaron aplicando los cuestionarios en línea a través de la herramienta Google Forms. Resultados: Veintitrésgerentesrespondieron los cuestionarios, que en el estudio sumaron un porcentaje del 48,9%. La mayoría de los entrevistados demostró conocimientos sobre las Prácticas, entre las que podemos mencionar como las más conocidas: Acupuntura, Meditación y Fitoterapia.Solo el 17,4% de las Unidades Básicas ofrecenestas prácticas, con Fitoterapia como la principal. En su mayoría, estas prácticas son aplicadas por enfermeras, con salud mental y dolores musculares como las indicaciones más habituales. El fracaso en el intento de implementar estas prácticas se atribuyó a falta de formación profesional y de recursos, mientras que su interrupción se debió a escasez de materiales y a la pandemia de COVID-19. Conclusiones: Este estudio detectóuna baja prevalencia de estas prácticas en la ciudad de Mossoró.Se destaca la necesidad de cualificación y formación de los profesionales de Atención Primaria de la Salud en Prácticas Integradorasy Complementarias, así como mejor gestión de los recursos para efectiva implementación en el municipio,dada su importancia para el cuidado de la salud integral y la prevención de enfermedades (AU).

Quarantine, physical distancing and social isolation measures in individuals potentially exposed to SARS-CoV-2 in community settings and health services: a scoping review.

To provide a synthesis of diverse evidence on the impact of the non-therapeutic preventive measures, specifically quarantine, physical distancing and social isolation, on the control of COVID-19. A scoping review conducted in the PubMed, Embase, LILACS, CENTRAL and SCOPUS databases between 2019 and August 28th, 2020. The descriptors used were the following: "quarantine", "physical distancing", "social isolation", "COVID-19" and "SARS-Cov2". Studies that addressed the non-therapeutic preventive measures in people exposed to SARs-CoV-2 in community settings and health services were included. A total of 14,442 records identified through a database search were reduced to 346 studies and, after a standardized selection process, a total of 68 articles were selected for analysis. A total of 35 descriptive, cross-sectional or longitudinal observational studies were identified, as well as 3 reviews, in addition to 30 studies with mathematical modeling. The main intervention assessed was social distancing (56.6%), followed by lockdown (25.0%) and quarantine (18.4%). The main evidence analyzed points to the need for rapid responses to reduce the number of infections, deaths and hospital admissions, especially in intensive care unit beds.The current review revealed consistent reports that the quarantine, physical distancing and social isolation are effective strategies to contain spread of the new coronavirus.

Plantas medicinais e fitoterápicos no cuidado da saúde mental em tempos de pandemia: uma revisão da literatura / Medicinal plants and herbal medicines in mental health care in times of pandemic: a literature review

Apesar do uso de plantas medicinais para tratamento de problemas de saúde ser tradicionalmente aceito, esta prática da medicina popular ainda encontra resistência por profissionais da saúde, sobretudo sob a alegação da falta de comprovação de seus efeitos. Durante o surto de Covid-19, houve aumento significativo do estresse, sintomas ansiosos e insônia e o uso de plantas medicinais e fitoterápicos surge como uma alternativa terapêutica. O objetivo deste estudo foi realizar uma revisão da literatura sobre a eficácia de plantas medicinais como terapia alternativa e/ou complementar para transtornos de ansiedade e insônia. As plantas investigadas foram selecionadas a partir do Formulário de Fitoterápicos e Memento Fitoterápico da Farmacopeia Brasileira, sendo utilizados como descritores o nome científico da planta e os termos "anxiety" e "insomnia" com recorte temporal de 2015 a 2020. 230 resultados foram encontrados, 42 selecionados (27 em humanos e 15 em animais). Foi possível demonstrar efeitos ansiolíticos para as plantas capim santo (Cymbopogon citratus), lavanda (Lavandula officinalis), melissa (Melissa officinalis), maracujá (Passiflora incarnata)e valeriana (Valeriana officinalis) e sedativos para melissa, maracujá e valeriana. A kava-kava (Piper methysticum) demonstrou apenas efeito sedativo e a camomila (Matricaria chamomilla) apresentou eficácia clínica ansiolítica. Portanto, a potencial aplicação clínica dessas plantas é indicada para tratamento dos sintomas de ansiedade e insônia, ajudando a reduzir os sintomas psicológicos decorrentes da pandemia de Covid-19. Contudo, vale ressaltar a necessidade da padronização dos procedimentos metodológicos e avanço da fitoterapia na prática médica. [au]

Although the use of medicinal plants to treat health problems is traditionally accepted, this practice of popular medicine still finds resistance from health professionals, especially under the allegation of lack of scientific proof of its effects. During the outbreak of COVID-19, there was a significant increase in stress, anxiety, and insomnia symptoms, and the use of plants and herbal medicines emerged as a possible therapeutic alternative. The objective of this study was to conduct a literature review about the effectiveness of medicinal plants as an alternative and/or complementary therapy for anxiety and insomnia disorders. The main medicinal plants were selected from the Phytotherapeutic Formulary and Phytotherapeutic Memento of the Brazilian Pharmacopoeia, using the 'scientific name' and terms 'anxiety' and 'insomnia' as descriptors between 2015-2020. 230 results were found and 42 studies were selected (27 in humans and 15 in animals). Anxiolytic effects have been demonstrated to Cymbopogon citratus, Lavandula officinalis, Melissa officinalis, Passiflora incarnata, and Valeriana officinalis and sedatives effects to M. officinalis, P. incarnata, and V. officinalis. Piper methysticum revealed only a sedative effect and Matricaria chamomilla showed anxiolytic clinical efficacy. Then, the potential clinical application of these plants in the treatment of anxiety and insomnia symptoms is indicated, helping to reduce the psychological symptoms resulting from the Covid-19 pandemic. However, it is worth emphasizing the need to standardize methodological procedures and advance phytotherapy in medical practice. [au]

Neryl butyrate induces contractile effects on isolated preparations of rat aorta.

Neryl butyrate is a constituent of volatile oils obtained from aromatic plants. Aliphatic organic compound analogues chemically close to neryl butyrate possess vasodilator properties in rat aorta. To evaluate whether neryl butyrate has relaxing properties, this study tested its effects on isolated rat aorta. Unlike the analogues, neryl butyrate did not show relaxant profile in aortic rings precontracted with phenylephrine, but induced a contraction when it stimulated aortic rings under resting tonus. The contractile effect augmented in endothelium-denuded aortic rings. Treatment of endothelium-intact preparations with the nitric oxide synthase inhibitor L-NAME or the guanylyl cyclase inhibitor ODQ also augmented the contractile effect of neryl butyrate. Such phenomenon was absent in the presence of the cyclooxygenase inhibitor indomethacin. Contractile responses decreased in the presence of verapamil, a L-type Ca2+ channel blocker, or when Ca2+ was removed from the extracellular solution. Antagonists of α-adrenergic receptors (prazosin and yohimbine), but not the thromboxane-prostanoid receptor seratrodast, reversed the contraction induced by neryl butyrate. The α1A selective antagonist RS-17053 antagonized the neryl butyrate-induced contraction. The contraction caused by neryl butyrate was decreased by inhibiting the phospholipase C or the rho-associated kinase with U-73122 or Y-27632, respectively. Injected intravenously to awake rats, neryl butyrate induced arterial hypotension and bradycardia. Decreased frequency was also present in isolated right atrium preparations. In conclusion, the contractile effects of neryl butyrate were inhibited by α-adrenergic antagonists, indicating the involvement of α-adrenoceptors in the mechanism of action. In vivo, neryl butyrate caused hypotension, suggesting that other systemic influence than vasoconstriction may occur.

Endothelium-dependent and endothelium-independent effects of 1-nitro-2-propylbenzene on rat aorta.

A group of nitro compounds contains a benzene ring in a short aliphatic chain with the NO2 group, property that supposedly favors its vasodilator profile. In this study, we evaluated in isolated rat aorta the effects of 1-nitro-2-propylbenzene (NPB), a nitro compound containing the NO2 in the aromatic ring. In aorta precontracted with KCl, NPB (1-3000 µm) induced full endothelium-independent relaxation. In endothelium-intact preparations, phenylephrine-induced contractions were fully relaxed by NPB, effect unaltered by N(ω)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). In the concentration range of 30-300 µm, NPB slightly but significantly potentiated the phenylephrine-induced contraction. Such potentiation was unaltered by the thromboxane-prostanoid receptor antagonist seratrodast, but was abolished by endothelium removal or by preincubation of endothelium-intact preparations with L-NAME, ODQ or by ruthenium red and HC-030031, blockers of subtype 1 of ankyrin transient receptor potential (TRPA1 ) channels. Verapamil exacerbated the potentiating effect of NPB. The potentiating effect was undetectable in preparations precontracted by 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α (U-46619). Relaxation was reduced by ruthenium red while it was enhanced by HC-030031. In conclusion, NPB has vasodilator properties but with a mechanism of action distinct from its analogues. Contrary to other nitro compounds, its relaxing effects did not involve recruitment of the guanylyl cyclase pathway. NPB has also endothelium-dependent potentiating properties on phenylephrine-induced contractions, a phenomenon that putatively required a role of endothelial TRPA1 channels. The present findings reinforce the notion that the functional group NO2 in the aliphatic chain of these nitro compounds determines favorably their vasodilator properties.

Dual excitatory and smooth muscle-relaxant effect of ß-phenylethylamine on gastric fundus strips in rats.

ß-Phenylethylamine (ß-PEA) is a trace amine with chemical proximity to biogenic amines and amphetamines. It is an endogenous agonist of trace amine-associated receptors (TAARs) that acts as a neuromodulator of classic neurotransmitters in the central nervous system. At high concentrations, ß-PEA contracts smooth muscle, and a role for TAARs in these responses has been postulated. The high dietary intake of trace amines has been associated with such symptoms as hypertension and migraine, especially after the intake of foods containing such compounds. In gastrointestinal tissues, TAAR expression was reported, although the effect of ß-PEA on gastric contractile behaviour is unknown. Here, isolated strips that were obtained from the rat gastric fundus were stimulated with high micromolar concentrations of ß-PEA. Under resting tonus, ß-PEA induced contractions. In contrast, when the strips were previously contracted with KCl, a relaxant response to ß-PEA was observed. The contractile effect of ß-PEA was inhibited by 5-hydroxytryptamine (5-HT) receptor antagonists (i.e., cyproheptadine and ketanserin) but not by the TAAR1 antagonist EPPTB. In gastric fundus strips that were previously contracted with 80 mmol/L KCl, the relaxant effect of ß-PEA intensified in the presence of 5-HT receptor antagonists, which was inhibited by EPPTB and the adenylyl cyclase inhibitor MDL-12,330A. The guanylyl cyclase inhibitor ODQ did not alter the relaxant effects of ß-PEA. In conclusion, ß-PEA exerted dual contractile and relaxant effects on rat gastric fundus. The contractile effect appeared to involve the recruitment of 5-HT receptors, and the relaxant effect of ß-PEA on KCl-elicited contractions likely involved TAAR1 .

The triterpenoid alpha, beta-amyrin prevents the impaired aortic vascular reactivity in high-fat diet-induced obese mice.

To characterize the protective effects of the triterpenoid mixture alpha, beta-amyrin (AMY, 20 mg/kg, during 15 days) on the reactivity of isolated aorta of high-fat diet (HFD)-induced obese mice. Male Swiss mice were fed with HFD or normal diet (ND) for 15 weeks. Contractions of thoracic aorta in response to KCl or phenylephrine (PHE) and relaxation by acetylcholine (ACh) or sodium nitroprusside (SNP) were analyzed. HFD-fed mice developed hyperglycemia, hyperlipidemia, and significant body weight gain, parameters prevented by AMY treatment. Whereas aortic contractility did not differ in response to KCl, contractions induced by PHE (1 µM) as well as relaxation induced by ACh (1-30 µM) or SNP (1 nM-0.1 mM) on PHE-contracted aorta were decreased (p < 0.05) in tissues of HFD compared to ND mice, phenomenon significantly (p < 0.05) diminished in HFD mice treated with AMY. The relaxant actions of ACh and SNP were inhibited (p < 0.05) by tetraethylammonium (TEA, 5 mM), apamin (0.1 µM), and 4-aminopyridine (4-AP; 3 mM) in aortae from ND group, but not from HFD. Treatment of HFD mice with AMY rescued the inhibitory effect of TEA (p < 0.05) on vasorelaxant actions of ACh and SNP. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) inhibited similarly the relaxant effects of SNP in all groups. 8-Br-cGMP relaxed with similar profile aortae of all groups. By preventing HFD-induced obesity in mice, AMY rescued the blunted contractile response to PHE, and the attenuated vasorelaxation and K+ channel activation (opening) induced by ACh and SNP in isolated aorta.

A simple laboratory exercise with rat isolated esophagus and stomach fundus to reveal functional differences between striated and smooth muscle cells.

This study describes an undergraduate student laboratory activity using isolated preparations from rat gastrointestinal tissues that possess contractile profiles typically exhibited by striated and smooth muscle cells. While students are introduced to an ex vivo methodology, they can compare differences in trace experiments, twitch aspects, phasic and tonic properties, force-frequency relationships, and pharmacological responsiveness of esophageal (striated) and fundic (smooth muscle) segments. Muscle strips were subjected to electrical field stimulation (EFS) applied by platinum electrodes immersed in the physiological solution. The contractile profile of EFS responses varied between these two types of gut preparations. Atropine and tubocurarine revealed differential inhibitory influences in esophagus or fundus tissues; caffeine and procaine produced similar effects, i.e., potentiation and blockade of the EFS-induced contractile response in these tissues, respectively. Experimental results obtained during the activity helped the improvement of student learning about basic concepts previously discussed in theoretical lectures. To measure student learning with this laboratory exercise, a questionnaire was applied before and after the activity, and the number of expected correct answers, concerning the mechanisms of contraction in striated and smooth muscle, could be clearly evidenced.

Vasorelaxant effects of 2-nitro-1-phenyl-1-propanol in rat aorta.

2-Nitro-1-phenyl-1-propanol (NPP) is a nitro alcohol that is known as an intermediate in the synthesis of sympathomimetic agents, such as norephedrine. The present study investigated the vasoactive effects of NPP on rat aorta. In endothelium-intact aortic rings, NPP fully relaxed contractions that were induced by phenylephrine, KCl, and U-46619. The relaxant effects of NPP on phenylephrine-elicited contractions remained unaffected by NG-nitro-l-arginine methyl ester (l-NAME), indomethacin, propranolol, tetraethylammonium, 4-aminopyridine, and glibenclamide. Conversely, pretreatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine hydrochloride (MDL-12,330A), and N-[2-(P-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89) reduced the ability of NPP to relax contractions that were elicited by phenylephrine. NPP inhibited the vasoconstrictor response that was induced by Ca2+ in aortic rings that were stimulated by pharmacomechanical or electromechanical coupling with phenylephrine and 60 mmol/L KCl, respectively, and after the depletion of intracellular Ca2+ stores. Such effects of NPP were significantly reversed by pretreatment with the guanylyl cyclase inhibitor ODQ and weakly influenced by the adenylyl cyclase inhibitor MDL-12,330A. In Ca2+ -free medium, NPP inhibited transient contractions that were induced by phenylephrine but not caffeine. In homogenates of aortic rings, NPP increased cyclic guanosine 3',5'-monophosphate (cGMP) and cyclic adenosine 3'-5'-monophosphate levels, but this effect was statistically significant only for cGMP. In conclusion, in contrast to the vasoconstrictor amine norephedrine, NPP is a vasodilator in rat aorta, and its relaxant effects are likely attributable to cGMP production.

Metabolic acidosis aggravates experimental acute kidney injury.

AIMS: Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury. MAIN METHODS: Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9). KEY FINDINGS: Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury. SIGNIFICANCE: Acute ischemic kidney injury is exacerbated by acidic conditions.

Vasorelaxation induced by methyl cinnamate, the major constituent of the essential oil of Ocimum micranthum, in rat isolated aorta.

The aim of the present study was to investigate the vascular effects of the E-isomer of methyl cinnamate (E-MC) in rat isolated aortic rings and the putative mechanisms underlying these effects. At 1-3000 µmol/L, E-MC concentration-dependently relaxed endothelium-intact aortic preparations that had been precontracted with phenylephrine (PHE; 1 µmol/L), with an IC50 value (geometric mean) of 877.6 µmol/L (95% confidence interval (CI) 784.1-982.2 µmol/L). These vasorelaxant effects of E-MC remained unchanged after removal of the vascular endothelium (IC50 725.5 µmol/L; 95% CI 546.4-963.6 µmol/L) and pretreatment with 100 µmol/L N(G) -nitro-l-arginine methyl ester (IC50 749.0 µmol/L; 95% CI 557.8-1005.7 µmol/L) or 10 µmol/L 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (IC50 837.2 µmol/L; 95% CI 511.4-1370.5 µmol/L). Over the concentration range 1-3000 µmol/L, E-MC relaxed K(+) -induced contractions in mesenteric artery preparations (IC50 314.5 µmol/L; 95% CI 141.9-697.0 µmol/L) with greater potency than in aortic preparations (IC50 1144.7 µmol/L; 95% CI 823.2-1591.9 µmol/L). In the presence of a saturating contractile concentration of K(+) (150 mmol/L) in Ca(2+) -containing medium combined with 3 µmol/L PHE, 1000 µmol/L E-MC only partially reversed the contractile response. In contrast, under similar conditions, E-MC nearly fully relaxed PHE-induced contractions in aortic rings in a Ba(2+) -containing medium. In preparations that were maintained under Ca(2+) -free conditions, 600 and 1000 µmol/L E-MC significantly reduced the contractions induced by exogenous Ca(2+) or Ba(2+) in KCl-precontracted preparations, but not in PHE-precontracted preparations (in the presence of 1 µmol/L verapamil). In addition, E-MC (1-3000 µmol/L) concentration-dependently relaxed the contractions induced by 2 mmol/L sodium orthovanadate. Based on these observations, E-MC-induced endothelium-independent vasorelaxant effects appear to be preferentially mediated by inhibition of plasmalemmal Ca(2+) influx through voltage-dependent Ca(2+) channels. However, the involvement of a myogenic mechanism in the effects of E-MC is also possible.

Phytochemical study guided by the myorelaxant activity of the crude extract, fractions and constituent from stem bark of Hymenaea courbaril L.

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenaea courbaril L. (Caesalpinoideae) is used in Brazilian folk medicine to treat anemia, kidney problems, sore throat and other dysfunctions of the respiratory system, such as bronchitis and asthma, although such properties are yet to be scientifically validated. AIM OF THE STUDY: In order to give a scientific basis to support the traditional use of Hymenaea courbaril, this study was designed to evaluate antioxidant, myorelaxant and anti-inflammatory properties of the ethanol extract from stem bark and its fractions. The myorelaxant effect of astilbin, a flavonoid isolated from the bioactive ethyl acetate fraction (EAF), has also been evaluated. MATERIAL AND METHODS: In the present study ethanol extract from stem bark (EEHC) and fractions were analyzed using bioassay-guided fractionation. The following activities were investigated: antioxidant by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, myorelaxant on rat tracheal smooth muscle, and anti-inflammatory using ovalbumin-induced leukocytosis and airway hyperresponsiveness in rats. RESULTS: The results of the present investigation show that the whole extract of Hymenaea courbaril and some of its fractions strongly scavenged DPPH radical. The extract showed myorelaxant activity on rat trachea, being EAF its highest efficient fraction. Bio-guided study allowed the isolation of astilbin, a well-known flavonoid. The activity induced by this compound indicates that it may be partly responsible for the myorelaxant effect of EAF. EAF reduced contractions that depended on divalent cation inflow through voltage-operated Ca(2+) channels (VOCCs) or receptor-operated Ca(2+) channels (ROCCs), but it was more potent to inhibit VOCC- than ROCC-dependent contraction induced by Ca(2+) addition in ACh-enriched Ca(2+)-free medium. Oral pretreatment of antigen-challenged animals with EAF prevented airway hyperresponsiveness on KCl-induced contraction and reduced the number of total white cells, particularly eosinophils and neutrophils in bronchoalveolar lavage. CONCLUSIONS: This study provided scientific basis that Hymenaea courbaril presents potential antioxidant, myorelaxant and anti-inflammatory actions, which support its use in folk medicine to treat inflammatory airway diseases.

1-Nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, elicits a vago-vagal bradycardiac and depressor reflex in normotensive rats.

Previously, it was shown that intravenous (i.v.) treatment with the essential oil of Aniba canelilla (EOAC) elicited a hypotensive response that is due to active vascular relaxation rather than to the withdrawal of sympathetic tone. The present study investigated mechanisms underlying the cardiovascular responses to 1-nitro-2-phenylethane, the main constituent of the EOAC. In pentobarbital-anesthetized normotensive rats, 1-nitro-2-phenylethane (1-10mg/kg, i.v.) elicited dose-dependent hypotensive and bradycardiac effects which were characterized in two periods (phases 1 and 2). The first rapid component (phase 1) evoked by 1-nitro-2-phenylethane (10mg/kg) was fully abolished by bilateral vagotomy, perineural treatment of both cervical vagus nerves with capsaicin (250 microg/ml) and was absent after left ventricle injection. However, pretreatment with capsazepine (1mg/kg, i.v.) or ondansetron (30 microg/kg, i.v.) did not alter phase 1 of the cardiovascular responses to 1-nitro-2-phenylethane (10mg/kg, i.v.). In conscious rats, 1-nitro-2-phenylethane (1-10mg/kg, i.v.) evoked rapid hypotensive and bradycardiac (phase 1) effects that were fully abolished by methylatropine (1mg/kg, i.v.). It is concluded that 1-nitro-2-phenylethane induces a vago-vagal bradycardiac and depressor reflex (phase 1) that apparently results from the stimulation of vagal pulmonary rather than cardiac C-fiber afferents. The transduction mechanism of the 1-nitro-2-phenylethane excitation of C-fiber endings is not fully understood and does not appear to involve activation of either Vanilloid TPRV(1) or 5-HT(3) receptors. The phase 2 hypotensive response to 1-nitro-2-phenylethane seems to result, at least in part, from a direct vasodilatory effect since 1-nitro-2-phenylethane (1-300 microg/ml) induced a concentration-dependent reduction of phenylephrine-induced contraction in rat endothelium-containing aorta preparations.