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Leishmaniasis is a neglected disease that affects 15 million people worldwide. Existing treatments are associated with limitations, including high costs and toxicity. Several classes of natural substances have been reported to display leishmanicidal activity in the literature. Isoquinoline alkaloids, which are commonly found in the Annonaceae family, represent an important skeleton for the development of anti-leishmaniasis products. This study presents an overview of the potential use of Annonaceae alkaloids to treat leishmaniasis and describes a molecular docking study examining 215 isoquinoline alkaloids. All selected compounds contain a bisbenzyltetrahydroisoquinoline, suggesting the affinity of this skeleton for the target.

O objetivo do trabalho foi investigar o efeito agudo do óleo essencial de eucalipto (OEE) nas respostas cardiovasculares de repouso e após sessão de exercício resistido isométrico (ERI). Vinte idosos, após serem submetidos a sessões experimentais com inalação de OEE ou condição controle, permaneceram em recuperação durante 60 min (Rec-60’) para depois realizaram três séries de 1 min (1 min de recuperação entre séries) no ERI, para membro superior dominante em aparelho de preensão manual, com intensidade de 30% da contração voluntária máxima (ERI-30%). Intervalos R-R (iRR) e medidas no domínio da frequência (low frequency – LF e high frequency – HF) além da pressão arterial (PA), frequência cardíaca (FC) e duplo produto (DP) foram avaliados. Não ocorreram diferenças (p>0,05) quando comparadas as sessões (OEE vs.controle) na Rec-60’ e ERI-30%. Diferenças foram encontradas no fator tempo do repouso para Rec-60’ nas variáveis FC e iRR e do repouso para ERI-30% na PA sistólica, PA diastólica e DP. A inalação do OEE não proporcionou alterações significativas nas respostas cardiovasculares e autonômicas de idosos no repouso e após sessão de ERI-30%.

Mastitis is one of the most important diseases in dairy milk systems. Molecular studies of the principal agents that are involved, as well as tests of bacterial sensitivity to plant extracts, are currently the most common forms of research related to this disease. The aim of the present study was to molecularly characterize isolates from cases of subclinical mastitis and to investigate the production of biofilm associated with extracts from Hymenaea martiana. The phytochemical screening of the crude ethanolic extract (CEE) confirmed the presence of phenolic substances, flavonoids, steroids and terpenoids. The antimicrobial susceptibility profile of the isolates that were assessed exhibited variations, with a notably high sensitivity to gentamicin. After the addition of the extract, 77.3, 81.8 and 86.3% of the isolates exhibited a reduction in biofilm production in the ethyl acetate, chloroform and hexane fractions, respectively. An extensive production of biofilm can be observed in the isolates that were not in contact with the natural extract. However, when in contact with the plant extract, there was a reduction in biofilm production, thereby demonstrating the therapeutic potential of the natural extract of H. martiana in mastitis caused by Staphylococcus spp. Key words: Mastitis, pathogens, resistance genes, sensitivity tests.

Lobularia maritima (Alyssum maritimum, Brassicaceae), commonly known as sweet alyssum, is an annual ornamental halophyte widely spread along the Tunisian seashore. Lobularia maritima leaf ethanol e...

Objective The objective of this work was evaluate the cytotoxic, leishmanicidal and tripanocidal activity, as well as to evaluate its antimicrobial and modulatory activity in association with different antibiotics of the hydroethanolic extract of the Ximenia Americana stem bark (EHXA). Method In vitro tests against Trypanosoma cruzi, Leishmania sp. and citotoxicity were performed. The evaluation of the antibacterial and bacterial resistance modulatory effect was given by the microdilution method. Results The chemical profile show different classes of compounds with significant presence of quercetrin and caffeic acid. The EHXA demonstrated activity only in the concentration of 1000 μg/mL against the L. infantum and L. brasiliensis promastigotes, causing mortality percentage of 40.66 and 27.62%, respectively. The extract presented a significant toxicity only in the concentration of 1000 μg/mL, causing a mortality of 55.42% of fibroblasts. The antibacterial activity of the EHXA demonstrated a MIC value ≥1024 μg/mL against all the tested bacteria. However, in the modulation assay with EHXA in association with different antibiotics the extract had a synergistic effect against S. aureus strains when associated with norfloxacin. Conclusion The results of this investigation demonstrate for the first time the chemical composition of the hydroethanolic extract of the Ximenia Americana stem bark, your potential antiparasitic and modulatory effect. The low cytotoxic and biological potential against S. aureus open therapeutic perspectives against leishmaniosis and bacterial infections.

Background Arthritis is a syndrome associated with exacerbated inflammation, joint destruction and chronic pain and disability. Chronic treatment of arthritis is associated with several side effects and high abandonment. Therefore, there has been an ongoing search for alternative treatments to overcome these problems. Purpose Natural products, which are already widely used for their biological, cosmetic and pharmacotechnic properties, are a possible source for new drugs. Terpenes, a large class of organic compounds produced mainly by plants and trees, are a promising natural product and have already been shown to be effective in treating chronic pain, particularly of an inflammatory origin. Study Design and Methods This review identifies the main terpenes with anti-arthritic activity reported in the last 10 years. A survey was conducted between December 2017 and June 2018 in the PUBMED, SCOPUS and Science Direct databases using combinations of the descriptors terpenes, arthritis and inflammation. Results The results showed that terpenes have promising biological effects in relation to the treatment of arthritis, with the 24 terpenes identified in our survey being effective in the modulation of inflammatory mediators important to the physiopathology of arthritis, such as IL-6, IL-17, TNF-α, NFκB, and COX-2, among others. It is important to note that most of the studies used animal models, which limits, at least in part, the direct translation to humans of the experimental evidence produced by the studies. Conclusion Together, our finds suggest that terpenes can modulate the immuno-regulatory and destructive tissue events that underlie the clinical presentation and the progression of arthritis and are worthy of further clinical investigation.

Background Bothropic venoms cause intense local damage, pain, edema, and myonecrosis. Morus nigra L. (Moraceae) has several uses in folk medicine and can be a promising candidate for the treatment of several inflammatory disorders. Hypothesis/Purpose The present study aims to evaluate the anti-inflammatory and antinociceptive effects of the ethanolic extract of Morus nigra L. (Mn-EtOH) on paw lesions induced by Bothrops jararacussu snake venom (BjcuV) in mice. Methods UV–vis absorption of BjcuV was evaluated. A phytochemical study was performed, which led to the isolation and characterization of three compounds. These compounds were identified using spectrometric methods, namely LC–MS and NMR (1D and 2D), followed by the validation of their spectra with the data available in the literature. Further, the flavonoids i.e. rutin and quercetin (chemical markers of M. nigra), Mn-EtOH or Mn-EtOH-encapsulated electrospun fibers of Eudragit L100 (FB/Mn-EtOH), and Mn-EtOH-encapsulated microparticles of Eudragit L100 (MP/Mn-EtOH) were evaluated, in paw edema test induced by BjcuV. Results UV–vis spectra showed the presence of phospholipases A2 as component of BjcuV. The chemical examination resulted in the isolation of β-sitosterol, quercetin-3-O-glucopyranoside, and kaempferol-3-O-glucopyranoside. Mn-EtOH, FB/Mn-EtOH, MP/Mn-EtOH, rutin, and quercetin reduced the local edema induced by BjcuV. The Mn-EtOH also prevented edema provoked by serotonin and bradykinin. Moreover, it reduced paw edema and peritoneal leukocyte infiltration induced by carrageenan, and decreased the mechanical hypernociception of BjcuV. Mn-EtOH exerted anti-inflammatory and antinociceptive effects, possibly by the inhibition of leukocyte migration and the modulation of serotonin and bradykinin actions. This anti-inflammatory activity was maintained even upon incorporation of the M. nigra extract into the drug delivery systems (i.e., Mn-EtOH-encapsulated FBs and MPs of Eudragit L100). Conclusion These results reinforce the therapeutic potential of M. nigra in the treatment of inflammatory conditions, in addition to, its role as a complementary treatment of snakebites.

Annona vepretorum is endemic from the Brazilian Caatinga biome and is used in human nutrition. The present study aimed to investigate the toxic effects of the ethanolic extract from the leaves of this species. The leaves of A. vepretorum were collected, dried, pulverized, and macerated with ethanol to yield the crude ethanol extract of A. vepretorum. HPLC-diode array detection was used to determine the fingerprint chromatogram of the extract. In toxicity studies, the acute toxicity experimental group was administered a single dose of the ethanol extract of A. vepretorum (1 g/kg), while in the subacute toxicity experimental group, the ethanol extract of A. vepretorum was administered orally, daily for 30 days, at doses of 100 and 400 mg/kg. Death and signs of toxicity were observed and at the end, the animals were anesthetized, and blood and organs were then collected. The presence of the flavonoid rutin in the extract was confirmed using HPLC-diode array detection. In the evaluation of acute and subacute toxicity, there were no behavioral and physiological changes or signs of toxicity, and no occurrences of mice deaths were registered. The organs had normal color and preserved architecture, and no statistical variations in weight were observed. The results of the hematological and biochemical parameters after the administration of the ethanol extract of A. vepretorum showed no significant change, except in the count of the number of leukocytes and triglycerides. The histopathologic analysis of the liver, kidneys, and stomach indicated architecture with normal aspects. Thus, the toxicity study indicates low toxicity of the ethanol extract of A. vepretorum. Such information will be helpful in future clinical studies.

Ethanol extracts of different parts of Passiflora cincinnata were obtained by maceration. The total phenolic and flavonoid contents were evaluated. The antioxidant activities were determined by β-c...

Saponins are glycosides which, after acid hydrolysis, liberate sugar(s) and an aglycone (sapogenin) which can be triterpenoid or steroidal in nature. Steroidal saponins and sapogenins have attracted significant attention as important natural anti-inflammatory compounds capable of acting on the activity of several inflammatory cytokines in various inflammatory models.The aim of this review is to collect preclinical in vivo studies on the anti-inflammatory activity of steroidal saponins through the modulation of inflammatory cytokines.This review was carried out through a specialized search in three databases, that were accessed between September and October, 2021, and the publication period of the articles was not limited. Information about the name of the steroidal saponins, the animals used, the dose and route of administration, the model of pain or inflammation used, the tissue and experimental method used in the measurement of the cytokines, and the results observed on the levels of cytokines was retrieved.Forty-five (45) articles met the inclusion criteria, involving the saponins cantalasaponin-1, α-chaconine, dioscin, DT-13, lycoperoside H, protodioscin, α-solanine, timosaponin AIII and BII, trillin, and the sapogenins diosgenin, hecogenin, and ruscogenin. The surveys were carried out in seven different countries and only articles between 2007 and 2021 were found. The studies included in the review showed that the saponins and sapogenins were anti-inflammatory, antinociceptive and antioxidant and they modulate inflammatory cytokines mainly through the Nf-κB, TLR4 and MAPKs pathways.Steroidal saponins and sapogenins are promising compounds in handling of pain and inflammation for the development of natural product-derived drugs. However, it is necessary to increase the methodological quality of preclinical studies, mainly blinding and sample size calculation.

Complex regional pain syndrome type 1 (CRPS-1) is a painful syndrome without effective treatment. In order to explore possible new treatments, we used an animal model of CRPS-1 to examine the effects of β-Citronellol (βCT), a monoterpene found in a variety of plants that has been shown to have analgesic effects. We aimed to assess its effects alone, and complexed with β-cyclodextrin (βCD), which has been previously used to enhance the effects of a number of medicines. The βCT-βCD was characterized physiochemically using high performance liquid chromatography (HPLC) and differential scanning calorimetry (DSC) and shown to have 80% efficiency. In the animal model, Swiss mice were treated with βCT, βCT-βCD, vehicle, pregabalin or sham and evaluated for hyperalgesia and motor coordination. Inflammatory mediators were measured by Western blot or ELISA and the descending pain pathway by immunofluorescence. βCT was shown to have an anti-hyperalgesic effect (without affecting motor coordination) that reduced inflammatory mediators and activated the descending pain pathway, and these effects were increased with complexation in βCD. Our results showed βCT-βCD to be a promising treatment for CRPS-1.

Fat burners are a category of nutritional supplements that are claimed to increase the metabolism and promote greater energy expenditure, leading to weight loss. However, little is known about the side effects on gastrointestinal motility. In this study, we evaluated the effect of ingestion with a fat burner named Thermbuterol® (THERM) on the gastric motility and food behavior of mice. THERM compounds were identified using nuclear magnetic resonance (NMR). Mice received variable doses of THERM (10, 50, 100 or 300 ​mg/kg, p.o.) or NaCl 0.15 ​M (control). Gastric emptying (GE) was assessed using the phenol red technique. Another set of mice was pretreated with intraperitoneal administration of hexamethonium (HEXA, 10 ​mg/kg), prazosin (PRAZ, 0.25 ​mg/kg), propranolol (PROP, 2 ​mg/kg), parachlorophenylalanine (PCPA, 300 ​mg/kg) or ondansetron (ONDA, 50 ​μg/kg) 30 ​min before THERM treatment for evaluation of GE. We assessed the gastrointestinal responsiveness in vitro as well as THERM's effects on food behavior. Caffeine was the major compound of THERM, identified by NMR. THERM 100 and 300 ​mg/kg decreased GE compared to the respective controls. Pretreatment with PRAZ or PROP did not prevent gastric dysmotility induced by THERM 100 ​mg/kg. However, the pretreatment with HEXA, ONDA or PCPA prevented GE delay induced by THERM. In vitro, THERM relaxed contractions in strips of longitudinal gastric fundus and duodenum. THERM also increased food intake, which was prevented by PCPA and ONDA treatments. THERM decreased GE of a liquid and increased food intake in mice, a phenomenon mediated by the autonomic nicotinic receptors and serotoninergic receptor., Graphical abstract Image 1, Highlights • Gastric emptying delay induced by THERM was mediated by nicotinic and 5-HT3 receptors. • THERM increased the food intake mediated by the 5-HT3 receptors. • THERM decreased gastric and duodenal contractility in vitro. • Caffeine was the major component of THERM and it decreased gastric emptying delay.

Microdilution assays were performed in order to evaluate the antimicrobial activity of the ethanoic extract from the leaves of Bauhinia forficate (EEBF) against different microorganisms. The extract did not present inner antimicrobial activities against the tested strains. However, EEBF was able to modulate the norfloxacin-resistance against Staphylococcus aureus SA1199-B that overproduce the NorA efflux pump, once sub-inhibitory concentrations of EEBF reduced the minimal inhibitory concentratio of the norfloxacin in 87.5%. This modulatory effect was also found when the antibiotic was replaced by ethidium bromide, suggesting that EEBF acts probably by inhibition of NorA, allowing the antibiotic accumulation intracellularly, and making the line more sensitive. These results point out the EEBF potential as a source of NorA inhibitors that could be used in combination with norfloxacin for treatment of infections caused by multidrug-resistant S. aureus.

Background Limonene (LIM) and its main metabolite perillyl alcohol (POH) are ingredients found in food with promising chemical entities due to their pharmacological profile. In this study, we hypothesized that LIM and POH are two molecules capable of accelerating the regenerative process and alleviating neuropathic pain. Methods: Animals were treated daily (LIM, POH and saline) for 28 days and during this period evaluated for mechanical hyperalgesia, astrocyte participation by immunofluorescence for GFAP, and ELISA was used to quantify IL-1β and TNF-α in the spinal cord. Western blot analysis of the following proteins was also performed: GFAP, GAP-43, NGF and ERK. For motor deficit analysis, tests were performed to assess hind paw muscle strength and footprints through gait (SFI). Results: Both POH and LIM accelerated the regenerative process and improved motor deficits comparing to positive control; however, POH was more effective, particularly between the 2nd and 3rd week after the nerve injury, increasing GAP-43, NGF and the phosphorylated ERK immunocontent. Moreover, POH and LIM were able to reduce hyperalgesia and astrocytosis. Conclusions: Both substances, LIM and POH, improved the regeneration process and sensory and motor function recovery in the PNI model in mice by mitigating the inflammatory reactions and up-regulating the neurotrophic process.

Neuropathic pain develops due to injury to the somatosensory system, affecting the patient's quality of life. In view of the ineffectiveness of the current pharmacotherapy, substances obtained from natural products (NPs) are a promising alternative. One NP that has been discussed in the literature is hecogenin acetate (HA), a steroidal sapogenin with anti-inflammatory and antinociceptive activity. However, HA has low water solubility, which affects its bioavailability. Thus, the objective of this study was to evaluate the anti-hyperalgesic activity of pure and complexed hecogenin acetate (HA/βCD) in an animal model of chronic neuropathic and inflammatory pain. The inclusion complex was prepared at a molar ratio of 1:2 (HA:βCD) by the lyophilization method. For the induction of chronic inflammatory pain, the mice received an intraplantar injection of CFA (complete Freund's adjuvant), and were evaluated for mechanical hyperalgesia and for the levels of myeloperoxidase (MPO) in the skin of the paw after eight days of treatment. HA and HA/βCD reduced mechanical hyperalgesia in relation to the vehicle group until the fourth and fifth hours, respectively, in the acute evaluation, with a superior effect of the complexed form over the pure form in the second and third hour after treatment (p 0.001). In the chronic evaluation, HA and HA/βCD reduced hyperalgesia in relation to the vehicle in the eight days of treatment (p 0.001). Both pure (p 0.01) and complexed (p 0.001) forms reduced myeloperoxidase activity in the skin of the animals' paw. Groups of animals subjected to the same pharmacological protocol were submitted to the partial sciatic nerve ligation (PSNL) model and evaluated for mechanical and thermal hyperalgesia, and cold allodynia. HA and HA/βCD reduced mechanical hyperalgesia until the fourth and sixth hours, respectively, and both reduced hyperalgesia in relation to the vehicle in the chronic evaluation (p 0.001). HA and HA/βCD also reduced thermal hyperalgesia and cold allodynia (p 0.05 and p 0.001, respectively). The analysis of the spinal cord of these animals showed a decrease in the levels of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and a reduction in the phosphorylation of NFκB and p38MAPK, as well as a decrease in microglioses compared to the vehicle group. In addition, HA/βCD reduced the nociception induced by intraplantar injection of agonist TRPA1 (p 0.01) and TRPM8 (p 0.05). Treatment for eight days with HA and HA/βCD showed no signs of gastric or liver damage. HA and HA/βCD were, therefore, shown to have antinociceptive effects in chronic pain models. Based on our exploration of the mechanisms of the action of HA, these effects are likely to be related to inhibited leukocyte migration, interaction with the TRPA1 and TRPM8 receptors, reduced pro-inflammatory cytokines levels, microglial expression and suppression of NF-κB p65 and p38 MAPK pathway signaling. Therefore, HA/βCD has great potential for use in the treatment of chronic pain.

A series of 10 natural and semisynthetic flavonoids (1 to 10) were obtained from Gardenia oudiepe (Rubiaceae), an endemic plant from New Caledonia. Most of them were polymethoxylated flavones (PMFs) of rare occurrence. After a cell viability screening test, PMFs 2 and 3 showed significant cytotoxic activity against A2058 human melanoma cells (IC50 = 3.92 and 8.18 μM, respectively) and were selected for in-depth pharmacological assays. Both compounds inhibited cell migration and induced apoptosis and cell cycle arrest after 72h of treatment. Immunofluorescence assays indicated that these outcomes were possibly related to the induction of cytoskeleton disruption associated to actin and tubulin depolymerization. These data were confirmed by molecular docking studies, which showed a good interaction between PMFs 2 and 3 and tubulin, particularly at the colchicine binding site. As A2058 are considered as chemoresistant to conventional chemotherapy, compounds 2 and 3 (½IC50) were associated to clinically-used antimelanoma drugs (vemurafenib and dacarbazine) and combined therapies efficacy was assessed by the MTT assay. PMFs 2 restored the sensitivity of A2058 cells to dacarbazine treatment (IC50 = 49.38 μM vs. >100 μM). Taken together, these data suggest that PMFs from G. oudiepe could be potential leaders for the design of new antimelanoma drugs.

Morus nigra, popularly known as mulberry, has been traditionally used as anti-diabetic herbal medication. This study focused on hexane fraction from Brazilian M. nigra leaves (Hex-Mn) effects on digestion and absorption of carbohydrate in diabetic mice. The high-performance liquid chromatography (HPLC) analysis was performed, and showed the presence of flavonoids isoquercetin and kaempferol-3-O-rhamnoside. Hex-Mn did not alter oral glucose tolerance test; however, it prevented hyperglycemia in oral sucrose and starch tolerance test in diabetic mice. Also, Hex-Mn was more efficient to inhibit the α-glucosidase, showing lower inhibitory effect on α-amylase activity in vitro. The results suggest that Hex-Mn may delay the carbohydrate digestion, but not glucose transport through brush border membrane of the intestine, which contribute with reduction in postprandial hyperglycemia in mice. Hex-Mn has antihyperglycemic effect by attenuating the carbohydrate digestion in diabetic mice, which could be explained, at least in part, by the presence of isoquercetin and kaempferol-3-O-rhamnoside.

This work aimed to investigate the chemical composition, antimicrobial, antinociceptive, acute toxicity and antioxidant activity of the essential oil of Algrizea minor (EOAm). The essential oil presented as the major constituents β-Pinene (56.99%), α-Pinene (16.57%), Germacrene D (4.67%), Bicyclogermacrene (4.66%), (E)-Caryophyllene (3.76%) and Limonene (1.71%). It was verified that the essential oil did not show acute toxicity in the maximum dose of 5,000 mg/kg. In the evaluation of the antinociceptive activity it was verified that the essential oil reduced in 65.84% the number of writhing in the mice, reducing the pain in 59.17%, and the mechanism of action in pain reduction was opioid, similar to morphine. The essential oil also presented significant antimicrobial against Gram positive and Gram-negative bacteria and fungi, and the antioxidant activity was relevant. Therefore, these results demonstrate the great potential for the future development of pharmaceutical products with the essential oil of Algrizea minor (EOAm).

La aparición de cepas bacterianas resistentes y los efectos secundarios de sus fármacos disponibles han hecho investigar nuevos compuestos antibacterianos bioactivos. Jatropha mollissima es una planta endémica del bioma Caatinga, Brasil. Existen informes en la literatura de que esta especie tiene acción antioxidante, antibacteriana y antiproliferativa. El presente estudio tuvo como objetivo evaluar el potencial antibacteriano y modulador de J. mollissima contra cepas bacterianas multirresistentes. El perfil fitoquímico se obtuvo por cromatografía de gases junto con espectrometría de masas. J. mollissima mostró actividad antibacteriana moderada y moduló la actividad del antibiótico Norfloxacino, promoviendo una relación antagonista. Este fue el primer estudio de este tipo realizado con J. mollissima. The emergence of resistant bacterial strains and the significant increase in side effects of currently available antibacterial drugs have made it urgent to develop research to identify new bioactives antibacterial compounds. Jatropha mollissima is a plant endemic to the Caatinga biome, Brazil and this species has antioxidant, antibacterial and antiproliferative action. The present study aimed to evaluate the antibacterial and modulatory potentials of J. mollissima against multiresistant bacterial strains. The phytochemical profile was obtained from gas chromatography coupled to mass spectrometry. J. mollissima presented moderate antibacterial activity and modulated the activity of the antibiotic Norfloxacin, promoting an antagonistic relationship. This was the first study of this nature carried out with J. mollissima.

Background Spondias tuberosa is a plant that produces a fruit crop with high economic relevance at Brazilian Caatinga. Its roots and leaves are used in folk medicine. Methods Chemical composition of a hexane extract from S. tuberosa leaves was evaluated by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and 1H nuclear magnetic resonance (NMR). Antioxidant potential was investigated by DPPH and ABTS assays. Antifungal action on Candida species was evaluated determining the minimal inhibitory concentration (MIC50) and putative mechanisms were determined by flow cytometry analysis. In addition, hemolytic activity on human erythrocytes was assessed and the concentration required to promote 50% hemolysis (EC50) was determined. Results Phytochemical analysis by TLC showed the presence of flavonoids, hydrolysable tannins, saponins and terpenes. The HPLC profile of the extract suggested the presence of gallic acid (0.28 ± 0.01 g%) and hyperoside (1.27 ± 0.01 g%). The representative 1H NMR spectrum showed saturated and unsaturated fatty acids among the main components. The extract showed weak and moderate antioxidant activity in DPPH (IC50: 234.00 μg/mL) and ABTS (IC50: 123.33 μg/mL) assays, respectively. It was able to inhibit the growth of C. albicans and C. glabrata with MIC50 of 2.0 and 0.078 mg/mL, respectively. The treatment of C. glabrata cells with the extract increased levels of mitochondrial superoxide anion, caused hyperpolarization of mitochondrial membrane, and compromised the lysosomal membrane. Weak hemolytic activity (EC50: 740.8 μg/mL) was detected. Conclusion The results demonstrate the pharmacological potential of the extract as antioxidant and antifungal agent, aggregating biotechnological value to this plant and stimulating its conservation.

In this study, we report the effects of arbuscular mycorrhizal fungi (AMF) and increasing doses of phosphorus (P) on the growth and production of secondary metabolites in Mimosa tenuiflora, a medicinal species native to Brazil. We used a completely randomized design with four inoculation treatments: Control not inoculated (1); Claroideoglomus etunicatum (2); Gigaspora albida (3); and C. etunicatum + G. albida (4) and four doses of P; P0 – baseline dose, P8, P16 and P32. After 70 d in a greenhouse, growth, mycorrhizal variables, biochemical and phytochemical parameters were evaluated. Compared to non-mycorrhizal plants, mycorrhized M. tenuiflora seedlings showed greater: growth, greater photosynthetic performance and content of soluble carbohydrates and secondary metabolites, with the most significant benefits occurring in soil with low to moderate P content (up to 16 mg kg−1). The plant growth is severely restricted at low P levels, but the addition of AMF appears to remove this limiting factor. Although M. tenuiflora responds to levels of phosphate fertilization, it responds well to mycorrhizal inoculation, especially with G. albida, which promotes benefits for the initial growth and secondary metabolite content in this plant species of medical and potential commercial interest and may be used instead of phosphate fertilizer.

Spondias tuberosa Arruda (Anacardiaceae) is an endemic tree in the Caatinga Brazilian Biome, known locally as "umbuzeiro" and used for various purposes, especially as food and folk medicine. In this study, it was realized for the first time, the extraction and characterization by gas chromatography-mass spectrometry (GC-MS) of the fixed oils of barks, leaves and stems of S. tuberosa. The constituents of the oils were identified by comparing the mass spectra obtained with those of the equipment database. The major component of fixed oil obtained from barks was the 3-n-Pentadecylphenol (44.91 %), in the leaves and stems was observed presence of the tetratetracontane (38.17 and 28.57%, respectively). Antioxidant activity was evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and β-carotene-linoleic acid bleaching test. The fixed oil obtained from the leaves presented the best antioxidant activity (51.13%±11.8) in β-carotene-linoleic acid bleaching test. This study described for the first time identification and quantification of the components present in the fixed oils of the bark, leaves and stems of Spondias tuberosa. Key words: Natural products, fatty acids, gas chromatography-mass spectrometry (GC-MS), antioxidant.

The aim of this study was to evaluate the chemical composition, antioxidant and antibacterial activities and cytotoxicity of fractions from Selaginella convoluta, obtained by liquid–liquid extraction using hexane (Sc-Hex), chloroform (Sc-CHCl3) and ethyl acetate (Sc-AcOEt). The phenolic and flavonoid contents were measured by the Folin-Ciocalteu and aluminium chloride methods, respectively. Antioxidant activities were evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and β-carotene-linoleic acid bleaching test. The antibacterial effect was evaluated by the method of microdilution and the cytotoxicity analysis in HCT-116 (colon), OVCAR-8 (ovarian) and SF-295 (brain) cells were carried out for MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) test. The fractions were positive for the presence of anthracene derivatives, flavonoids, lignans, naphthoquinones, steroids and triterpenoids. The Sc-Hex and Sc-AcOEt showed good antioxidant activities. The fractions of S. convoluta demonstrated antibacterial activity and showed weak cytotoxicity. These activities were correlated with presence of phenolic compounds in active fractions.

Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.

Background: The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue. Objective: To study the influence of flavonoid on overall modulation mechanisms of insulin secretion. Methods: The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells. Results: Twelve articles were included and represent the basis of discussion on mechanisms of insulin secretion of flavonoids. Papers in ISI Web of Knowledge were in number of 1, Scopus 44, PubMed 264, ScienceDirect 511, and no papers from LILACS and SciELO databases. Conclusion: According to the literature, the majority of flavonoid subclasses can modulate insulin secretion through several pathways, in an indication that corresponding molecule is a potential candidate for active materials to be applied in the treatment of diabetes. SUMMARY The action of natural products on insulin secretion represents an important investigation topic due to their importance in the diabetes controlIn addition to their typical antioxidant properties, flavonoids contribute to the insulin secretionThe modulation of insulin secretion is induced by flavonoids according to different mechanisms. Abbreviations used: KATP channels: ATP-sensitive K+ channels, GLUT4: Glucose transporter 4, ERK1/2: Extracellular signal-regulated protein kinases 1 and 2, L-VDCCs: L-type voltage-dependent Ca+2 channels, GLUT1: Glucose transporter 1, AMPK: Adenosine monophosphate-activated protein kinase, PTP1B: Protein tyrosine phosphatase 1B, GLUT2: Glucose transporter 2, cAMP: Cyclic adenosine monophosphate, PKA: Protein kinase A, PTK: Protein tyrosine kinase, CaMK II: Ca2+/calmodulin-dependent protein kinase II, GSIS: Glucose-stimulated insulin secretion, Insig-1: Insulin-induced gene 1, IRS-2: Insulin receptor substrate 2, PDX-1: Pancreatic and duodenal homeobox 1, SREBP-1c: Sterol regulatory element binding protein-1c, DMC: Dihydroxy-6’-methoxy-3’,5’-dimethylchalcone, GLP-1: Glucagon-like peptide-1, GLP-1R: Glucagon-like peptide 1 receptor.

In this study, an inclusion complex with β-cyclodextrin and farnesol (βCD/FAR) was used to improve the physico-chemical and pharmacological properties of farnesol. The samples were obtained using the physical mixture, paste and slurry complexation methods and characterized by variety of methods. To evaluate the pharmacological effect, an animal model of orofacial pain induced by formalin, glutamate and capsaicin was used, and its possible mechanisms of action were evaluated. The slurry complexation method was produced with a formation energy of 3.45 kcal/mol and exhibited a better complexation profile as it presented smaller, deformed crystals compared to the other methods, with a stable complex formed. The formation energy was 3.45 kcal/mol. In the orofacial pain test induced by formalin, capsaicin and glutamate the results show that farnesol and its complex at doses of 50 and 100 mg/kg significantly decreased (p + channel (K + ATP ) and 5-hydroxytryptamine (5-HT 3 ) channels/receptors. A rota-rod test did not show any significant alterations in motor performance in the groups treated with farnesol and its complex. In conclusion, farnesol and βCD/FAR reduced orofacial pain, possibly mediated by K + ATP channels and 5-HT 3 receptors.

Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. In this study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis‑1-benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans‑N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Additionally, the ex vivo antiparasitic activity of oxazines was assessed against Schistosoma mansoni, a helminth that is one of the major agents of the disease schistosomiasis Also, oxazines were evaluated on three tumor cell lines, NCI-H292 (human lung carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (human cervix carcinoma), and two normal cell lines (Vero and red blood cells). Bioassays revealed that oxazine 2 is more effective against bacteria than oxazine 1, with the lowest MIC and MBC values of 3.91 and 32.5 μg/mL, respectively. Similarly, compound 2 demonstrated higher antiparasitic activity than 1, and scanning electron microscopy analysis showed several morphological alterations in the tegument of worms in a concentration-dependent manner. In contrast, both oxazines exhibited low cytotoxic effects on cancer and normal cell lines. These results indicated that oxazines exerted direct effects on bacteria and parasite schistosomes. More importantly, since schistosomiasis control programs rely on one drug, praziquantel, oxazines may have the potential to become new antischistosomal agents. Fil: de Brito, Maria R.M.. Federal University of Piauí; Brasil Fil: Peláez, Walter José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Faillace, Martín Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Militão, Gardenia C.G.. Federal University of Pernambuco; Brasil Fil: Almeida, Jackson R.G.S.. Federal University Of San Francisco Valley; Brasil Fil: Argüello, Gustavo Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina Fil: Szakonyi, Zsolt. University of Szeged; Hungría Fil: Fülöp, Ferenc. University of Szeged; Hungría Fil: Salvadori, Maria C.. Universidade de Sao Paulo; Brasil Fil: Teixeira, Fernanda S.. Universidade de Sao Paulo; Brasil Fil: Freitas, Rivelilson M.. Federal University of Piauí; Brasil Fil: Pinto, Pedro L.S.. Instituto Adolfo Lutz; Brasil Fil: Mengarda, Ana C.. Universidade Guarulhos; Brasil Fil: Silva, Marcos P.N.. Universidade Guarulhos; Brasil Fil: Da Silva Filho, Ademar A.. Universidade Federal de Juiz de Fora; Brasil Fil: de Moraes, Josué. Universidade Guarulhos; Brasil

This study was carried out to assess the antibacterial, cytotoxic and antioxidant activities of extracts of Morus nigra L. HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract (Mn-EtOH). The antibacterial effect was assessed through the method of microdilution. The cytotoxicity was tested against human tumour cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also assessed through the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and β-carotene-linoleic acid bleaching methods. The presence of phenolic compounds in Mn-EtOH was confirmed using HPLC. The extracts showed activity against most microorganisms tested. The extracts did not show any expressive antiproliferative effect in the assessment of cytotoxicity. The most significant total phenolic content was 153.00 ± 11.34 mg of gallic acid equivalent/g to the ethyl acetate extract (AcOEt). The total flavonoid content was 292.50 ± 70.34 mg of catechin equivalent/g to the AcOEt extract, which presented the best antioxidant activity (IC50 50.40 ± 1.16 μg/mL) for DPPH scavenging. We can conclude that this species shows strong antibacterial and antioxidant activities, as well as weak cytotoxic effects. Resumo Este estudo foi realizado para avaliar as atividades antibacteriana, citotóxica e antioxidante de extratos de Morus nigra L. HPLC foi utilizado para determinar o perfil de compostos fenólicos do extrato etanólico bruto (Mn-EtOH). O efeito antibacteriano foi avaliado através do método de microdiluição. A citotoxicidade foi testada contra linhagens celulares de tumores humanos utilizando o ensaio do brometo de 3-(4,5-dimetil-2-tiazolil)-2,5-difenil-2H-tetrazólio (MTT). O conteúdo total de compostos fenólicos e flavonoides também foi avaliado por meio dos métodos de Folin-Ciocalteu e cloreto de alumínio, respectivamente. A atividade antioxidante dos extratos foi avaliada por meio do sequestro do radical livre 2,2-difenil-1-picrilhidrazil (DPPH) e co-oxidação do sistema β-caroteno-ácido linoleico. A presença de compostos fenólicos em Mn-EtOH foi confirmada utilizando HPLC. Os extratos mostraram atividade contra a maioria dos microrganismos testados. Os extratos não mostraram qualquer efeito antiproliferativo expressivo na avaliação da citotoxicidade. O conteúdo fenólico total mais significativo foi de 153,00 ± 11,34 mg de equivalente de ácido gálico/g para o extrato acetato de etila (AcOEt). O conteúdo de flavonoides totais foi de 292,50 ± 70,34 mg de equivalente de catequina/g para o extrato AcOEt, que apresentou a melhor atividade antioxidante (IC50 50,40 ± 1,16 mg/mL) para o sequestro do DPPH. Podemos concluir que esta espécie apresenta forte atividade antibacteriana e antioxidante, bem como fraca atividade citotóxica.

Hecogenin acetate (HA), a steroidal acetylated-sapogenin, has an analgesic profile already assigned, but its low water solubility and short half-life limit its use in chronic conditions. β-cyclodextrin (β-CD) can improve the chemical and pharmacological property of nonpolar compounds such as HA. Therefore, a HA complexed with β-CD (HA-CD) was prepared and characterized by thermal, morphological and spectroscopic analysis. A model of chronic musculoskeletal pain was induced by means of two injections of pH 4.0 saline (20 μL) into the left gastrocnemius 5 days apart was used. After confirming hyperalgesia, male mice were treated with HA, HA-CD (20 mg/kg; p.o.) or vehicle (saline 0.9%, p.o.). Motor coordination tests, substance P (SP) levels in a lumbosacral (L4-S2) spinal cord sample and a docking study were equally assessed to check for a possible action on the opioid receptors. Oral pretreatment with HA or HA-CD produced a significant antinociceptive (p

Atemoya, from family Annonaceae, is an interspecific hybrid between Annona cherimola Mill and Annona squamosa L. It is a tree from a region in diversity of plants, the Caatinga, one of the main Brazilian biomes. In this research, the effects of ethanolic extract of atemoya (Acs-EtOH) were investigated in relief of pain and inflammation in experimental models in rodents. The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing, formalin and hot plate tests, while air pouch and carrageenan-induced peritonitis were used for anti-inflammatory profile. The motor coordination evaluation was performed by rota-rod test. Acs-EtOH (25, 50 and 100 mg/kg, p.o.) significantly reduced the number of writhes with significant (p < 0.001) and decreased (p < 0.001) paw licking time in both phases of the formalin test. In the hot plate test, the latency was significant, reducing painful stimulus. In the anti-inflammatory models, Acs-EtOH inhibited significantly (p < 0.001) the migration of leukocytes in the air pouch and peritonitis tests. Significant inhibition of migration of leukocytes in the treated groups with different doses of the extract was observed. The results indicate that Acs-EtOH may provide a source of plant compounds with antinociceptive and anti-inflammatory activities. Key words: Annonaceae, pain, inflammation, medicinal plants, caatinga.

Background Croton rhamnifolioides Pax is a plant species that have been used in the folk medicine to treat ulcers, inflammations and hypertension. However, despite the relevant data obtained from ethnopharmacological studies, the pharmacological properties endorsing the efficacy of this plant to treat ulcer remain to be elucidated. Hypothesis/Purpose The present study aimed to characterize the chemical profile and evaluate the gastroprotective activity of the essential oil obtained from C. rhamnifolioides Pax (OECC) in mice. Methods The essential oil of Croton rhamnifolioides was obtained by hydrodistillation and analyzed by gas-phase chromatography coupled to mass spectrometry (GC/MS). The median lethal dose was determined employing an acute toxicity test. The gastroprotective activity of the OECC was investigated using animal models of gastric ulcer induced by the administration of absolute ethanol, acidified ethanol or indomethacin. Mechanisms of action were investigated using the physical barrier test and by in vivo evaluation of the involvement of the following molecular pathways: nitric oxide, ATP – dependent potassium channels, α2 – noradrenergic receptors, capsaicin – sensitive afferent neurons and opioid receptor. Results We identified the presence of 21 compounds in OECC, including spathulenol and 1,8 – cineole as major constituents. In orally administered mice, OECC caused no significant toxicity. OECC significantly prevented gastric lesions in all mice models. The barrier test demonstrated that the gastroprotective activity of OECC occurs in a systemic dimension. Our results demonstrated that the gastroprotective effect of OECC involves mechanisms that are related to modulation of opioid receptors and nitric oxide. Conclusion In conclusion, OECC demonstrated significant gastroprotective activity associated with low toxicity, providing scientific evidences that C. rhamnifolioides have the potential for the development of new antiulcer drugs.

Simira gardneriana is a Rubiaceae species commonly found in the Brazilian Northeast region, presented several therapeutic and biotechnological applications. In this paper, the antioxidant and photoprotective properties of extracts from the seeds of S. gardneriana were highlighted. The antioxidant activity of ethanol and methanol extracts (Si-EtOH and Si-MeOH, respectively) was determined, using 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay. The photoprotective activity of the extracts was evaluated using a spectrophotometric method. Total phenolic and flavonoid content was determined. In addition, a qualitative analysis of phytochemical markers and a high-performance liquid chromatography-diode-array detector (HPLC-DAD) analysis were also performed for both extracts. Concerning the antioxidant activity in vitro, Si-MeOH (EC50 = 70.94±2.17 µg/ml) showed greater activity in comparison to Si-EtOH (EC50 = 138.60±7.39 µg/ml). Once the sun protection factor spectrophotometric (SPFspectrophotometric) of samples was calculated, it was demonstrated that the extracts show a similar photoprotective effect on all concentrations tested. Si-EtOH and Si-MeOH tested on a concentration of 100 mg/l, exhibited SPF values equal to 3.37±0.006 and 3.36±0.007, respectively. HPLC fingerprints was recorded and showed the presence of characteristic peaks for phenolic compounds. The extracts showed significant phenols and flavonoids content according to the quantification methods used. According to the results, it was concluded that Si-EtOH and Si-MeOH have significant antioxidant and photoprotective activities. These activities are probably related to the profile of flavonoids and phenolic compounds found in this species. Key words: Phenolic and flavonoids compounds, photoprotective, oxidative stress, plant, Rubiaceae.

The aim of this study was to identify the presence of tannins, phenols and flavonoids on the hydroalcoholic extract of Caryocar coriaceum leaves (HECCL) and to determine the antioxidant and antibacterial activity of this extract. The extract was tested alone (1024-1 μg/mL) or associated (MIC/8) with several antibiotics in order to identify any antibacterial activity against multiresistant bacterial strains (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa). The existence of tannins, total phenols (901.31 mg/g) and flavonoids (89.68 mg/g) was confirmed in the HECCL. The presence of rutin and quercetin were confirmed by Thin-layer chromatography (TLC). Using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, the antioxidant activity of the extract (9 μg/mL) was determined. Moreover, the Minimum Inhibitory Concentration (MIC) value found for HECCL was 1024 μg/mL and the association between HECCL (MIC/8) with benzylpenicillin significantly changed its minimum inhibitory concentration from 2500 to 625 μg/mL against E. coli.

Bothropic venoms cause intense local damage, pain, edema, and myonecrosis. Cocos nucifera is the naturally most widespread fruit plant on Earth, and both the fruit and the plant have been used in folk medicine for the treatment of several inflammatory disorders. We evaluated the anti-inflammatory and analgesic effects of virgin coconut oil that was obtained from C. nucifera on paw lesions that were induced by venom from the Bothrops jararacussu snake in mice. Nuclear magnetic resonance spectroscopy was used to determine the chemical profile of virgin coconut oil. The analysis of the main components showed that saturated and unsaturated fatty acids were prominent components of the oil. Virgin coconut oil at doses of 100, 200, and 400 mg reduced local edema that was induced by B. jararacussu venom. The 200-mg dose of virgin coconut oil prevented edema that was induced by histamine, serotonin, and bradykinin. However, virgin coconut oil did not prevent edema that was induced by substance P or prostaglandin E2. Virgin coconut oil also reduced peritoneal leukocyte infiltration that was induced by carrageenan and also decreased B. jararacussu venom-induced mechanical hypernociception of the paw. Virgin coconut oil exerted an anti-inflammatory effect on paw injury that was induced by B. jararacussu venom in mice, most likely by inhibiting leukocyte migration and reducing the action of the same inflammatory agents. The analgesic activity of virgin coconut oil appears to depend on opioid receptors.

Orofacial pain is associated with diagnosis of chronic pain of head, face, mouth, neck and all the intraoral structures. Carvacrol, a naturally occurring isoprenoid with diverse class of biological activities including anti-inflammatory, analgesic, antitumor and antioxidant properties. Now, the antinociceptive effect was studied in mice pretreatment with carvacrol (CARV) and β-cyclodextrin complex containing carvacrol (CARV-βCD) in formalin-, capsaicin-, and glutamate- induced orofacial nociception. Mice were pretreated with vehicle (0.9% Nacl, p.o.), CARV (10 and 20mg/kg, p.o.), CARV-βCD (10 and 20mg/kg, p.o.) or MOR (10mg/kg, i.p.) before the nociceptive behavior induced by subcutaneous injections (s.c.) of formalin (20μl, 2%), capsaicin (20μl, 2.5μg) or glutamate (20μl, 25μM) into the upper lip respectively. The interference on motor coordination was determined using rotarod and grip strength meter apparatus. CARV-βCD reduced the nociceptive during the two phases of the formalin test, whereas CARV did not produced the reduction in face-rubbing behavior in the initial phase. CARV-βCD (20mg/kg, p.o.) produced 49.3% behavior pain while CARV alone at 20mg/kg, p.o, produced 28.7% of analgesic inhibition in the second phase of formalin test. CARV, CARV-βCD and Morphine (MOR) showed a significant reduction against nociception caused by capsaicin or glutamate injection. Thus the encapsulation of carvacrol in β-cyclodextrin can acts as a considerable therapeutic agent with pharmacological interest for the orofacial pain management.

Cirsiliol is a flavone found in many Lamiaceae species with high cytotoxic activity against tumor cell lines. Although cirsiliol is being used in cancer therapy, its pharmacological potential is limited by its low solubility and bioavailability. In this paper, a cirsiliol-β-cyclodextrin inclusion complex was developed in order to increase its solubility and bioavailability. The formation of inclusion complex was proved by scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and solubility increment was verified through the ultraviolet-visible (UV-Vis) method. The cytotoxic effect against tumor cells (PC3, HCT-116 and HL-60 human cell lines, and S-180 murine cell line) and the antitumor activity in mice bearing sarcoma S-180 were also investigated. The inclusion complex was obtained with 71.45% of total recovery and solubility 2.1 times higher compared to the compound in its free form. This increment in solubility was responsible by a tumor growth inhibition potentiation (1.5 times greater compared to compound in its free form). In addition, this study showed that cirsiliol and its inclusion complex in β-cyclodextrin have strong antitumor potential at low doses without promoting side effects commonly observed for conventional drugs as doxorubicin.

International audience; Depressive disorders remain a current public health problem whose prevalence has increased in the past decades. In the constant search for new therapeutic alternatives, β-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 β-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 β-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, β-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, β-carbolines are multi-target antidepressant compounds and may be useful in the treatment of depressive disorders.

Ethnopharmacological relevance Hymenaea cangaceira Pinto, Mansano & Azevedo (Fabaceae) is a Brazilian medicinal plant widely known as “Jatoba”. In folk medicine, it is used to treat infections, respiratory problems, rheumatism, antitumoral, inflammation and pain, however, no activity has been scientifically validated. Aim of the study This study investigated chemical composition of essential oil from Hymenaea cangaceira (EOHc), antimicrobial, antinociceptive and antioxidant activities besides protection against DNA damage and hemolysis. Material and methods The essential oil was obtained by hydrodistillation, and characterized by GC-MS and GC-FID. The evaluation of antimicrobial activity was performed by microdilution method. The evaluation of the antioxidant activity was performed using the radicals DPPH, ABTS, O2- and OH-, and the protection of DNA damage using plasmid pBR322. Different experimental models were used to evaluate the antinociceptive effect (acetic acid and formalin), and evaluate the mechanisms of action involved with pharmacological antagonists (naloxone, atropine and gibenclamide) in mice. The essential oil was evaluated for hemolysis on human erythrocytes. Results The extraction of EOHc showed a yield of 0.18% on a dry basis, presenting high content of hydrocarbon sesquiterpenes (79.04%), high antioxidant activity and protect DNA from damage, besides presenting antifungal and antibacterial activity against Gram-positive and Gram-negative bacteria in vitro. It was found that the essential oil had no acute toxicity in mice up to 5000 mg/kg oral administration (o.a.), in addition to no hemolysis on human erythrocytes. The reduction of antinociceptive activity was 75%, with the opioid system as the mechanism of action. Conclusion Our results validate the main activities by the traditional use attributed to H. cangaceira for antimicrobial and analgesic activity. In addition, the oil has a potent antioxidant activity, protecting the body against oxidative stress damage, adding new value to an endemic species not known to the industry.

Selaginella convoluta (Arn.) Spring is a species popularly known as “jericó”, and used in folk medicine as analgesic and anti-inflammatory. This study aimed to investigate in mice the antinociceptive and anti-inflammatory activities of the hexane (Sc-Hex) and chloroform (Sc-CHCl3) fractions (100, 200 and 400 mg/kg) obtained by partition of crude ethanol extract from S. convoluta. The preliminary phytochemical analysis of the fractions was performed. Antinociceptive activity was evaluated by writhing, formalin and hot-plate tests. Anti-inflammatory activity was evaluated using carrageenan-induced pleurisy. The rota-rod test was used to evaluate motor coordination. Preliminary phytochemical screening showed that the Sc-Hex and the Sc-CHCl3 were positive for the presence of flavonoids, anthracene derivatives, quinones, triterpenes and steroids. Inhibition of writhing was observed for fractions tested. The Sc-Hex at all doses tested was effective in reducing the nociceptive behavior produced by formalin only in the second phase. However, the Sc-CHCl3 decreased the paw licking time in the first and second phases. In the hot plate no significant effect was observed for any fraction. In the rota-rod test, treated mice did not demonstrate any significant motor performance changes. In the carrageenan-induced pleurisy, Sc-CHCl3 (200 mg/kg) reduced cell migration to the pleural cavity. These results reveal the antinociceptive properties of S. convoluta , which support, in part, its traditional use, since the fractions did not presented significant activity in the inflammatory response profile. We further verify that this antinociceptive effect could be by activation of nociceptive peripheral pathway. Resumo Selaginella convoluta é uma espécie popularmente conhecida como “jericó”, e usada na medicina popular como analgésica e anti-inflamatória. Este estudo teve como objetivo investigar em camundongos as atividades antinociceptiva e anti-inflamatória das frações hexânica (Sc-Hex) e clorofórmica (Sc-CHCl3) (100, 200 e 400 mg/kg) obtidas por partição do extrato etanólico bruto de S. convoluta . A análise fitoquímica preliminar das frações foi realizada. A atividade antinociceptiva foi avaliada pelos testes de contorções abdominais, formalina e placa quente. A atividade anti-inflamatória foi avaliada usando pleurisia induzida por carragenina. O teste do rota-rod foi utilizado para avaliar a coordenação motora. A triagem fitoquímica preliminar mostrou que Sc-Hex e Sc-CHCl3 apresentaram reação positiva para a presença de flavonoides, derivados antracênicos, quinonas, triterpenos e esteroides. A inibição das contorções foi observada para as frações testadas. Sc-Hex em todas as doses testadas foi efetivo na redução do comportamento nociceptivo produzido pela formalina somente na segunda fase. No entanto, Sc-CHCl3 diminuiu o tempo de lambida da pata na primeira e segunda fases. Na placa quente, nenhum efeito significativo foi observado para qualquer fração. No teste do rota-rod os camundongos tratados não demonstraram mudanças significativas na coordenação motora. Na pleurisia induzida por carragenina, Sc-CHCl3 (200 mg/kg) reduziu a migração celular para a cavidade pleural. Estes resultados revelam a propriedade antinociceptiva de S. convoluta, justificando, em parte, seu uso tradicional, uma vez que os extratos não apresentaram atividade significativa no perfil de resposta inflamatória. Verificamos ainda que esse efeito antinociceptivo mostrou-se ligado à ativação da via periférica nociceptiva.

The genus Jatropha belongs to the Euphorbiaceae family and has about 175 species. Originally from tropical America, the Jatropha genus can be found all over the tropics and subtropics of Asia and Africa. Jatropha species are recognized to be important sources of secondary metabolites with a broad spectrum of biological functions. Extracts and isolated compounds from species of this genus have been known to have properties of cytotoxicity, antimicrobial, antifungal, anti-inflammatory, antioxidant, insecticidal, larvicidal, inhibition AChE, and toxicity activities. Investigations on the chemical aspects of the genus Jatropha have led to the identification of cyclic peptides, lignans, flavonoids, coumarins, alkaloids, eudesmenoic acids, and mainly terpenes. In this review, we provide a comprehensive picture of the phytochemical and biological characteristics of Jatropha species. The information gathered and approached in this paper might support the planning and discussion of future studies on the topic.

Inflammatory response can be driven by cytokine production and is a pivotal target in the management of inflammatory diseases. Monoterpenes have shown that promising profile as agents which reduce the inflammatory process and also modulate the key chemical mediators of inflammation, such as pro and anti-inflammatory cytokines. The main interest focused on monoterpenes were to develop the analgesic and anti-inflammatory drugs. In this review, we summarized current knowledge on monoterpenes that produce anti-inflammatory effects by modulating the release of cytokines, as well as suggesting that which monoterpenoid molecules may be most effective in the treatment of inflammatory disease. Several different inflammatory markers were evaluated as a target of monoterpenes. The proinflammatory and anti-inflammatory cytokines were found TNF-α, IL-1β, IL-2, IL-5, IL-4, IL-6, IL-8, IL-10, IL-12 IL-13, IL-17A, IFNγ, TGF-β1 and IFN-γ. Our review found evidence that NF-κB and MAPK signaling are important pathways for the anti-inflammatory action of monoterpenes. We found 24 monoterpenes that modulate the production of cytokines, which appears to be the major pharmacological mechanism these compounds possess in relation to the attenuation of inflammatory response. Despite the compelling evidence supporting the anti-inflammatory effect of monoterpenes, further studies are necessary to fully explore their potential as anti-inflammatory compounds.