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Applying elicitors in plants growing under natural conditions change the metabolic content of volatile compounds extracted from their tissues. Here, we have investigated how abiotic elicitors influence the volatile composition of the ethyl acetate extract of Anacardium othonianum seedlings propagated in vitro and ex-vitro cultures. Abiotic factors such as salicylic acid, silver nitrate, light quality, and cultivation mode affected the composition of volatile compounds in ethyl acetate extract of A. othonianum leaves seedlings. GC/MS analysis demonstrated that α-tocopherol was the main metabolite in cultures added with chemical elicitors, reaching 22.48 ± 4.06% in the case of 30 µM salicylic acid. Higher concentrations of salicylic acid decreased the amount of α-tocopherol. The addition of AgNO 3 had a linear effect on α-tocopherol. Thus, the production of this metabolite indicates that salicylic acid and AgNO 3 elicitors positively affect α-tocopherol production at specific concentrations helping to understand how plant culture can be better manipulated.

Neglected tropical diseases are significant causes of death and temporary or permanent disability for millions living in developing countries. Unfortunately, there is no effective treatment for these diseases. Thus, this work aimed to conduct a chemical analysis using HPLC/UV and GC/MS to identify the major constituents of the hydroalcoholic extracts of Capsicum frutescens and Capsicum baccatum fruits, evaluating these extracts and their constituents' schistosomicidal, leishmanicidal and trypanocidal activities. The results obtained for the extracts of C. frutescens are better when compared to those obtained for C. baccatum , which can be related to the different concentrations of capsaicin ( 1 ) present in the extracts. The lysis of trypomastigote forms results for capsaicin ( 1 ) led to a significant value of IC 50 = 6.23 µM. Thus, the results point to capsaicin ( 1 ) as a possible active constituent in these extracts.

We report the chemical composition of the crude leaf extracts obtained from Stizophyllum perforatum (Cham.) Miers (Bignoniaceae), a simple high-performance liquid chromatography-diode array detection (HPLC-DAD) method based on mangiferin as an internal standard to quantify verbascoside, and the verbascoside acute oral toxicity and antileishmanial activity. HPLC-high-resolution mass spectrometry-DAD (HPLC-HRMS-DAD) analyses of the crude ethanol S. perforatum leaf extracts (CE-1 and CE-2) revealed that verbascoside was the major constituent in both extracts. CE-1 was purified, and verbascoside and casticin, among other compounds, were isolated. The developed HPLC-DAD method was validated and met the required standards. Investigation of the CE-2 acute toxicity indicated a lethal dose (LD 50 ) greater than 2,000 mg/kg of body weight. Both CE-1 and CE-2 exhibited antileishmanial activity. The isolated compounds, verbascoside and casticin, also displayed antileishmanial activity with effective concentrations (IC 50 ) of 6.23 and 24.20 µM against promastigote forms and 3.71 and 18.97 µM against amastigote forms of Leishmania amazonensis , respectively, but they were not cytotoxic to J774A.1 macrophages. Scanning electron microscopy of the L. amazonensis promastigotes showed that the parasites became more rounded and that their plasma membrane was altered in the presence of verbascoside. Additionally, transmission electron microscopy demonstrated that vacuoles emerged, lipids accumulated, kinetoplast size increased, and interstitial extravasation occurred in L. amazonensis promastigotes exposed to verbascoside. These findings suggest that S. perforatum is a promising candidate for further in vivo investigations against L. amazonensis ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alves, Ozelin, Magalhães, Candido, Gimenez, Silva, Cunha, Januário, Tavares, Magalhães and Pauletti.)

Schistosomiasis, caused by Schistosoma mansoni Sambon, 1907, is a severe and widely distributed parasitic disease, affecting about 200 million people worldwide. The disease is recognized by elevated mortality rates, especially among those living in areas of poor sanitation. Currently, the chemotherapeutic treatment is solely based on using the praziquantel drug. Therefore, there is a need for the discovery of new medicines for the treatment of this parasitosis. Thus, this work aimed to evaluate the schistosomicidal activity of ethanolic crude extracts from the branches, leaves, flowers, and fruits of Handroanthus impetiginosus (Mart ex DC.) Masttos and characterize its metabolic profile by UPLC-ESI-QTOF analysis. Evaluation of plant extract on S. mansoni was carried out in adult worms in vitro, in which the mortality rate was quantified, and the damages in the tegument of the worms were monitored. All extracts induced changes in the viability of adult males of S. mansoni, causing the death of the parasites, which was directly dependent of the concentration.

This study demonstrates in vivo analgesic and anti-inflammatory properties of hydroalcoholic extracts of leaves, bark and flowers from the Handroanthus impetiginosus (Bignoniaceae) plant, recognized as 'Ipê roxo' in Brazil. The extracts were evaluated in male Swiss albino mice via oral administration. Moreover, results of the in vivo paw oedema test induced by carrageenan revealed that extracts of leaves and bark displayed relevant anti-inflammatory activity potential at the dosage of 100 mg/kg, 300 mg/kg, and 500 mg/kg. Likewise, the results obtained for leaves and flowers extracts suggested potent analgesic action in the conventional hot plate test. UPLC/MS analysis of the hydroalcoholic extracts samples identified metabolites belonging to several classes, mainly naphthoquinones and iridoids derivatives as well as flavonoids. Thus, the obtained results indicate that the extracts of H. impetiginosus plant parts could be considered as a complementary herbal medicine for the treatment of pain and inflammation disorders.

Lignan dinitrohinokinin displays important biological activities, which led to the preparation of its poly-ε-caprolactone nanoparticles. Kinetics analysis revealed initially slow drug release followed by a prolonged, moderate release 6 h later due to DNHK diffusion through the polymeric matrix. Molecular dynamics simulations show that DNHK molecules that interact stronger with other DNHK molecules near the PCL/DNHK surface are more difficult to dissociate from the nanoparticle. The smaller diameter nanocapsules with negative surface charge conferred good colloidal stability. The formulations showed a size distribution with monodisperse systems formation. In vivo evaluation of schistosomicidal activity against Schistosoma mansoni showed that DNHK, when incorporated into nanoparticles, caused egg number reduction of 4.2% and 28.1% at 40 mg/kg and 94.2% and 84.4% at 400 mg/kg in the liver and the spleen, respectively. The PCL nanoparticles were stable in aqueous dispersion and could be optimized to be used as a promising lignan release agent.

Schistosomiasis mansoni is an infectious parasitic disease caused by worms of the genus Schistosoma, and praziquantel (PZQ) is the medication available for the treatment of schistosomiasis. However, the existence of resistant strains reinforces the need to develop new schistosomicidal drugs safely and effectively. Thus, the (±)-licarin A neolignan incorporated into poly-Ɛ-caprolactone (PCL) nanoparticles and not incorporated were evaluated for their in vivo schistosomicidal activity. The (±)-licarin A -loaded poly(ε-caprolactone) nanoparticles and the pure (±)-licarin A showed a reduction in the number of worm eggs present in spleens of mice infected with Schistosoma mansoni. In addition, the (±)-licarin A incorporated in the concentration of 20 mg/kg and 200 mg/kg reduced the number of worms, presenting percentages of 56.3% and 41.7%, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Origanum vulgare, known for its medicinal value, is officially accepted in many countries. The flowers and leaves are used globally in homeopathy. In Brazilian folk medicine, O. vulgare has been used to treat diabetes mellitus. This study evaluated the hypoglycemic activity of an infusion extract (RosCE) of commercially available O. vulgare leaves in alloxan-induced diabetic rats. Oral administration of RosCE resulted in the reduction of blood glucose levels after the first day of treatment, compared to the diabetic control group. These results showed that RosCE displays hypoglycemic activity, which may be due to the combined effect of rosmarinic acid, and other minor compounds. Reversed phase-high performance liquid chromatography-diode array detection was used to identify and quantify the major constituents of RosCE. This study presents evidence that supports the folkloric use of O. vulgare for the treatment of hyperglycemia, confirming the use of its infusion as an antidiabetic herbal medicine.

The genus Absidia is widely used in the biotransformation of different classes of natural products. This study evaluates the ability of the Absidia coerulea 3A9 marine derived strain isolated from the ascidian Distaplia stilyfera to perform biotransformations by conducting assays with (-)-cubebin, as substrate. The experiment was optimized using the experimental design proposed by Plackett-Burman for seven factors and eight experiments, to establish the biotransformation conditions that would allow maximum production of biotransformed dibenzylbutyrolactone (-)-hinokinin. An analytical method based on Reverse-Phase-High Performance Liquid Chromatography (RP-HPLC) was developed to quantify the fungal biotransformation product. The factor that influenced the (-)-hinokinin peak area the most positively was the percentage of seawater (%seawater) given that its %relative standard deviation (%RSD) showed a 32.92% deviation from the real value., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Styrax camporum Pohl, a typical species from the Brazilian cerrado, commonly known as "benjoeiro", is used to treat gastroduodenal diseases. In previous studies carried out by our research group, hydroalcoholic extract of S. camporum stems (SCHE) exhibited antigenotoxic and antiproliferative effects. For a comparative analysis of the chemopreventive effect of SCHE, the aim of this study was to investigate the influence of SCHE against carcinogen 1,2-dimethylhydrazine (DMH)-induced DNA damage and pre-neoplastic lesions in Wistar rat colon. Animals were treated orally with SCHE at 250, 500 or 1000 mg/kg body weight in conjunction with a subcutaneous injection of DMH. DNA damage was assessed using the comet assay while tpre-neoplastic lesions by aberrant crypt foci (ACF) assay. The following hepatic oxidative stress markers were determined including activities of catalase (CAT) and glutathione S-transferase (GST) as well as levels of reduced glutathione (GSH) and malondialdehyde (MDA). Treatment with SCHE was not genotoxic or carcinogenic at the highest dose tested (1000 mg/kg b.w.). The extract effectively inhibited DNA damage and pre-neoplastic lesions induced by DMH administration at all concentrations tested. Measurement of CAT, and GST activities and levels of GSH showed that SCHE did not reduce oxidative processes. In contrast, treatment with SCHE (1000 mg/kg b.w.) decreased liver MDA levels. Taken together, these findings suggested the chemopreventive effect attributed to SCHE in colon carcinogenesis, may be related to its capacity to inhibit DNA damage as well as an antioxidant action associated with its chemical constituents egonol and homoegonol.

Candidiasis therapy, especially for candidiasis caused by Candida non- albicans species, is limited by the relatively reduced number of antifungal drugs and the emergence of antifungal tolerance. This study evaluates the anticandidal activity of 41 plant-derived products against Candida species, in both planktonic and biofilm cells. This study also evaluates the toxicity and the therapeutic action of the most active compounds by using the Caenorhabditis elegans-Candida model. The planktonic cells were cultured with various concentrations of the tested agents. The Cupressus sempervirens , Citrus limon , and Litsea cubeba essential oils as well as gallic acid were the most active anticandidal compounds. Candida cell re-growth after treatment with these agents for 48 h demonstrated that the L. cubeba essential oil and gallic acid displayed fungistatic activity, whereas the C. limon and C. sempervirens essential oils exhibited fungicidal activity. The C. sempervirens essential oil was not toxic and increased the survival of C. elegans worms infected with C. glabrata or C. orthopsilosis . All the plant-derived products assayed at 250 µg/mL affected C. krusei biofilms. The tested plant-derived products proved to be potential therapeutic agents against Candida , especially Candida non- albicans species, and should be considered when developing new anticandidal agents.

The occurrence of sulfated steroids and phenolics in marine organisms is quite widespread, being typically reported from Echinoderms. In contrast, alkane and alkene aliphatic sulfates are considerably rarer with examples being reported from a diverse array of organisms including echinoderms, sponges and ascidians. While no ecological roles for these metabolites have been proposed, they do exhibit a diverse array of biological activities including thrombin inhibition; the ability to induce metamorphosis in larvae; antiproliferative, antibacterial and antifungal properties; and metalloproteinase inhibition. Of particular interest and an avenue for future development is the finding of antifouling properties with low or nontoxic effects to the environment. This review focuses on alkyl sulfates and related sulfamates, their structures and biological activities. Spectroscopic and spectrometric techniques that can be used to recognize the presence of sulfate groups are also discussed, data for which will enhance the ability of researchers to recognize this class of chemically- and biologically-interesting marine natural products.

Six dibenzylbutyrolactonic lignans ((-)-hinokinin (1), (-)-cubebin (2), (-)-yatein (3), (-)-5-methoxyyatein (4), dihydrocubebin (5) and dihydroclusin (6)) were isolated from Piper cubeba seed extract and evaluated against Schistosoma mansoni. All lignans, except 5, were able to separate the adult worm pairs and reduce the egg numbers during 24 h of incubation. Lignans 1, 3 and 4 (containing a lactone ring) were the most efficient concerning antiparasitary activity. Comparing structures 3 and 4, the presence of the methoxy group at position 5 appears to be important for this activity. Considering 1 and 3, it is possible to see that the substitution pattern change (methylenedioxy or methoxy groups) in positions 3' and 4' alter the biological response, with 1 being the second most active compound. Computational calculations suggest that the activity of compound 4 can be correlated with the largest lipophilicity value., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

(-)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (-)-hinokinin (HK) and (-)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 - cyclooxygenase-2) interaction in comparison with CUB and HK., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This article reports on the in vitro activity of the hydroalcoholic extract of Pfaffia glomerata roots, its hydrolyzed fractions, and pfaffic acid against Trypanosoma cruzi. The hydroalcoholic extract obtained from dried, milled P. glomerata roots was submitted to acid hydrolysis followed by partition with CHCl 3 . The concentrated CHCl 3 fraction was suspended in MeOH/H 2 O and partitioned with hexane (F1), CHCl 3 (F2), and AcOEt (F3), in this sequence. The trypanocidal activity of the hydrolyzed extract and its fractions was evaluated in vitro. The hydroalcoholic extract displayed low activity, but fraction F1 was active against trypomastigotes of the Y strain of T. cruzi, with IC 50 = 47.89 μg/ml. The steroids campesterol (7.7%), stigmasterol (18.7%), β-sitosterol (16.8%), Δ 7 -stigmastenol (4.6%), and Δ 7 -spinasterol (7.5%) were the major constituents of F1, along with fatty acid esters (7.6%) and eight aliphatic hydrocarbons (30.1%). Fractions F2 and F3 exhibited moderate activity, and pfaffic acid, one of the main chemical constituents of these fractions, displayed IC 50 = 44.78 μm (21.06 μg/ml). On the other hand, the hydroalcoholic extract of P. glomerata roots, which is rich in pfaffosides, was inactive. Therefore, the main aglycone of pfaffosides, pfaffic acid, is much more active against trypomastigotes of the Y strain of T. cruzi than its corresponding glycosides and should be further investigated., (© 2017 Wiley-VHCA AG, Zurich, Switzerland.)

Bioassay-guided study of the ethanol extract from the cashew Anacardium occidentale furnished cardol triene (1), cardol diene (2), anacardic acid triene (3), cardol monoene (4), anacardic acid diene (5), 2-methylcardol triene (6), and 2-methylcardol diene (7). 1D- and 2D-NMR experiments and HRMS analysis confirmed the structures of compounds 1-7. Compounds 2 and 7 were active against Schistosoma mansoni adult worms in vitro, with LC 50 values of 32.2 and 14.5 μM and selectivity indices of 6.1 and 21.2, respectively. Scanning electron microscopy of the tegument of male worms in the presence of compound 7 at 25 μM after 24 h of incubation showed severe damage as well as peeling and reduction in the number of spine tubercles. Transmission electron microscopy analyses revealed swollen mitochondrial membrane, vacuoles, and altered tegument in worms incubated with compound 2 (25 μM after 24 h). Worms incubated with compound 7 (25 μM after 24 h) had lysed interstitial tissue, degenerated mitochondria, and drastically altered tegument. Together, the results indicated that compound 7 presents promising in vitro schistosomicidal activity.

The benzofuran lignans egonol and homoegonol are found in all species of the genus Styrax. Since natural products are important sources of new anticancer drugs, this study evaluated the cytotoxic activity of a hydroalcoholic extract of the stems of S. camporum (SCHE) and their chemical markers, egonol (EG) and homoegonol (HE), against different tumor cell lines (B16F10, MCF-7, HeLa, HepG2, and MO59J). A normal human cell line (GM07492A) was included. Cytotoxic activity was evaluated at different treatment times (24, 48 and 72 h) using the XTT assay. More effective results were observed after 72 h of treatment. The lowest IC50 values were found for the HepG2 cell line, ranging from 11.2 to 55.0 µg/mL. The combination of EG and HE exerted higher cytotoxic activity than SCHE or treatment with either lignan alone, with the lowest IC50 (13.31 µg/mL) being observed for the MCF-7 line. Furthermore, treatment with these lignans was significantly more cytotoxic for some tumor cell lines compared to the normal cell line, GM07492A, indicating selectivity. These results suggest that these lignans may be used to treat cancer without affecting normal cells.

The antimicrobial activity and possible synergistic effects of extracts and compounds isolated from Usnea steineri were evaluated against four resistant bacterial species. A phytochemical study of the acetone extract of U. steineri resulted in the isolation and characterization of difractaic acid and (+)-usnic acid as the main compounds. The acetone extract showed strong activity (less than 10 µg/mL) against resistant strains of Staphylococcus epidermidis and Enterococcus faecalis, and (+)-usnic acid exhibited strong activity against S. epidermidis (MIC 3.12 µg/mL), S. aureus and S. haemnolyticus (MIC 12.5 µg/mL). Combinations of penicillin and tetracycline with (+)-usnic acid did not show any synergistic antimicrobial effects. Difractaic acid was inactive. Our results showed that the acetone extract of U. steineri possesses significant in vitro antimicrobial activity, which is likely related to the presence of (+)-usnic acid.

This study evaluated the influence of Styrax camporum stems hydroalcoholic extract (SCHE) and of chemical markers of the genus, egonol (EG) and homoegonol (HE), on DNA damage induced in V79 cells by mutagens with different mechanisms of action. These natural products were combined with different mutagens [methyl methanesulfonate (MMS), hydrogen peroxide (H 2 O 2 ), (S)-(+)-camptothecin (CPT), and etoposide (VP-16)] to evaluate the modulatory effect on DNA damage. The results showed that SCHE was genotoxic at the highest concentration tested (60 µg/mL). Treatment with EG or HE alone induced no genotoxic effect, while genotoxic activity was observed when the two compounds were combined. The SCHE extract was able to reduce the frequency of micronuclei induced by H 2 O 2 and VP-16. Similar results were observed when the cell cultures were treated with EG and/or HE plus VP-16. In contrast, the highest concentration (40 µg/mL) SCHE potentiated DNA damage induced by VP-16. Neolignan EG alone or combined with HE also potentiated H 2 O 2 -induced genotoxicity. However, these natural products did not influence the frequency of DNA damage induced by MMS or CPT. Therefore, the influence of SCHE and of chemical markers (EG and HE) of the genus on the induction of DNA damage depends on the concentration tested and on the mutagen used.

The chemotherapy of schistosomiasis relies on the use of praziquantel. However, concerns over drug resistance have encouraged the search for new drug leads. This paper is the first report on the in vitro and in vivo activity of (-)-6,6'-dinitrohinokinin (DNK) against Schistosoma mansoni. In vitro, the lethal concentrations for 50% of parasites (LC50) of DNK against adult worms were 103.9±3.6 and 102.5±4.8μM at 24 and 72h, respectively. Scanning electron microscopy images showed extensive tegumental alterations such as peeling and smaller numbers of tubercles in the spine of adult worms. DNK also elicited high mortality of schistosomula, with LC50 values of 57.4±2.3, 32.5±0.9, and 20.4±1.2μM at 24, 48, and 72h, respectively. DNK displayed moderate activity against the juvenile liver parasite, with an LC50 value of 179.5±2.3 μM at 72h. This compound reduced the total number of eggs by over 83%, and it affected the development of eggs produced by adult worms. The selectivity index showed that at 24h, DNK was 8.5 and 15.4 times more toxic to the adult worms and schistosomula than to Chinese hamster lung fibroblast cells, respectively. Treatment of infected mice with DNK moderately decreased worm burden (33.8-52.3%), egg production (40.7-60.0%), and spleen and liver weights. Together, our results indicated that DNK presents moderate in vitro and in vivo activities against S. mansoni, and it might therefore be interesting to explore the structure-activity relationship of the antischistosomal activity of this compound., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This paper reports on the in vitro antibacterial and in vivo anti-inflammatory properties of a hydroethanolic extract of the aerial parts of Gochnatia pulchra (HEGP). It also describes the antibacterial activity of HEGP fractions and of the isolated compounds genkwanin, scutellarin, apigenin, and 3,5-O-dicaffeoylquinic acid, as evaluated by a broth microdilution method. While HEGP and its fractions did not provide promising results, the isolated compounds exhibited pronounced antibacterial activity. The most sensitive microorganism was Streptococcus pyogenes, with minimum inhibitory concentration (MIC) values of 100, 50 and 25 µg/mL for genkwanin and the flavonoids apigenin and scutellarin, respectively. Genkwanin produced an MIC value of 25 µg/mL against Enterococcus faecalis. A paw edema model in rats and a pleurisy inflammation model in mice aided investigation of the anti-inflammatory effects of HEGP. This study also evaluated the ability of HEGP to modulate carrageenan-induced interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) production. Orally administered HEGP (250 and 500 mg/kg) inhibited carrageenan-induced paw edema. Regarding carrageenan-induced pleurisy, HEGP at 50, 100, and 250 mg/kg diminished leukocyte migration by 71.43%, 69.24%, and 73.34% (P<0.05), respectively. HEGP suppressed IL-1β and MCP-1 production by 55% and 50% at 50 mg/kg (P<0.05) and 60% and 25% at 100 mg/kg (P<0.05), respectively. HEGP abated TNF-α production by macrophages by 6.6%, 33.3%, and 53.3% at 100, 250, and 500 mg/kg (P<0.05), respectively. HEGP probably exerts anti-inflammatory effects by inhibiting production of the pro-inflammatory cytokines TNF-α, IL-1β, and MCP-1.

This work evaluated the in vitro inhibitory activity of the crude ethanolic extract from the aerial parts of Cuspidaria pulchra (Cham.) L.G. Lohmann against 15-lipoxygenase (15-LOX). The bioassay-guided fractionation of the n-butanol fraction, which displayed the highest activity, led to the isolation of three compounds: caffeoylcalleryanin (1), verbascoside (2) and 6-hydroxyluteolin-7-O-β-glucoside (3). Assessment of the ability of the isolated compounds to inhibit 15-LOX revealed that compounds 1, 2 and 3 exerted strong 15-LOX inhibitory activity; IC50 values were 1.59, 1.76 and 2.35 μM respectively. The XTT assay showed that none of the isolated compounds seemed to be significantly toxic.

Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities of quinones, hydroquinones, rossinones, longithorones, longithorols, floresolides, scabellones, conicaquinones, aplidinones, thiaplidiaquinones, and conithiaquinones. A compilation of the 13C-NMR spectral data of these compounds is also presented.

Protozoans of the trypanosomatid family cause the neglected tropical diseases leishmaniasis and trypanosomiasis, for which few drugs are available. In this context our group has recently reported that the essential oil obtained by steam distillation of the fruits of Piper cubeba is active against Schistosoma mansoni. Therefore, we have investigated the in vitro effects of the essential oil against the trypomastigote and amastigote forms of Trypanosoma cruzi isolated from an LLCMK₂ cell line culture and the promastigote forms of Leishmania amazonensis. The in vitro activity of the essential oil against trypomastigotes of T. cruzi increased upon rising concentrations, giving IC₅₀ values of 45.5 and 87.9 µg · mL⁻¹ against trypomastigotes and amastigotes, respectively. The essential oil was not active against L. amazonensis, since it displayed lyses of only 24 % at 400 µg · mL⁻¹, and an IC₅₀ of 326.5 µg · mL⁻¹. Therefore, the essential oil should be further investigated to determine the compounds responsible for the observed activities, as well as its mechanism of action., (Georg Thieme Verlag KG Stuttgart · New York.)

Context: Despite several pharmacological applications of Rosmarinus officinalis L. (Lamiaceae), studies on its analgesic and anti-inflammatory properties have been scarce., Objective: The aim of this work was to use in vivo models to evaluate the analgesic and anti-inflammatory activities of the aqueous extracts obtained from leaves (AEL) and stems (AES) of Rosmarinus officinalis, as well as its isolated compound--rosmarinic acid (RA). We also prepared and assessed the acetyl ester derivative of RA., Materials and Methods: The analgesic activity was evaluated using abdominal constriction and formalin tests. For the evaluation of the anti-inflammatory effects, carrageenin-induced paw edema in rats were used. The extracts were used at doses of 100, 200 and 400 mg kg⁻¹ compounds were tested at 10, 20 and 40 mg kg⁻¹., Results: Orally administered AEL, AES and RA were not significantly active at any of the doses tested during the abdominal constriction test; the acetyl ester derivative of RA displayed significant analgesic activity. In the carrageenin-induced paw edema assay, the acetyl derivative of RA at all the tested doses produced significant anti-inflammatory effects and reduced the number of paw licks in the second phase of the formalin test., Discussion and Conclusion: The results suggest that the analgesic effects of the acetyl derivative of RA operate via a peripheral-mediated mechanism. The acetyl ester derivative of RA is potentially applicable as a new lead compound for the management of pain and inflammation.

Styrax camporum Pohl is a tall shrub or a tree with small white flowers, which grows in the states of São Paulo and Minas Gerais and is popularly used for the treatment of gastroduodenal diseases. Considering this last fact, the aim of this study was to evaluate the genotoxic potential of S. camporum hydroalcoholic extract and its influence on genotoxicity induced by doxorubicin and methyl methanesulfonate in Swiss mice using the micronucleus and comet assays, respectively. The animals were treated by gavage with different doses of the extract (250, 500, and 1000 mg/kg body weight). For antigenotoxicity assessment, different doses of the S. camporum extract were administered simultaneously with doxorubicin (micronucleus test; 15 mg/kg) and methanesulfonate (comet assay; 40 mg/kg). The results showed that the S. camporum extract itself was not genotoxic in the mouse micronucleus or comet assay. The number of micronucleated polychromatic erythrocytes was significantly lower in animals treated with the S. camporum extract and doxorubicin when compared to animals treated only with doxorubicin. In the comet assay, the S. camporum extract, at the doses tested, significantly reduced the extent of DNA damage in liver cells induced by methanesulfonate. The putative activity of the active compounds of S. camporum extract may explain the effect of this plant on genotoxicity induced by doxorubicin and methanesulfonate., (Georg Thieme Verlag KG Stuttgart · New York.)

Context: Schistosomiasis is a major health problem worldwide. Thus, the search for new schistosomicidal agents from natural sources can provide prototypes for drug discovery., Objective: The present study investigated the chemical composition of the EtOAc fractions of Styrax pohlii Pohl (Styracaceae) (EF-SP) aerial parts and S. camporum A. DC. leaves (EF-SC), as well as schistosomicidal activities against Schistosoma mansoni adult worms, which have not yet been studied., Materials and Methods: The crude ethanol extracts of S. camporum leaves and S. pohlii aerial parts (EE-SC and EE-SP) were partitioned with n-hexane, EtOAc, and n-BuOH. The EtOAc fractions were purified by preparative HPLC. The crude extracts, EtOAc fractions and pure compounds were tested against S. mansoni adult worms in vitro., Results: The purification procedure resulted in the isolation of kaempferol-3-O-(2'',4''-di-O-(E)-p-coumaroyl)-β-d-glucopyranoside (1), kaempferol-3-O-(2'',6''-di-O-(E)-p-coumaroyl)-β-d-glucopyranoside (2), quercetin (3), and kaempferol (4). The bioassay results indicated that EE-SC, EF-SC, EF-SP, and compounds 2 and 4 are able to separate coupled S. mansoni adult worms. Additionally, EE-SC, EF-SP, and compound 4 killed the adult schistosomes in vitro at 100 µg/mL and 100 µM., Discussion and Conclusion: This is the first time that the presence of compounds 1-2 in S. pohlii and 3-4 in S. camporum has been reported. Additionally, biological results indicated that S. pohlii and S. camporum have great potential as a source of active compounds.

Styrax camporum Pohl, known in Brazil as 'estoraque do campo' or 'cuia de brejo', has been used in the treatment of gastrointestinal diseases. The therapeutic action of S. camporum has been attributed to the ethyl acetate fraction, although the chemical composition of this fraction has not yet been analyzed. In this study, a high-performance liquid chromatography photodiode array detection (HPLC-PAD) method for analysis of Brazilian Styrax species has been developed. The compounds egonol (1) and homoegonol (2) were found to be present in all the samples investigated by HPLC. These compounds were isolated by open column chromatography followed by preparative TLC, and were identified by ¹H NMR. Compounds 1 and 2 were thus proposed as phytochemical markers for Styrax, owing to their biological properties and presence in other Styrax species. The developed method has been validated and successfully applied for quantification of 1 and 2 in S. camporum dried leaves and crude ethanolic extracts from S. ferrugineus and S. pohlii aerial parts., (Copyright © 2011 John Wiley & Sons, Ltd.)

Chemical investigation of the n-hexane and EtOAc fractions of the ethanolic extract from Styrax pohlii (Styracaceae) aerial parts resulted in the isolation of the benzofuran nor-neolignan derivatives egonol (1), homoegonol (2), homoegonol gentiobioside (3), homoegonol glucoside (4) and egonol gentiobioside (5). This is the first report of compounds 1-5 in S. pohlii. Compounds 1-5, the acetyl derivatives 1 a and 2 a, the ethanolic extract (EE), the n-hexane fraction (HF) and EtOAc fraction (EF) were tested for their inhibitory activities against COX-1 and COX-2. The results showed that EE, HF, EF and compounds 1-5 and 1 a-2 a shown weak to moderate inhibition of COX-1 and COX-2. Among the assayed nor-neolignans, 4 gave a COX-1 inhibition of 35.7% at 30 µM. Compound 5 displayed a COX-2 inhibition of 19.7% at 30 µM.

Miconia langsdorffii Cogn. (Melastomataceae), Roupala montana Aubl. (Proteaceae), Struthanthus syringifolius (Mart.) (Loranthaceae), and Schefflera vinosa (Cham. & Schltdl.) Frodin (Araliaceae) are plant species from the Brazilian Cerrado whose schistosomicidal potential has not yet been described. The crude extracts, fractions, the triterpenes betulin, oleanolic acid, ursolic acid and the flavonoids quercetin 3-O-β-D-rhamnoside, quercetin 3-O-β-D-glucoside, quercetin 3-O-β-D-glucopyranosyl-(1-2)-α-L-rhamnopyranoside and isorhamnetin 3-O-β-D-glucopyranosyl-(1-2)-α-L-rhamnopyranoside were evaluated in vitro against Schistosoma mansoni adult worms and the bioactive n-hexane fractions of the mentioned species were also analyzed by GC-MS. Betulin was able to cause worm death percentage values of 25% after 120 h (at 100 μM), and 25% and 50% after 24 and 120 h (at 200 μM), respectively; besides the flavonoid quercetin 3-O-β-D-rhamnoside promoted 25% of death of the parasites at 100 μM. Farther the flavonoids quercetin 3-O-β-D-glucoside and quercetin 3-O-β-D-rhamnoside at 100 μM exhibited significantly reduction in motor activity, 75% and 87.5%, respectively. Biological results indicated that crude extracts of R. montana, S. vinosa, and M. langsdorffii and some n-hexane and EtOAc fractions of this species were able to induce worm death to some extent. The results suggest that lupane-type triterpenes and flavonoid monoglycosides should be considered for further antiparasites studies.

(±)-Licarin A (1), a neolignan obtained by the oxidative coupling reaction of isoeugenol, had in this study its enantiomers resolved. A novel, quick and efficient enantiomeric resolution of 1 was directly performed by chiral high-performance liquid chromatography (HPLC-PDA) protocol (CHIRALPACK(®) AD column; 9:1 (v/v) n-hexane:2-propanol; 1.0 mL/min). This method provided a chromatogram profile with a well-resolved peak separation. After isolation of each enantiomer with ee>99.9%, they were analysed in a polarimeter. Compound 2, which showed a retention time (t(r)) of 12.13 min, was the (+)-enantiomer and compound 3 (t(r)=18.90 min) was the (-)-enantiomer., (Copyright © 2011 Elsevier B.V. All rights reserved.)

No fully effective treatment has been developed since the discovery of Chagas' disease. Since drug-resistant Trypanosoma cruzi strains are occurring and the current therapy is effective in the acute phase but with various adverse side effects, more studies are needed to characterize the susceptibility of T. cruzi to new drugs. Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing, which is unusual RNA processing reaction, and it implies the processing of polycistronic transcription units into individual mRNAs; a short transcript spliced leader (SL RNA) is trans-spliced to the acceptor pre-mRNA, giving origin to the mature mRNA. Cubebin derivatives seem to provide treatments with less collateral effects than benznidazole and showed similar or better trypanocidal activities than benznidazole. Therefore, the cubebin derivatives ((-)-6,6'-dinitrohinokinin (DNH) and (-)-hinokinin (HQ)) interference in the mRNA processing was evaluated using T. cruzi permeable cells (Y and BOL (Bolivia) strains) following by RNase protection reaction. These substances seem to intervene in any step of the RNA transcription, promoting alterations in the RNA synthesis, even though the RNA processing mechanism still occurs. Furthermore, HQ presented better activity against the parasites than DNH, meaning that BOL strain seems to be more resistant than Y.

The in vitro inhibitory activity of crude EtOH/H2O extracts from the leaves and stems of Rosmarinus officinalis L. was evaluated against the following microorganisms responsible for initiating dental caries: Streptococcus mutans, S. salivarius, S. sobrinus, S. mitis, S. sanguinis, and Enterococcus faecalis. Minimum inhibitory concentrations (MIC) were determined with the broth microdilution method. The bioassay-guided fractionation of the leaf extract, which displayed the higher antibacterial activity than the stem extract, led to the identification of carnosic acid (2) and carnosol (3) as the major compounds in the fraction displaying the highest activity, as identified by HPLC analysis. Rosmarinic acid (1), detected in another fraction, did not display any activity against the selected microorganisms. HPLC Analysis revealed the presence of low amounts of ursolic acid (4) and oleanolic acid (5) in the obtained fractions. The results suggest that the antimicrobial activity of the extract from the leaves of R. officinalis may be ascribed mainly to the action of 2 and 3.

This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the (13)C-NMR spectral data of these selected natural indole alkaloids is also provided.

Baccharis dracunculifolia (Asteraceae), the most important plant source of the Brazilian green propolis (GPE), displayed in vitro activity against Leishmania donovani, with an IC(50) value of 45 microg/mL, while GPE presented an IC(50) value of 49 microg/mL. Among the isolated compounds of B. dracunculifolia, ursolic acid, and hautriwaic acid lactone showed IC(50) values of 3.7 microg/mL and 7.0 microg/mL, respectively. Uvaol, acacetin, and ermanin displayed moderate antileishmanial activity. Regarding the antiplasmodial assay against Plasmodium falciparum, BdE and GPE gave similar IC(50) values (about 20 microg/mL), while Hautriwaic acid lactone led to an IC(50) value of 0.8 microg/mL (D6 clone).

Chemical investigation of the EtOAc fraction (EF) obtained from the ethanolic extract of Zanthoxylum naranjillo (Rutaceae) leaves (EE) by preparative HPLC resulted in the isolation of protocatechuic acid (1), gallic acid (2), p-hydroxybenzoic acid (3), and 5-O-caffeoylshikimic acid (4). This is the first time that the presence of compounds 1-4 in Z. naranjillo has been reported. Compounds 1-4, the EE, and EF were tested in vitro against Schistosoma mansoni adult worms. The results showed that the S. mansoni daily egg production decreased by 29.8%, 13.5%, 28.4%, 17.7%, 16.3%, and 6.4%, respectively. Compounds 1 and 3 were also able to separate adult worm pairs into male and female. This activity may be correlated with the reduction in egg production, since 1 and 3 showed better inhibitory properties compared with 2 and 4.

Two new flavone glucosides, nitensosides A and B (1, 2), together with four known compounds, sorbifolin (3), sorbifolin 6-O-beta-glucopyranoside (4), pedalitin (5), and pedalitin 6-O-beta-glucopyranoside (6) were isolated from Pterogyne nitens. Their structures were elucidated from 1D and 2D NMR analysis, as well as by high resolution mass spectrometry. All the isolated flavones were evaluated for their myeloperoxidase (MPO) inhibitory activity. The most active compound, pedalitin, exhibited IC50 value of 3.75 nM on MPO. Additionally, the radical-scavenging capacity of flavones 1-6 was evaluated towards ABTS and DPPH radicals and compared to standard compounds quercetin and Trolox.

Three new C-glucosylxanthones, 2-(2'-O-trans-caffeoyl)-C-beta-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (1), 2-(2'-O-trans-cinnamoyl)-C-beta-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (2), and 2-(2'-O-trans-coumaroyl)-C-beta-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (3), were isolated from the stems of Arrabidaea samydoides, in addition to three known C-glucosylxanthones, mangiferin (4), 2-(2'-O-benzoyl)-C-beta-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (5), and muraxanthone (6). Their chemical structures were assigned on the basis of MS and 1D and 2D NMR experiments. Xanthones 1-6 showed moderate free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as antioxidant activity evidenced by redox properties measured on ElCD-HPLC.

Chemical examination of the leaves of Styrax ferrugineus yielded 5-[3''-(beta-D-glucopyranosyloxy)propyl]-7-methoxy-2-(3',4'-dimethoxyphenyl) benzofuran, along with the known nor-lignans 5-(3''-hydroxypropyl)-7-methoxy-2-(3',4'-methylenedioxyphenyl) benzofuran, 5-(3''-hydroxypropyl)-7-methoxy-2-(3',4'-dimethoxyphenyl)benzofuran, 5-[3''-(beta-D-glucopyranosyloxy)propyl]-7-methoxy-2-(3',4'-methylenedioxyphenyl)benzofuran and the lignan, dihydrodehydrodiconiferyl alcohol. All arylpropanoids isolated showed antibacterial and antifungal activities. The structures of the isolates were established by spectroscopic analysis.