This work evaluated the in vitro cytotoxic activity of laticifer proteins (LP) recovered from the latex of the medicinal plant
Calotropis procera. The LP displayed considerable cytotoxicity with IC
...50 values ranging from 0.42 to 1.36
μg/ml to SF295 and MDA-MB-435 cell lines, respectively. In healthy peripheral blood mononuclear cells exposed to LP (10
μg/ml) for 72
h, no noticeable effects on viability or cell morphology were seen. The fractionating of LP on an ion exchange chromatography gave rise to a new fraction (PI) that retained almost all cytotoxicity. The cytotoxic effects of both LP and PI were diminished when previously treated with pronase, or 2-mercaptoethanol, suggesting a protein nature of active molecules, however, pre-incubation with dithiothreitol (DTT) only reduced PI activity. PI did not exhibit cysteine proteinase activity, indicating that cysteine proteinases, abundantly found in LP, are not implicated in LP cytotoxicity. In this study, using HL-60 cell as a model, LP was shown to inhibit DNA synthesis. This is probably due to alterations in the topology of DNA, since it was observed that LP is able to interfere in topoisomerase I activity by somehow acting upon DNA. LP provoked reduction in cell number but it did not cause any significant increase in the number of non-viable cells. These findings corroborated with the morphologic analysis, where cells treated with LP showed morphology of apoptotic process with abundant vacuoles, chromatin condensation and fragmentation of the nuclei. The results of this study suggests that LP is a target for DNA topoisomerase I triggering apoptosis in cancer cell lines.
Leishmaniasis is a widespread tropical infection caused by different species of Leishmania protozoa. Many of the available drugs against the disease are toxic and in certain cases parasite drug ...resistance is developed. The discovery of drugs for the treatment of leishmaniasis is a pressing concern. In the present work, we describe in vitro studies of the phenolic compound methyl gallate (MG) against Leishmania (Leishmania) amazonensis and its possible mechanisms of action. The in vitro activity of MG was assayed against L. amazonensis (promastigotes, axenic amastigotes, and intramacrophagic amastigotes). Cytotoxicity tests were performed with J774A.1 macrophages and THP-1 cell derived macrophages. To evaluate mechanisms of action, we analyzed cellular TNF-α, IL-12, IFN-γ, IL-10, IL-6, NO, ROS levels, arginase activity, and structural mechanisms (phagocytic and lysosomal activities) involving macrophage activation. Meglumine antimoniate and amphotericin B were used as reference drugs. It was observed that MG effectively inhibited the growth of both promastigote (IC50 5.71 μM) and amastigote-like forms (EC50 5.39 μM), with much higher selectivity indexes than the reference drugs, being more benign towards J774A.1 macrophages than meglumine antimoniate and amphotericin B, at 1631- and 70.92-fold respectively, with respect to the promastigote form. Additionally, MG proved to be even more active against intracellular amastigotes of the parasite (EC50 4.24 μM). Our results showed that antileishmania activity was associated with increased TNF-α, IL-12, NO and ROS levels, as well as decreased IL-6 and decreased arginase activity. In addition, MG induced increased phagocytic capability, and lysosomal volume in macrophages; structural parameters of microbicidal activity. Taken together, our results suggest that MG may be a promising candidate for new drug development against leishmaniasis.
•Methyl gallate showed antileishmanial activity in vitro to L. amazonensis.•Methyl gallate exhibited selectivity indexes (SI) greater than reference drugs.•Methyl gallate reduced the infection index of macrophages by L. amazonensis.•Methyl gallate stimulated TNF-α, IL-12, ROS and NO production in macrophages infected.•Methyl gallate reduced IL-10 in macrophages infected.
Resistance to antimicrobials is a challenging issue that complicates the treatment of infections caused by bacteria and fungi, thus requiring new therapeutic options. Oncocalyxone A, a benzoquinone ...obtained from Auxemma oncocalyx (Allem) Taub has several biological effects; however, there is no data on its antimicrobial action. In this study, its antimicrobial and antibiofilm activities were evaluated against bacteria and fungi of clinical interest. Strains of Gram-positive and Gram-negative bacteria, and filamentous fungi and yeasts were selected to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of oncocalyxone A. The antibacterial effect of oncocalyxone A was studied using survival curves, atomic force microscopy (AFM), and the involvement of oxidative stress. We examined the inhibitory action of the molecule on biofilm formation and its hemolytic activity against human erythrocytes. Our results showed that among the strains tested, Staphylococcus epidermidis was highly sensitive to the action of oncocalyxone A, with an MIC of 9.43 μg/mL. In most bacterial strains analyzed, a bacteriostatic effect was observed, though the molecule showed no antifungal activity. Antibiofilm activity was observed against the methicillin-resistant S. aureus bacteria. Additionally, results from atomic force microscopy imaging showed that oncocalyxone A significantly altered bacterial morphology. Further, oncocalyxone A showed no hemolytic activity at concentrations ≥151 μg/mL. Together, our results demonstrate the antibacterial and antibiofilm potential of oncocalyxone A, indicating its therapeutic potential against bacterial resistance.
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•Antibacterial activity of oncocalixone A against sensitive and resistant bacteria.•Study of antibacterial activity by AFM technique.•Study of the participation of oxidative stress in antibacterial activity.•Antibiofilm activity of oncocalixone A.
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•The extracts presented similar phytochemical composition.•The Mimosa extracts presented antioxidant and antimicrobial activity.•First reports about the biological potential of Mimosa ...pteridifolia Benth.•The extracts did not show toxicity in cancer and normal cells.
Plant extracts and components are commonly used in popular medicine to relieve the symptoms of several diseases. They can also be used scientifically for drug testing due to their wide biological potential, acting as antibacterial, antifungal, and anticancer agents, for example. Some plants belonging to the Fabaceae family, Mimosa genus, which are popularly known as Jurema, have been used for a long time by indigenous people and are still widely used in popular medicine. The presence of different secondary metabolites, such as phenolic compounds, like flavonoids and tannins, for example, attribute to these plants several biological applications, such as antibacterial and antifungal properties, supporting their use in traditional medicine. In this study, ethanolic extracts were produced using the barks of three plants of the Mimosa genus. Phytochemical assays were performed to analyze the composition of the extracts and their antimicrobial, cytotoxic, hemolytic, and antioxidant activities were evaluated. To the best of our knowledge, the present study may be the pioneer in the investigation of the biological activities of Mimosa pteridifolia. Besides, all the extracts showed considerable biological activity, mainly because of their phytochemical composition, which consists of tannins and flavonoids. Further studies should be carried out to identify the active principle and investigate the mechanisms of action responsible for these biological activities.
We herein report the antitumor activity of several substituted α- and β-dihydrofuran naphthoquinones against 4 human tumor cell lines, HL-60 (leukemia), SF-295 (CNS), HCT-8 (colon) and MDA-MB435 ...(melanoma), and their electrochemical parameters, in the absence and presence of oxygen, in comparison with their non-substituted precursors. These compounds were prepared from readily available lawsone and olefins in the presence of cerium (IV) ammonium nitrate. The β-dihydrofuran naphthoquinones were shown to be highly cytotoxic, while their positional α-isomers were considered less active. The level of intracellular ROS release and the first wave redox potentials were also analyzed and compared with the kinetic constants of the reactivity of quinones with oxygen (kapp) obtained through cyclic voltammetry. Significantly positive correlations between ROS release and oxygen reactivity were obtained, while IC50vs. ROS release; −EpIcvs. kapp or ROS values correlated in an inverse manner, i.e., the less negative the potential, higher the activities. These findings reinforce the effectiveness of the combination of pharmacology and electrochemistry in medicinal chemistry, in the search of lead anticancer compounds.
The chemical investigation of the brown alga Dictyota menstrualis provided three previously unreported prenylated guaiane diterpenes derivatives named as dictyols K, M and N (1 - 3), along with five ...structurally known diterpenoids (4 - 8). The structures of the new compounds, including their relative stereochemistry, were established by nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) data analysis. In addition, their structures were improved by quantum mechanical calculations. Anti-inflammatory, antimicrobial and cytotoxic assays were performed with the isolated compounds, however, only the anti-inflammatory activity was particularly prominent. The cell viability effects of 1 - 8 on murine macrophage cell line (RAW 264.7) showed IC50 values ranging from 1.12 to 2.53 μM, and the inhibitory activity against the nitric oxide production over the lipopolysaccharide-stimulated RAW 264.7 cell was observed for all compounds with IC50 values ranging to 0.12 - 0.23 μM.
Tree-exuded gums are natural polymers that represent an abundant raw material in the food and pharmaceutical industries. The cashew gum can be obtained by exudation of trees of the genus Anacardium, ...a native species of the Brazilian northeast; its polymer consists of monosaccharide units propitious to the action of chemical reactions that tend to improve their intrinsic characteristics among them, as the degree of hydro-solubility. The objective of this work was to modify the exudate gum of Anacardium occidentale (cashew gum (CG)) through an amine reaction. The modification was confirmed by Nuclear Magnetic Resonance (sup.1H NMR), infrared spectroscopy (FTIR), gel permeation chromatography (GPC), zeta potential, and thermogravimetric analysis (TG). In addition, the chemical modification altered the molar mass and surface charge of the CG, and the amino group binding to the CG polymers was confirmed by FTIR spectra. In addition, cytotoxicity tests were performed where cell viability was estimated by an MTT assay on RAW 264.7 macrophages. Through these tests, it was found that the amine caused an increase in the thermal stability of the amino compounds and did not present cytotoxic potential at concentrations below 50.0 mg/L.
Tree-exuded gums are natural polymers that represent an abundant raw material in the food and pharmaceutical industries. The cashew gum can be obtained by exudation of trees of the genus Anacardium, ...a native species of the Brazilian northeast; its polymer consists of monosaccharide units propitious to the action of chemical reactions that tend to improve their intrinsic characteristics among them, as the degree of hydro-solubility. The objective of this work was to modify the exudate gum of
(cashew gum (CG)) through an amine reaction. The modification was confirmed by Nuclear Magnetic Resonance (
H NMR), infrared spectroscopy (FTIR), gel permeation chromatography (GPC), zeta potential, and thermogravimetric analysis (TG). In addition, the chemical modification altered the molar mass and surface charge of the CG, and the amino group binding to the CG polymers was confirmed by FTIR spectra. In addition, cytotoxicity tests were performed where cell viability was estimated by an MTT assay on RAW 264.7 macrophages. Through these tests, it was found that the amine caused an increase in the thermal stability of the amino compounds and did not present cytotoxic potential at concentrations below 50.0 mg/L.
Keywords alpha, beta-Amyrin; 3T3-L1 cells; Adipocyte differentiation; PPARgamma; C/EBPalpha; GLUT4; Anti-adipogenecity Highlights * The triterpenoid, alpha, beta-Amyrin manifests anti-adipogenicity ...in 3T3-L1 cells. * alpha, beta-Amyrin inhibits preadipocyte differentiation. * alpha,beta-Amyrin suppresses adipogenic transcription factors, PPARgamma and C/EBPalpha. * alpha,beta-Amyrin stimulates the glucose transporter GLUT4 and promotes AMPK phosphorylation. Previous studies have reported the anti-obesity effects of alpha, beta-Amyrin in high fat-fed mice. This study aimed to evaluate whether alpha, beta-Amyrin has an anti-adipogenic effect in 3T3-L1 murine adipocytes and to explore the possible underlying mechanisms. 3T3-L1 pre-adipocytes were differentiated in a medium containing insulin, dexamethasone, and 1-methyl-3-isobutylxanthine. Cytotoxicity of alpha, beta-Amyrin was assessed by MTT assay. Lipid content in adipocytes was determined by Oil-Red O staining. In addition, the protein expression levels of peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT/enhancer binding proteins alpha (C/EBPalpha), beta (C/EBPbeta), and delta (C/EBPdelta) and glucose transporter 4 (GLUT4) were determined by qRT-PCR and western blot analysis. Oil-Red O staining revealed markedly reduced fat accumulation by alpha, beta-Amyrin (6.25--50 mug/mL) without affecting cell viability. Furthermore, our results indicate that alpha, beta-Amyrin can significantly suppress the adipocyte differentiation by downregulating the expression levels of adipogenesis-related key transcription factors such as PPARgamma and C/EBPalpha, but not C/EBPbeta or C/EPBdelta. In addition, the protein expression of membrane GLUT4 in 3T3- L1 adipocytes treated with alpha, beta-Amyrin was significantly higher than in control cells, indicating that alpha, beta-Amyrin augments glucose uptake. These findings suggest that alpha, beta-Amyrin exerts an anti-adipogenic effect principally via modulation of lipid and carbohydrate metabolism in 3T3-L1cells. The present in vitro findings, taken together with our earlier observation of the anti-obesity effect in vivo, suggest that alpha, beta-Amyrin can be developed as a new therapeutic agent for treatment and prevention of obesity. Author Affiliation: (a) Postgraduate Program in Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil (b) Postgraduate Program in Medical Sciences, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil (c) Research Center on Biodiversity and Biotechnology, Federal University of Piaui, Parnaiba, Piaui, Brazil (d) Department of Organic Chemistry, Federal University of Piaui, Teresina, Piaui, Brazil (e) Department of Physiology and Pharmacology, Natural Products Laboratory, Faculty of Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil * Corresponding author at: Department of Physiology and Pharmacology, Natural Products Laboratory, Faculty of Medicine, Federal University of Ceara, Cel Nunes de Melo, 1315, Fortaleza, Ceara, 60430-270, Brazil. Article History: Received 19 June 2018; Revised 3 November 2018; Accepted 6 November 2018 Byline: Karina Moura de Melo (a), Francisca Tuelly Bandeira de Oliveira (b), Rose Anny Costa Silva (b), Ana Luiza Gomes Quindere (b), Jose Delano Barreto Marinho Filho (c), Ana Jersia Araujo (c), Eanes Delgado Barros Pereira (b), Adonias Almeida Carvalho (d), Mariana Helena Chaves (d), Vietla Satyanarayana Rao (e), Flavia Almeida Santos fasufc@gmail.com (e,*)
![[alpha], [beta]-Amyrin, a p...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0753-3322/small "[alpha], [beta]-Amyrin, a pentacyclic triterpenoid from Protium heptaphyllum suppresses adipocyte differentiation accompanied by down regulation of PPAR[gamma] and C/EBP[alpha] in 3T3-L1 cells")