ETHNOPHARMACOLOGICAL RELEVANCE:Cardiovascular diseases (CVDs) are the leading cause of hospitalization and death worldwide. The use of complementary therapies, particularly medicinal plants, has become increasingly prevalent as a therapeutic option. Petiveria alliacea L. (Phytolaccaceae) is a prominent species widely distributed across Brazil. Regarding its ethnopharmacological application, studies involving folk healers have documented the use of this species to treat various disorders of the cardiovascular system. AIM OF THE STUDY:To investigate the cardioprotective effects of an ethanol-soluble fraction obtained from the aerial parts of P. alliacea in hypertensive rats subjected to isoprenaline-induced cardiac stress. MATERIALS AND METHODS:Aerial parts of P. alliacea were collected, and an aqueous extract was prepared via infusion. This extract was subsequently treated with ethanol to yield the ethanol-soluble fraction of P. alliacea (ESPA). Wistar-Kyoto and spontaneously hypertensive rats (SHR) were assigned to the following experimental groups: naïve, negative control (vehicle), metoprolol (10 mg/kg), and ESPA (30, 100, and 300 mg/kg). All hypertensive groups received isoprenaline (4.5 mg/kg, s.c.) once daily for four consecutive days. After a 28-day treatment period, renal function, electrocardiographic parameters, blood pressure, and mesenteric vascular bed reactivity were assessed. Biochemical markers, histopathology, and cardiac morphometry were also evaluated. Additionally, intracellular cyclic guanosine monophosphate (cGMP) levels were measured in SHR aortic rings. RESULTS:On the first day, treatment with ESPA (30 mg/kg) induced a significant natriuretic response, increasing urinary Na+ excretion by ∼ 18% compared to the negative control group; after 28 days, animals treated with 100 and 300 mg/kg of ESPA showed a reduction in systolic blood pressure by ∼ 21%, diastolic blood pressure by ∼ 31%, and lipid peroxidation by ∼ 93%, while nitrite levels rose by ∼ 49% compared to negative control animals. Furthermore, treatment with doses of 100 and 300 mg/kg attenuated plasma angiotensin-converting enzyme activity by approximately 38% and aldosterone levels by ∼26%, restoring them to values comparable to the naïve group. Additionally, ESPA (100 and 300 mg/kg) prevented increases in relative heart weight, left ventricular wall thickness, and interventricular septum thickness, specifically reducing left ventricular wall thickness by ∼ 67% compared to the negative control rats. Finally, incubation with ESPA (0.1 and 1 mg/mL) increased intracellular cGMP levels by approximately 42% and 102%, respectively, in SHR rat aortic rings, evidencing an activation of the nitric oxide (NO)/cGMP pathway. CONCLUSION:Long-term treatment (28 days) with ESPA exerts significant cardioprotective effects in isoprenaline-induced hypertensive rats. This effect appears to be dependent on the activation of the NO/cGMP pathway, coupled with the inhibition of angiotensin-converting enzyme.

Biological control using fungi of the Trichoderma genus has been gaining increasing prominence as a sustainable alternative to synthetic pesticides, particularly due to its ability to suppress phytopathogens and promote plant growth. While the beneficial role of Trichoderma species is well established, research involving native strains from Brazilian biomes remains limited. The present work comprised the investigation of 55 isolates of Trichoderma spp., isolated from the soil or endophytic from the plant species natives to the Pantanal and Cerrado of Mato Grosso do Sul (Brazil), regarding their capacity to inhibit the growth and spread of the phytopathogen Sclerotinia sclerotiorum (Lib.) de Bary. The results from confrontation assays (15.74-30.04 % growth of S. sclerotiorum), paired plate cultures (5.76-39.53 % growth of S. sclerotiorum), and cell wall-degrading enzyme (CWDEs) activity assays-whose activities ranged from 8.791 to 197.593 U mg-1 for glucanase, 0.059-333.864 U mg-1 for NAGase, 0.082-37.110 U mg-1 for acid phosphatase, 1.234-45.716 U mg-1 for chitinase, and 3.261-304.807 U mg-1 for protease-were used to select Trichoderma spp. Five strains were selected: Trichoderma sp. T24, Trichoderma zelobreve T26, Trichoderma longibrachiatum T44, T. zelobreve T53, and Trichoderma sp. T55. Except for strain T44, all other strains demonstrated effectiveness in biological control of S. sclerotiorum (disease severity index ≤25 %) and plant growth promotion in Phaseolus vulgaris L. cultivation (vigor index ≥268). The volatile organic compounds (VOCs) produced by five Trichoderma spp. strains post-exposure to S. sclerotiorum were analyzed by Gas Chromatography-Mass Spectrometry (GC/MS) were identified, among these VOCs with known antifungal activity, such as β-cedrene (6), β-funebrene (7), and α-acoradiene (12). Trichoderma sp. T24, T. zelobreve T53, and Trichoderma sp. T55 have potential as biocontrol agents against S. sclerotiorum and as biostimulants, increasing plant growth and development.

The species Smilax fluminensis Steud. (Smilacaceae), popularly known as "cipo-quina" and "ijuapeca guasu", originates from Brazil and has several uses in folk medicine and indigenous peoples for the treatment of persistent wounds, arthritis, bone pain, urinary problems, and rheumatism, as well as being used as a blood purifier, tonic, antipyretic and antisyphilitic. The aim of this study was to assess the influence of Smilax fluminensis extract and fractions on seed germination and seedling development of mono and eudicotyledonous species. Ethyl esters and phytol were characterized as the major compounds found in hexane fraction. In the polar samples, the main compounds annotated were kaempferol, luteolin and quercetin derivatives, and saponins. The ethanol extract (EE) and hexane (HEXF), dichloromethane (DCMF) and hydroethanol (HIDF) fractions increased the in vitro germination of Allium cepa seeds compared to controls, mainly at 125 mu g/mL and 1000 mu g/mL (100% germination) for EE and at 1000 mu g/mL for HIDF. In addition, in the presence of EE at 250 mu g/mL seedlings presented a greater number of roots, length and dry mass compared to 2,4-D and BAP. Ethyl acetate fraction (EACF) inhibited seed germination and seedling development. In Nicotiana tabacum, 100% germination was observed in the presence of EE at 125 mu g/mL, 250 mu g/mL and 500 mu g/mL, when compared to the controls. However, the seedlings reduced the number of nodes, shoots and leaves, the length and dry mass of the stem and roots. In general, the fractions inhibited the germination of N. tabacum seeds, except 250 mu g/mL of HEXF and 750 mu g/mL of HIDF, where 100% germination was observed. The fractions also reduced the seedlings development, mainly at 750 mu g/mL and 1000 mu g/mL, compared to the controls. Thus, this study suggests that the extract and fractions of S. fluminensis exhibited an effect more similar to plant hormones on A. cepa (monocotyledonous) and bioherbicide on N. tabacum (eudicotyledonous), and may therefore play an have an important role in sustainable agriculture.

Orchidaceae family is a valuable source of bioactive compounds, particularly phenanthrenes and stilbenoids, which exhibit promising pharmacological properties. Cattleya nobilior Rchb. F. remains chemically and biologically unexplored, yet its potential bioactivity warrants investigation. This study aimed to identify phenanthrenes and stilbenoids from C. nobilior and evaluate their anti-Trypanosoma cruzi and cytotoxic activities. Extracts from leaves, pseudobulbs, roots, and rhizomes were obtained using sequential solvent extraction by accelerated solvent extraction. Their biological effects were assessed against T. cruzi epimastigotes and cancer cell lines (Kasumi-1, CCRF-CEM, HCT-116, and MCF-7). Metabolomic profiling (liquid chromatography-diode array detection-mass spectrometry (LC-DAD-MS)) and multivariate analyses correlated chemical composition with bioactivity. Rhizome extracts (CnRz-DM5, CnRz-DM50) inhibited HCT-116 cells (> 80%), while CnBb-DM5, CnRz-DM5, and CnRo-DM5 inhibited > 90% of leukemic cells. CnRo-DM5 also exhibited moderate anti-T. cruzi activity (half-maximal inhibitory concentration (IC50) = 33.3 µg mL–1). Metabolomic analysis suggested 67 phenanthrenes and stilbenoids associated with cytotoxicity. Guided by these findings, the most active extract was fractionated, leading to the isolation of gigantol and batatasin III. This study provides the first chemical and biological insights into C. nobilior, reinforcing its potential as a source of bioactive phenanthrenes and stilbenoids with anticancer and antiparasitic properties.

ETHNOPHARMACOLOGICAL RELEVANCE:Baccharis dracunculifolia DC. (Asteraceae) is an aromatic and medicinal species that is native to Brazil and other South American countries. It is popularly known as "alecrim-do-campo", "alecrim-de-vassoura", and "vassourinha", being used as infusions for various ailments. Moreover, in Brazil, this species is commonly utilized for treating cardiovascular disorders. Despite its common use , there is no evidence in the literature demonstrating the effects of B. dracunculifolia leaves on the cardiovascular system. AIM OF THE STUDY:We aimed to investigate the cardiorenal properties of the aqueous extract (ESBD) and essential oil (EOBD) of B. dracunculifolia aerial parts on Wistar rats. MATERIALS AND METHODS:First, the plant material was collected and identified, its essential oil (EOBD) was extracted by hydro-distillation, while an ethanolic fraction was prepared after the obtention of the aqueous extract by infusion (ESBD). The chemical compositions of EOBD and ESBD were determined by GC-MS and LC-DAD-HRMS, respectively. The acute toxicity test was performed on female Wistar rats to determine the toxic effects after a single administration. Finally, the potential diuretic and hypotensive effects of ESBD and EOBD (doses at 30, 100, and 300 mg/kg) were evaluated on normotensive male Wistar rats. RESULTS:Thirty-eight compounds were annotated in EOBD by GC-MS (thirty-one identified), which was mainly composed by monoterpene hydrocarbons (81.9 %), highlighting α-pinene (14.2 %), β-pinene (39.8 %), and limonene (21.3 %). LC-DAD-HRMS analysis from ESBD revealed twenty-three compounds, including flavonoids (C-glycosylated flavones, O-glycosylated flavonols, and an aglycone flavanonol), and phenolic acid derivatives such as caffeoylquinic (chlorogenic), coumaroylquinic, and feruloylquinic acids. No signs of toxicity were observed after acute treatment with ESBD and EOBD, and it was suggested that the oral median lethal dose (LD50) of the extracts is above 2000 mg/kg. In addition, a 7-day oral treatment with ESBD at a dose of 300 mg/kg was able to significantly increase urinary volume (thus, acting as diuretics) and renal excretion of sodium and chloride (saluretic action). CONCLUSIONS:The findings of this study showed that a fraction derived from of the ethanol-soluble fraction of the aqueous extract (ESBD) and essential oil (EOBD) of B. dracunculifolia leaves is safe for acute administration on female Wistar rats. Additionally, oral treatment with ESBD (dose at 300 mg/kg) showed potential diuretic and saluretic effects in normotensive male Wistar rats.

Commelina benghalensis L., Commelinaceae, a species widely distributed in Brazil where it is commonly known as 'trapoeraba'. Ethnobotanical surveys in Lesotho and Cameroon have documented the use of aqueous stem extracts from C. benghalensis for their purported diuretic activities. Nevertheless, the cardiorenal effects attributed to this plant have not yet been scientifically substantiated. This study aimed to evaluate the cardiorenal effects and safety of an ethanol-soluble fraction obtained from the aqueous extract of the aerial parts of C. benghalensis in Wistar rats. The work also included the morphological characterization of the plant's aerial parts and the phytochemical characterization of the aqueous extract of C. benghalensis. The morphological features of the plant's aerial parts were characterized using light and scanning electron microscopy. The chemical constituents of the aqueous extract of C. benghalensis were putatively identified by liquid chromatography with a diode-array detector and mass spectrometry. An acute oral toxicity study of the aqueous extract of C. benghalensis was conducted in female Wistar rats. Subsequently, its diuretic, hypotensive, and electrocardiographic effects were investigated following acute and 7-day oral administration. Serum biochemical markers of renal function and oxidative stress were also measured. To elucidate the mechanism of action, the roles of Na⁺/K⁺-ATPase, carbonic anhydrase, angiotensin-converting enzyme, prostaglandins, bradykinin, and nitric oxide in the ESCB-induced diuresis were investigated. Phytochemical analysis revealed that the aqueous extract of C. benghalensis is rich in phenolic acids, flavonoids, and phenylpropanoids. No signs of acute toxicity were observed. Aqueous extract of C. benghalensis (30 mg/kg) elicited significant diuretic and antioxidant effects, as evidenced by a significant reduction in serum levels of malondialdehyde, a well-established biomarker of oxidative stress. The diuretic response appears to be mediated by a prostaglandin-dependent pathway, as the effect was abolished by treatment with indomethacin and 2',5'-dideoxyadenosine. In conclusion, our results indicate that the 30 mg/kg dose of aqueous extract of C. benghalensis has potential diuretic efficacy in the model studied. Further clinical studies are warranted to confirm its therapeutic potential.

The chemodiversity of plants is a valuable resource for drug discovery, and its combination with modern approaches can reduce the time consumption for bioactive metabolite discovery. This study aimed to evaluate the chemical constituents from 18 plant species of different families against leukemia cancer cells and the application of statistical analysis from metabolomic data and molecular networking for the prediction of bioactive metabolites. The samples, extracted by an accelerated solvent extractor using ethanol and water 7:3 (v/v), were analyzed by LC-DAD-MS and evaluated against leukemia cancer cells (Kasumi-1, KG-1, and K-562). Chemical data were aligned, analyzed by statistics, and applied to create the molecular network. Sesbania virgata, Aeschynomene denticulata, Erythroxylum angiufugum, Psidium guineense, Astronium fraxinifolium, Coccoloba ochreolata, Solanum glaucophyllum (S. glaucophyllum), and Paullinia pinnata inhibited K-562 leukemia cancer cell viability by approximately 70% at 100 μg/mL, while Ocotea diospyrifolia showed 35% inhibition for the KG-1 lineage. Alkaloid fractions from S. glaucophyllum and O. diospyrifolia revealed EC50 values ranging from 13.9 to 6.4 μg/mL for K-562 and KG-1 cell lines, effectively inducing cell death with apoptotic characteristics, membrane integrity loss, and signs of late apoptosis. The molecular networking was essential and crucial to complement the statistical analysis, which was performed from 430 features and targeted steroidal and aporphine alkaloids. Boldine revealed EC50 values of 46, 116, and 145 μM for Kasumi, KG-1, and K-562 cancer cell lines, respectively. The findings marked the relevance of a broader chemical data analysis to predict bioactive compounds, emphasizing potential benefits in the search for metabolites against leukemia cancer cells, particularly steroidal and aporphine alkaloids.

The therapeutic management of hypertension involves both pharmacological and non-pharmacological interventions. However, control remains inadequate despite effective treatments, often due to poor adherence. In this context, herbal medicines offer a complementary approach to conventional therapy. Citrullus lanatus (watermelon) seeds, frequently discarded as agricultural byproducts, represent a promising source of bioactive compounds. This study evaluated the cardiorenal properties of three extracts obtained from dried C. lanatus seeds, including an ethanol-soluble fraction from an aqueous extract (ESCL), a hydroethanolic extract, and an aqueous extract obtained by turbolysis. These extracts were chemically characterized using liquid chromatography coupled with diode array detection and mass spectrometry. Diuretic and hypotensive activities were assessed in vivo in normotensive female Wistar rats, while vasodilatory mechanisms were investigated ex vivo in isolated mesenteric vascular beds. Among the preparations screened, only the ESCL fraction displayed significant cardiorenal activity, reducing blood pressure and peripheral vascular resistance. Mechanistic investigation revealed that this vascular response is mediated via the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling cascade. These findings highlight the pharmacological potential of ESCL as a candidate for the development of novel hypotensive agents.

Green cosmetics using native species promote sustainability both through species preservation and by generating value for local communities, a movement increasingly appreciated by consumers. An example of a native Brazilian species is Passiflora cincinnata, which is rich in phenolic compounds and resilient to the Caatinga, an extremely hostile Brazilian biome. In this study, using mass spectrometry and molecular networking, to determine the chemical composition of the species and investigate the influence of the dry and rainy seasons on its antioxidant activity through multivariate analyses. The chemical information supported the development of a nanoemulsion formulation using a spontaneous emulsification method. For this development, a 22 + 2 axial point central composite design of experiments was applied. The chemical profile of P. cincinnata demonstrated an abundance of flavonoids. The metabolite intensities were not influenced by the different seasons. High antioxidant activity was shown, which was also unaffected by seasonality. Nanoemulsions presented droplet sizes between 95 and 170 nm, zeta potential between -19 and -38 mV, and PDI between 0.11 and 0.47 and were considered stable after the stability studies. Finally, it was possible to develop a potential new pro-aging cosmetic using green extract from a native species, highlighting Brazilian natural resources.

This study investigated the essential oils (EOs) from leaf, bark, and fruit of Mespilodaphne cymbarum (Kunth) Trofimov (Lauraceae), focusing on their chemical composition and antimicrobial and antibiofilm activities. EOs were extracted from plants collected in the Amazon during dry and flood seasons and analyzed by gas chromatography–mass spectrometry. Although chemical differences were evident among plant organs and chemotypes, the influence of seasonality was not pronounced. Fruit EO was dominated by α- and β-santalene and limonene. Bark EO was rich in phenylpropanoids, including methyl eugenol, myristicin, and elemicin. Leaf EO showed the greatest metabolic diversity, with chemotype-specific variations. Leaf and bark EOs demonstrated superior antibacterial and antibiofilm activities compared to fruit EO, especially against Gram-positive bacteria such as Staphylococcus epidermidis, Staphylococcus aureus, and Micrococcus luteus. Chemotype-1 leaf and bark EOs inhibited S. epidermidis biofilm formation, while chemotype-2 reduced bacterial growth. The leaf EOs from both chemotypes reduced bacterial growth against S. aureus, and bark EO decreased biofilm formation. All leaf and bark EOs showed antibiofilm activity against M. luteus. These findings highlight the potential of M. cymbarum EOs as natural sources of bioactive compounds and emphasize the importance of chemotype and plant organ selection for optimized applications.

Snake bites are a severe problem in the countryside of Brazil and are usually attributed to snakes of the genera Bothrops, Crotalus, and Lachesis. Snake venom can release ectoenzymes and nucleotidases that modulate the purinergic system. In addition to serum therapy against snake poisoning, medicinal plants with anti-inflammatory activities, such as Tabebuia aurea, is empirically applied in accidents that occur in difficult-to-access areas. This study aimed was to verify the presence and activity of nucleotidases in the crude venom of Bothrops mattogrossensis (BmtV) in vitro and characterize the modulation of purinergic components, myeloid differentiation, and inflammatory/oxidative stress markers by BmtV in vivo and in vitro. Moreover, our study assessed the inhibitory activities of specioside, an iridoid isolated from Tabebuia aurea, against the effects of BmtV. Proteomic analysis of venom content and nucleotidase activity confirm the presence of ectonucleotidase-like enzymes in BmtV. In in vivo experiments, BmtV altered purinergic component expression (P2X7 receptor, CD39 and CD73), increased neutrophil numbers in peripheral blood, and elevated oxidative stress/inflammatory parameters such as lipid peroxidation and myeloperoxidase activity. BmtV also decreased viability and increased spreading index and phagocytic activity on macrophages. Specioside inhibited nucleotidase activity, restored neutrophil numbers, and mediate the oxidative/inflammatory effects produced by BmtV. We highlight the effects produced by BmtV in purinergic system components, myeloid differentiation, and inflammatory/oxidative stress parameters, while specioside reduced the main BmtV-dependent effects.

A previous optimization of supercritical extraction from guarana seeds was performed applying orthogonal array design (OA9(34)). The antioxidant and antimicrobial activities of these extracts, as well as metabolomic profiling and correlations from the compounds by statistical analysis were determined. Extracts 1 (40% ethanol; 20 min; 40 °C and 100 bar), 2 (40% methanol; 60 min; 40 °C and 200 bar), and 8 (40% methanol; 40 min; 60 °C and 100 bar) had the highest combined values of antioxidant capacity for the DPPH, FRAP, ABTS and xanthine oxidase system methods, and were identified by chemometric analysis. Similar chemical profiles of the extracts were obtained by LC-DAD-MS, and were identified: methyl-xanthine, (epi)catechin and dimers and trimers of type A and B proanthocyanidins. The heat map analysis showed positive correlation between antioxidant methods DPPH, FRAP and ABTS and with flavan-3-ols and proanthocyanidins. Extract 3 was active against Gram-negative and -positive bacteria and Candida tropicalis.

Traditional medicine is a frequently utilized method to treat cardiovascular disease and its primary risk factors, including hypertension and dyslipidemia. Aloysia polystachya is a species that is commonly employed to treat various pathological conditions, and it has already been identified as having some cardioprotective effects. This study aimed to investigate the protective effects of the essential oil extracted from the leaves of A. polystachya in a rat model that simulates multiple cardiovascular risk factors. We evaluate the acute toxicity, as well as the cardioprotective effects, by giving different doses of A. polystachya essential oil (1.47 mg/kg, 4.40 mg/kg, and 13.20 mg/kg) over a period of 42 days. The control group was treated with rosuvastatin (5 mg/kg). At the end of the treatments, the renal function, electrocardiography, blood pressure, vascular reactivity, serum biochemical profile, and organ histopathology were evaluated. The main compounds identified in the essential oil of A. polystachya using gas chromatography coupled with mass spectrometry were beta-myrcene (1.08%), limonene (40.13%), and carvone (56.47%). The essential oil of A. polystachya not only lacks acute toxicity but also mitigates the reduction in the excretion of sodium, chloride, and creatinine in urine. Furthermore, it reduces electrocardiographic abnormalities and decreases blood pressure levels. Moreover, this treatment prevents an elevation in markers of inflammation and oxidative stress in the bloodstream. Our findings indicate significant cardioprotective effects of the essential oil of A. polystachya against multiple risk factors for cardiovascular diseases in hypertensive rats.

Pseudomonas are known as higher producers of secondary metabolites with antimicrobial properties and plant growth promoters, including resistance induction. These mechanisms should be an alternative to pesticide use in crop production. Phakopsora pachyrhizi causes Asian soybean rust, representing a high loss of yield around the world. The objective of this paper was to evaluate the application of secondary metabolites produced by Pseudomonas aeruginosa LV strain from the semi-purified fraction F4A in soybean plants to induce plant resistance against P. pachyrhizi in field conditions. The experimental design was performed in randomized blocks with three replicates using two F4A doses (1 and 10 μg mL−1) combined or not with fungicides (Unizeb Gold® or Sphere Max®). The control treatment, with Uni + Sph, saponins, flavonoids, and sphingolipids, showed higher intensities in the plants. In contrast, plants treated with the F4A fraction mainly exhibited fatty acid derivatives and some non-identified compounds with nitrogen. Plants treated with Sphere Max®, with or without F4A10, showed higher intensities of glycosylated flavonoids, such as kaempferol, luteolin, narigenin, and apigenin. Plants treated with F4A showed higher intensities of genistein and fatty acid derivatives. These increases in flavonoid compound biosynthesis and antioxidant properties probably contribute to the protection against reactive oxygen species (ROS).

ETHNOPHARMACOLOGICAL RELEVANCE:Baccharis milleflora (Less.) DC. is a plant native to Brazil that is frequently used in traditional medicine as a diuretic and antihypertensive. However, even though it is traditionally used for these purposes, its diuretic and hypotensive effects have not been fully elucidated. AIM:Investigate the cardiorenal effects of the ethanol-soluble fraction (ESBM) of Baccharis milleflora in normotensive rats. MATERIALS AND METHODS:Cladodes of B. milleflora were analyzed using light and scanning electron microscopy to provide anatomical data to support quality control. Subsequently, the ESBM was obtained and analyzed using LC-DAD-MS, and its components were annotated. The acute toxicity of ESBM was assessed in female Wistar rats. The acute and prolonged diuretic and hypotensive effects were then studied in Wistar rats. Finally, we assessed the mechanisms responsible for the diuretic effects of ESBM, including the activity of renal Na+/K+/ATPase, angiotensin-converting enzyme, and erythrocyte carbonic anhydrase. Additionally, we also investigated the involvement of bradykinin, prostaglandins, and nitric oxide. RESULTS:From LC-DAD-MS data, thirty-three metabolites were identified from ESBM, including chlorogenic acids, glycosylated phenolic derivatives, C-glycosylated flavones, and O-glycosylated flavonols. No signs of acute toxicity were observed in female rats. The findings showed that ESBM had significant diuretic and natriuretic effects, as well as a potassium-sparing effect. The treatment with ESBM was able to significantly decrease serum levels of creatinine and malondialdehyde, and also significantly increase levels of nitrite, an indirect marker of nitric oxide bioavailability. Furthermore, pre-treatment with L-NAME abolished all diuretic effects induced by ESBM. CONCLUSION:This study presented important morpho-anatomical and phytochemical data that support the quality control of Baccharis milleflora. The ESBM exhibited a significant diuretic and natriuretic effect following acute and seven-days repeated treatment in Wistar rats, without affecting renal potassium elimination. These effects appear to be dependent on the activation of the nitric oxide-cyclic GMP pathway. This study suggests the potential use of B. milleflora preparations in clinical situations where a diuretic effect is needed.

OBJECTIVE:The study's aim was to evaluate Brazilian Brown Propolis (BBP) and Artepillin C (ARC) chemopreventive action in Wistar rats' colons.METHODS:Fifty male Wistar rats were divided into ten experimental groups, including control groups, groups with and without 1,2-dimethylhydrazine (DMH) induction, and BBP, ARC, and ARC enriched fraction (EFR) treatments, for sixteen weeks. Aberrant crypt foci (ACF) were classified as hyperplastic or dysplastic, and proliferating cell nuclear antigen (PCNA) expression was quantified.RESULT:ACF amounts in experimental groups (induced or not) decreased in both colon portions, while the isolated Aberrant Crypt (AC) number increased. Experimental groups of animals showed higher hyperplasia and dysplasia amounts compared with control groups. The ACF dysplastic amount present in groups induced and treated, in both colon portions, had similar values to IDMH (DMH induction group without treatment). In addition, DMH was effective in ACF inducing and there was positive staining for PCNA in basal and upper dysplastic foci portions in all experimental groups, in the mitotic index (MI) evaluation. To conclude, considering all the experimental groups, the one treated with EFR (fraction enriched with ARC) had the lowest rates of cell proliferation.CONCLUSION:BBP and its derivatives prevented crypt cell clonal expansion.

Smilax fluminensis Steud. is distributed in Central and South America, commonly named as 'salsaparilha' or 'japicanga'. In the present work, the chemical composition was determined, antioxidant and cytotoxic effects were evaluated for the ethanol extract (EE) and fractions from leaves. Fatty acid esters and phytol were characterised in the hexane (HEX) fraction. O-glycosylated flavonols and flavones, caffeic acid derivatives, and steroidal saponins were annotated for EE, and dichloromethane (DCM), ethyl acetate (AC), and hydroethanol (HE) fractions. The samples contain flavonoids and phenolic compounds, and the AC fraction displayed the biggest concentration of these substances. Antioxidant potential was observed in all samples, being especially pronounced in the AC fraction by DPPH and FRAP assays, with IC50 values of 8.18 and 2.35 µg/mL, respectively. AC and HEX fractions showed 35% and 5% lethality at 1000 μg/mL, in the Artemia salina assay, and the other samples did not show a toxic effect.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was carried out by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins, and DNA. Cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extracts contained catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile showed obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with an IC50 of 4.86 ± 0.51 μg/mL and 8.33 ± 0.90 μg/mL in the ABTS assay for ELSR and ERSR, respectively. Furthermore, in the DPPH• assay, the IC50 was 19.98 ± 1.96 μg/mL for ELSR and 13.37 ± 1.05 μg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 μg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 h of treatment. After 48 h, results against the K562 cell line demonstrate an IC50 of 242.54 ± 2.38 μg/mL and 223.00 ± 2.34 μg/mL for ELSR and ERSR, respectively. While against the Jurkat cell line, these extracts showed an IC50 of 171.45 ± 2.25 μg/mL and 189.30 ± 2.27 μg/mL, respectively. The results pertaining to PBMC viability demonstrated that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions and expand their significant pharmacological potential in oxidative stress and leukemia conditions.

A series of 28 compounds, 3-nitro-1H-1,2,4-triazole, were synthesized by click-chemistry with diverse substitution patterns using medicinal chemistry approaches, such as bioisosterism, Craig-plot, and the Topliss set with excellent yields. Overall, the analogs demonstrated relevant in vitro antitrypanosomatid activity. Analog 15g (R-1 = 4-OCF3-Ph, IC50 = 0.09 mu M, SI = >555.5) exhibited an outstanding antichagasic activity (Trypanosoma cruzi, Tulahuen LacZ strain) 68-fold more active than benznidazole (BZN, IC50 = 6.15 mu M, SI = >8.13) with relevant selectivity index, and suitable LipE = 5.31. 15g was considered an appropriate substrate for the type I nitro reductases (TcNTR I), contributing to a likely potential mechanism of action for antichagasic activity. Finally, 15g showed nonmutagenic potential against Salmonella typhimurium strains (TA98, TA100, and TA102). Therefore, 3-nitro-1H-1,2,4-triazole 15g is a promising antitrypanosomatid candidate for in vivo studies.

Psychotria carthagenensis is a shrubby plant, often consumed by traditional populations in religious rituals. Previous studies have shown that this plant's infusion can inhibit the activity of Acetylcholinesterase (AChE) in rats. Despite the therapeutic potential, there is a lack of research regarding its possible toxicological and genotoxic effects. Hence, this study aimed to analyze the chemical profile of the ethanol extract from P. carthagenensis leaves by LC-DAD-MS and assess its possible toxicity and genotoxicity in zebrafish (Danio rerio). Adult zebrafish (N = 9/group) were exposed at different concentrations and the LC50 was calculated. Frequencies of micronucleus (MN) and nuclear abnormalities (NA) were estimated for genotoxic effects, and degree of tissue changes (DTC) was used to assess the liver and gill histopathology. From the LC-DAD-MS analyses, the identified compounds included N-fructosyl valine, ethyl hexoside, 5-O-E-caffeoylquinic acid, N-feruloylagmatime, roseoside, di-O-deoxyhexoyl-hexosyl quercetin, loiolide, and oleamide. The calculated values of LC50 did not vary significantly during the time of exposure. At the concentrations of 1.25, 2.5, 3.75, 5, 7.5, 10 and 15 mg/L, there was no genotoxicity, and only low to moderate toxicity for the tissues was observed, despite mortality of 100% at doses of 20-100 mg/L of P. carthagenensis ethanolic leaf extract. There were changes in cytoplasm of hepatocytes at 1.25 mg/L, and karyorrhexis, karyolysis and megalocytosis at 10 mg/L. In the gills, the alterations were primary lamellar hyperplasia in all concentrations, and at 10 mg/L, secondary lamellar edema and vascular hyperemia were common. Additionally, the chemical composition of P. carthagenensis was expanded.