The bioprospecting potential of Clusia fluminensis Planch. & Triana: a scoping review.

Many biological activities are described for the Clusiaceae family. Clusia fluminensis, a species from Brazilian flora, is mainly employed for ornamental purposes. This review aimed to depict the current knowledge of C. fluminensis from a bioprospecting standpoint. "Clusia fluminensis" search term was applied in Scopus, Web of Science, PubMed and Bireme databases according to PRISMA-ScR statement. Selected papers on Phytochemistry or Bioactivity followed hand searching procedures. Bioactivity preclinical studies considered in vitro or in vivo biological systems, treated with plant extracts or isolated compounds. The outcomes were compared with standard or no treatment control groups. Critical appraisal of individual trials considered completeness in the research fields. Our results showed that 81% of the selected papers presented high level of completeness, 69% revealed phytochemical parameters and 31% biological applications of plant extracts and isolated compounds. Polyisoprenylated benzophenones, terpenoids, sterols and phenolic compounds were identified. Antiviral, insecticidal and snake antivenom activities were reported. In conclusion, the phytochemical data reinforce the reported activities. Potential applications in personal care, nutritional supplementation and pharmaceutical, food, chemical or textile industries were also identified. Toxicological and phytochemical complementary studies may be required.

Novel polyprenylated benzophenone derivatives from Clusia burle-marxii.

Three new caged polyprenylated benzophenone derivatives named burlemarxiones D-F (1-3) were isolated from the hexane extract of Clusia burle-marxii trunks. Burlemarxione D (1) contains the tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton also observed for burlemarxione A, its probable immediate precursor. However, two additional rings are formed to produce an unprecedented complex-caged core skeleton. These additional rings could be formed by a radical cyclization reaction of one prenyl group at C-5 with C-1 and C-33, followed by oxidative dehydrogenation (rearomatization) or by an intramolecular [4 + 2] radical cycloaddition (Diels-Alder reaction), followed by an enolization reaction (rearomatization). Burlemarxiones E and F were isolated after methylation with diazomethane that was necessary to avoid the interconversion of the pair of ß-diketones in tautomeric equilibrium. The proposed biosynthetic pathway for burlemarxiones D-F involves the condensation of either lavandulyl pyrophosphate or 2-(1-methylvinyl)-hexa-5-enyl pyrophosphate with the acylphloroglucinol derivative 6-benzoyl-5-hydroxy-5-cyclohexen-1,3-dione, followed by consecutive prenylation reactions. Therefore, Clusia burle-marxii reinforces the claim that the genus Clusia is an important source of sophisticated caged polyprenylated benzophenone derivatives.

Anatomical, Histochemical and Biological Studies of Clusia grandiflora Splitg. (Clusiaceae)

Abstract Clusia grandiflora belongs to an important botanical family which is known for its medicinal value, however there are few reports in literature about the species, highlighting the relevance of this study. Anatomical studies with leaves and stems were performed using traditional techniques. In this investigation it was identified particularities of the species such as the presence of vascular system arranged in an opened arc-shaped with the flexed ends towards the inside of the arch with accessory bundles in the petiole. In histochemical studies, performed with different reagents, alkaloids, phenols substances, carbohydrates and lipids were located. The cytotoxic activity of the extracts was performed by tetrazole salt and showed promising results for ethanolic extracts of stems (IC50 human colon cells of 24.30 μg/ mL) and leaves (IC50 ascites gastric cells of 44.15 μg/ mL), without cell membrane disruption of erythrocytes. The antibacterial activity was evaluated by tryptic soy agar and minimal inhibitory concentration assays and showed positive results for Pseudomonas aeruginosa and Escherichia coli, with better result for adventitious roots (32 μg/ mL and 16 μg/ mL, respectively), stems (64 μg/ mL and 32 μg/ mL, respectively) and leaves (64 μg/ mL and 32 μg/ mL, respectively) ethanolic extracts. Thus, these studies were able to characterize the species and show its potential as promising source of active substances.

Polyprenylated benzophenone derivatives with a novel tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton from Clusia burle-marxii exhibited cytotoxicity against GL-15 glioblastoma-derived human cell line.

Three new polyprenylated benzophenone derivatives (1-3) were identified in the hexane extract of Clusia burle-marxii trunks, through the isolation and structural elucidation of their methyl derivatives, along with two known polyprenylated benzophenone derivatives sampsonine N (4) and obdeltifolione C (5). Burlemarxiones A (1) and B (2) show an unprecedent tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton. These compounds are a pair of ß-diketones in tautomeric equilibrium, whereas isonemorosonol (3) is the respective ß-diketone pair in tautomeric equilibrium with nemorosonol. Burlemarxione A methyl derivative (1a) and sampsonine N exhibited strong in vitro cytotoxic activity against GL-15 glioblastoma-derived human cell line.

Utilization of the Plant Clusia Fluminensis Planch & Triana Against Some Toxic Activities of the Venom of Bothrops jararaca and B. jararacussu Snake Venom Toxic Activities.

BACKGROUND: In Brazil, the Bothrops genus accounts for 87% of registered snakebites, which are characterized by hemorrhage, tissue necrosis, hemostatic disturbances, and death. The treatment recommended by governments is the administration of specific antivenoms. Although antivenom efficiently prevents venom-induced lethality, it has limited efficacy in terms of preventing local tissue damage. Thus, researchers are seeking alternative therapies able to inhibit the main toxic effects of venoms, without compromising safety. OBJECTIVE: The study aimed to test the ability of aqueous extracts of leaves, stems, and fruits of the plant Clusia fluminensis to neutralize some toxic effects induced by the venoms of Bothrops jararaca and Bothrops jararacussu. METHODS: The plant extracts were incubated with venoms for 30 min. at 25 °C, and then in vitro (coagulant and proteolytic) and in vivo (hemorrhagic, myotoxic, and edematogenic) activities were evaluated. In addition, the extracts were administered to animals (by oral, intravenous or subcutaneous routes) before or after the injection of venom samples, and then hemorrhage and edema assays were performed. In addition, a gel solution of the fruit extract was produced and tested in terms of reducing hemorrhage effects. A chemical prospection was performed to identify the main classes of compounds present in the extracts. RESULTS: All the extracts inhibited the activities of the two venoms, regardless of the experimental protocol or route of administration of the extracts. Moreover, the gel of the fruit extract inhibited the venom-induced-hemorrhage. The extracts comprised of tannins, flavonoids, saponins, steroids, and terpenoids. CONCLUSION: Antivenom properties of C. fluminensis extracts deserve further investigation in order to gain detailed knowledge regarding the neutralization profile of these extracts.

Clusia criuva Cambess. (Clusiaceae): anatomical characterization, chemical prospecting and antioxidant activity

ABSTRACT This study aims the anatomical description and chemical characterization of aerial parts of Clusia criuva Cambess., Clusiaceae in addition to the evaluation of the antioxidant activity of crude extracts, correlated to the flavonoid content. The morphological characterization was performed using traditional techniques of plant anatomy. For phytochemical studies, crude extracts were obtained by static maceration and analyzed by thin layer chromatography. The antioxidant activity and the flavonoids content were determined by colorimetric methods involving, respectively, 2,2-diphenyl-1-picrylhydrazyl free radical and aluminum chloride. C. criuva has uniseriate epidermis, paracytic stomata, hypostomatic leaves, cuticular flanges and cordiform vascular cylinder with accessory bundles. Chemical prospecting confirmed the abundant presence of terpenes and phenols in the extracts of leaves and of fruits. The methanolic extract of seeds showed the lowest EC50 value, but the methanolic extract of pericarps exhibited the highest maximum antioxidant activity. The results suggested a high percentage of flavonoids in the hexanic extract of pericarps, however, this could represent, in fact, the presence of benzophenones. Secretory ducts and the shape of the midrib are diagnostic for C. criuva. The antioxidant activity is not directly related to the flavonoids. The results indicate the importance of future studies with C. criuva chemical constituents.

Clusia criuva Cambess. (Clusiaceae): anatomical characterization, chemical prospecting and antioxidant activity.

This study aims the anatomical description and chemical characterization of aerial parts of Clusia criuva Cambess., Clusiaceae in addition to the evaluation of the antioxidant activity of crude extracts, correlated to the flavonoid content. The morphological characterization was performed using traditional techniques of plant anatomy. For phytochemical studies, crude extracts were obtained by static maceration and analyzed by thin layer chromatography. The antioxidant activity and the flavonoids content were determined by colorimetric methods involving, respectively, 2,2-diphenyl-1-picrylhydrazyl free radical and aluminum chloride. C. criuva has uniseriate epidermis, paracytic stomata, hypostomatic leaves, cuticular flanges and cordiform vascular cylinder with accessory bundles. Chemical prospecting confirmed the abundant presence of terpenes and phenols in the extracts of leaves and of fruits. The methanolic extract of seeds showed the lowest EC50 value, but the methanolic extract of pericarps exhibited the highest maximum antioxidant activity. The results suggested a high percentage of flavonoids in the hexanic extract of pericarps, however, this could represent, in fact, the presence of benzophenones. Secretory ducts and the shape of the midrib are diagnostic for C. criuva. The antioxidant activity is not directly related to the flavonoids. The results indicate the importance of future studies with C. criuva chemical constituents.

Atividade moduladora de extratos etanólico das folhas de Clusia nemorosa G. Mey. (Clusiaceae) sobre drogas antimicrobianas / Actividad moduladora de extractos de las hojas de Clusia nemorosa G. Mey (clusiaceae) sobre drogas antimicrobianas / Modulatory activity of ethanolic extracts of the leaves of Clusia nemorosa G. Mey (Clusiaceae) on antimicrobial drugs

Introduction: the fast development of drug resistance and the slowdown of the development of new active drugs, drew attention to the treatment with the drug combination. Objective: to analyze the antimicrobial activity of the ethanol extract of Cluisa nemorosa (Clusiaceae) against multiresistant strains and standards as well as the modulating action with aminoglycoside amikacin, gentamicin and neomycin. Methods: the plant material (leaves) was collected in Araripe, crushed and put into ethanol 96 % as solvent. Distillation of the solvent was then performed in a rotary evaporator to produce the gross ethanol extrato. A microdilution assay was conducted to verify antibacterial activity and the possible interactions of aminoglycosides associated with the study samples. A sub-inhibitory concentration of 128 µg/mL (Minimum Inhibitory concentration/8) was used. Results: the activity of the extract against the strains isolated patterns had an Minimum Inhibitory concentration > 1024 mg/mL, the action of antibiotics was modulated synergistically by the extract against multidrug-resistant Gram-positive bacteria Staphylococcus aureus and Gram-negative Escherichia coli and Pseudomonas aeruginosa. Conclusions: the synergism of the ethanol extract was verified by microdilution method. Therefore, it is suggested that the extract of Clusia nemorosa be used as a source of natural products for antimicrobial therapy and to combat bacterial multidrug resistance(AU)

Introducción: el rápido desarrollo de resistencia de las drogas y la relentización en el desarrollo de nuevas drogas activas llaman la atención al tratamiento de combinación de drogas. Objetivos: analizar la actividad antimicrobiana del extracto etanólico de Clusia nemorosa (Clusiaceae) frente a cepas multirresistentes y normas, así como la acción modulante con aminoglucósido amikacina, gentamicina y la neomicina. Métodos: el material vegetal (hojas), colectado en el Araripe, fue triturado y sumergido en etanol 96 percent como solvente. De inmediato, fue sometido a destilación del solvente en un evaporador rotativo para la producción de lo extrato etanólico bruto. Se llevó a cabo un ensayo de microdilución para verificar la actividad antibacteriana y las posibles interacciones de aminoglucósidos asociados con las muestras estudiadas, se utilizó una concentración sub-inhibitoria de 128 µg/mL (Concentración mínima inhibitoria/8). Resultados: la actividad del extracto frente a las cepas aisladas patrones tenía una Concentración mínima inhibitoria> 1024mg/mL; la acción de los antibióticos fue modulada por el extracto de forma sinérgica contra multirresistente Gram-positivo Staphylococcus aureus y bacterias Gram-negativas Escherichia coli y Pseudomonas aeruginosa. El sinergismo del extracto de etanol se verificó mediante el método de microdilución. Conclusiones: el extracto de las hojas de C. nemorosa actuaron como un agente modulador. Se sugiere que el extracto de C. nemorosa puede ser utilizado como una fuente de productos naturales en la terapia antimicrobiana y en el combate de la resistencia a múltiples fármacos bacterianos(AU)

Introdução: o rápido desenvolvimento de resistência às drogas e a desaceleração no desenvolvimento de novas drogas ativas, chamaram a atenção para o tratamento com combinação de drogas. Objetivos: analisar a atividade antimicrobiana do extrato etanólico de Clusia nemorosa (Clusiaceae) frente a cepas padrões e multirresistentes bem como a ação moduladora com aminoglicosídeos amicacina, neomicina e gentamicina. Métodos: o material vegetal (folhas), coletado na Chapada do Araripe, foi triturado e submerso em solvente etanol 96 por cento e submetido à destilação do solvente no aparelho evaporador rotativo para a produção do extrato etanólico bruto. Um ensaio de microdiluição foi realizado para verificar a atividade antibacteriana e as possíveis interações dos aminoglicosídeos associados às amostras estudadas, utilizando uma concentração sub-inibitória de 128 µg/mL (concentração inibitória mínima/8). Resultados: a ação do extrato isolado frente às cepas padrões teve uma concentração inibitória mínima > 1024 µg/mL, a ação dos antibióticos foi modulada sinergicamente pelo extrato contra as bactérias multirresistentes Gram-positiva Staphylococcus aureus e Gram-negativas Escherichia coli e Pseudomonas aeruginosa. Conclusões: o extrato das folhas de C. nemorosa atuou como um agente modulador da atividade antimicrobiana. É sugerido que o extrato de Clusia nemorosa pode ser utilizado como uma fonte de produtos naturais na terapêutica antimicrobiana e no combate a multirresistência bacteriana(AU)

Biocontrol evaluation of extracts and a major component, clusianone, from Clusia fluminensisPlanch. & Triana againstAedes aegypti

Studies evaluated the effects of hexanic extracts from the fruits and flowers ofClusia fluminensis and the main component of the flower extract, a purified benzophenone (clusianone), against Aedes aegypti. The treatment of larvae with the crude fruit or flower extracts from C. fluminensis did not affect the survival ofAe. aegypti (50 mg/L), however, the flower extracts significantly delayed development of Ae. aegypti. In contrast, the clusianone (50 mg/L) isolate from the flower extract, representing 54.85% of this sample composition, showed a highly significant inhibition of survival, killing 93.3% of the larvae and completely blocking development of Ae. aegypti. The results showed, for the first time, high activity of clusianone against Ae. aegypti that both killed and inhibited mosquito development. Therefore, clusianone has potential for development as a biopesticide for controlling insect vectors of tropical diseases. Future work will elucidate the mode of action of clusianone isolated from C. fluminensis.

Biocontrol evaluation of extracts and a major component, clusianone, from Clusia fluminensis Planch. & Triana against Aedes aegypti.

Studies evaluated the effects of hexanic extracts from the fruits and flowers of Clusia fluminensis and the main component of the flower extract, a purified benzophenone (clusianone), against Aedes aegypti. The treatment of larvae with the crude fruit or flower extracts from C. fluminensis did not affect the survival ofAe. aegypti (50 mg/L), however, the flower extracts significantly delayed development of Ae. aegypti. In contrast, the clusianone (50 mg/L) isolate from the flower extract, representing 54.85% of this sample composition, showed a highly significant inhibition of survival, killing 93.3% of the larvae and completely blocking development of Ae. aegypti. The results showed, for the first time, high activity of clusianone against Ae. aegypti that both killed and inhibited mosquito development. Therefore, clusianone has potential for development as a biopesticide for controlling insect vectors of tropical diseases. Future work will elucidate the mode of action of clusianone isolated from C. fluminensis.

Effects of nemorosone, isolated from the plant Clusia rosea, on the cell cycle and gene expression in MCF-7 BUS breast cancer cell lines.

BACKGROUND: Breast cancer is the cause of considerable morbidity and mortality in women. While estrogen receptor antagonists have been widely used in breast cancer treatment, patients have increasingly shown resistance to these agents and the identification of novel targeted therapies is therefore required. Nemorosone is the major constituent of the floral resin from Clusia rosea and belongs to the class of polycyclic polyisoprenylated benzophenones of the acylphloroglucinol group. The cytotoxicity of nemorosone in human cancer cell lines has been reported in recent years and has been related to estrogen receptors in breast cancer cells. METHODS: Changes induced by nemorosone in the cell cycle and gene expression of the MCF-7 BUS (estrogen-dependent) breast cancer cell line were analyzed using flow cytometry and the RT(2) Profiler PCR array, respectively. RESULTS: In comparison to breast cancer cells without treatment, nemorosone induced discrete cell cycle arrest in the G1 phase and significant depletion in the G2 phase. Moreover, the compound altered the expression of 19 genes related to different pathways, especially the cell cycle, apoptosis and hormone receptors. CONCLUSION: These promising results justify further studies to clarify mechanisms of action of nemorosone, in view of evaluate the possible use of this benzophenone as adjuvant in the treatment of breast cancer.

Inhibitory effect of the plant Clusia fluminensis against biological activities of Bothrops jararaca snake venom.

The ability of extracts of the plant Clusia fluminensis Planch & Triana (Clusiaceae Lindl.) to neutralize proteolysis, clotting, hemolysis, hemorrhagic and lethality activities of Bothrops jararaca snake venom was studied. Clusianone and lanosterol from the flower and fruit extracts, respectively, were also tested. The extracts of different organs of C. fluminensis inhibited proteolysis and hemolysis induced by B. jararaca venom, but with different potencies. Only the stems prevented blood clotting. Only the acetone extract of the fruit protected mice from hemorrhage while the acetone or methanol extracts prevented mice from death. Clusianone and lanosterol did not inhibit clotting or hemorrhage, but the former inhibited proteolysis and the latter hemolysis.

Leaf extract from Clusia nemorosa induces an antinociceptive effect in mice via a mechanism that is adrenergic systems dependent.

Previous studies on the genus Clusia have shown anti-inflammatory and antiproliferative effects of the leaf extracts, but its antinociceptive activity has never been characterized. In the present study, the antinociceptive activity of the hexane extract of the leaves of Clusia nemorosa G. Mey, called HECn, was examined. Antinociceptive activity was evaluated using acetic acid-induced writhing, formalin, and hot-plate tests. All experiments were carried out on male Swiss mice. The extract (1-400 mg·kg(-1)), given by intraperitoneal route (i.p.) 1 h prior to testing, produced a dose-dependent inhibition on the number of abdominal writhings, with an ID50 of 62 mg·kg(-1). In addition, HECn was able to prevent the visceral pain induced by acetic acid in mice for at least 2 h. In the formalin test, HECn had no effect in the first phase, but produced an analgesic effect on the second phase with the inhibition of licking time. The HECn did not show a significant analgesic effect in the hot plate test. Pretreatment with yohimbine attenuated the antinociceptive effect induced by HECn in the writhing test. However, naloxone, atropine, or haloperidol did not affect antinociception induced by HECn in the writhing test. Together, these results indicate that the extract from the leaves of Clusia nemorosa produces antinociception in models of chemical pain through mechanisms that suggest participation of the adrenergic systems pathway.

Leaf extract from Clusia nemorosa induces an antinociceptive effect in mice via a mechanism that is adrenergic systems dependent / 中国天然药物

Previous studies on the genus Clusia have shown anti-inflammatory and antiproliferative effects of the leaf extracts, but its antinociceptive activity has never been characterized. In the present study, the antinociceptive activity of the hexane extract of the leaves of Clusia nemorosa G. Mey, called HECn, was examined. Antinociceptive activity was evaluated using acetic acid-induced writhing, formalin, and hot-plate tests. All experiments were carried out on male Swiss mice. The extract (1-400 mg·kg(-1)), given by intraperitoneal route (i.p.) 1 h prior to testing, produced a dose-dependent inhibition on the number of abdominal writhings, with an ID50 of 62 mg·kg(-1). In addition, HECn was able to prevent the visceral pain induced by acetic acid in mice for at least 2 h. In the formalin test, HECn had no effect in the first phase, but produced an analgesic effect on the second phase with the inhibition of licking time. The HECn did not show a significant analgesic effect in the hot plate test. Pretreatment with yohimbine attenuated the antinociceptive effect induced by HECn in the writhing test. However, naloxone, atropine, or haloperidol did not affect antinociception induced by HECn in the writhing test. Together, these results indicate that the extract from the leaves of Clusia nemorosa produces antinociception in models of chemical pain through mechanisms that suggest participation of the adrenergic systems pathway.

7-epi-nemorosone from Clusia rosea induces apoptosis, androgen receptor down-regulation and dysregulation of PSA levels in LNCaP prostate carcinoma cells.

The aim of this work was to characterize the antitumoral activity of the plant compound 7-epi-nemorosone in prostate carcinoma cell lines. Prostate cancer is the most frequently diagnosed malignancy and the second-leading cause of cancer death in men. In spite of the current therapeutic options for this cancer entity, many patients die due to metastases in distant organs and acquired chemotherapy resistance. Thus, approaches to provide improvements in outcome and quality of life for such patients are urgently needed. Recently, the polyisoprenylated benzophenone 7-epi-nemorosone, originally collected by honeybees from Clusia rosea and Clusia grandiflora (Clusiaceae), has been described to be a potent antitumoral agent. Here, its activity in prostate carcinoma is reported. 7-epi-nemorosone was isolated from Caribbean propolis employing RP-HPLC techniques. Its cytotoxicity was assessed using the MTT proliferation assay in human androgen-dependent prostate carcinoma LNCaP cells including an MDR1(+) sub-line. No cross-resistance was detected. FACS-based cell cycle analysis revealed a significant increase in the sub-G0/G1, G1, and depletion in the S phase populations. A concomitant down-regulation of cyclins D1/D3 and CDK 4/6 in LNCaP cells was detected by Western blot. Annexin-V-FITC labeling and caspase-3 cleavage assays showed that 7-epi-nemorosone induced apoptotic events. Major signal transduction elements such as p38 MAPK and Akt/PKB as well as androgen receptor AR and PSA production were found to be down-regulated after exposure to the drug. ERK1/2 protein levels and phosphorylation status were down-regulated accompanied by up-regulation but inhibition of the activity of their immediate upstream kinases MEK1/2. Additionally, Akt/PKB enzymatic activity was effectively inhibited at a similar concentration as for MEK1/2. Here, we demonstrate for the first time that 7-epi-nemorosone exerts cytotoxicity in an androgen-dependent prostate carcinoma entity by targeting the MEK1/2 signal transducer.

Antioxidant activity and flavonoid content of Clusia fluminensis Planch. & Triana.

Clusia fluminensis Planch. & Triana (Clusiaceae Lindl.) is a native species found in regions of high luminosity and water restriction. The aim of this study was to evaluate the antioxidant activity of Clusia fluminensis crude extracts through the scavenging of the stable free radical DPPH, and the determination of flavones and flavonols content in these extracts. The fruit acetonic extract showed the lowest EC(50) value (2.71 ± 0.34 g extract / g DPPH), the lowest percentage of remaining DPPH at the concentrations of 125 and 250 µg/mL (about 4% in both), and also the greatest percentage of flavones and flavonols (13.93 ± 0.21 %). Statistical analysis suggests a positive correlation between the presence of flavonoids and the antioxidant activity of this extract. From the obtained results it can be inferred that the acetonic extract of C. fluminensis fruits is an interesting target for the search of substances with antioxidant activity, especially flavonoids.

Aspects of reproductive ecology of Clusia valerioi Standl. and Clusia peninsulae Hammel (sp. nov.), two Central American species of Clusiaceae with resin flowers.

Clusia valerioi Standl. and C. peninsulae Hammel, sp. nov. (formally established in the Appendix), two Central American species of Clusiaceae offering resin as a floral reward, were studied in the Piedras Blancas National Park, SW Costa Rica. Basic data on phenology, flower structure, course of anthesis, flower visitors, flower visitation and pollination processes, fruit development and seed dispersal are communicated. Resin collection and pollen release are reported and documented in greater detail. The significance of stingless bees for pollination is confirmed, but honeybees were also observed to visit the flowers and to collect resin. The seeds of C. valerioi, exhibiting a clearly ornithochorous character syndrome, were observed to be eaten and dispersed by four species of the tanager family (Thraupidae) and one species of finch (Fringillidae). Ants were also observed to carry away the seeds.

Modulation of inflammatory processes by leaves extract from Clusia nemorosa both in vitro and in vivo animal models.

The present study was carried out to investigate the anti-inflammatory effect of the hexane extract of the leaves from Clusia nemorosa G. Mey, called HECn, using carrageenan-induced mice pleurisy and cotton pellet-induced mice granuloma. Additionally, the ability of HECn to affect both neutrophil migration as viability was investigated by use of the Boyden chamber assay and flow cytometry, respectively. The HECn significantly inhibited exudation, total leukocytes and neutrophils influx, as well as TNFα levels in carrageenan-induced pleurisy. However, the extract not suppressed the granulomatous tissue formation in the cotton pellet-induced granuloma test. Experiments performed in vitro revealed that HECn on human neutrophils inhibited a dose-dependent manner the CXCL1-induced neutrophil chemotaxis. Furthermore, HECn also inhibited the chemoattraction of human neutrophils induced by formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4) and platelet activating factor (PAF) in a Boyden chamber. However, this same treatment not was able to induce apoptosis. The results obtained in this study showed that the extract from leaves of C. nemorosa possess a potent inhibitory activity in acute model of inflammation, being the effects mediated, in part, by inhibition of neutrophil responsiveness. These results indicate that C. nemorosa could be a good source for anti-inflammatory compounds.

Biflavonoids from the unripe fruits of Clusia paralicola and their antioxidant activity.

Investigation of the green fruits of Clusia paralicola (Clusiaceae) led to the isolation and characterization of two 3,8"-biflavonoids, 2R, 3S, 2"R, 3"R-GB1-7"-O-beta-glucoside (1) and 2R, 3S, 2"R, 3,8"-binaringenin-7"-O-beta-glucoside (2), together with four known compounds: beta-sitosterol, stigmasterol, beta-amyrin, and epicatechin. The structures were established from the IR, LC-ESI-MS and NMR spectral data, including 2D-NMR experiments. The absolute configurations of 1 and 2 were determined by CD spectra. The total extract and the biflavonoids demonstrated significant antioxidant activity in DPPH, ABTS, and betacarotene/linoleic acid tests.

A new biphenyl and antimicrobial activity of extracts and compounds from Clusia burlemarxii.

Phytochemical investigation on Clusia burlemarxii (Clusiaceae) led to isolation and identification of nine compounds. Were isolated from leaves 3-O-α-L- rhamnopyranosylquercetin, 3-O-α-L-rhamnopyranosylkaempferol, 4-hydroxy-5,5-dimethyldihydrofuran-2-one, 2Z-δ-tocotrienoloic acid and friedelin and were isolated from trunk betulinic acid, protocatechuic acid, lyoniresinol, and a new biphenyl 2,2-dimethyl-3,5-dihydroxy-7-(4-hydroxyphenyl)chromane. The structures were determined by ¹H, ¹³C-NMR, DEPT, HMBC, HMQC, HRESIMS. The Minimal Inhibitory Concentration against Streptococcus mutans, Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Escherichia coli, Salmonella choleraesuis, Pseudomonas aeruginosa, Aspergillus niger and Cladosporium cladosporioides was also determined. Extracts and compounds showed significant activity against tested Gram-positive bacteria, none activity against tested Gram-negative bacteria and fungi.