Publications by authors named "Wagner Vilegas"

212 Publications

Novel transdermal bioadhesive surfactant-based system for release and solubility improvement of antimalarial drugs Artemether-Lumefantrine.

Biomed Mater 2021 Sep 20. Epub 2021 Sep 20.

Faculdade de Ciências Farmacêuticas, UNICAMP, Rua Candido Portinari, 200, Campinas, 13083871, BRAZIL.

Artemether (ART) and lumefantrine (LUM) are the gold standard antimalarial drugs used for the treatment of malaria in children and pregnant women. Typically, ART and LUM are delivered orally in the form of a combined tablet, however, the appropriateness of this route of administration for these drugs is questionable due to the poor absorption and therefore bioavailability observed unless administered alongside lipid-rich foods.Transdermal drug delivery in the form of a patch-type system has been identified as a viable alternative to the conventional tablet-based therapy. A novel, surfactant-based ART-LUM formulation (S3AL), developed for transdermal delivery, may eliminate the shortcomingsassociated with oral delivery; namely poor drug absorption which is caused by the inherently low solubility of ART and LUM. Moreover, by successfully delivering these antimalarials transdermally, first-pass metabolism will be avoidedleading to enhanced drug bioavailability in both cases. The S3AL formulationcontained ART and LUMat equal concentrations (2.5% w/wof each) as well as Procetyl® AWS (30% w/w), oleic acid (10% w/w), 1-methyl-2-pyrrolidone (10% w/w), and water (45% w/w). The addition of LUM to the formulation changedthe system from a striae structure toa dark field structure when visualized bya polarised light microscope. Additionally,this system possessedhigher viscosity and superior skin bioadhesion,as evidenced by mechanical characterisation, when compared to a similar formulation containing ARTalone. S3AL was also proven to be biocompatible to human keratinocyte cells (HaCaT). Finally, in vitro studies demonstrated the propensity of S3AL for successful delivery via the transdermal route, with 2279 ± 295 µg/cm2 of ART and 94 ± 13 µg/cm2 of LUM having permeated across dermatomed porcine skin after 24 h, highlighting its potential as a new candidate for the treatment of malaria.
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http://dx.doi.org/10.1088/1748-605X/ac2885DOI Listing
September 2021

UHPLC-(ESI)-HRMS and NMR-Based Metabolomics Approach to Access the Seasonality of and From Brazilian Cerrado Flora Diversity.

Front Chem 2021 6;9:710025. Epub 2021 Jul 6.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.

Seasonality is one of the major environmental factors that exert influence over the synthesis and accumulation of secondary metabolites in medicinal plants. The application of the metabolomics approach for quality control of plant extracts is essentially important because it helps one to establish a standard metabolite profile and to analyze factors that affect the effectiveness of the medicinal plants. The Brazilian Cerrado flora is characterized by a rich diversity of native plant species, and a number of these plant species have been found to have suitable medicinal properties. Some of these plant species include and . To better understand the chemical composition of these plant species, we conducted a study using the state-of-the-art techniques including the HPLC system coupled to an Exactive-Orbitrap high resolution mass spectrometer with electrospray ionization interface UHPLC-(ESI)-HRMS and by NMR being performed 2D -resolved and proton NMR spectroscopy. For the analysis, samples were harvested bimonthly during two consecutive years. UHPLC-(ESI)-HRMS data were preprocessed and the output data uploaded into an in-house Excel macro for peak dereplication. MS and NMR data were concatenated using the data fusion method and submitted to multivariate statistical analysis. The dereplication of LC-HRMS data helped in the annotation of the major compounds present in the extracts of the three plant species investigated allowing the annotation of 68 compounds in the extracts of (cinnamic acids, phenolic acids derived from galloyl quinic and shikimic acid, proanthocyanidins, glycosylated flavonoids, triterpenes and other phenols) and 81 compounds in the extracts of (phenolic acids, saponins, proanthocyanidins, glycosylated flavonoids among other compounds). For a better assessment of the great number of responses, the significance of the chemical variables for the differentiation and correlation of the seasons was determined using the variable importance on projection (VIP) technique and through the application of the false discovery rate (FDR) estimation. The statistical data obtained showed that seasonal factors played an important role on the production of metabolites in each plant species. Temperature conditions, drought and solar radiation were found to be the main factors that affected the variability of phenolic compounds in each species.
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http://dx.doi.org/10.3389/fchem.2021.710025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290060PMC
July 2021

Selective anticancer effects of Serjania marginata Casar. extract in gastric cells are mediated by antioxidant response.

Environ Toxicol 2021 Aug 22;36(8):1544-1556. Epub 2021 Apr 22.

Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina, Brazil.

Gastric cancer is the fifth most common malignancy worldwide. Serjania marginata Casar. (SM) displays anti-inflammatory properties and has been used to treat gastrointestinal disorders. In the current study, we examined whether the hydroethanolic extract of SM leaves exerted cytotoxic, mutagenic, and protective effects in non-tumor gastric epithelium cells (MNP01) and gastric adenocarcinoma cells (ACP02) in vitro and analyzed whether its action was selective. Initially, cell viability (MTT assay), cell cycle kinetics (flow cytometry), and cell proliferation (total protein content) were analyzed. In addition, genomic instability (cytokinesis-block micronucleus cytome assay), anti/pro-oxidant status (CM-H DCFDA probe), and transcriptional expression (RT-qPCR) of genes related to cell cycle, cell death, and antioxidant defense were also evaluated. The SM extract was cytotoxic toward MNP01 and ACP02 cells at concentrations greater than 300 and 100 μg·ml , respectively, and decreased protein content only toward ACP02 cells at 200 μg ml . In ACP02 cells, the SM extract at 100 μg·ml associated with doxorubicin (DXR; 0.2 μg ml ) clearly promoted cell cycle arrest at the G2/M phase. The extract alone was not mutagenic to either cell type and reversed DXR-induced DNA damage and H O -induced oxidative stress in MNP01 cells. The gene expression experiments showed that SM hydroethanolic extract exerts an antioxidant response via NFE2L2 activation in non-tumor gastric cells, and cell cycle arrest (G2/M) in ACP02 gastric cancer cells via the TP53 pathway. The selective action of SM indicates that it is a promising therapeutic agent to treat gastric diseases and merits further studies.
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http://dx.doi.org/10.1002/tox.23151DOI Listing
August 2021

Protective effect of flavonoids from Passiflora edulis Sims on diabetic complications in rats.

J Pharm Pharmacol 2021 Sep;73(10):1361-1368

Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas, Brazil.

Objectives: This study was carried out to evaluate the effects of flavonoids present in leaves of Passiflora edulis fruit on complications induced by diabetes in rats.

Methods: The extract of P. edulis leaf was obtained by 70% ethanol maceration. From the dry extract, the fractions were obtained by consecutive liquid-liquid partition with hexane, ethyl acetate and n-butanol. The content of isoorientin of ethyl acetate and n-butanol fractions was determined by ultra-performance liquid chromatography coupled with electrospray and triple quadrupole ionization (TQD) analysis in tandem mass spectrometry (UPLC-ESI-Tq-MS). Only Fr-BuOH was used to treat diabetic or not Wistar rats. Biochemical parameters, platelet aggregation and production of reactive species were evaluated.

Key Findings: The UPLC-ESI-Tq-MS analysis revealed the presence of several flavonoids, among which we identified five possible flavonoids c-heterosides (luteolin-7-O-pyranosyl-3-O-glucoside, apigenin-6-8-di-C-glycoside, apigenin-6-C-arabinoside-8-C-glycoside, isoorientin, isovitexin). The diabetic rats (treated intraperitoneally with alloxan, 150 mg/kg) treated with Fr-BuOH (20 mg/kg/day for 90 days) presented improvement in blood glucose, serum levels of fructosamine, lipid profile and urea. Furthermore, the Fr-BuOH reduced both platelet aggregation and the production of oxidant species in diabetic animals.

Conclusions: These results suggested that flavonoid C-glycosides present in the Fr-BuOH may be beneficial for the diabetic state, preventing complications induced by diabetes.
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http://dx.doi.org/10.1093/jpp/rgab046DOI Listing
September 2021

Antiproliferative activity of standardized phytopreparations from Ibervillea sonorae (S. Watson) Greene.

Steroids 2021 05 13;169:108824. Epub 2021 Mar 13.

Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Araraquara - São Paulo, Brasil. Rodovia Araraquara - Jaú, Km 1 - CEP: 14800-903; Universidade Estadual Paulista (UNESP), Coastal Campus of São Vicente, São Vicente, SP Praça Infante Dom Henrique s/n, CEP 11330-205. Electronic address:

Ibervillea sonorae (Cucurbitaceae) is a medicinal plant utilized in Northwest Mexico against Diabetes and cancer. This natural product is taken orally, its presentation is capsules containing the plant's dried and powdered caudices. There is no regulation or standardized dosage that allows reproducibility of its pharmacological effects. Cucurbitacins are the main group of compounds found in I. sonorae and are known for their antiproliferative activity in cancer cells. Cucurbitacin IIb (CIIb), one of the compounds present in I. sonorae, has demonstrated in experimental models with HeLa cervical cancer cells an apoptotic and anti-tumoral activity. The objective of this study is to obtain and standardize two phytopreparations of I. sonorae based on their CIIb content, evaluate their antiproliferative activity in cancer cell lines, and compare the results with those obtained with CIIb; expecting to find phytopreparations with anti-cancer potential. APCI-IT-MSn is utilized for the identification of cucurbitacins, FT-ICR-MS/MS for the quantification of CIIb, and the MTT assay for the evaluation of the antiproliferative activity. The CIIb content was 0.67% for Fito-Ison-EtOH and 1.84% for Fito-Ison-EtOAc. In both phytopreparations, six cucurbitacins have been identified, and a seventh one not previously identified. Phytopreparations were more effective against HeLa, with IC of 30.0 and 18.6 µg/mL for Fito-Ison-EtOH and Fito-Ison-EtOAc, respectively. This effect is lower than observed on CIIb in HeLa (5.8 µg/mL). There are no significant differences (p > 0.05) in the antiproliferative activity between Fito-Ison-EtOAc and CIIb in A549, LS180, and MDA-MB-231 cells. Phytopreparations of I. sonorae have potential for the development of anti-cancer products.
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http://dx.doi.org/10.1016/j.steroids.2021.108824DOI Listing
May 2021

Antifungal and Antibiofilm Activities of B-Type Oligomeric Procyanidins From Used Alone or in Combination With Fluconazole Against spp.

Front Microbiol 2021 22;12:613155. Epub 2021 Feb 22.

Laboratory of Pharmacognosy, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal, Brazil.

(Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of against spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of stem bark. The extract and the -butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by H NMR and MS analyses. spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the -butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 μg/mL and were found to significantly reduce the biofilm formed in all the strains investigated. BDP showed a fungicidal potential against strains of spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 μg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant spp. (FICI = 0.31-1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in , was found to exhibit antifungal effect against spp. either when applied alone or in combination with fluconazole.
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http://dx.doi.org/10.3389/fmicb.2021.613155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937886PMC
February 2021

In Vitro Anti-Inflammatory Activity in Arthritic Synoviocytes of Root Extracts and Its Unusual Dimeric Flavonoids.

Molecules 2020 Nov 9;25(21). Epub 2020 Nov 9.

School of Pharmaceutical Sciences, University of Geneva, 1211 Geneva-4, Switzerland.

is a plant commonly used for the treatment of kidney stones, arthritis and pain in traditional Brazilian medicine. Different in vitro and in vivo activities, ranging from antinociceptive to anti-, have been reported for the dichloromethane root extract of (DCMAB) and isolated compounds. This work aimed to assess the in vitro anti-inflammatory activity in arthritic synoviocytes of the DCMAB, the hydroethanolic extract (HEAB) and three dimeric flavonoids isolated from the DCMAB. These compounds, brachydin A (), B () and C (), were isolated both by medium pressure liquid and high-speed counter current chromatography. Their quantification was performed by mass spectrometry on both DCMAB and HEAB. IL-1β activated human fibroblast-like synoviocytes were incubated with both extracts and isolated compounds to determine the levels of pro-inflammatory cytokine IL-6 by enzyme-linked immunosorbent assay (ELISA). DCMAB inhibited 30% of IL-6 release at 25 µg/mL, when compared with controls while HEAB was inactive. IC values determined for and were 3-fold higher than . The DCMAB activity seems to be linked to higher proportions of compounds and in this extract. These observations could thus explain the traditional use of roots in the treatment of osteoarthritis.
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http://dx.doi.org/10.3390/molecules25215219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665123PMC
November 2020

An enquiry into antileishmanial activity and quantitative analysis of polyhydroxylated steroidal saponins from Solanum paniculatum L. leaves.

J Pharm Biomed Anal 2020 Nov 17;191:113635. Epub 2020 Sep 17.

UNESP, São Paulo State University, Institute of Chemistry, Rua Prof. Francisco Degni, 55, 14800-060, Araraquara, São Paulo, Brazil. Electronic address:

Solanum paniculatum L. is species whose fruits are widely consumed in Brazil as a tonic beverage with higher content of steroidal saponins. In this work, we developed an analytical method for the quantification of the eight saponins present in the 70 % ethanol extract from the leaves using ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS). Besides, the eight spirostanic saponins were screened for in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania (L.) amazonensis. Substances 1, 2 and 3 were found to be the most active compounds, with inhibitory concentration (IC) values of 8.51 ± 4.38, 10.75 ± 6.85 and 10.45 ± 4.21 μM, respectively, against promastigote forms and effective concentration (EC) values of >25, 17.73 ± 0.99 and 19.57 ± 0.84 μM, respectively, against amastigote forms. The cytotoxic test with compounds 1-3 evidenced low toxicity in murine macrophage cells, with values above 50 μM at concentration lower than 25 μM. These findings show that saponins 1-3 should be evaluated in further studies for the treatment of cutaneous leishmaniasis.
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http://dx.doi.org/10.1016/j.jpba.2020.113635DOI Listing
November 2020

Electrospun PCL-based nanofibers Arrabidaea chica Verlot - Pterodon pubescens Benth loaded: synergic effect in fibroblast formation.

Biomed Mater 2020 09 19;15(6):065001. Epub 2020 Sep 19.

Department of Manufacturing and Materials Engineering, School of Mechanical Engineering, University of Campinas - UNICAMP, Campinas, SP, Brazil.

The guided tissue regeneration (GTR) technique can be applied in dentistry and other medical specializations, such as orthopedics. In modern dentistry, GTR has been used in periodontics and implantology to treat periodontal defects, to reconstruct lost, damaged and atrophied bone tissue in dental implant procedures, and to preserve alveolar bases after tooth extraction. In order to create and improve new therapies and to develop new biomaterials that restore, improve and prevent aggravation of compromised tissue function, poly (ϵ-caprolactone) (PCL) polymer membranes were obtained by the electrospinning process and were associated with two plant extracts: Pterodon pubescens Benth (P. pubescens) and Arrabidaea chica Verlot (A. chica) which are characterized by their pharmacological activities of anti-inflammatory and healing actions, respectively. Fiber morphology was analyzed using scanning electron microscopy (SEM), where fiber average diameter was measured from SEM images. Contact angle measurements were performed in order to evaluate the hydrophilicity of electrospun membranes containing vegetal extract. High-performance liquid chromatography was used to evaluate the ability to release active ingredients. Cytotoxicity and cell proliferation assays were performed in vitro on NIH-3T3 cells for 1, 3 and 7 d. Electrospun PCL membranes associated with plant extracts P. pubescens and/or A. chica presented a controlled release profile of the active compounds induced fibroblast formation, suggesting that they are promising and suitable for applications in GTR.
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http://dx.doi.org/10.1088/1748-605X/ab9bb1DOI Listing
September 2020

Mass spectrometry characterization of Commiphora leptophloeos leaf extract and preclinical evaluation of toxicity and anti-inflammatory potential effect.

J Ethnopharmacol 2021 Jan 15;264:113229. Epub 2020 Aug 15.

Research Group on Bioactive Natural Products (PNBio), Laboratory of Pharmacognosy, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande Do Norte, Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis, 59012-570, Natal, Brazil. Electronic address:

Ethnopharmacological Relevance: Commiphora leptophloeos (Mart.) J.B. Gillett (Burseraceae) is a medicinal plant native from the brazilian northeast caatinga biome, known popularly as "imburana" or "imburana-de-cambão". The leaves of C. leptophloeos are widely used in folk medicine in the treatment of various inflammatory disorders. However, there is no scientific evidence to justify their popular use.

Aim Of The Study: This approach aimed to characterize the phytochemical profile of hydroethanolic leaf extract, as well as evaluate the anti-inflammatory and antioxidant potential activity and to investigate the acute toxicity with pre-clinical in vitro and in vivo methodologies.

Materials And Methods: The phytochemical profile was characterized by UPLC-MS and FIA-ESI-IT-MS/MS. The in vitro anti-inflammatory potential the hydroethanolic extract of C. leptophloeos (1, 10, 100 and 200 μg/mL) was investigated by lipopolysaccharide (LPS) induced nitric oxide assay, in order to analyze the potential decrease of nitric oxide (NO) production. For carrageenan-induced paw edema and zymosan-induced air pouch models, the extract (100, 200 and 400 mg/kg) was administrated by intragastric gavage (i.g.) route and used for evaluating the anti-inflammatory effect in vivo. Related to the first animal model, the antiedematogenic activity and myeloperoxidase (MPO) levels could be investigated. In addition, the zymosan-induced air pouch model allowed the analyses of leukocytes migration, total MPO, malondialdehyde (MDA) and cytokines (TNF-α and IL-10) levels. The toxicity in vitro of the extract (1, 10, 100 and 200 μg/mL) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acute toxicity in vivo was tested using the extract at 2000 mg/kg by i. g. route.

Results: The phytochemical analyses of C. leptophloeos leaf extract pointed the presence of six glycosylated flavonoids, identified as orientin, isoorientin, vitexin and isovitexin, quercetrin and isoquercitrin. A decrease of NO in vitro was noticed by the use of the extract in the LPS-induced nitric oxide assay and an expressive reduction of the paw-edema followed by a decrease of myeloperoxidase activity at doses of 200 and 400 mg/kg. The zymosan-induced air pouch model indicated that the extract, in all doses, significantly reduced the leukocytes migration, total protein concentration, MPO and MDA levels. The levels of cytokines were verified by the administration of extract in this model, revealing a lower of TNF-α level and an increase of the IL-10 production. In the toxicity study, the MTT assay evidenced no cytotoxicity of the tested concentrations and acute toxicity in vivo test did not result in any sign of toxicity and mortality or significant changes on the biochemical parameters.

Conclusion: Based on these results, is possible suggest that the anti-inflammatory activity revealed in this approach can be related to the modulating the level of cytokine, decrease of TNF-α, increase of IL-10 in vivo and also the inhibition of the production of nitric oxide RAW 264.7 activated by LPS. These results demonstrate the potential anti-inflammatory effect C. leptophloeos leaf extrat in inflammatory in vivo models, supporting its use in folk medicine for treatment of inflammatory diseases. Finally, glycosylated flavonoids can be responsible, at least in part, for this effect.
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http://dx.doi.org/10.1016/j.jep.2020.113229DOI Listing
January 2021

Phytochemical Profile, and Antiproliferative and Proapoptotic Effects of (Mart.) Radlk. Leaf Extract, and Its Synergism with Cisplatin in HepG2 Cells.

J Med Food 2021 May 4;24(5):452-463. Epub 2020 Aug 4.

Department of General Biology, Biological Science Center, Londrina State University-UEL, Londrina, PR, Brazil.

Different species of the genus have been used in folk medicine for the treatment of inflammation, fever, ulcers, diabetes, and diarrhea. We analyzed the phytochemical profile of the hydroethanolic extract from leaves by electrospray ionization ion trap tandem mass spectrometry and high-performance liquid chromatography-diode array detection, and examined whether it alone and in combination with cisplatin interfered with cell proliferation and death processes in HepG2 (human hepatocellular carcinoma) and FGH (human gingival fibroblasts) cells. Five compounds were identified in the extract: gallic acid, myricetin-3---l-arabinopyranoside, quercetin-3---d-galactopyranoside, myricetin-3---l-rhamnopyranoside, and myricetin-3---d-galactopyranoside. The extract was cytotoxic to both cell lines by inducing apoptotic cell death and acted in synergy with cisplatin; such effect was stronger in HepG2 cells than in FGH cells, demonstrating some selectivity to tumor cells. In HepG2 cells, the extract exerted antiproliferative effect mediated by induction of cell cycle arrest at the S and G2/M phases. Association of the extract with cisplatin enhanced the latter's antiproliferative effect, arrested the cell cycle at the S phase by modulation, and reduced the number of anti-cyclin D1-stained HepG2 cells. Simultaneous treatment with the extract and cisplatin increased the latter's cytotoxicity, apoptotic cell death, and expression in HepG2 cells. Altogether, the results reported herein indicate that extract is a possible adjuvant to cancer therapy, which can circumvent the cisplatin-mediated resistance mechanisms in cancer cells.
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http://dx.doi.org/10.1089/jmf.2020.0045DOI Listing
May 2021

Antiproliferative activity of cardenolides on cell line A549: structure-activity relationship analysis.

Mol Divers 2020 Jul 5. Epub 2020 Jul 5.

Unidad Regional Centro, Departamento de Ciencias, Químico Biológicas y de la Salud, Universidad de Sonora, Blvd. Encinas y Rosales S/N, Hermosillo, Sonora, Mexico.

Since the beginning, natural products have represented an important source of bioactive molecules for cancer treatment. Among them, cardenolides attract the attention of different research groups due to their cardiotonic and antitumor activity. The observed biological activity is closely related to their Na/K-ATPase inhibition potency. Currently, the discovery of new compounds against cancer is an urgent need in modern pharmaceutical research. Thus, the aim of this work is to determine the physicochemical properties and substituent effects that module the antiproliferative activity of cardenolides on the human lung cancer cell line A549. We build and curate a library with results obtained from literature; molecular descriptors were calculated in PaDEL software, and SAR/QSAR analysis was performed. The SAR results showed that cardenolides were sensitive to modifications in C and D steroidal ring and required substituent groups with the function of hydrogen bond acceptor at the C3 position. QSAR models to doubly linked-type cardenolides indicated that properties as lipoaffinity and atoms with the capacity to be hydrogen bond acceptors are involved in the increment of antiproliferative activity on A549 cell line. In contrast, the presence and position of very electro-negative atoms on the molecule decreased the antiproliferative effect on A549 cells. These results suggest that the antiproliferative capacity of cardenolides on the cell line A549 is strongly related to substituent groups on the C3 position, which must not be carbohydrate. Additionally, the steroidal rings C and D must remain without modifications.
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http://dx.doi.org/10.1007/s11030-020-10119-wDOI Listing
July 2020

Metabolomics of Populations in Brazilian Savanna Reveals Strong Influence of Environmental Factors on Its Specialized Metabolism.

Molecules 2020 Jun 26;25(12). Epub 2020 Jun 26.

School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva (IPSWS), CH-1211 Geneva 4, Switzerland.

Environmental conditions influence specialized plant metabolism. However, many studies aiming to understand these modulations have been conducted with model plants and/or under controlled conditions, thus not reflecting the complex interaction between plants and environment. To fully grasp these interactions, we investigated the specialized metabolism and genetic diversity of a native plant in its natural environment. We chose due to its medicinal interest and occurrence in Brazilian savanna regions with diverse climate and soil conditions. An LC-HRMS-based metabolomics approach was applied to analyze 271 samples harvested across seven regions during the dry and rainy season. Genetic diversity was assessed in a subset of 40 samples using amplified fragment length polymorphism. Meteorological factors including rainfall, temperature, radiation, humidity, and soil nutrient and mineral composition were recorded in each region and correlated with chemical variation through multivariate analysis (MVDA). Marker compounds were selected using a statistically informed molecular network and annotated by dereplication against an in silico database of natural products. The integrated results evidenced different chemotypes, with variation in flavonoid and tannin content mainly linked to soil conditions. Different levels of genetic diversity and distance of populations were found to be correlated with the identified chemotypes. These observations and the proposed analytical workflow contribute to the global understanding of the impact of abiotic factors and genotype on the accumulation of given metabolites and, therefore, could be valuable to guide further medicinal exploration of native species.
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http://dx.doi.org/10.3390/molecules25122954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356273PMC
June 2020

Croton urucurana Baillon stem bark ointment accelerates the closure of cutaneous wounds in knockout IL-10 mice.

J Ethnopharmacol 2020 Oct 10;261:113042. Epub 2020 Jun 10.

Department of Biochemistry and Molecular Biology, Viçosa Federal University, 35570-900, Viçosa, Minas Gerais, Brazil. Electronic address:

Ethnopharmacological Relevance: Croton urucurana Baill. (Euphorbiaceae) is a plant used in Brazilian popular medicine for the treatment of wound healing, inflammatory diseases, gastritis, infections, and hemorrhoids.

Aim: The present study aimed to evaluate the in vivo wound healing activity of an ointment based on ethanolic extract of C. urucurana stem bark, at concentrations of 5% and 10%, and to relate it with compounds that could be associated with this activity.

Materials And Methods: Analyses by FIA-ESI-IT-MS were carried out to investigate the chemical composition of C. urucurana. Knockout IL-10 (n = 60) mice and wild type C57 (n = 12) mice were separated into 6 groups to evaluate the wound healing activity. Knockout IL-10 mice: SAL (0.9% saline); BAS (ointment base); SS (1% silver sulfadiazine); CR1 (ointment with extract of C. urucurana 5%); CR2 (ointment with extract of C. urucurana 10%); and wild mice C57: SALC57 (Saline 0.9%). A circular wound with 10 mm in diameter was generated on the dorsal of the animals. Tissue specimen of the wounds were removed on days 7 and 14 of the treatment for histopathological, oxidative status and analyses of pro-and anti-inflammatory cytokines in scar tissue.

Results: In the phytochemical profile, twelve proanthocyanidins were identified (in the form of monomers, dimers, trimers, and tetramers), based on (epi)catechin and (epi)gallocatechin. Furthermore, two quercetin derivatives and two alkaloids were detected. The groups treated with CR1 and CR2 ointments presented higher rate of wound closure, increased total number of cells, mast cells, blood vessels and higher deposition of type III and I collagen. In addition, they showed increased amount of pro-inflammatory cytokines (IL- 2 and IFN-γ), and anti-inflmatory cytokines (IL-4), on the 7th day of treatment.

Conclusion: The results presented support the popular use of preparations based on the bark of C. urucurana as a healing compound.
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http://dx.doi.org/10.1016/j.jep.2020.113042DOI Listing
October 2020

Screening of plants from the Brazilian Atlantic Forest led to the identification of Athenaea velutina (Solanaceae) as a novel source of antimetastatic agents.

Int J Exp Pathol 2020 06 26;101(3-4):106-121. Epub 2020 May 26.

Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Minas Gerais, Brazil.

Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluated 196 extracts prepared by maceration of Brazilian Atlantic Forest trees with organic solvents and distilled water for cytotoxic and antimetastatic activity. The MTT assay was used to screen the extract activity in MCF-7, HepG2 and B16F10 cancer cells. The highest cytotoxic extract had antimetastatic activity, as determined in in vitro assays and melanoma murine model. The organic extract of the leaves of Athenaea velutina (EAv) significantly inhibited migration, adhesion, invasion and cell colony formation in B16F10 cells. The phenolic compounds and flavonoids in EAv were identified for the first time, using flow injection with electrospray negative ionization-ion trap tandem mass spectrometry analysis (FIA-ESI-IT-MS ). EAv markedly suppressed the development of pulmonary melanomas following the intravenous injection of melanoma cells to C57BL/6 mice. Stereological analysis of the spleen cross-sections showed enlargement of the red pulp area after EAv treatment, which indicated the activation of the haematopoietic system. The treatment of melanoma-bearing mice with EAv did not result in liver damage. In conclusion, these findings suggest that A velutina is a source of natural products with potent antimetastatic activity.
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http://dx.doi.org/10.1111/iep.12351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370850PMC
June 2020

Chemical Characterization and Wound Healing Property of Cham. (Bignoniaceae): An Experimental Study Based on Molecular Mechanisms.

Evid Based Complement Alternat Med 2020 20;2020:4749712. Epub 2020 Apr 20.

Physiological Sciences Department, Federal University of Maranhão, São Luís, Maranhão 65080-805, Brazil.

Background: Cham., known as carobinha, is prevalent in the Cerrado biome and presents popular use in treatment of dermatological diseases. The present study aimed to investigate the healing action of topical formulation of Cham. (FtEHJ) in mice cutaneous lesions.

Methods: Phytochemical analysis of hydroalcoholic extract was carried out by using HPLC-PDA-ESI-MS and FIA-ESI-IT-MSn. Swiss mice were treated topically with formulation base (FtB) or Fibrinase® or ointment FtEHJ (15 mg/g; 50 mg/Kg). At the end of treatment periods, the inflammatory cytokines (TNF-, IL-1 and IL-6) in the lesions were measured by using ELISA and gene expression of TGF-, Collagen I, and Collagen III was demonstrated by RTqPCR method and histological evaluation.

Results: Ten compounds were identified in the extract, distributed among the classes of flavonoids and triterpenes. Treatment with FtEHJ increased the wound contraction in 24 hours, such as reduction of TNF-, IL-1, and IL-6 (pg/mL) cytokines in the lesion. The TGF- and collagen gene expression was increased and the wound closure accelerated to nine days, with discrete inflammation, collagenization, and accented reepithelialization. Conclusions. The results obtained suggest chemical compounds present in the FtEHJ accelerates wound healing by being a gene expression modulator, and protein content of different molecules are involved in tissue repair.
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http://dx.doi.org/10.1155/2020/4749712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191437PMC
April 2020

Influence of the Phenological State of in the Antioxidant Potential and Chemical Composition of . Effects on the P-Glycoprotein Function.

Molecules 2020 May 2;25(9). Epub 2020 May 2.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano (SA), Italy.

(Kunth) R. M. King & H. Robinson is a species of flowering shrub in the family Asteraceae, native to the Caribbean and Texas. The aim of this work was to compare the quantitative chemical composition of extracts obtained from in its flowering and vegetative stages with the antioxidant potential and to determine the effects on P-glycoprotein (P-gp) function. The quantitative chemical composition of the extracts was determined quantifying their major flavonoids by UPLC-ESI-MS/MS and by PCA analysis. The effects of the extracts on P-gp activity was evaluated by Rhodamine 123 assay; antioxidant properties were determined by DPPH, FRAP and inhibition of lipid peroxidation methods. The obtained results show that major flavonoids were present in higher concentrations in vegetative stage than flowering stage. In particular, the extracts obtained in the flowering season showed a significantly higher ability to sequester free radicals compared to those of the vegetative season, meanwhile, the extracts obtained during the vegetative stage showed a significant inhibitory effect against brain lipid peroxidation and a strong reductive capacity. This study also showed the inhibitory effects of all ethanolic extracts on P-gp function in 4T1 cell line; these effects were unrelated to the phenological stage. This work shows, therefore, the first evidence on: the inhibition of P-gp function, the antioxidant effects and the content of major flavonoids of . According to the obtained results, the species (Kunth) R. M. King & H. Robinson could be a source of new potential inhibitors of drug efflux mediated by P-gp. A special focus on all these aspects must be taking into account for future studies.
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http://dx.doi.org/10.3390/molecules25092134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248889PMC
May 2020

(Vell.) Stellfeld Alleviates Acute Pain and Inflammation: Potential Mechanisms of Action.

Biomolecules 2020 04 11;10(4). Epub 2020 Apr 11.

Department of Structural and Functional Biology (Physiology), São Paulo State University (UNESP), Institute of Biosciences, Botucatu 18618-970, São Paulo, Brazil.

(Vell.) Stellfeld (Fabaceae) known in Brazil as "jacaranda de espinho" or "espinheira santa nativa" is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, L-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE) showed involvement of the COX pathway, based on observed decreases in PGE levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, β-amyrin, allantoin, apigenin-7-methoxy-6--β-D-glucopyranoside, and apigenin-6--β-D-glucopyranosyl-8--β-D-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE levels.
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http://dx.doi.org/10.3390/biom10040590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226113PMC
April 2020

Terminalia catappa L. infusion accelerates the healing process of gastric ischemia-reperfusion injury in rats.

J Ethnopharmacol 2020 Jun 30;256:112793. Epub 2020 Mar 30.

Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689, Botucatu, São Paulo, Brazil. Electronic address:

Ethnopharmacological Relevance: Terminalia catappa L. (Combretaceae), known as "amendoeira da praia" in Brazil, has been recognized as a medicinal plant in folk medicine for the treatment of gastrointestinal disorders and other inflammatory conditions. The present study aimed to investigate the preventive and healing effects of the infusion of leaves of T. catappa (ILTC) against gastric lesions caused by ischemia and reperfusion (I/R) injury and characterize its mechanism of action in the gastric mucosa of rats.

Materials And Methods: Different doses (30, 100, and 300 mg/kg) of ILTC were orally administered as acute and subacute treatments against I/R-induced gastric lesion in rats. After treatment, the stomach of rats was collected to measure the lesion area, redox parameters malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) and inflammatory parameters myeloperoxidase activity (MPO), interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). The activities of matrix metalloproteinases 2 and 9 (MMPs 2 and 9) were assessed by zymography method to clarify the mechanisms of the healing acceleration promoted by ILTC.

Results: Pretreatment with ILTC (100 mg/kg) was effective in preventing the aggravation of lesions in the acute model by reducing MPO activity by 38% relative to control group, despite the lack of clarity of this action at the macroscopical level at the lesion area (p < 0.05). After three days of treatment with ILTC (30 and 100 mg/kg), this infusion significantly reduced the lesion area by 95% and 89%, respectively, compared the control (p < 0.05). The gastric healing effect of all doses of ILTC was followed by a reduction in MPO activity (decrease by 70-78%). Compared to the negative control, an improvement in gastric healing owing to treatment with ILTC was observed and this was followed by an increase in MMP-2 (20-47%) (p < 0.05).

Conclusion: Three days of treatment with ILTC could accelerate the healing process in I/R-induced lesions in rats. By decreasing MPO levels, ILTC enabled the action of MMP-2, which led to tissue recovery in the gastric mucosa.
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http://dx.doi.org/10.1016/j.jep.2020.112793DOI Listing
June 2020

Therapeutical properties of Mimosa caesalpiniifolia in rat liver intoxicated with cadmium.

Environ Sci Pollut Res Int 2020 Apr 17;27(10):10981-10989. Epub 2020 Jan 17.

Department of Biosciences, Federal University of Sao Paulo, UNIFESP, Rua Silva Jardim, 136, Santos, SP, 11050-020, Brazil.

The aim of this study was to evaluate the therapeutic properties of Mimosa caesalpiniifolia in liver of rats exposed to cadmium under morphological, oxidative, inflammatory, and mutagenic parameters. A total of 40 Wistar rats (90 days, ~ 250 g) were distributed into eight groups (n = 5) as follows: (i) control; (ii) cadmium: cadmium chloride injection at 1.2 mg/kg; (iii) Mimosa extract: treatment with Mimosa extract at 250 mg/kg; (iv) Mimosa fraction: treatment with Mimosa acetate fraction at 62.5 mg/kg; (v) cadmium and Mimosa extract 62.5: submitted to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 62.5 mg/kg; (vi) cadmium and Mimosa extract 125: subjected to cadmium chloride at 1.2 mg/kg injection and treatment with Mimosa extract at 125 mg/kg; (vii) cadmium and Mimosa 250 extract: submitted to cadmium chloride 1.2 mg/kg injection and treatment with Mimosa extract at 250 mg/kg; (viii) cadmium treated with fraction of Mimosa acetate: submitted to cadmium chloride 1.2 mg/kg injection and treatment with acetate fraction of Mimosa extract at 62.5 mg/kg. In the animals intoxicated with cadmium and treated with fraction [62.5], increased expression of SOD-Mn reduced frequency of binucleated hepatocytes, karyolysis, and karyorrhexis, besides the antimutagenic and antioxidant action. The extract [62.5] was cytoprotective, antimutagenic, and reduced karyolysis. The extract [125] was cytoprotective, antioxidant, antifibrotic, anti-inflammatory, and reduced frequency of binucleated hepatocytes, while extract [250] was cytotoxic and mutagenic. In summary, the extract of Mimosa exerts some therapeutic properties in hepatic tissue after Cd intoxication, but only when it is administrated at intermediate doses. Probably, a high content of polyphenols in the EHM [250] and Fr-EtOAc groups exert pro-oxidant activities in the liver particularly when associated with Cd.
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http://dx.doi.org/10.1007/s11356-019-07455-2DOI Listing
April 2020

Gastroprotective activity of hydroalcoholic extract of the leaves of Urera baccifera in rodents.

J Ethnopharmacol 2020 Mar 11;250:112473. Epub 2019 Dec 11.

Programa de Pós-Graduação em Ciências da Saúde, Universidade Comunitária da Região de Chapecó, CEP 89809-900, Chapecó, SC, Brazil. Electronic address:

Ethnopharmacological Importance: The species Urera baccifera (L.) Gaudich. ex Wedd. (Urticaceae) is native to the Americas and is distributed widely throughout Brazil, where it is known as urtiga-brava, urtiga-vermelha, or urtigão. The leaves are often used as anti-inflammatory and antirheumatic agents and for the treatment of gastric disorders. However, the pharmacological mode of action underlying the gastroprotection induced by this species has not been investigated.

Aim Of The Study: To contribute to the knowledge of the gastroprotective mode of action of the hydroalcoholic extract of U. baccifera (HEU) leaves.

Materials And Methods: Antiulcerogenic effect of HEU against ethanol-induced acute gastric ulcer was evaluated in rats and mice at doses of 3-300 mg/kg. NO-synthase inhibitor (L-NAME), SH blocker (NEM), cyclooxygenase inhibitor (indomethacin) and alpha 2-adrenergic receptor antagonist yohimbine were used to evaluate the participation of cytoprotective factors in HEU gastroprotection. Moreover, the levels of reduced gluthatione (GSH) and cytokines (TNF, IL-6, IL4 and IL-10), as well as the enzymatic activity of gluthatione S-transferase (GST), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) were measure. Moreover, the samples were analyzed histologically and the antisecretory capability of HEU were quantified using pylorus ligated rats.

Results: The phytochemical analysis of HEU (UPLC/ESI-IT-MS) identified the flavonoids diosmetin and apigenin glucuronide. Furthermore, HEU decreased the occurrence of ethanol-induced ulcers at 30 and 300 mg/kg by 57% and 66%, respectively, compared with the vehicle. The gastroprotective effects were accompanied by increased GSH levels and GST and SOD activity as well as by reduced MPO activity in vivo and in vitro, revealing antioxidant effects and inhibition of neutrophil infiltration. The beneficial effects of 30 and 300 mg/kg HEU were also observed upon histological analyses. Regarding the mode of action, the gastroprotective effect of HEU was abolished by the pre-administration of L-NAME, NEM, indomethacin or yohimbine. Moreover, HEU was able to decrease the IL-6, IL-4 and IL-10 in ulcerated tissue, as well as the pepsin activity of the gastric juice in pylorus-ligated rats.

Conclusion: Together, the results confirmed that the gastroprotection elicited by HEU was due reduction in oxidative damage, neutrophil migration, and peptic activity. This work validates the popular use of U. baccifera to treat gastric disorders and supports important future research for the identification of gastroprotective molecules from this species.
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http://dx.doi.org/10.1016/j.jep.2019.112473DOI Listing
March 2020

Antifungal Activity of a Hydroethanolic Extract From Leaves Against and .

Front Microbiol 2019 15;10:2642. Epub 2019 Nov 15.

School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil.

We have previously reported on the activity of different extracts from sp. against , with the hydroethanolic extract prepared from leaves of , an arboreal species widely distributed in arid environments of South America and often used in folk medicine, displaying the highest activity. Here we have further evaluated the antifungal activity of this extract against strains of and , the two most common etiological agents of candidiasis. The extract was tested alone and loaded into a nanostructured lipid system (10% oil phase, 10% surfactant and 80% aqueous phase, 0.5% Poloxamer 407). susceptibility assays demonstrated the antifungal activity of the free extract and the microemulsion against both species, with increased activity against , including collection strains and clinical isolates displaying different levels of resistance against the most common clinically used antifungal drugs. Checkerboard results showed synergism when the free extract was combined with amphotericin B against . Serial passage experiments confirmed development of resistance to fluconazole but not to the free extract upon prolonged exposure. Although preformed biofilms were intrinsically resistant to treatment with the extract, it was able to inhibit biofilm formation by at concentrations comparable to those inhibiting planktonic growth. Cytotoxicity assays in different cell lines as well as an alternative model using L. confirmed a good safety profile of the both free and loaded extracts, and an assay demonstrated the efficacy of the free and loaded extracts when used topically in a rat model of vaginal candidiasis. Overall, these results reveal the promise of the leaves extract to be further investigated and developed as an antifungal.
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http://dx.doi.org/10.3389/fmicb.2019.02642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873212PMC
November 2019

Polyphenol rich fruit attenuates genomic instability, modulates inflammation and cell cycle progression of offspring from fatty acid intake maternal.

Pathophysiology 2019 Sep - Dec;26(3-4):369-374. Epub 2019 Nov 22.

Department of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil.

The aim of this study was to investigate the effect of juçara (Euterpe edulis Mart.) supplementation on the maternal trans fatty acids intake in the livers of 21-day-old offspring. In order for this to happen, histopathological analysis, cytogenetic status, inflammation (COX-2 and TNF-alpha) and cell cycle progression were investigated in this setting. On the first day of pregnancy, female rats were distributed into four groups, as follows: control diet (C), control diet with 0.5 % juçara supplementation (CJ), diet enriched with hydrogenated vegetable fat, rich in TFAs (T), or T diet supplemented with 0.5 % juçara (TJ) during pregnancy and lactation. Juçara pulp induced liver regeneration in newborns exposed to maternal trans fatty acids. A significant decrease in the number of micronucleated hepatocytes was observed in animals exposed to trans fatty acids and treated with juçara. COX-2 and TNF immunoexpression was reduced in animals treated with juçara pulp. Furthermore, a decrease of Ki-67 immunoexpression was detected after treating trans fatty acids intake with juçara. Taken together, our results demonstrate that juçara pulp is able to prevent tissue degeneration and mutagenicity because it decreases inflammation and cell cycle control induced by maternal trans fatty acids in liver cells of rat offspring.
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http://dx.doi.org/10.1016/j.pathophys.2019.11.002DOI Listing
November 2019

Fluorescence spectroscopic and dynamics simulation studies on isoorientin binding with human serum albumin.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Mar 4;228:117738. Epub 2019 Nov 4.

Departamento de Física, Instituto de Biociências, Letras e Ciências Exatas (IBILCE), UNESP, Rua Cristovão Colombo 2265, CEP 15054-000, São José do Rio Preto, SP, Brazil. Electronic address:

Isoorientin (ISOO) a glycosylated flavonoid found in acai berry exhibits relevant activities such as antidiabetic and antidepressant. However, its physicochemical action on any molecular target is scarcely known. In this work, we tackle the problem about the binding of ISOO to human serum albumin (HSA) applying fluorescence spectroscopy bimodal analysis aided by computational simulations. A static quenching process was detected having hypsochromic shift with implication in the polarizability around the endogenous probe (Trp 214) during complex formation. The binding mechanism reveals that all sites are equivalents and independents with binding constant value of 9.1 × 10 M and, a total of six sites accessed whereas three of them were identified experimentally. The thermodynamic evaluation indicates that the complex formation is spontaneous (ΔG<0). The dynamics and docking simulations corroborated the experimental data by adding details of each site and its respective microenvironment.
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http://dx.doi.org/10.1016/j.saa.2019.117738DOI Listing
March 2020

Passiflora edulis Leaf Extract: Evidence of Antidiabetic and Antiplatelet Effects in Rats.

Biol Pharm Bull 2020 Jan 22;43(1):169-174. Epub 2019 Oct 22.

Department of Clinical Analysis and Toxicology, College of Pharmaceutical Sciences, Federal University of Alfenas.

Different Passiflora species have been appointed as a promising herbal medicine due to antioxidant properties; however, their effect on oxidative process induced by diabetes is still controversial. We aimed to evaluate effects of hydroethanolic extract 70% from P. edulis leaf on biochemical blood markers, collagen glycation, production of oxidant species and platelet aggregation in diabetic rats. The phytochemical analysis of the extract was performed by dereplication using LC coupled to the Photodiode Array Detector and Mass Spectrometer detector. Male Wistar rats were assigned to the control group and groups treated with alloxan (150 mg/kg) intraperitoneally, extract (200 mg/kg/d, for 90 d) and combination of alloxan and extract. The phytochemical analysis suggested the presence of flavonoids C-glycosides in the extract. The diabetic animals treated with the extract presented improvement in glycaemic control, reduced glycation collagen, levels of non-high density lipoprotein (non-HDL) cholesterol, total cholesterol and creatinine, production of oxidant species and aggregation in platelet in relation to diabetic animals non-treated. Our results showed that P. edulis leaf extract presents a health benefit to the diabetic state, preventing the appearance of its complications. Its effect can be associated with flavonoids, among which is the flavonoid C-glycoside isoorientin.
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http://dx.doi.org/10.1248/bpb.b18-00952DOI Listing
January 2020

Bioassay-Guided Isolation of Fungistatic Compounds from Mimosa caesalpiniifolia Leaves.

J Nat Prod 2019 Jun 18. Epub 2019 Jun 18.

Grupo de Alelopatía, Departamento de Química Orgánica, Instituto de Biomoléculas (INBIO), Facultad de Ciencias , Universidad de Cádiz , C/República Saharaui, 7 , 11510 - Puerto Real ( Cádiz ), Spain.

A bioassay-guided phytochemical study of a Mimosa caesalpiniifolia leaf extract with antifungal activity permitted the identification of 28 compounds, including the new 6-(β -boivinopyranosyl)apigenin (1), 8-(β -oliopyranosyl)apigenin (2), ( E)-6-(2-carboxyethenyl)apigenin (3), ( E)-8-(2-carboxyethenyl)apigenin (4), and 7,5″-anhydro-6-(α-2,6-dideoxy-5-hydroxyarabinohexopyranosyl)apigenin (5). The structures of the new compounds were determined by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, and by mass spectrometry. Compound 3 showed promising activity and selectivity against Candida krusei (IC 44 nM), which exhibits resistance to azoles. The association of the major components 3-β-d-glucopyranosyloxysitosterol (8) and ethyl gallate (10) was synergistic against C. krusei, especially the IC values of compound 10, which were reduced by more than 100-fold.
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http://dx.doi.org/10.1021/acs.jnatprod.8b01025DOI Listing
June 2019

An extract from Myracrodruon urundeuva inhibits matrix mineralization in human osteoblasts.

J Ethnopharmacol 2019 Jun 21;237:192-201. Epub 2019 Mar 21.

Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil. Electronic address:

Ethnopharmacological Relevance: Phytotherapy based on plant-derived compounds is an alternative medicinal strategy for the relief of symptoms and the curing of diseases. The leaves of Myracrodruon urundeuva a medicinal plant also known as "aroeira", has been used in traditional medicine as healing, antiulcer and anti-inflammatory to treat skeletal diseases in Brazil, but its role in bone cell toxicity, as well as in bone formation, remains to be established.

Aim Of The Study: We sought to determine the in vitro osteogenic effects of a hydroalcoholic M. urundeuva leaves extract in primary human osteoblasts.

Materials And Methods: Cell viability, reactive oxygen species (ROS) production, alkaline phosphatase (ALP) activity and matrix mineralization were evaluated by MTT assay, DCFH-DA probe, colorimetric-based enzymatic assay and Alizarin Red-staining, respectively. Besides, the matrix metalloproteinase (MMP)-2 and progressive ankylosis protein homolog (ANKH) gene expression were determined by real-time RT-qPCR and MMP-2 activity by zymography.

Results: Exposure of osteoblasts to M. urundeuva extract significantly decreased viability and increased reactive oxygen species (ROS) production, regardless of the extract concentration. The M. urundeuva extract at 10 μg/mL also downregulated matrix metalloproteinase (MMP)-2, while upregulating progressive ankylosis protein homolog (ANKH) gene expression. By contrast, the MMP-2 activity was unchanged. The M. urundeuva extract at 10 μg/mL also reduced alkaline phosphatase (ALP) activity and mineralization.

Conclusions: Overall, our findings suggest that the inhibition of osteogenic differentiation and matrix mineralization promoted by M. urundeuva may be due more to an increase in oxidative stress than to the modulation of MMP-2 and ANKH expression.
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http://dx.doi.org/10.1016/j.jep.2019.03.052DOI Listing
June 2019

Byrsonima intermedia A. Juss partitions promote gastroprotection against peptic ulcers and improve healing through antioxidant and anti-inflammatory activities.

Biomed Pharmacother 2019 Mar 12;111:1112-1123. Epub 2019 Jan 12.

Departamento de Fisiologia, UNESP - Universidade Estadual Paulista, Instituto de Biociências, CEP 18618-970, Botucatu, São Paulo, Brazil. Electronic address:

Byrsonima intermedia is a species of bush popularly used to treat gastrointestinal disorders, such as gastric ulcers, gastritis, and diarrhea. Previous studies have revealed that the methanolic crude extract of B. intermedia leaves has gastroprotective and healing properties. In this new study, we specifically investigated two purified partitions, ethyl acetate (EtOAc) and water (AcoAq), obtained from the crude extract to characterize the antiulcer effects of these two partitions and the mechanisms of action of this medicinal plant. The healing effects of these partitions on the gastric and duodenal mucosa were assessed after ischemia-reperfusion (I/R) or acetic acid-induced injury. The involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 1β (IL-1β), interleukin 10 (IL-10), and myeloperoxidase (MPO) activity and glutathione (GSH) levels were determined. The antibacterial activity against Helicobacter pylori was evaluated using microdilution methods. The phytochemical analysis of AcoAq revealed a predominance of oligomeric proanthocyanidins and galloyl quinic esters, whereas EtOAc was found to contain concentrated flavonoids. Both partitions led to a significant reduction in gastric lesions, but AcoAq was more effective than EtOAc with regard to anti-Helicobacter pylori activity in addition to protecting the gastric mucosa against ethanol, non-steroidal anti-inflammatory drugs (NSAIDs) and duodenal mucosal damage induced by cysteamine. Additionally, both partitions were associated with a significant increase in gastric and duodenal healing and increased gastric mucosal GSH content after damage induced by acetic acid. On the other hand, after 6 days of treatment, EtOAc was more effective than AcoAq in ameliorating gastric damage upon initiation of the gastric I/R, which was accompanied by a significant reduction in the activity of gastric mucosal MPO, IL 1-β and TNF-alpha, as well as an elevation in IL-10 and GSH content. These results demonstrate that the oligomeric proanthocyanidins and galloyl quinic esters present in AcoAq were more effective in the prevention of gastric and duodenal ulcers due to the antioxidant effects of these compounds, whereas the flavonoids present in EtOAc were more effective due to their anti-inflammatory activity on the gastric and duodenal tissue. All these results confirm that the rich phytochemical diversity of B. intermedia contributes to the pharmacological actions of this medicinal plant on the gastrointestinal tract in addition to its activity against H. pylori.
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http://dx.doi.org/10.1016/j.biopha.2018.12.132DOI Listing
March 2019

New Benzaldehyde and Benzopyran Compounds from the Endophytic Fungus Paraphaeosphaeria sp. F03 and Their Antimicrobial and Cytotoxic Activities.

Planta Med 2019 Aug 19;85(11-12):957-964. Epub 2019 Feb 19.

Institute of Chemistry, São Paulo State University (Unesp), Araraquara, SP, Brazil.

Three new benzaldehyde derivatives, sporulosaldeins A - C (1: -3: ), and 3 new benzopyran derivatives, sporulosaldeins D - F (4: -6: ), were discovered from an endophytic fungus, sp. F03, which was isolated from leaves. Compounds 1: -6: were elucidated by 1- and 2-dimensional nuclear magnetic resonance experiments and high-resolution mass spectrometry analysis. The absolute configuration of compound 5: was determined through the comparison of experimental and calculated electronic circular dichroism data. Compounds 1: -6: were found to exhibit antifungal activity with minimum inhibitory concentration (MIC) values of 7.8 - 250 µg/mL and racemic mixture of compound 6: exhibited weak cytotoxicity against MCF-7 and LM3 with IC values of 34.4 and 39.2 µM, respectively.
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http://dx.doi.org/10.1055/a-0853-7793DOI Listing
August 2019
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