Pharmacological and toxicological effects of Amaryllidaceae.

The Amaryllidaceae family is widely distributed in the tropics, presenting biological activity attributed mostly to alkaloids, such as an important inhibitory activity of acetylcholinesterase (AChE), antifungal, antibacterial, and cytotoxic activities. The present study aims to review the spectrum of action of the main biological activities and toxicity of secondary metabolites found in Amaryllidaceae through a literature review, using Prisma and the descriptors "Pharmacological effects of Amaryllidaceae" and "Amaryllidaceae family" and "Pharmacological actions of Amaryllidaceae", used in English and Portuguese. The literature search was done in March and May 2023. Original works published from 2012 to 2023, available in full, and presenting experimental and clinical studies were included. After the selection considering the inclusion and exclusion criteria, 60 articles fulfilled the defined criteria. From a pharmacological point of view, the highlight is due to the alkaloid galantamine, which has the potential- and is already used - for treating Alzheimer's. The toxicological aspect must be considered and evaluated carefully, as alkaloids have been associated with adverse effects such as nausea, vomiting, diarrhea, abdominal pain, and cardiovascular, neurological, and respiratory changes. Furthermore, some studies indicate that consuming these plants in significant quantities can lead to hepatic and renal toxicity. Therefore, the therapeutical use of this family's plant drugs and derivatives requires further studies to elucidate its effects and point out metabolites with therapeutic potential.

Determinação de ácido rosmarínico em Cordia verbenacea por cromatografia líquida: aplicabilidade em estudo sazonal / Determination of rosmarinic acid in Cordia verbenacea by liquid chromatography: applicability in seasonal study

RESUMO Neste estudo, uma técnica de cromatografia líquida de alta resolução em fase reversa (CLAE-FR) para a determinação de ácido rosmarínico em Cordia verbenacea foi desenvolvida e validada. A análise de regressão foi avaliada, com observação de uma boa linearidade (r = 0,9997). Os valores obtidos para a precisão e exatidão estão de acordo com as diretrizes do ICH e com a legislação brasileira. Os valores de repetibilidade e precisão intermediária foram 2,79% e 4,76%, respectivamente. Os limites de detecção e de quantificação de ácido rosmarínico foram de 1,92 µg/mL e 5,81 µg/mL, respectivamente. Os resultados mostraram que o método desenvolvido é uma técnica por CLAE-FR de confiança para a determinação de ácido rosmarínico em tintura de C. verbenacea. Além disso, essa metodologia foi aplicada em estudo sazonal, que revela uma correlação positiva relativamente forte entre o período de chuvas e o teor de ácido rosmarínico.

ABSTRACT In this study, a reverse phase-high performance liquid chromatography (RP-HPLC) technique for determination of rosmarinic acid in the Cordia verbenacea was developed and validated. A regression analysis was performed, with the observation of good linearity (r =0.999949). The values obtained for precision and accuracy determination are in agreement with ICH guidelines and the Brazilian legislation. The values of repeatability and intermediate precision were 2.79% and 4.76%, respectively. The detection and the quantitation limits of the rosmarinic acid were 1.92 µg/mL and 5.81 µg/mL, respectively. The results demonstrated that the developed method is a reliable RP-HPLC technique for the determination of rosmarinic acid in C. verbenacea tincture. In addition, this methodology was applied at a seasonal study indicating relatively strong positive correlation between the rain period and the rosmarinic acid content.

Avaliação da atividade antibacteriana do óleo essencial de Rosmarinus officinalis L. e tintura de própolis frente à bactéria causadora da acne Propionibacterium acnes / Evaluation of the antibacterial activity of the essential oil of Rosmarinus officinalis L. and propolis tincture against the bacterium that causes acne: Propionibacterium acnes

A acne é uma doença de pele extremamente comum. Sua patogênese é multifatorial, incluindo hiperqueratinização folicular, hiperplasia sebácea, hipercolonização bacteriana. A Propionibacterium acnes possui um papel relevante na resposta inflamatória da patogênese da acne. Os antibióticos representam uma das classes de medicamentos utilizadas no tratamento da acne. No entanto, as reações adversas causadas por esses fármacos tornam o tratamento desagradável, além de casos relatados de resistência bacteriana. Por esse motivo, o uso de produtos naturais tem sido destaque na área de dermatologia. O presente trabalho visou avaliar "in vitro" os possíveis efeitos antimicrobianos do óleo essencial de Rosmarinus officinalis e da tintura de própolis sobre cepa de Propionibacterium acnes (ATCC 1969). O óleo essencial foi extraído pela técnica de hidrodestilação e obteve-se a tintura de própolis por maceração. O ensaio antimicrobiano foi realizado pela técnica da diluição em tubos. O óleo foi testado em diferentes concentrações, variando de 16% a 0,0625% e a tintura de 10% a 0,072312%. Pode-se verificar que o óleo essencial de Rosmarinus officinalis L. não apresentou atividade antibacteriana contra a cepa de Propionibacterium acnes. A tintura de própolis teve ação em várias concentrações, sendo a concentração inibitória mínima de 0,625%.

Acne is an extremely common skin disease. The pathogenesis of acne is multifactorial, including follicular hyperkeratinization, sebaceous hyperplasia and hypercolonization of bacteria. The Propionibacterium acnes has an important role in the inflammatory response of the pathogenesis of acne. Antibiotics are one of the drugs used in the treatment of acne. However, the adverse reactions caused by these drugs turn the treatment unpleasant, besides the existence of cases of bacterial resistance. For this reason, the use of natural products has been prominent in the dermatology area. This work intended to perform an in vitro evaluation of the possible antimicrobial effects of the essential oil of Rosmarinus officinalis and propolis tincture on the Propionibacterium acnes (ATCC 1969) strain. The essential oil was extracted by hydrodistillation, and the propolis tincture was obtained by maceration. The antimicrobial test was conducted by the tube dilution technique. The oil was tested in different concentrations varying between 16% and 0.0625%, and the tincture, between 10% and 0.072312%. We verified that the essential oil of Rosmarinus officinalis has no effects against the Propionibacterium acnes strain. The propolis tincture showed some action in several concentrations, being the minimal inhibitory concentration: 0.625%.

Antinociceptive and anti-inflammatory activities of Bowdichia virgilioides (sucupira).

ETHNOPHARMACOLOGICAL RELEVANCE: Bowdichia virgilioides Kunth (Leguminosae Papilonoideae) is a plant with anti-inflammatory activity used in folk medicine. The importance of this plant promoted its inclusion in Brazilian Pharmacopoeia. AIM OF THE STUDY: In order to evaluate the actions of this plant, studies were performed on antinociceptive and anti-inflammatory activities. MATERIALS AND METHODS: The aqueous extracts (AE) of Bowdichia virgilioides inner bark and leaves were used at 100, 200, and 400mg/kg. Antinociceptive activity of plant extract was evaluated by writhing, hot-plate and formalin tests. Anti-inflammatory activity was evaluated using paw oedema and peritonitis methods. RESULTS: Oral treatment with the AE of inner bark or leaves elicited inhibitory activity (P<0.01) on acetic acid effect at 200 and 400mg/kg, and reduced the formalin effect at the second-phase (200 and 400mg/kg, P<0.01), however it did not elicit any inhibitory effect on hot-plate test. The indomethacin inhibited the acetic acid-induced writhing and the formalin effect at the second-phase (P<0.001), and the morphine reduced the both phases of formalin test (P<0.001). Carrageenan-induced oedema formation and neutrophil migration into the peritoneal cavity were reduced with the AE of inner bark or leaves at 100, 200, and 400mg/kg (P<0.05), and by the reference compounds aspirin (P<0.001) and dexamethasone (P<0.001), respectively. CONCLUSIONS: The AE of Bowdichia virgilioides shows antinociceptive and anti-inflammatory activities, supporting the folkloric usage of the plant to treat various inflammatory diseases.

Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis.

This paper aims to evaluate the anti-emetic efficacy of cannabinoids in cancer patients receiving chemotherapy using a systematic review of literature searched within electronic databases such as PUBMED, EMBASE, PSYCINFO, LILACS, and 'The Cochrane Collaboration Controlled Trials Register'. Studies chosen were randomized clinical trials comprising all publications of each database until December 2006. From 12 749 initially identified papers, 30 fulfilled the inclusion criteria for this review, with demonstration of superiority of the anti-emetic efficacy of cannabinoids compared with conventional drugs and placebo. The adverse effects were more intense and occurred more often among patients who used cannabinoids. Five meta-analyses were carried out: (1) dronabinol versus placebo [n=185; relative risk (RR)=0.47; confidence interval (CI)=0.19-1.16]; (2) Dronabinol versus neuroleptics [n=325; RR=0.67; CI=0.47-0.96; number needed to treat (NNT)=3.4]; (3) nabilone versus neuroleptics (n=277; RR=0.88; CI=0.72-1.08); (4) levonantradol versus neuroleptics (n=194; RR=0.94; CI=0.75-1.18); and (5) patients' preference for cannabis or other drugs (n=1138; RR=0.33; CI=0.24-0.44; NNT=1.8). The superiority of the anti-emetic efficacy of cannabinoids was demonstrated through meta-analysis.

Amazonian plant crude extract screening for activity against multidrug-resistant bacteria.

Antimicrobial resistance is a subject of great concern in public health and also in the designing of strategies for current therapeutic protocols all over the world. New drugs, including those necessary for a reserve armamentarium and exhibiting less side effects deserve special attention. In rural areas, particularly in Brazil, a huge number of natural products, in different artisanal preparations, mainly from plants, have been used by traditional populations to cure diseases. Despite some of these plants have been studied, many of them are awaiting to have their compounds chemically characterized and investigated their pharmacodynamics properties. Further, as well known, the environment plays a crucial role in the metabolism of these plants, yielding different and varied molecular complexes depending on the period of collection, climate conditions, kind of soil and also the plant speciation. In this report, ethanol crude extract of 10 different botanical specimens from the Amazon region of Brazil, in the Amapa State, were screened for antibacterial activity of 7 clinical resistant microorganisms utilizing as control ATCC bacterial species by the Kirby-Bauer method. Plant extracts of Geissospermum argenteum, Uncaria guianensis, Brosimum acutifolium, Copaifera reticulate, Licania macrophylla, Ptycopetalum olacoides and Dalbergia subcymosa yielded activity against Staphylococcus aureus and Pseudomonas aeruginosa, both multidrug resistant, and Staphylococcus aureus ATCC strain.

Antinociceptive effect from Ipomoea cairica extract.

Ipomoea cairica L. Sweet (Convolvulaceae) is used in Brazilian folk medicine for the treatment of rheumatism and inflammations. Ipomoea cairica ethanolic extract (100, 300, 1000 and 3000 mg/kg; per os) induced dose-dependent reduction of response in the formalin test inflammatory phase in mice. The same dose range did not modify neurogenic pain in formalin test, tail-flick reflex latency, carrageenan-induced paw edema, and Rota-Rod test motor performance. From the bio-active fraction 3,5-di-O-caffeoylquinic acid and 4,5-di-O-caffeoylquinic acid were obtained. These compounds have been previously reported to have analgesic and antioxidative effects. A possible explanation for the antinociception is that somehow the compounds present in the extract reduced the release of pro-nociceptive mediators unrelated to carrageenan-induced edema, such as histamine. Interestingly, caffeoylquinic acid derivatives have been reported to inhibit histamine release on in vitro models. The isolated caffeoylquinic acids could explain, at least in part, the antinociceptive effect of Ipomoea cairica polar extract.

Lateral asymmetry in activation of hypothalamic neurons with unilateral amygdaloid seizures.

PURPOSE: Reproductive disorders are unusually frequent among women with temporal lobe seizures. The particular type of disorder may be related to the laterality and focality of epileptiform discharges. Here we examined whether unilateral amygdaloid seizures activate hypothalamic neurons involved in reproductive function and reproductive endocrine secretion in female rats and whether such activation shows lateral asymmetry. METHODS: Numbers of Fos-immunoreactive (Fos-ir) neurons in various hypothalamic regions were compared for three groups of animals: (a) unilateral amygdala-kindled, (b) implanted but unstimulated, and (c) unimplanted. RESULTS: Fos-ir neurons showed strong ipsilateral occurrence in the medial preoptic, ventrolateral part of the ventromedial, and ventral premammillary nuclei, sexually dimorphic regions involved in reproductive endocrine regulation. No significant lateral asymmetry was observed for other investigated hypothalamic regions. CONCLUSIONS: Unilateral amygdaloid seizures activate hypothalamic neurons that regulate reproductive endocrine secretion in a laterally asymmetric fashion. This may explain the clinical association of different reproductive endocrine disorders with left and right temporal epileptiform discharges.

Therapeutic use of cannabis by crack addicts in Brazil.

This study ensued from clinical observations based on spontaneous accounts by crack abusers undergoing their first psychiatric assessment, where they reported using cannabis in an attempt to ease their own withdrawal symptoms. Throughout a period of nine months, the researchers followed up on 25 male patients aged 16 to 28 who were strongly addicted to crack, as diagnosed through the Composite International Diagnostic Interview (CIDI), according to CID-10 and DSM-IV diagnostic criteria. Most of the subjects (68%, or 17 individuals) ceased to use crack and reported that the use of cannabis had reduced their craving symptoms, and produced subjective and concrete changes in their behavior, helping them to overcome crack addiction. The authors discuss some psychological, pharmacological and cultural aspects of these findings.

[Cursive and gelastic manifestations of epilepsies]. / Manifestações cursivas e gelásticas das epilepsias.

Seven cases of cursive and two cases of gelastic manifestations of epileptic seizures are presented. The cases were documented with computerized tomography and electroencephalography (EEG). Most of patients with cursive seizures showed temporal lobe epileptiform discharge in EEG. The authors discuss the theme in relation to pathophysiology and conclude that they are not a homogeneous group according to prognosis and nosology. Every case presented complex partial seizures with or without tonic-clonic seizures.

Preclinical antitumor activity and pharmacological properties of deoxyspergualin.

A new antibiotic, deoxyspergualin (DSG), demonstrated antitumor activity against L1210 leukemia in mice. The life span of mice bearing either i.p. or s.c.-implanted L1210 increased greater than 150% following i.p. administration of 25 mg/kg DSG on days 1-9. Activity obtained with i.p. bolus treatments was schedule dependent. The tumor burden in mice bearing the s.c. implanted L1210 was reduced by 4-6 log10 units at the end of treatment when DSG was administered every 3 h for 8 injections on days 1, 5, and 9. By contrast, single injections of DSG on days 1, 5, and 9 allowed the tumor burden to increase at least 100-fold during treatment and daily single injections for 9 days reduced the tumor burden by 2 log10 units. The therapeutic advantage for i.p.-implanted L1210 of maintaining plasma concentrations of DSG was indicated further by infusion studies using s.c.-implanted Alzet osmotic pumps. Tumor burden was reduced by 3.5 and 6 log10 units following s.c. bolus treatments every 3 h on day 1 and a 24 h-infusion, respectively. The optimal infusion time for an infusion rate in mice of 179 mg/kg/day appeared to be 72 h. Pharmacokinetic studies following bolus i.v. injection revealed a rapid plasma clearance of parent drug (20.8 ml/min/kg) and a beta half-life of approximately 12 min. The bolus dose kinetics was used to predict the steady state plasma concentrations resulting from s.c. infusion; good agreement was observed between predicted values and experimental results. Based on these preclinical data, DSG has been developed to clinical trial. Initial Phase I protocols involve a 120-h infusion schedule.