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•The triterpenoid, α, β-Amyrin manifests anti-adipogenicity in 3T3-L1 cells.•α, β-Amyrin inhibits preadipocyte differentiation.•α,β-Amyrin suppresses adipogenic transcription factors, ...PPARγ and C/EBPα.•α,β-Amyrin stimulates the glucose transporter GLUT4 and promotes AMPK phosphorylation.
Previous studies have reported the anti-obesity effects of α, β-Amyrin in high fat-fed mice. This study aimed to evaluate whether α, β-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 α, β-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 (PPARγ), CCAAT/enhancer binding proteins alpha (C/EBPα), beta (C/EBPβ), and delta (C/EBPδ) and glucose transporter 4 (GLUT4) were determined by qRT-PCR and western blot analysis. Oil-Red O staining revealed markedly reduced fat accumulation by α, β-Amyrin (6.25–50 μg/mL) without affecting cell viability. Furthermore, our results indicate that α, β-Amyrin can significantly suppress the adipocyte differentiation by downregulating the expression levels of adipogenesis-related key transcription factors such as PPARγ and C/EBPα, but not C/EBPβ or C/EPBδ. In addition, the protein expression of membrane GLUT4 in 3T3- L1 adipocytes treated with α, β-Amyrin was significantly higher than in control cells, indicating that α, β-Amyrin augments glucose uptake. These findings suggest that α, β-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 α, β-Amyrin can be developed as a new therapeutic agent for treatment and prevention of obesity.
Alendronate is a bisphosphonate widely used for the treatment of osteoporosis; however, one of its main adverse reactions is gastric ulcer. Metformin is an oral antihyperglycemic agent that has ...several beneficial effects, including healing, gastroprotective and anti-tumoral action. This study aimed to evaluate the gastroprotective activity of metformin in alendronate-induced gastric damage in normoglycemic and hyperglycemic rats. The treatment with 100 mg/kg of metformin showed a significant gastroprotective effect in damage induced by alendronate (50 mg/kg) in macroscopic analysis and the analysis of light microscopy and atomic force microscopy. The results suggested metformin decreased the inflammatory response by reducing the expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6), myeloperoxidase activity, and malondialdehyde levels. Also, the results suggested that metformin induces the maintenance of basal levels of collagen and increase the production of mucus. Interestingly, with the presence of the AMPK inhibitor (Compound C), metformin presented impairment of its gastroprotective action. The gastroprotective effect of metformin might be related to the activation of the AMPK pathway. These findings revealed that metformin has a gastroprotective action and may be considered a therapeutic potential for the prevention and treatment of gastric lesions induced by alendronate.
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Salinaphthoquinones A–E (1–5) were isolated from a marine Salininispora arenicola strain, recovered from sediments of the St. Peter and St. Paul Archipelago, Brazil. The structures of the compounds ...were elucidated using a combination of spectroscopic (NMR, IR, HRESIMS) data, including single-crystal X-ray diffraction analysis. A plausible biosynthetic pathway for 1–5 is proposed. Compounds 1 to 4 displayed moderate activity against Staphylococcus aureus and Enterococcus faecalis with MIC values of 125 to 16 μg/mL.
The aim of this study was to investigate the antibacterial and antibiofilm potential of cordiaquinones B, E, L, N, and O against different Staphylococci strains, in addition to analyzing in silico ...the observed effect.
The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined according to CLSI guidelines. The inhibition of biofilm formation was investigated at sub-MICs. Atomic force microscopy (AFM) and density functional theory method were performed. The tested strains of Staphylococcus spp. were susceptible to cordiaquinones B, E, and L, among which cordiaquinone B exerted a bactericidal effect, confirmed by a bacterial growth curve study, against Staphylococcus saprophyticus. Cordiaquinones B and E showed lowest MBC values against S. saprophyticus. AFM revealed that cordiaquinone L reduced the mean cell size of S. saprophyticus. Cordiaquinones B and E inhibited the biofilm formation ability of S. aureus by ∼90%. The in silico analysis suggested that the antimicrobial activity of cordiaquinones is driven by their electron donation capability.
Cordiaquinones inhibit the growth and biofilm formation (virulence factor) of both methicillin-sensitive and methicillin-resistant Staphylococci strains, indicating their antimicrobial potential.
Hydrogels made with depolymerized guar gum, oxidized with theoretical oxidation degrees of 20, 35 and 50 %, were obtained via Schiff's base reaction with N-succinyl chitosan. The materials obtained ...were subjected to characterization by FT-IR, rheology, swelling, degradation, and morphology. Additionally, their gelation time categorized all three hydrogels as injectable. The materials' swelling degrees in Phosphate-Buffered Saline (PBS) were in the range of 26–35 g of fluid/g gel and their pore size distribution was heterogeneous, with pores varying from 67 to 93 μm. All hydrogels degraded in PBS solution, but maintained around 40 % of their initial mass after 28 days, which was more than enough time for wound healing. The biomaterials were also flexible, self-repairing, adhesive and cytocompatible and presented intrinsic actions, regardless of the presence of additives or antibiotics, against gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative bacteria (Escherichia coli). However, the most pronounced bactericidal effect was against resistant Staphylococcus aureus - MRSA. In vivo assays, performed with 50 % oxidized gum gel, demonstrated that this material exerted anti-inflammatory effects, accelerating the healing process and restoring tissues by approximately 99 % within 14 days. In conclusion, these hydrogels have unique characteristics, making them excellent candidates for wound-healing dressings.
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•Injectable, adhesive and self-healing hydrogels based on Guar Gum and Chitosan.•Hydrogel dressing that reduces inflammatory signs and accelerates the wound closure.•Innate antibacterial mechanism efficient without side effects against S. aureus, S. epidermidis, E.coli and S. aureus-MRSA strains.
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 (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.
Gums are a group of naturally occurring polysaccharides that have the ability to form viscous gels and solutions. Gum arabic is a branched polysaccharide, chemically complex and widely used as ...emulsifier and stabilizer by the pharmaceutical and the food industry. Quaternization is a chemical modification reaction capable of altering the physicochemical properties of polysaccharides while keeping their fundamental properties intact, giving rise to derivatives with characteristics distinct from native polysaccharides. Therefore, gum arabic at a concentration of 10 g was quaternized using 3-chloro-2-hydroxypropyltrimethyl ammonium chloride (CHPTAC) at different reaction times (3, 7 and 14 h) and temperatures (50, 70 and 90ºC). Quaternization of all samples was confirmed by FTIR. The highest degree of substitution was observed for the GAQ-1 derivative, obtained to 50 °C e 3 h of reaction. All derivatives demonstrated thermal stability. Quaternized samples showed cytotoxicity when in contact with colorectal cancer cells HCT-116 at a concentration of 2 mg/mL. The quaternized derivatives proved to be safe when in contact with normal cells and the initial studies point to a possible use in biological applications as a potential coadjunct in the treatment of some types of cancer. However, further studies are needed to confirm its applicability.
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•The quaternization of arabic gum was performed for the first time.•Quaternized derivatives showed antitumor activity against colorectal cancer cells.•All derivatives have been shown to be safe in normal cells.
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.
A new trachylobane diterpene ent-trachyloban-18,19-diol (1) was isolated from root bark of Croton floribundus, along with known diterpenes ent-trachyloban-19-oic acid (2), ...15b-hydroxy-ent-trachyloban-19-oic acid (3), ent-trachyloban-19-ol (4), ent-kaur-16-en-19-oic acid (5), ent-kaur-16-ene-6a,19-diol (6) and ent-16a-hydroxykaur-11-en-19-oic acid (7). ent-trachyloban-18,19-diol (1) was submitted to derivatization reactions affording four new compounds (8-11). Cytotoxic activity of diterpenes 1, 3, 4, 7-11 against three human cancer cell lines was evaluated. No compounds showed cytotoxic potential with IC50 values greater than 25 mg/mL. Compound 6 was evaluated against five human cancer cell lines, showing moderate effect against three cancer cell lines, MDA-MB-435, HCT-8 and HCT-116, with IC50 values of 14.32, 13.47 and 12.1 mg/mL, respectively.
In the present study, the effect of sulfonamide-chalcone 185 (SSC185) was investigated against B16–F10 metastatic melanoma cells aggressive actions, besides migration and adhesion processes, by in ...silico and in vitro assays. In silico studies were used to characterize the pharmacokinetic profile and possible targets of SSC185, using the pkCSM web server, and docking simulations with AutoDock Tools. Furthermore, the antimetastatic effect of SSC185 was investigated by in vitro experiments using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), colony, scratch, and cell adhesion assays, and atomic force microscopy (AFM). The molecular docking results show better affinity of SSC185 with the metalloproteinases-2 (MMP-2) and α5β1 integrin. SSC185 effectively restricts the formation of colonies, migration, and adhesion of B16–F10 metastatic melanoma cells. Through the AFM images changes in cells morphology was identified, with a decrease in the filopodia and increase in the average cellular roughness. The results obtained demonstrate the potential of this molecule in inhibit the primordial steps for metastasis, which is responsible for a worse prognosis of late stage cancer, being the main cause of morbidity among cancer patients.
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•MMP-2 and α5β1 integrin are putative targets of SSC185.•SSC185 decreased migration and adhesion of metastatic cells in vitro.•SSC185 causes changes in cell morphology with loss of filopodia and rearrangements in the cytoskeleton.
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