Antioxidant activity, cytotoxicity, phenolic content, and phytochemical composition of Pithecellobium Diversifolium benth: a pilot study / Atividade antioxidante, citotóxica, conteúdo fenólico e composição fitoquímica de Pithecellobium Diversifolium benth: um estudo piloto / Actividad antioxidante, citotóxica, contenido fenólico y composición fitoquímica de Pithecellobium Diversifolium benth: un estudio piloto

Species of Pithecellobium (Fabaceae) are used in traditional medicine to treat diabetes, cough, bronchitis, and inflammation. This study aims to evaluate the content and determine the antioxidant activity, phenolic compounds content, and cytotoxicity of the extract and the fractions of Pithecellobium diversifolium. This is unprecedented research with an exotic species from the Caatinga, northeastern Brazil, using High-performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (HPLC-ESI-MS). The MeOH fractions of leaves and stem barks showed a high content of flavonoids (198.1 ± 106.50 and 542.7 ± 2.52 mg EqQ/g). The CH2Cl2 fraction of peels showed a high content of total phenolic compounds (516.7 ± 3.00 mg EqAG /g). The DPPH test showed that the CH2Cl2 fraction (leaves) held an EC50 of 0.08 ± 0.02, a higher value than that observed for the standards used in the test­Butylated hydroxyanisole (BHA), Butylated hydroxytoluene (BHT), and ascorbic acid. The AcOEt and MeOH fractions of peels presented moderate cytotoxicity with values below 500 µg/mL. The MeOH fraction of leaves showed seven major compounds: myricetin, quercetin, quercetin-arabinofuranoside, apigenin-triglycosides, and apigenin-diglucoside, being the last three unpublished in studies involving the genus. The tests conducted in this study show the potential of P. diversifolium as a promising source of biomolecules with therapeutic applicability.

Espécies de Pithecellobium (Fabaceae) são usadas na medicina tradicional para tratar diabetes, tosse, bronquite e inflamação. Este estudo teve como objetivo avaliar o teor e determinar a atividade antioxidante, o teor de compostos fenólicos e a citotoxicidade do extrato e das frações de Pithecellobium diversifolium, uma pesquisa inédita com uma espécie exótica da Caatinga do Nordeste do Brasil, utilizando a instrumentação Clae-IES. As frações MeOH das folhas e cascas do caule apresentaram alto teor de flavonoides (198,1 ± 106,50 e 542,7 ± 2,52 mg EqQ/g). A fração CH2Cl2 das cascas apresentou um elevado teor de compostos fenólicos totais (516,7 ± 3,00 mg EqAG/g). O teste DPPH mostrou que a fração CH2Cl2 (folhas) apresentou um EC50 de 0,08 ± 0,02, valor superior ao observado para os padrões utilizados no teste ­ Butil hidroxianisol (BHA), Butil hidroxitolueno (BHT) e ácido ascórbico. As frações AcOEt e MeOH das cascas apresentaram citotoxicidade moderada com valores inferiores a 500 µg/mL. A fração MeOH das folhas apresentou sete compostos majoritários: miricetina, quercetina, quercetina-arabinofuranosídeo, apigenina-triglicosídeos e apigenina-diglucosídeo, sendo os três últimos inéditos em estudos envolvendo o gênero. Os testes realizados demonstram o potencial de P. diversifolium, uma promissora fonte de biomoléculas com aplicabilidade terapêutica.

Las especies de Pithecellobium (Fabaceae) se utilizan en la medicina tradicional para tratar diabetes, tos, bronquitis e inflamación. Este estudio tuvo como objetivo evaluar el contenido y determinar la actividad antioxidante, el contenido de compuestos fenólicos y la citotoxicidad del extracto y de las fracciones de Pithecellobium diversifolium, un estudio inédito con una especie exótica de la Caatinga de la región Nordeste de Brasil, que utilizó la instrumentación HPLC-ESI. Las fracciones MeOH de hojas y cortezas de tallo mostraron un alto contenido de flavonoides (198,1 ± 106,50 y 542,7 ± 2,52 mg EqQ/g). La fracción CH2Cl2 de las cortezas presentó un alto contenido de compuestos fenólicos totales (516,7 ± 3,00 mg EqAG/g). El ensayo DPPH mostró que la fracción CH2Cl2 (hojas) tenía EC50 de 0,08 ± 0,02, valor superior a lo observado para los estándares utilizados en el ensayo ­Butilhidroxianisol (BHA), butilhidroxitolueno (BHT) y ácido ascórbico. Las fracciones AcOEt y MeOH de las cortezas presentaron una citotoxicidad moderada con valores inferiores a 500 µ g/mL. La fracción MeOH de las hojas contiene siete compuestos principales: miricetina, quercetina, quercetina-arabinofuranosido, apigenina-triglucósidos y apigenina-diglucósido, de los cuales los tres últimos son inéditos en estudios sobre el género. Las pruebas realizadas demuestran el potencial de P. diversifolium, una fuente prometedora de biomoléculas con aplicabilidad terapéutica.

Genus Triplaris (Polygonaceae): A review on traditional medicinal use, phytochemistry and biological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Triplaris (Polygonaceae) comprises approximately 25 species distributed throughout South and Central America. Some species have been used in folk medicine, mainly, to treat malaria, leishmaniasis, diarrheia, dysenteria, pain and inflammation. AIM OF THE STUDY: The purpose of this review is to provide information on the traditional uses, phytochemistry and known biological activities of Triplaris, an important genus for South America research groups on medicinal plants, in order to explore its therapeutic potential to direct future research in the search for new bioactive molecules. MATERIALS AND METHODS: The available information on the genus Triplaris was gathered from scientific databases (LILACS, Pubmed, SciELO, Science Direct, Scopus, CAPES Periodicals Portal and Theses and Dissertations Catalog) before March 2020 using the keyword "Triplaris". Works related to traditional uses, phytochemistry and biological activities of plants were included in this review. RESULTS: Most of the studies involving Triplaris were conducted by research groups located in Brazil, Peru e Bolivia. Probably, because the genus has been used in folk medicine only by these countries. Regarding the annual evolution of the publications, a larger number of articles published in 2010 were observed. Flavonols represent the main classe of secondary metabolites from Triplaris. In terms of the pharmacological investigations, T. americana and T. gardneriana are considered the most studied species, with extensive promising biological activities. The pharmacological activities can be attributed to bioactive phytochemicals. CONCLUSIONS: All findings indicate that Triplaris is an important genus of the Polygonaceae family. However, considering its chemical and pharmacological importance, the studies developed with Triplaris species are still limited, representing an opportunity to investigate new bioactive molecules and extracts. The review shows that little pre-clinical or in vivo research is available to prove the ethnopharmacological records in the genre. Therefore, this review encourages further studies on Triplaris in the search for a wide range of therapeutic products.

Corrigendum to: "Inclusion of vitexin in ß-cyclodextrin: preparation, characterization and expectorant/antitussive activities" [Heliyon 6 (12) (December 2020) e05461].

[This corrects the article DOI: 10.1016/j.heliyon.2020.e05461.].

Cannabis roots: Pharmacological and toxicological studies in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: There are many studies and therapeutic properties attributed to the flowers and leaves of the Cannabis species, but even with few pharmacological studies, Cannabis sativa L. (Cannabaceae) roots presents several therapeutic indications in folk medicine. AIM OF THE STUDY: This study aimed to evaluate the anti-inflammatory and spasmolytic effects as well as the toxicological profile of the aqueous extract of Cannabis sativa roots (CsAqEx) in mice. MATERIALS AND METHODS: We assessed the anti-inflammatory effect with carrageenan-induced leukocyte migration assay, and carrageenan and histamine-induced paw edema methods; The spasmolytic effect was assessed through in vitro assays with isolated mice trachea. To assess motor coordination and mobility, mice went through the rotarod and open field tests, respectively. For the single-dose toxicity study, we administered CsAqEx at the dose of 1000 mg/kg by gavage. In a repeated dose toxicity study, animals received CsAqEx at doses of 25 mg or 100 mg/kg for 28 days. RESULTS: The CsAqEx inhibited the migration of leukocytes at the doses of 25, 50, and 100 mg/kg. The CsAqEx showed anti-inflammatory activity after the intraplantar injection of carrageenan, presenting a reduction in edema formation at all tested doses (12.5, 25, 50 and 100 mg/kg). The dose of 12.5 mg/kg of CsAqEx prevented edema formation after intraplantar injection of histamine. In an organ bath, 729 µg/mL of CsAqEx did not promote spasmolytic effect on isolated mice tracheal rings contracted by carbachol (CCh) or potassium chloride (KCl). We did not observe clinical signs of toxicity in the animals after acute treatment with CsAqEx, which suggested that the median lethal dose (LD50) is greater than 1000 mg/kg. Repeated dose exposure to the CsAqEx did not produce significant changes in hematological, biochemical, or organ histology parameters. CONCLUSIONS: The results suggest that the anti-inflammatory effect of CsAqEx is related to the reduction of vascular extravasation and migration of inflammatory cells, without effects on the central nervous system. Moreover, there was no spasmolytic effect on airway smooth muscle and no toxicity was observed on mice.

Jatropha mutabilis, a new source of vitexin: HPLC quantification and pharmacological evaluation.

Jatropha mutabilis (Pohl) Baill is an endemic species of the Caatinga biome, little studied in terms of chemical composition. The objective of this work was to develop an analytical methodology to quantify vitexin in the ethanolic extract of J. mutabilis and to evaluate the expectorant and antitussive activities in mice. The expectorant activity was performed by measuring the phenol red obtained from the bronchoalveolar fluid in animals and the antitussive activity was evaluated by the cough method induced by citric acid (0.4 M). The method developed by HPLC-DAD proved to be simple, linear, precise, accurate, robust and specific. Besides, both vitexin (0.2, 1 and 5 mg/kg) and the extract of J. mutabilis (20, 102, 510 mg/kg) showed efficacy in decrease cough and increase aqueous mucus in mice, but vitexin was more potent. Lastly, the identification of vitexin opens the possibility of new studies for J. mutabilis.

Inclusion of vitexin in ß-cyclodextrin: preparation, characterization and expectorant/antitussive activities.

The study aimed to include the isolated vitexin of Jatropha mutabilis in the ß-cyclodextrin cavity to improve the solubility of this flavone. Its characterization was performed by techniques such as 1H NMR/ROESY (Nuclear Magnetic Resonance Spectroscopy), FT-IR (Infrared Spectroscopy with Fourier Transform), SEM (Morphological analysis of IC by Scanning Electron Microscopy) and dissolution study in vitro. In addition, the following activities were evaluated in the animal models: expectorant, phenol red dosage in bronchoalveolar lavage and antitussive, cough induced by citric acid. In the characterization of the complex, interaction between hydrogens of ring B of vitexin and (H3) of ß-CD was observed, in addition to changes in morphology. In the dissolution test, an increase in the rate of dissolution of vitexin was observed in the first 30 min for the CI vitexin/ß-CD when compared with vitexin. Regarding the pharmacological activity, it was observed that the inclusion complex (IC) vitexin/ß-CD in the equivalent doses of 0.2, 1 and 5 mg/kg of flavone presented higher expectorant activity when compared to vitexin (p < 0.05), suggesting increased bioavailability. As for the antitussive activity, both vitexin and the complex had similar effects and were dose independent. In the toxicity test using Artemia salina, vitexin and IC vitexin/ß-CD were considered non-toxic. At last, the study efficacy of vitexin/ß-CD IC as an expectorant and of vitexin as antitussive. All of these data are being described for the first time.

Complexation with ß-cyclodextrin enhances apoptosis-mediated cytotoxic effect of harman in chemoresistant BRAF-mutated melanoma cells.

Harman, a natural ß-carboline alkaloid, has recently gained considerable interest due to its anticancer properties. However, its physicochemical characteristics and poor oral bioavailability have been limiting factors for its pharmaceutical development. In this paper, we described the complexation of harman (HAR) with ß-cyclodextrin (ßCD) as a promising alternative to improve its solubility and consequently its cytotoxic effect in chemoresistant melanoma cells (A2058 cell line). Inclusion complexes (ßCD-HAR) were prepared using a simple method and then characterized by FTIR, NMR and SEM techniques. Through in silico studies, the mechanism of complexation of HAR with ßCD was elucidated in detail. Both HAR and ßCD-HAR promoted cytotoxicity, apoptosis, cell cycle arrest and inhibition of cell migration in melanoma cells. Interestingly, complexation of HAR with ßCD enhanced its pro-apoptotic effect by increasing of caspase-3 activity (p < 0.05), probably due to an improvement in HAR solubility. In addition, HAR and ßCD-HAR sensitized A2058 cells to vemurafenib, dacarbazine and 5FU treatments, potentializing their cytotoxic activity. These findings suggest that complexation of HAR with natural polymers such as ßCD can be useful to improve its bioavailability and antimelanoma activity.

Pre-clinical investigations of ß-carboline alkaloids as antidepressant agents: A systematic review.

Depressive disorders remain a current public health problem whose prevalence has increased in the past decades. In the constant search for new therapeutic alternatives, ß-carboline alkaloids have been identified as good candidates for new antidepressant drugs. In this systematic review, we summarized all pre-clinical investigations involving the use of natural or semisynthetic ß-carboline in depression models. A literature search was conducted in August 2018, using PubMed, Scopus and Science Direct databases. All reports were carefully analyzed, and data extraction was conducted through standardized forms. Methodological quality assessment of in vivo studies was also performed. The entire systematic review was performed according to PRISMA statement. From a total of 373 articles, 26 met all inclusion criteria. In vitro and in vivo studies have evaluated a wide variety of ß-carbolines through enzymatic and binding assays, and acute or chronic animal models. Most of the in vivo and in vitro studies is concentrated on two molecules: harman and harmine. They have been investigated in several animal models and some mechanisms of action have been proposed for their antidepressant activity. In general, ß-carbolines modulate 5-HT and GABA systems, promote neurogenesis, induce neuroendocrine response and restore astrocytic function, being effective when administrated acutely or chronically in different animal models, including chronic mild stress protocols. In short, ß-carbolines are multi-target antidepressant compounds and may be useful in the treatment of depressive disorders.

TRPM8 Channel Activation Induced by Monoterpenoid Rotundifolone Underlies Mesenteric Artery Relaxation.

In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the understanding of the role of these thermosensitive TRP channels in vascular tissue. Thus, message and protein levels of TRPM8 were measured by semi-quantitative PCR and western blotting in superior mesenteric arteries from 12 week-old Spague-Dawley (SD) rats. Isometric tension recordings evaluated the relaxant response in mesenteric rings were also performed. Additionally, the intracellular Ca2+ changes in mesenteric artery myocytes were measured using confocal microscopy. Using PCR and western blotting, both TRPM8 channel mRNA and protein expression was measured in SD rat mesenteric artery. Rotundifolone and menthol induced relaxation in the isolated superior mesenteric artery from SD rats and improved the relaxant response induced by cool temperatures. Also, this monoterpene induced an increase in transient intracellular Ca2+. These responses were significantly attenuated by pretreatment with capsazepine or BCTC, both TRPM8 channels blockers. The response induced by rotundifolone was not significantly attenuated by ruthenium red, a non-selective TRP channels blocker, or following capsaicin-mediated desensitization of TRPV1. Our findings suggest that rotundifolone induces relaxation by activating TRPM8 channels in rat superior mesenteric artery, more selectively than menthol, the classic TRPM8 agonist, and TRPM8 channels participates in vasodilatory pathways in isolated rat mesenteric arteries.

Dried extracts of Encholirium spectabile (Bromeliaceae) present antioxidant and photoprotective activities in vitro.

The antioxidant and photoprotective activities of dried extracts from the leaves of Encholirium spectabile were investigated. It was also evaluated the total phenolic and flavonoid contents by the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using of 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and ß-carotene-linoleic acid bleaching and compared with ascorbic acid, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) used as reference compounds. The photoprotective effect was evaluated by the spectrophotometric method. The most significant total phenolic and flavonoid contents was of 188.50 ± 27.50 mg of gallic acid equivalent/g and 129.70 ± 4.59 mg of catechin equivalent/g, respectively, for chloroform fraction (Es-CHCl3). The Es-CHCl3 also presented the best antioxidant activity (IC50 25.35 ± 4.35 µg/ml) for DPPH scavenging. The ethanol extract (Es-EtOH), Es-CHCl3 and the fraction ethyl acetate (Es-AcOEt) showed characteristic absorption bands in regions UVB and UVA in a concentration-dependent manner. Es-CHCl3 presented the highest sun protection factor SPF (8.89 ± 2.11). It shows the possibility to use this extract as sunscreen in pharmaceutical preparations.

Antinociceptive effect of ethanolic extract of Selaginella convoluta in mice.

BACKGROUND: Selaginella convoluta (Arn.) Spring (Selaginellaceae), commonly known as "jericó", is a medicinal plant found in northeastern Brazil. S. convoluta is used in folk medicine as an antidepressant, aphrodisiac, diuretic, analgesic, anti-inflammatory and it is used to combat amenorrhea, coughing and bleeding. This study was performed to evaluate the antinociceptive effects of ethanolic extract from S. convoluta in mice exposed to chemical and thermal models of nociception. METHODS: Preliminary phytochemical analysis of the ethanolic extract was performed. The ethanolic extract from Selaginella convoluta (Sc-EtOH) was examined for its intraperitoneal (i.p.) antinociceptive activity at the doses of 100, 200 and 400 mg/kg body weight. Acetic acid-induced writhing, formalin injection and hot plate tests were used to evaluate the antinociceptive activity of Sc-EtOH extract. The rota-rod test was used to evaluate motor coordination. RESULTS: A preliminary analysis of Sc-EtOH revealed that it contained phenols, steroids, terpenoids and flavonoids. In the acetic acid-induced writhing test, mice treated with Sc-EtOH (100, 200 and 400 mg/kg, i.p.) exhibited reduced writhing (58.46, 75.63 and 82.23%, respectively). Secondly, Sc-EtOH treatment (100, 200 and 400 mg/kg, i.p.) decreased the paw licking time in mice during the first phase of the formalin test (by 44.90, 33.33 and 34.16%, respectively), as well as during the second phase of the test (by 86.44, 56.20 and 94.95%, respectively). Additionally, Sc-EtOH treatment at doses of 200 and 400 mg/kg increased the latency time in the hot plate test after 60 and 90 minutes, respectively. In addition, Sc-EtOH did not impair motor coordination. CONCLUSION: Overall, these results indicate that Sc-EtOH is effective as an analgesic agent in various pain models. The activity of Sc-EtOH is most likely mediated via the inhibition of peripheral mediators and central inhibitory mechanisms. This study supports previous claims of traditional uses for S. convoluta.

Antinociceptive activity of ethanol extract from Duguetia chrysocarpa Maas (Annonaceae).

The ethanol extract from the fruits of Duguetia chrysocarpa was evaluated for its antinociceptive activity in chemical and thermal models of nociception in mice. The intraperitoneal administration of the ethanol extract (100, 200, and 400 mg/kg body weight) showed a dose-dependent inhibition of acetic-acid-induced abdominal writhes. The extract also produced a significant inhibition of both phases of the formalin test in all doses tested and increased the reaction time in hot-plate test at dose of 200 mg/kg. The data obtained suggest that the antinociceptive effect of the extract may be mediated via both peripheral and central mechanisms. The phytochemical investigation yielded the isolation of the benzenoid derivative 3-methoxy-4-ethoxy benzoic acid which is being reported for the first time in this genus.

Mechanisms involved in the antinociceptive effects of 7-hydroxycoumarin.

7-Hydroxycoumarin (umbelliferone, 1), the main metabolite of coumarin, has been reported to produce potent antinociceptive effects in animal models of pain. However, the biochemical events involved in antinociception mediated by 1 are currently not well understood. In the present study, the mechanisms by which 1 exerts its pharmacological actions were investigated. Acute pretreatment of mice with 1 produced a long-lasting antinociceptive effect against complete Freund's adjuvant (CFA)-induced hyperalgesia. The subchronic administration of 1 inhibited CFA-induced hyperalgesia and paw edema, while it did not cause any apparent toxicity. Another set of experiments showed that 1 inhibited carrageenan-induced mechanical hyperalgesia, but not mechanical hyperalgesia induced by prostaglandin E(2) (PGE(2)), suggesting that it acts upstream of PGE(2.) Treatment with 1 was able to prevent the plantar tissue neutrophil influx induced by local inflammatory stimuli. In addition, 1 exhibited inhibitory effects on the release of hyperalgesic cytokines (TNF-α and IL-1ß) and the production of PGE(2), a directly acting hyperalgesic mediator. The present results suggest that the antinociceptive effect of 1 is correlated with the inhibition of neutrophil migration, cytokine release, and PGE(2) production and are supportive of the further investigation of the therapeutic potential of 1 to control inflammatory pain.

Antimicrobial activity of the essential oil of Bowdichia virgilioides Kunt. / Atividade antimicrobiana do óleo essencial de Bowdichia virgilioides Kunt.

The essential oil of Bowdichia virgilioides Kunt. (Fabaceae) leaves was tested for their antimicrobial activity against eighteen pathogenic microorganisms using standard gel diffusion method. It showed activity against Candida albicans, Candida guilliermondii, Candida stellatoidea, Micrococcus luteus and Trichophyton rubrum.

O óleo essencial das folhas de Bowdichia virgilioides Kunt. (Fabaceae) foi testado para a verificação da sua atividade antimicrobiana contra dezoito microorganismos patogênicos, usando o método de difusão em meio sólido. Foi observada atividade contra Candida albicans, Candida guilliermondii, Candida stellatoidea, Micrococcus luteus e Trichophyton rubrum.

Antimicrobial activity of the essential oil of Sida cordifolia L. / Atividade antimicrobiana do óleo essencial de Sida cordifolia L.

The analysis of the antimicrobial activity of the essential oil of Sida cordifolia was evaluated with four different strains of bacteria and nine fungi. The essential oil was tested "in natura" (100 percent) and diluted from 32 until 2 percent. The microorganisms, bacteria and fungi, were spread in agar Muller-Hinton and Sabouraud dextrose, respectively. S. cordifolia showed inhibitory activity against the microorganisms tested with efficacy of 80 percent. When tested against Staphylococcus aureus, Staphyllococus epidermidis, Candida guilliermondii and Trichosporon inkin the essential oil showed the best performance.

A análise da atividade antimicrobiana do óleo essencial de Sida cordifolia foi avaliada com quatro diferentes cepas de bactérias e nove de fungos. O óleo essencial foi testado "in natura" 100 por cento e diluído de 32 até 2 por cento. Os microrganismos, bactérias e fungos, foram semeados em ágar Muller-Hinton e Sabouraud dextrose, respectivamente. S. cordifolia mostrou atividade inibitória contra os microrganismos testados com eficácia de 80 por cento. Quando testado contra Staphyllococus aureus, Staphyllococus epidermidis, Candida guilliermondii e Trichosporon inkin o óleo essencial mostrou um melhor desempenho.

Antimicrobial activity of a mixture of two isomeric phenylpropanoid glycosides from Arrabidaes harleyi A.H. Gentry(Bignoniaceae)

Arrabidaea harleyi A.H. Gentry (Bignoniaceae) is an ornamental plant found in some regions of the Atlanticforest in Brazil. From its bark a mixture of verbascoside and isoverbascoside was isolated. This mixture was shown to be active against Staphylococcus aureus, Micrococcus luteus, Bacillus subtilis, Bacillus mycoides, Enterecoccus faecalis, Escherichia coli, Serratia marcensis and Candida albicans. The minimal inhibitory concentration (MIC) was established by diffusion method