Chloroplast genome characterization of Uncaria guianensis and Uncaria tomentosa and evolutive dynamics of the Cinchonoideae subfamily.

Uncaria species are used in traditional medicine and are considered of high therapeutic value and economic importance. This work describes the assembly and annotation of the chloroplast genomes of U. guianensis and U. tomentosa, as well as a comparative analysis. The genomes were sequenced on MiSeq Illumina, assembled with NovoPlasty, and annotated using CHLOROBOX GeSeq. Addictionaly, comparative analysis were performed with six species from NCBI databases and primers were designed in Primer3 for hypervariable regions based on the consensus sequence of 16 species of the Rubiaceae family and validated on an in-silico PCR in OpenPrimeR. The genome size of U. guianensis and U. tomentosa was 155,505 bp and 156,390 bp, respectively. Both Species have 131 genes and GC content of 37.50%. The regions rpl32-ccsA, ycf1, and ndhF-ccsA showed the three highest values of nucleotide diversity within the species of the Rubiaceae family and within the Uncaria genus, these regions were trnH-psbA, psbM-trnY, and rps16-psbK. Our results indicates that the primer of the region ndhA had an amplification success for all species tested and can be promising for usage in the Rubiaceae family. The phylogenetic analysis recovered a congruent topology to APG IV. The gene content and the chloroplast genome structure of the analyzed species are conserved and most of the genes are under negative selection. We provide the cpDNA of Neotropical Uncaria species, an important genomic resource for evolutionary studies of the group.

Consumption of medicinal plants and herbal medicines by children and adolescents with chronic conditions: a survey in a tertiary-care outpatient clinic / Utilização de plantas medicinais e derivados por crianças e adolescentes com condições crônicas: levantamento em um serviço pediátrico terciário

Objectives: Medicinal plants and herbal medicines are widely used worldwide. However, patients with chronic health conditions or their caregivers do not often disclose these practices to their healthcare providers, leading to potentially severe interactions with current treatments, especially in children. We aimed to describe the prevalence of the use of medicinal plants and herbal medicines by children and adolescents with chronic health conditions and whether their physicians were informed about it. Methods: We conducted a cross-sectional electronic survey on parents and caregivers of children and adolescents with chronic health conditions seen at a university, tertiary-care pediatric outpatient clinic. The common names of the plants cited by respondents were reviewed and Latin names of the species were provided whenever possible. Results: From 20,213 text messages sent in May and June 2021, 521 valid responses were obtained. The prevalence of the use of medicinal plants and herbal medicines was 34.6%, most without a medical prescription (self-medication), and few physicians (4.0%) were aware of it. The five most used species were: Mentha spicata L. (mint), Foeniculum vulgare Mill. (fennel), "cidreira" (a common name possibly corresponding to Cymbopogon citratus (DC.) Stapf, Melissa officinalis L. or Lippia alba (Mill.) N.E. Br. ex Britton & Wilson, P.), Matricaria chamomilla L. (German chamomile), and Plectranthus barbatus Andrews (boldo). Conclusions: The prevalence of the use of medicinal plants and herbal medicines by children and adolescents with chronic health conditions in a tertiary-care outpatient clinic was 34.6%, and only a few physicians were aware of it (AU).

Objetivos: Plantas medicinais e seus derivados são amplamente utilizados no mundo todo. Entretanto, pacientes com condições crônicas de saúde ou seus cuidadores frequentemente não informam essas práticas para seus profissionais de saúde, levando a interações potencialmente graves com os demais tratamentos, especialmente em crianças. Nós objetivamos descrever a prevalência do uso de plantas medicinais e derivados por crianças e adolescentes com condições crônicas de saúde, e se seus médicos foram informados sobre isto. Métodos: Levantamento eletrônico transversal junto a pais e cuidadores de crianças e adolescentes com condições crônicas de saúde atendidos em um serviço ambulatorial pediátrico universitário terciário. Os nomes comuns das plantas citadas pelos participantes foram revisados e os nomes latinos das espécies foram identificados, sempre que possível. Resultados: De 20.213 mensagens de texto enviadas em maio e junho de 2021, 521 respostas válidas foram obtidas. A prevalência de utilização de plantas medicinais e derivados foi de 34,6%, sendo a maioria sem prescrição médica (automedicação), e poucos médicos (4,0%) estavam cientes disto. As cinco plantas mais comumente utilizadas foram: Mentha spicata L. (hortelã), Foeniculum vulgare Mill. (funcho), "cidreira" (possivelmente correspondendo a Cymbopogon citratus (DC.) Stapf, Melissa officinalis L. ou Lippia alba (Mill.) N.E. Br. ex Britton & Wilson, P.), Matricaria chamomilla L. (camomila) e Plectranthus barbatus Andrews (boldo nacional). Conclusões: A prevalência de uso de plantas medicinais e derivados por crianças e adolescentes com condições crônicas de saúde em um serviço ambulatorial pediátrico terciário foi de 34,6%, com grande potencial para interações, e somente poucos médicos estavam cientes disto

Anti-asthmatic activity of standardized hydro-ethanolic and aqueous extracts of Stachytarpheta cayennensis (Rich.) Vahl in a murine model.

ETHNOPHARMACOLOGICAL RELEVANCE: Stachytarpheta cayennensis (Verbenaceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory diseases. AIMS OF THE STUDY: To investigate the effects of different doses of standardized hydro-ethanolic (SCH) and aqueous (SCA) extracts of aerial parts of S. cayennensis using a murine ovalbumin (OVA)-induced asthma model. MATERIALS AND METHODS: The major constituents of the plant extracts were identified and standardized by ultra-performance liquid chromatography coupled with mass spectrometry. Balb/c mice were challenged with OVA solution and treated concomitantly by intraperitoneal injection of standardized SCH or SCA extracts at 50, 100, and 200 mg/kg concentrations. OVA-challenged control animals were treated with either dexamethasone (OVA-DEX) or saline solution (OVA-SAL). After challenge, we assessed in vivo bronchial hyperresponsiveness, airway inflammation (number of cells), peribronchial inflammation (histological analysis) and production of OVA-specific IgE and interleukin (IL)-4, IL-5, and IL-13 (ELISA). RESULTS: Acteoside, isoacteoside, and ipolamiide were the major constituents of SCH and SCA. The respective concentrations of acteoside in SCH and SCA were 78 and 98 µg/mL, while those of ipolamiide were 30 and 19 µg/mL. Treatment with 200 mg/kg of SCH or SCA decreased IL-4, IL-5, and IL-13 in lung homogenates. These reductions were accompanied by a lower influx of inflammatory cells (eosinophils, lymphocytes, and macrophages) to the airways and lungs. In addition to the anti-inflammatory effects, administration of SCA, but not SCH, ameliorated the parameters of bronchial hyperresponsiveness and decreased levels of circulating OVA-specific IgE. CONCLUSION: The results presented herein demonstrate for the first time the anti-asthmatic activity of S. cayennensis extracts in a murine model, thereby supporting the ethnopharmacological uses of the plant.

Dynamized Aloysia Polystachya (Griseb.) Essential Oil: A Promising Antimicrobial Product.

BACKGROUND: Compounds from vegetal matter have therapeutic potential to control highly prevalent microorganisms that are resistant to commonly used antimicrobial drugs. Dynamization of compounds can either maintain or improve their therapeutic effects, and make their use safer, especially those compounds whose therapeutic dose is close to the toxic limit. Aloysia polystachya (Griseb.) stands out among aromatic plants with antimicrobial potential. OBJECTIVE: The aim of this study was to evaluate the antimicrobial activity of dynamized and crude forms of A. polystachya essential oil against Candida albicans, Escherichia coli and Staphylococcus aureus. METHODS: Essential oil was extracted from A. polystachya dry leaves, solubilized, and dynamized at 1 cH potency as recommended by the Brazilian Homeopathic Pharmacopoeia. Antimicrobial activity against C. albicans, E. coli and S. aureus of the samples was assayed using the plate microdilution method. RESULTS: Dynamized A. polystachya essential oil at the concentration of 1 µg/mL inhibited the growth of all the microbial species analyzed. The minimum inhibitory concentration of dynamized essential oil was smaller than crude essential oil for S. aureus, E. coli and C. albicans. CONCLUSION: It is reported for the first time that A. polystachya dynamized essential oil can effectively suppress microbial growth, and it is a promising adjuvant to treat infections with pathogenic S. aureus, E. coli and C. albicans.

Preservation of phenolic compounds on dried leaf infusion of Bauhinia forficata Link

Abstract Bauhinia forficata Link aqueous extract is usually recommended as a phytomedicine to reduce blood glucose levels and its biological activity has been linked to the presence of phenolic compounds from B. forficata preparations. Several drying processes are used in the production of dry herbal extracts, which may influence the chemical composition and efficacy of final herbal medicines. Due to significant chemical changes, defining appropriate drying processes is essential for phytopharmaceutical drug development. In view of this, we analyzed dried B. forficata leaf infusion (BFLI) extracts by HPLC-UV-MSn, followed by molecular networking analysis to evaluate the chemical profiles from dried extracts yielded by freeze-and spray-drying processes. The main metabolites detected included 11 ferulic/isoferulic acid derivatives and 13 glycosylated flavonoids. The qualitative chemical profiles were alike for both drying processes, whereas the relative abundance of some flavonoids was higher using spray-drying. Taken together, our results showed that freeze-and spray-drying preserved the phenolic profile of BFLI and suggested that spray-drying may be the most suitable to obtain its dried products. Along with studying the chemical profiles of dried herbal extracts, evaluating the influence of drying processes on the quality and chemical profiles of final products is pivotal and may benefit future research.

Genetic diversity and verbascoside content in natural populations of Pyrostegia venusta (Ker Gawl.) Miers.

BACKGROUND: Pyrostegia venusta (Ker Gawl.) Miers occurs in threatened biodiversity hotspots of Cerrado and Atlantic forest biomes in Brazil and is used in traditional medicine to treat various respiratory and skin diseases. METHODS AND RESULTS: This study (i) examined the genetic diversity and structure of six natural populations of P. venusta from different Brazilian regions using sequence-related amplified polymorphism (SRAP) markers; and (ii) compared the intra- and inter-populational levels of the bioactive component verbascoside using high-performance liquid chromatography. The population from Nova Mutum, Mato Grosso, presented the highest genetic variability (Nei index H = 0.2759; Shannon index I = 0.4170; 85.14% polymorphic loci), whereas the population from Araxá, Minas Gerais, presented the lowest genetic variability (H = 0.1811; I = 0.2820; 70.27% polymorphic loci). The intra-populational variability (79%) was significantly higher (p = 0.001) than the inter-populational variability (21%). The populations were clustered into two groups but their genetic differentiation was not associated with geographical origin (Mantel test, r = 0.328; p > 0.05). The verbascoside content significantly differed (p > 0.05) among the six populations and between the individuals from each population. The highest verbascoside levels (> 200 µg/mg extract) were detected in populations from Araxá and Serrana, while the lowest verbacoside levels were detected in populations from Paranaíta and Sinop. CONCLUSIONS: This is the first report on the use of SRAP markers to analyze genetic variability in the family Bignoniaceae. Our findings shall help to better understand the genetic and chemical diversity of P. venusta populations, as well as provide useful information to select the most appropriate individuals to prepare phytomedicines.

Evaluation of the in vitrofungicidal activity of the dynamized essential oil of Aloysia polystachyabefore and after freezing

The method of preserving substances of natural origin should not only maintain the microbiological safety of the product but also the integrity of its therapeutic potential. Essential oils obtained from plants are complex mixtures of substances and it issuggested to keep them under refrigeration for better conservation. On the other hand, homeopathic mother tincture prepared from plant is kept at room temperature. Aim: This work aimed to evaluate if the freezing process changes the in vitro antifungal activity potential of the homeopathic preparation Aloysia polystachya1CH against Candida albicans. Methodology:The inoculum of C. albicansATCC 10231 was cultivated in culture médium Sabouroud (Himedia®), standardized on a spectrometer and distributed in a 96-well plate. Then, A. polystachya1CH was added to the wells, prepared accordingtothe Brazilian Homeopathic Pharmacopoeia (FHB, 3rd edition) from A. polystachya essencial oil. An aliquot of this homeopathic preparation was frozen and after 40 days it was submitted to the same methodology for evaluation of the antifungal activity. After incubation, the plates were read with triphenyltetrazolic (TTC) (Vetec®). Results and discussion: The results of the in vitroevaluation showed that the freezing process retained the antifungal activity of the dynamized essential oil of A. polystachya1CH against C. albicans. Conclusion: Under the conditions evaluated in this study, the freezing method presented as a viable method of conservation of dynamized plant material.

Momordica charantia L. improves airway hyperresponsiveness and suppresses inflammation in a murine model of allergic asthma.

OBJECTIVE: To evaluate the effect of a hydroethanolic extract of Momordica charantia L. ("bitter melon", Cucurbitaceae) leaves (MCHA) on ovalbumin (OVA)-induced asthma model. Balb/c mice were sensitized twice and challenged for 4 alternate days with OVA and then treated with MCHA (500 mg/kg) for 7 consecutive days. METHODS: Control groups received treatment with normal saline or dexamethasone (2 mg/kg) on the same day. We assessed in vivo bronchial hyperresponsiveness and ex-vivo inflammation and mucus production in bronchoalveolar lavage (BAL), lung homogenates, and lung tissue. RESULTS: MCHA significantly improved airway hyperresponsiveness near baseline levels. MCHA administration significantly improved airway and lung inflammation, demonstrated by decreased total and inflammatory cells in BAL, lower levels of IL-5 and IL-13 in lung homogenate, and fewer inflammatory cells in lung tissue. Additionally, MCHA significantly diminished goblet cells in lung tissue. CONCLUSIONS: Administration of a hydroethanolic extract of M. charantia leaves was effective in treating OVA-induced asthma in an animal model.

Genetic diversity among genotypes of Uncaria guianensis (Aubl.) J.F. Gmel. maintained in an in vitro germplasm bank.

Phytotherapeutic preparations from Uncaria guianensis (Aubl.) J.F. Gmel. (Rubiaceae) are marketed worldwide and are mainly used for their anti-inflammatory activity. The species has not yet been domesticated and is threatened by deforestation and overexploitation. It is, therefore, important to preserve and manage this genetic resource in germplasm banks, so that the extractive provision of plant material can be replaced by cultivated production. The aim of this study was to evaluate the genetic diversity among 20 genotypes maintained under in vitro conditions using 9 primers start codon targeted (SCoT) polymorphism, and to determine the concentrations of the pentacyclic oxindole alkaloids (POAs); mitraphylline and isomitraphylline in methanolic extracts by high-performance liquid chromatography (HPLC). Plantlets were cultivated on woody plant medium supplemented with 20 g.L-1 sucrose and 4.4 µM benzylaminopurine and incubated under a 16 h photoperiod for 45 days. SCoT analysis separated the genotypes into four divergent clusters and confirmed significant genetic diversity with up to 70% dissimilarity. Moreover, HPLC revealed considerable chemical variability and allowed the separation of the tested genotypes into high, medium and low producers of mitraphylline/isomitraphylline. Genotypes with the highest concentrations of POAs originated from the state of Acre and Amapá, while those with the lowest levels were from the state of Pará. The results demonstrate that the genetic diversity within the in vitro germplasm bank is sufficient to support breeding studies, selection of elite genotypes and the large-scale multiplication of plants that could serve as feedstock for the industrial-scale production of phytomedicines. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03016-y.

Pharmacological characterisation of anticonvulsant effects elicited by erythrartine.

OBJECTIVES: The erythrinan alkaloids erythravine and 11α-hydroxy-erythravine from Erythrina verna (Vell.) have been extensively investigated for their anxiolytic and anticonvulsant effects. Both are structurally similar to the erythrartine that also exhibit anxiolytic effects, but there is no report on its anticonvulsant potential. Since some anxiolytic drugs can be useful in the management of epileptic seizures, we investigated whether erythrartine could prevent seizures induced by different chemoconvulsants. METHODS: Experiments were performed using different concentrations of erythrartine injected via intracerebroventricular in rats submitted to pilocarpine, kainic acid, pentylenetetrazol or picrotoxin-induced seizures. Moreover, the rotarod test was performed to verify the effects of erythrartine on animal motor coordination. RESULTS: Our data showed for the first time that erythrartine prevented the occurrence of seizures induced by all of the chemoconvulsants tested and did not affect locomotor performance neither produced sedative effect on animals. CONCLUSION: Obtained results validate the ethnopharmacological significance of E. verna and provide new information on erythrartine, another erythrinian alkaloid of biotechnological and medicinal interest.

Development and characterization of microsatellite markers in Stryphnodendron adstringens (Leguminosae).

In this study, we report the development and characterization of 15 new microsatellite markers for Stryphnodendron adstringens (Leguminosae) in order to support future analyses of genetic diversity in populations of this species. In screening with 48 individuals from three different populations of S. adstringens, we tested the amplification of 20 microsatellite loci, of which five are not useful for population genetic studies due to the lack of polymorphisms or amplification failures. For the final set of 15 loci, the number of alleles ranged from 2 to 15, with a total of 116 alleles. The expected heterozygosity ranged from 0.1219 to 0.8965, with an average of 0.6694 per locus. The combined probability of genetic identity (PI = 8.12 × 10-15) and paternity exclusion (Q = 0.99999) estimations showed that the loci may be useful to discriminate between individuals of S. adstringens. Initial cross-amplification tests were satisfactory in three species of the genus Stryphnodendron: S. rotundifolium, S. coriaceum and S. polyphyllum. This new set of markers will be a useful tool for population genetic studies, contributing to the knowledge about the evolutionary history of S. adstringens and, additionally, correlated species.

The Effect of Rutin and Extracts of Uncaria guianensis (Aubl.) J. F. Gmeland on Primary Endometriotic Cells: A 2D and 3D Study.

There is increasing interest in the potential of natural compounds to treat diseases, such as endometriosis, a gynecological disorder that affects 10-15% of women of reproductive age, and it is related to severe pelvic pain and infertility. We have evaluated the in vitro effects of rutin and the aqueous bark, roots, and leaf extracts (ABE, ARE, and ALE, respectively) and isolated components of Uncaria guianensis on stromal cells from eutopic endometrium and lesions of patients with endometriosis. Two- and three-dimensional cultures were used to assess the cell death and production of reactive oxygen species (ROS), cytokines and growth factors of cells following exposure to these natural products. The applied treatments did not reduce cellular viability, but ROS production did increase. In addition, significant increases in the levels of interleukin (IL)-15, IL-17A, IL-4, IL-6, tumor necrosis factor-α, and vascular endothelium growth factor were observed when 2D-cells from endometrium of patients with endometriosis were treated with ABE, while exposure to ALE induced significant increases in epidermal growth factor in lesion cells.

Anticancer Activities of the Quinone-Methide Triterpenes Maytenin and 22-ß-hydroxymaytenin Obtained from Cultivated Maytenus ilicifolia Roots Associated with Down-Regulation of miRNA-27a and miR-20a/miR-17-5p.

Natural triterpenes exhibit a wide range of biological activities. Since this group of secondary metabolites is structurally diverse, effects may vary due to distinct biochemical interactions within biological systems. In this work, we investigated the anticancer-related activities of the quinone-methide triterpene maytenin and its derivative compound 22-ß-hydroxymaytenin, obtained from Maytenus ilicifolia roots cultivated in vitro. Their antiproliferative and pro-apoptotic activities were evaluated in monolayer and three-dimensional cultures of immortalized cell lines. Additionally, we investigated the toxicity of maytenin in SCID mice harboring tumors derived from a squamous cell carcinoma cell line. Both isolated molecules presented pronounced pro-apoptotic activities in four cell lines derived from head and neck squamous cell carcinomas, including a metastasis-derived cell line. The molecules also induced reactive oxygen species (ROS) and down-regulated microRNA-27a and microRNA-20a/miR-17-5p, corroborating with the literature data for triterpenoids. Intraperitoneal administration of maytenin to tumor-bearing mice did not lead to pronounced histopathological changes in kidney tissue, suggesting low nephrotoxicity. The wide-ranging activity of maytenin and 22-ß-hydroxymaytenin in head and neck cancer cells indicates that these molecules should be further explored in plant biochemistry and biotechnology for therapeutic applications.

Maytenin Plays a Special Role in the Regulation of the Endophytic Bacillus megaterium in Peritassa campestris Adventitious Roots.

Peritassa campestris (Celastraceae) root bark accumulates potent antitumor quinonemethide triterpenes (QMTs). When grown in their natural habitat, plants of the family Celastraceae produce different QMTs such as celastrol (3) and pristimerin (4). However, when they are inserted in in vitro culture systems, they accumulate maytenin (1) as the main compound. Recently, Bacillus megaterium was detected as an endophytic microorganism (EM) living inside P. campestris roots cultured in vitro. We hypothesized that compound (1) controls EM growth more efficiently, and that the presence of EMs in the root culture causes compound (1) to accumulate. For the first time, this work has explored plant-microorganism interaction in a species of the family Celastraceae by co-culture with an EM. Live endophytic bacteria were used, and QMT accumulation in P. campestris adventitious roots was our main focus. The antimicrobial activity of the main QMTs against endophytic B. megaterium was also evaluated. Our results showed that compound (1) and maytenol (5) were more effective than their precursors QMTs (3) and (4) in controlling the EM. Co-culture of B. megaterium with roots significantly reduced bacterial growth whereas root development remained unaffected. Compound (1) production was 24 times higher after 48 hr in the presence of the highest B. megaterium concentration as compared to the control. Therefore, P. campestris adventitious roots affect the development of the endophyte B. megaterium through production of QMTs, which in turn can modulate production of compound (1).

Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) powdered leaves are effective in treating anxiety symptoms: A phase-2, randomized, placebo-controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) is a plant traditionally used as medicine for anxiety symptoms. This activity was confirmed in preclinical studies. However, its efficacy was never studied in human clinical trials. AIM OF THE STUDY: We aimed to test the hypothesis that the herbal medicine of A. polystachya is superior to placebo for the treatment of anxiety-related symptoms in adults after 8 weeks. PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled, phase-2 clinical trial. Fifty-four adults with self-reported anxiety symptoms were randomly allocated to receive either capsules containing A. polystachya powdered leaves (300 mg, twice a day) or placebo (maltodextrin), for 8 weeks. The intensity of anxiety symptoms was assessed by the Hamilton Anxiety Ranking Scale (HAM-A) at baseline and after 2, 4 and 8 weeks. All analyses were adjusted for physical activity (assessed by the International Physical Activity Questionnaire [IPAQ], short version) and gender. RESULTS: We confirmed the presence of acteoside (chromatographic analysis) and carvone and limonene (gas chromatography) as major constituents in our plant material. Only patients that received A. polystachya experienced a significant decrease in their HAM-A scores, with none or mild side-effects. CONCLUSION: Administration of powdered leaves of A. polystachya, rich in acteoside, carvone and limonene, to adults with anxiety symptoms was significantly superior to placebo in decreasing HAM-A scores after 8 weeks. This finding confirms the ethnopharmacological use of this plant for anxiety symptoms.

Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment. AIM OF THE STUDY: We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests. RESULTS: Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longa experienced less frequent nighttime awakenings, less frequent use of short-acting ß-adrenergic agonists, and better disease control after 3 and 6 months. CONCLUSION: The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short-acting ß-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo.

Efficacy of a Homeopathic Medicine of Capsicum frutescens L. (Solanaceae) in the Treatment of Hot Flashes in Menopausal Women: A Phase-2 Randomized Controlled Trial.

BACKGROUND: Hot flashes are common in women during menopause, and are an important cause of discomfort, increasing the number of medical appointments. Hormone replacement therapy is an effective treatment, but it can bring undesirable consequences. Alternative treatments exist but they are not universally accepted or effective. The ingestion of malagueta peppers (popular name for fruits of Capsicum frutescens L., Solanaceae) causes sensations similar to those experienced by women during hot flashes. Using the homeopathic law of similars (let like be cured by like), we hypothesized that a homeopathic remedy made of malagueta peppers can be effective in alleviating menopausal hot flashes. We named this remedy Malagueta. METHODS: This randomized, placebo-controlled, double-blind, phase-2 clinical trial was designed to test the hypothesis that, in menopausal women, the homeopathic medicine Malagueta (30 CH), compared with placebo, will significantly reduce the intensity of hot flashes, after 4 weeks of treatment. The primary outcome was the intensity of hot flashes, measured by the Measure Yourself Medical Outcome Profile (MYMOP) instrument. A total of 40 women were enrolled in the study, 20 in each group. RESULTS: The effect of Malagueta on the primary outcome, the intensity of hot flashes, assessed by MYMOP, was superior to that of placebo over the 4 weeks of treatment, with worsening in both groups after treatment was interrupted (after week 4, p < 0.001 in ordinal logistic regression). The odds ratio for treatment response (reduction of at least three MYMOP categories) was 2.78 (95% confidence interval, 0.77 to 10.05). Treatment with Malagueta, compared with placebo, also reduced the intensity of the secondary symptoms (p = 0.001) and improved level of activity (p = 0.025) and well-being (p = 0.008). CONCLUSION: The homeopathic medicine of Capsicum frutescens (Malagueta) was superior to placebo in reducing the intensity of hot flashes in menopausal women after 4 weeks of treatment.

The ethanolic extract from Erythrina mulungu Benth. flowers attenuates allergic airway inflammation and hyperresponsiveness in a murine model of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Erythrina mulungu Benth. ("mulungu", Fabaceae) is a Brazilian native species with ethnopharmacological use for respiratory diseases. However, the effects of E. mulungu on the respiratory were never studied. AIMS OF THE STUDY: To evaluate the effects of an ethanolic extract from flowers of E. mulungu in ovalbumin (OVA)-induced asthma in mice, and to study the mechanisms involved. MATERIALS AND METHODS: OVA-sensitized mice were intraperitoneally (i.p.) treated with four doses (200, 400, 600, and 800 mg/kg) of the E. mulungu extract or dexamethasone (DEXA, 2 mg/kg) during seven consecutive days and simultaneously challenged with intranasal OVA. Bronchial hyperresponsiveness was evaluated in vivo, 24 h after the last OVA challenge. Bronchoalveolar lavage (BAL) was collected for counting the number of total and differential inflammatory cells. Blood was collected for measurement of anti-OVA IgE levels. Levels of cytokines interleukin (IL)- 4, IL-5, IL-10, IL-13, and interferon (INF)-γ were measured in pulmonary homogenate by ELISA. The recruitment of inflammatory cells to the lung tissue was determined using hematoxylin and eosin staining (H&E). The extract's chromatographic profile was evaluated by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). RESULTS: The treatment with E. mulungu extract significantly reduced bronchial hyperresponsiveness, significantly reduced the number of leukocytes, eosinophils, and lymphocytes in BAL, and significantly decreased the levels of IL-4 and IL-5, while increased levels of IL-13 and INF-γ. In addition, E. mulungu significantly decreased the cellular inflammatory infiltration in the lung tissue. Erysotrine, erysotrine-N-oxide, and hypaphorine were the major constituents identified in the extract. CONCLUSION: Collectively, these results confirm the potential of E. mulungu for asthma treatment, through modulation of inflammatory response, supporting its ethnopharmacological use for respiratory diseases.

Aqueous extracts from Uncaria tomentosa (Willd. ex Schult.) DC. reduce bronchial hyperresponsiveness and inflammation in a murine model of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willd. Ex Schult) DC is used by indigenous tribes in the Amazonian region of Central and South America to treat inflammation, allergies and asthma. The therapeutic properties of U. tomentosa have been attributed to the presence of tetracyclic and pentacyclic oxindole alkaloids and to phenolic acids. AIMS OF THE STUDY: To characterize aqueous bark extracts (ABE) and aqueous leaf extracts (ALE) of U. tomentosa and to compare their anti-inflammatory effects. MATERIALS AND METHODS: Constituents of the extracts were identified by ultra performance liquid chromatography-mass spectrometry. Anti-inflammatory activities were assessed in vitro by exposing lipopolysaccharide-stimulated macrophage cells (RAW264.7-Luc) to ABE, ALE and standard mitraphylline. In vivo assays were performed using a murine model of ovalbumin (OVA)-induced asthma. OVA-sensitized animals were treated with ABE or ALE while controls received dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, total and differential counts of inflammatory cells in the bronchoalveolar lavage (BAL) and lung tissue were determined. RESULTS: Mitraphylline, isomitraphylline, chlorogenic acid and quinic acid were detected in both extracts, while isorhyncophylline and rutin were detected only in ALE. ABE, ALE and mitraphylline inhibited the transcription of nuclear factor kappa-B in cell cultures, ALE and mitraphylline reduced the production of interleukin (IL)-6, and mitraphylline reduced production of tumor necrosis factor-alpha. Treatment with ABE and ALE at 50 and 200 mg kg-1, respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200 mg kg-1 reduced the levels of IL-4 and IL-5 in the lung homogenate. Peribronchial inflammation was significantly reduced by treatment with ABE and ALE at 50 and 100 mg kg-1 respectively. CONCLUSION: The results clarify for the first time the anti-inflammatory activity of U. tomentosa in a murine model of asthma. Although ABE and ALE exhibited distinct chemical compositions, both extracts inhibited the production of pro-inflammatory cytokines in vitro. In vivo assays revealed that ABE was more effective in treating asthmatic inflammation while ALE was more successful in controlling respiratory mechanics. Both extracts may have promising applications in the phytotherapy of allergic asthma.

Availability of herbal medicines and medicinal plants in the primary health facilities of the state of São Paulo, Southeast Brazil: results from the National Program for Access and Quality Improvement in Primary Care. / Disponibilidade de medicamentos fitoterápicos e plantas medicinais nas unidades de atenção básica do Estado de São Paulo: resultados do Programa Nacional de Melhoria do Acesso e da Qualidade da Atenção Básica (PMAQ).

This study aims to describe the availability of herbal medicines and medicinal plants in the primary care facilities in the state of São Paulo, Southeast Brazil, from the results of the first cycle of the National Program for Access and Quality Improvement in Primary Care (PMAQ). The PMAQ uses a national cross-sectional multicenter design, with data from 4,249 health facilities distributed among 645 municipalities of the state of São Paulo. Of these facilities, 467 (11%) had herbal medicines and/or medicinal plants. Among the 645 municipalities, 104 (16.1%) had at least one health facility that provided these drugs. We observed that the availability of herbal medicines is greater in larger cities with better social and economic conditions. Furthermore, we found that use of industrialized herbal medicines prevailed over that of vegetal drugs or compounded herbal medicines.