RESUMO
INTRODUCTION: This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. METHODS: Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. RESULTS: FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. CONCLUSION: The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.
Assuntos
Dieta Hiperlipídica , Ácidos Linoleicos Conjugados , Metabolismo dos Lipídeos , Fígado , PPAR alfa , Proteína de Ligação a Elemento Regulador de Esterol 1 , Triglicerídeos , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Masculino , Triglicerídeos/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , PPAR alfa/metabolismo , PPAR alfa/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Ácidos Linoleicos Conjugados/farmacologia , Lipogênese/efeitos dos fármacos , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genética , Proteína Desacopladora 2/metabolismo , Proteína Desacopladora 2/genética , Fitosteróis/farmacologia , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos , Lipase Lipoproteica/metabolismo , Lipase Lipoproteica/genéticaRESUMO
Candida auris, a pathogenic fungus, has posed significant challenges to conventional medical treatments due to its increasing resistance to antifungal agents. Consequently, due to their promising pharmacological properties, there is a compelling interest in exploring novel bioactive compounds, such as phytosterols and triterpenes. This study aimed to conduct virtual screening utilizing computational methods, including ADMET, molecular docking, and molecular dynamics, to assess the activity and feasibility of phytosterols extracted from Cryptostegia grandiflora as potential therapeutic agents. Computational predictions suggest that compounds bearing structural similarities to Fsp3-rich molecules hold promise for inhibiting enzymes and G protein-coupled receptor (GPCR) modulators, with particular emphasis on ursolic acid, which, in its conjugated form, exhibits high oral bioavailability and metabolic stability, rendering it a compelling drug candidate. Molecular docking calculations identified ursolic acid and stigmasterol as promising ligands. While stigmasterol displayed superior affinity during molecular dynamics simulations, it exhibited instability, contrasting with ursolic acid's slightly lower affinity yet sustained stability throughout the dynamic assessments. This suggests that ursolic acid is a robust candidate for inhibiting the FKBP12 isomerase in C. auris. Moreover, further investigations could focus on experimentally validating the molecular docking predictions and evaluating the efficacy of ursolic acid as an FKBP12 isomerase inhibitor in models of C. auris infection.
Assuntos
Antifúngicos , Candida , Simulação de Acoplamento Molecular , Fitosteróis , Triterpenos , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , Candida/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Ligantes , Fitosteróis/química , Fitosteróis/farmacologia , Fitosteróis/isolamento & purificação , Simulação de Dinâmica Molecular , Testes de Sensibilidade Microbiana , Ácido UrsólicoRESUMO
Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV-vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov .
Assuntos
Estudos Cross-Over , Suplementos Nutricionais , Hipercolesterolemia , Fitosteróis , Fitosteróis/farmacologia , Fitosteróis/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Hipercolesterolemia/dietoterapia , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Lipoproteínas LDL/sangue , Estudos Prospectivos , Adulto , LDL-Colesterol/sangue , Projetos Piloto , Lipoproteínas/sangueRESUMO
OBJECTIVE: To evaluate the effect of a herbal preparation containing glucosinolates, phytosterols and citrus flavonoids (supplement) on body weight and metabolic parameters usually impaired by menopause. METHODS: A pre-clinical experimental study carried out in twenty-five Swiss strain mice (Mus musculus) randomly distributed (1:1:1:1:1 ratio) to five groups to receive for ten weeks: (1) oral gelatinized maca extract 0.5625 mg/kg/day + bilateral ovariectomy (Maca + OVX); (2) oral supplement 0.5625 mg/kg/day + bilateral ovariectomy (S1 + OVX); (3) oral supplement 1.6875 mg/kg/day + bilateral ovariectomy (S2 + OVX); (4) oral saline 100 µl/kg/day + bilateral ovariectomy (OVX); and (5) oral saline 100 µl/kg/day + sham surgery (sham). The primary endpoint was change in body weight gain from baseline to final. Secondary endpoints were uterine weight and cholesterol, triglyceride, glucose, and glucose/triglycerides index values at the end of the study. A modified intention-to-treat analysis was performed through linear regression models and using the Bonferroni method to penalized p-values by multiple comparisons. RESULTS: Twenty-three animals completed the study. There was a significant average difference in weight gain, with a greater reduction in the S2 + OVX group compared to the OVX group (difference= -3.5; 95% CI (-5.27; -1.74); p < .001). S2 + OVX group also displayed a significant average reduction of total blood cholesterol (difference: -16.94; 95% CI (-33.73; -0.15); p = .037). No significant effects of the supplement were found on other secondary endpoints. CONCLUSION: In this murine menopausal model, triple oral supplement dose resulted in an average reduction of weight gain and total cholesterol levels, suggesting that the compound could have a potential effect at regulating menopausal altered metabolism.
Assuntos
Glucosinolatos/farmacologia , Hesperidina/farmacologia , Lepidium , Menopausa , Ovariectomia , Fitosteróis/farmacologia , Preparações de Plantas/farmacologia , Aumento de Peso/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Suplementos Nutricionais , Feminino , Camundongos , Tamanho do Órgão , Extratos Vegetais/farmacologia , Sitosteroides/farmacologia , Triglicerídeos/sangue , Útero/efeitos dos fármacos , Útero/patologiaRESUMO
Experimental and clinical studies have demonstrated the effect of phytosterols (PS) on reducing plasma levels of cholesterol and LDL-c, but the effects of plant sterols beyond cholesterol-lowering are still questionable. Since inflammation and endothelial dysfunction are involved in the pathogenesis of atherosclerosis, this study aims to evaluate the effect of PS on biomarkers involved in atherosclerosis progression and whether these effects are independent of alterations in plasma LDL-c levels. Thirty-eight moderately hypercholesterolemic volunteers (58 ± 12 years; LDL-c ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and lipid profiles and biomarkers for inflammation and endothelial dysfunction determined. The results showed that PS treatment reduced endothelin-1 plasma concentration by 11% (p = 0.02) independently of variations in plasma levels of LDL-c. No alterations were observed regarding fibrinogen, IL-6, hs-CRP, SAA, TNFα, or VCAM-1 between placebo and PS-treated groups. Furthermore, PS reduced total plasma cholesterol concentration (-5,5%, p < 0.001), LDL-c (-6.4%, p < 0.05), triglycerides (-8.3%, p < 0.05), and apo B (-5.3%, p < 0.05), without changing HDL-c concentration (p > 0.05). Therefore, PS supplementation effectively lowers endothelin-1 independently of the reductions in plasma levels of LDL-c, contributing to the comprehension of the effect of plant sterols on endothelial function and prevention of cardiovascular diseases.
Assuntos
Colesterol/sangue , Suplementos Nutricionais , Endotelina-1/sangue , Hipercolesterolemia/tratamento farmacológico , Fitosteróis/farmacologia , Adulto , Idoso , Apolipoproteínas B , Aterosclerose , Biomarcadores/sangue , Brasil , Proteína C-Reativa , LDL-Colesterol/sangue , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Inflamação , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Plasma , Leite de Soja/administração & dosagem , Esteróis/sangue , Triglicerídeos/sangueRESUMO
Phytosterol metabolism is unknown in the hypercholesterolemia of genetic origin. We investigated the metabolism of phytosterols in a cholesterol-free, phytosterol-containing standard diet in hypercholesterolemic mice knockouts for low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) mice compared to wild-type mice (controls). Phytosterols were measured in mice tissues by GCMS. ApoE-KO mice absorbed less phytosterols than LDLR-KO and the latter absorbed less phytosterols than control mice, because the intestinal campesterol content was low in both KO mice, and sitosterol was low in the intestine in apoE-KO mice as compared to LDLR-KO mice. Although the diet contained nine times more sitosterol than campesterol, the concentration of sitosterol was lower than that of campesterol in plasma in LDLR-KO, and in the liver in controls and in LDLR-KO, but only in apoE-KO. On the other hand, in the intestine sitosterol was higher than campesterol in controls, and in LDLR-KO but with a tendency only in apoE-KO. Because of the high dietary supply of sitosterol, sitosterol was better taken up by the intestine than campesterol, but the amount of sitosterol was lower than that of campesterol in the liver, while in the whole body the amounts of these phytosterols do not differ from each other. Therefore, via intestinal lymph less sitosterol than campesterol was transferred to the body. However, as compared to controls, in apoE-KO mice, but not in LDLR-KO mice, the increase in campesterol and sitosterol in plasma and in the whole body indicating that apoE-KO mice have a marked defect in the elimination of both phytosterols from the body.
Assuntos
Ração Animal , Colesterol/análogos & derivados , Fígado/metabolismo , Fitosteróis , Receptores de LDL/deficiência , Sitosteroides , Animais , Colesterol/farmacocinética , Colesterol/farmacologia , Fígado/patologia , Camundongos , Camundongos Knockout para ApoE , Fitosteróis/farmacocinética , Fitosteróis/farmacologia , Receptores de LDL/metabolismo , Sitosteroides/farmacocinética , Sitosteroides/farmacologia , Especificidade da EspécieRESUMO
BACKGROUND: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fígado/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Fitosteróis/uso terapêutico , Triterpenos/uso terapêutico , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/prevenção & controle , Humanos , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/prevenção & controle , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fitosteróis/química , Fitosteróis/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Twenty compounds were isolated from the hydroethanolic extract of the stems of Siolmatra brasiliensis, five flavonoids, two lignans, one glucosyl phytosterol, seven nor-cucurbitacins, one new phenolic derivative named siolmatrin (1) and four new dammarane-type saponins named siolmatrosides II-V (2-5), the structures of the compounds were assigned by means of 1D and 2D NMR experiments and HRESIMS of the natural compounds and some acetyl derivatives. The effects of the crude hydroethanolic extract (SbExt) and the ethyl acetate fraction (SbEtAc) of Siolmatra brasiliensis stems on the formation of advanced glycation end-products (AGEs) were also investigated. In the in vitro model system of protein glycation using bovine serum albumin (BSA) and glucose, addition of SbExt or SbEtAc inhibited the formation of fluorescent AGEs, in parallel to minor levels of fructosamine (SbEtAc) and markers of tyrosine and tryptophan oxidation (SbExt and SbEtAc). Protein crosslinking, which represents changes of late stages of protein glycation, was reduced in the presence of SbExt and SbEtAc. Siolmatra brasiliensis stems seem to be a promising source of compounds having ability to prevent glycoxidation changes, arising as an interesting option to be studied as a complementary therapy for complications of diabetes.
Assuntos
Cucurbitaceae/química , Flavonoides/farmacologia , Fenóis/farmacologia , Fitosteróis/farmacologia , Saponinas/farmacologia , Flavonoides/isolamento & purificação , Produtos Finais de Glicação Avançada/metabolismo , Glicosilação , Estrutura Molecular , Oxirredução , Fenóis/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Fitosteróis/isolamento & purificação , Extratos Vegetais/química , Caules de Planta/química , Saponinas/isolamento & purificaçãoRESUMO
BACKGROUND: P. mucronata (Pm) comes from South America, Brazil and is characterized as "Maracujá de Restinga". It is used in folk medicine for its soothing properties and in treating insomnia. OBJECTIVE: The present study for the first time analyzed the antioxidant and cytotoxicity of the hydroalcoholic leaves extract and fractions from Pm. METHOD: The cytotoxicity test will be evaluated by different assays (MTT and CV) against human prostate cancer (PC3) and mouse malignant melanoma (B16F10) cell lines, and the antioxidant test by DPPH method. RESULTS: ß-Amyrin, oleanolic acid, ß-sitosterol and stigmasterol were isolated of the most active, hexane fraction. These substances were tested against the tumor cell lines: ß-sitosterol and stigmasterol showed the most relevant activity to PC3 in CV assay and, oleanolic acid to B16F10 by the MTT assay. In addition, it was possible to indicate that the mode of cell death for stigmasterol, presumably is apoptosis. In terms of antioxidant activity, the hydroalcoholic leaves extract presented higher activity (EC50 133.3 µg/mL) compared to the flower (EC50 152.3 µg/mL) and fruit (EC50 207.9 µg/mL) extracts. By the HPLC-MS, it was possible to identify the presence of flavones in the leaf extract (isoschaftoside, schaftoside, isovitexin, vitexin, isoorientin, orientin). CONCLUSIONS: P. mucronata hexane fraction showed promising cytotoxic effect against cancer cell lines, and stigmasterol contributes to this activity, inducing apoptosis of these cells. Furthermore, as other Passiflora species, Pm extract showed antioxidant activity and flavones are its major phenolic compounds.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Passiflora/química , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Camundongos , Conformação Molecular , Fitosteróis/química , Fitosteróis/isolamento & purificação , Fitosteróis/farmacologia , Picratos/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Different pharmacological interventions have been applied with success to reduce the progression of atherosclerosis. However, many patients are not good responders or must interrupt treatment due to adverse effects. Bioactive compounds such as omega-3 fatty acids (n-3 FA), plant sterol esters (PSE) and phenolic compounds (PHC) are natural molecules with great potential to reduce the atherosclerosis burden by reducing inflammation, LDL cholesterol (LDL-C) and oxidative stress, respectively. Although their physiological effects on biomarkers are much lower than those expected by drugs used for the same purpose, bioactive compounds can easily be incorporated into the daily diet and present no adverse effects. However, little is known about the combination of n-3 FA, PSE, PHC, and drugs in atherosclerosis progression. This review article summarizes potential effects of co-therapies involving n-3 FA, PSE, and PHC combined with major hypolipidemic drugs on atherosclerosis biomarkers and clinical outcomes. Evidence of additive and/or complementary effects regarding drugs action reveals possible roles for bioactive compounds in disease management. Pharmaceutical companies, physicians, and food scientists should be prepared to better understand this type of interaction and its consequences in terms of efficacy and life quality.