Pentacyclic triterpenes in general exert beneficial effects in metabolic disorders. This study investigated the effects of α, β-amyrin, a pentacyclic triterpene mixture from the resin of Protium heptaphyllum on blood sugar level and lipid profile in normal and streptozotocin (STZ)-induced diabetic mice, and in mice fed on a high-fat diet (HFD). Mice treated with α, β-amyrin (10, 30 and 100 mg/kg, p.o.) or glibenclamide (10 mg/kg, p.o.) had significantly reduced STZ-induced increases in blood glucose (BG), total cholesterol (TC) and serum triglycerides (TGs). Unlike glibenclamide that showed significant reductions in BG, TC and TGs in normoglycemic mice, α, β-amyrin did not lower normal blood sugar levels but at 100 mg/kg, manifested a hypolipidemic effect. Also, α, β-amyrin effectively reduced the elevated plasma glucose levels during the oral glucose tolerance test. Moreover, the plasma insulin level and histopathological analysis of pancreas revealed the beneficial effect of α, β-amyrin in the preservation of beta cell integrity. In mice treated orally with α, β-amyrin (10, 30 and 100 mg/kg) or fenofibrate (200 mg/kg), the HFD-associated rise in serum TC and TGs were significantly less. The hypocholesterolemic effect of α, β-amyrin appeared more prominent at 100 mg/kg with significant decreases in VLDL and LDL cholesterol and an elevation of HDL cholesterol. Besides, the atherogenic index was significantly reduced by α, β-amyrin. These findings reflect the potential antihyperglycemic and hypolipidemic effects of α, β-amyrin mixture and suggest that it could be a lead compound for drug development effective in diabetes and atherosclerosis.

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.

O presente artigo relata o isolamento e identificação do palmitato, oleato e linoleato de sitosterila, sitosterol, estigmasterol, 3-O-β-D-galactopiranosídeo do sitosterol, 3-O-β-Dgalactopiranosídeo do estigmasterol, 3-O-β-D-glicopiranosídeo do sitosterol e uma mistura de ácidos anacárdicos (monoeno e dieno) do extrato etanólico de cascas do caule de Anacardium occidentale L., Anacardiaceae, bem como do sitosterol, estigmasterol, lupeol, β-amirina, catequina e epicatequina do extrato etanólico do tegumento da castanha de caju in natura. Os extratos EtOH da casca e do tegumento foram avaliados quanto ao conteúdo de fenóis totais e atividade antioxidante. O extrato etanólico das cascas do caule apresentou maior conteúdo de compostos fenólicos e percentual de atividade antioxidante. This paper describes the isolation and identification of a mixture of sitosteryl ester derivatives of fatty acids (palmitic, oleic and linoleic), sitosterol, stigmasterol, sitosterol-3-O-β-galactopyranoside, stigmasterol-3-O-β-galactopyranoside, sitosterol-3-O-β-glucopyranoside and a mixture of anacardic acids (monoene and diene) from stem bark of Anacardium occidentale L., Anacardiaceae, as well as sitosterol, stigmasterol, lupeol, β-amyrin, catechin and epicatechin from in natura cashew nut testa. Ethanol extracts from stem bark and testa were analyzed for antioxidant activity and total phenol content. The ethanol extract from stem bark exhibited the maximum of antioxidant activity and phenol content

Combretum leprosum Mart. (Combretaceae), a shrub popularly known as mofumbo, is used in folk medicine for treatment of uterine bleeding, pertussis, gastric pain, and as a sedative. The aim of this study was to (1) determine the phytochemical profile,(2) identify chemical constituents and (3) examine antioxidant and cytogenotoxic activity of ethanolic extracts and fractions of stem bark and leaves. The plant material (leaf and stem bark) was submitted to extraction with ethanol, followed by partition using hexane, chloroform, and ethyl acetate. It was possible to identify and quantify the epicatechin in the ethanolic stem bark extract (0.065 mg/g extract) and rutin in the leaf extract (3.33 mg/g extract). Based upon in vitro tests a significant relationship was noted between findings from antioxidant tests and levels of total phenolic and flavonoid. Comparing all samples (extracts and fractions), the ethyl acetate fractions of stem bark (411.40 ± 15.38 GAE/g) and leaves (225.49 ± 9.47 GAE/g) exhibited higher phenolic content, whereas hexanic fraction of stem bark (124.28 ± 56 mg/g sample) and ethyl acetate fraction of leaves (238.91 ± 1.73 mg/g sample) demonstrated a higher content of flavonoids. Among the antioxidant tests, the intermediate fraction of stem bark (28.5 ± 0.60 μg/ml) and ethyl acetate fraction of leaves (40 ± 0.56 μg/ml) displayed a higher % inhibition of free radical DPPH activity, whereas intermediate fraction of stem bark (27.5 ± 0.9 μg/ml) and hydromethanol fraction of leaves (81 ± 1.4 μg/ml) demonstrated inhibition of the free radical ABTS. In biological tests (Allium cepa and micronucleus in peripheral blood), data showed that none of the tested concentrations of ethanolic extracts of leaves and stem bark produced significant cytotoxicity, genotoxicity, and mutagenic activity.Abbreviations AA%: percentage of antioxidant activity; ABTS: 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid); CEUA: Ethics Committee in the Use of Animals; TLC: Thin Layer Chromatography; DNA: deoxyribonucleic acid; DPPH: 1,1-diphenyl-2-picrylhydrazyl; ROS: Reactive oxygen species; EEB: ethanol extract of the stem bark; HFB: Hexanic fraction of stem bark; IFB: Intermediate fraction of stem bark; CFB: Chloroform fraction of stem bark; EAFB: Ethyl acetate fraction of stem bark; HMFB: Hydromethanol fraction of the stem bark; EEL: Ethanol extract from leaves; HFL: Hexane fraction of leaves; CFL: Chloroform fraction of leaves; EAFL: Ethyl acetate fraction of leaves; HMFL: Hydromethanol fraction of leaves; GAE: Gallic Acid Equivalent; IC₅₀: 50% inhibition concentration; HCOOH: Formic acid; HCl: hydrochloric acid; HPLC: High-performance liquid chromatography; MN: micronucleus; WHO: World Health Organization; UFLC: Ultra-Fast Liquid Chromatography; UESPI: State University of Piauí.

We encapsulated MSZ in zein nanoparticles (NP-ZN) using a desolvation method followed by drying in a mini spray dryer. These nanoparticles exhibited a size of 266.6 ± 52 nm, IPD of 0.14 ± 1.1 and zeta potential of −36.4 ± 1.5 mV, suggesting colloidal stability. Quantification using HPLC showed a drug-loaded of 43.8 µg/mg. SEM demonstrated a spherical morphology with a size variation from 220 to 400 nm. A FTIR analysis did not show drug spectra in the NPs in relation to the physical mixture, which suggests drug encapsulation without changing its chemical structure. A TGA analysis showed thermal stability up to 300 °C. In vitro release studies demonstrated gastroresistance and a sustained drug release at pH 7.4 (97.67 ± 0.32%) in 120 h. The kinetic model used for the release of MSZ from the NP-ZN in a pH 1.2 medium was the Fickian diffusion, in a pH 6.8 medium it was the Peppas–Sahlin model with the polymeric relaxation mechanism and in a pH 7.4 medium it was the Korsmeyer–Peppas model with the Fickian release mechanism, or “Case I”. An in vitro cytotoxicity study in the CT26.WT cell line showed no basal cytotoxicity up to 500 μg/mL. The NP-ZN showed to be a promising vector for the sustained release of MSZ in the colon by oral route.

This study aimed to identify potential inhibitors and investigate the mechanism of action on SARS-CoV-2 ACE2 receptors using a molecular modeling study and theoretical determination of biological activity. Hydroxychloroquine was used as a pivot structure and antimalarial analogues of 1,2,4,5 tetraoxanes were used for the construction and evaluation of pharmacophoric models. The pharmacophore-based virtual screening was performed on the Molport^® database (~7.9 million compounds) and obtained 313 structures. Additionally, a pharmacokinetic study was developed, obtaining 174 structures with 99% confidence for human intestinal absorption and penetration into the blood–brain barrier (BBB); posteriorly, a study of toxicological properties was realized. Toxicological predictions showed that the selected molecules do not present a risk of hepatotoxicity, carcinogenicity, mutagenicity, and skin irritation. Only 54 structures were selected for molecular docking studies, and five structures showed binding affinity (ΔG) values satisfactory for ACE2 receptors (PDB 6M0J), in which the molecule MolPort-007-913-111 had the best ΔG value of −8.540 Kcal/mol, followed by MolPort-002-693-933 with ΔG = −8.440 Kcal/mol. Theoretical determination of biological activity was realized for 54 structures, and five molecules showed potential protease inhibitors. Additionally, we investigated the Mpro receptor (6M0K) for the five structures via molecular docking, and we confirmed the possible interaction with the target. In parallel, we selected the TopsHits 9 with antiviral potential that evaluated synthetic accessibility for future synthesis studies and in vivo and in vitro tests.