RESUMO
Atherosclerosis is the main process behind cardiovascular diseases (CVD), maladies which continue to be responsible for up to 70% of death worldwide. Despite the ongoing development of new and potent drugs, their incomplete efficacy, partial intolerance and numerous side effects make the search for new alternatives worthwhile. The focus of the scientific world turned to the potential of natural active compounds to prevent and treat CVD. Essential for effective prevention or treatment based on phytochemicals is to know their mechanisms of action according to their bioavailability and dosage. The present review is focused on the latest data about phenolic compounds and aims to collect and correlate the reliable existing knowledge concerning their molecular mechanisms of action to counteract important risk factors that contribute to the initiation and development of atherosclerosis: dyslipidemia, and oxidative and inflammatory-stress. The selection of phenolic compounds was made to prove their multiple benefic effects and endorse them as CVD remedies, complementary to allopathic drugs. The review also highlights some aspects that still need clear scientific explanations and draws up some new molecular approaches to validate phenolic compounds for CVD complementary therapy in the near future.
Assuntos
Anti-Inflamatórios/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Terapias Complementares , Epigênese Genética , Lipídeos/química , Fenóis/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Epigênese Genética/efeitos dos fármacos , Humanos , Fenóis/químicaRESUMO
SCOPE: To assess the impact of ginger extract (GIN) in stimulating the production of quality HDL and the cholesterol efflux in the small intestine (SI), key processes in the management of hyperlipidemia (HL)-induced hepatic steatosis, and atherosclerosis. METHODS AND RESULTS: Three groups of hamsters are used: (i) N, fed standard diet, (ii) HL, fed high-fat diet for 21 weeks, and (iii) HL-GIN, HL treated with GIN for the last 5 weeks of diet. Apolipoprotein A-I (apoA-I), malondialdehyde-apoA-I (MDA-apoA-I), paraoxonase1 (PON1), and myeloperoxidase (MPO) are measured in plasma and SI. ATP-binding cassette A1 transporter (ABCA1), ABCG5/G8, liver X receptor α/ß (LXRα/ß), peroxisome proliferator-activated receptor γ (PPARγ), and sirtuin1 (SIRT1) are assessed in the SI. Results show that in HL plasma, GIN decreases MDA-apoA-I, MPO/PON1 ratio and increases HDL-cholesterol/total cholesterol. In HL-SI, GIN decreases MDA-apoA-I and MPO, increases ApoA-I, PON1, and ABCA1, and restores cholesterol efflux disturbed by HL (SIRT1-LXRα/ß-PPARγ-ABCG8). GIN administration is associated with the reduction of the aortic valves lipid-deposits. CONCLUSION: In HL conditions, GIN stimulates the functional HDL production by restoring apoA-I quality and quantity through inhibition of the oxidative stress, and increases cholesterol efflux in the SI. These effects are associated with the restoration of SIRT1-LXRα/ß-PPARγ pathway.
Assuntos
Colesterol/metabolismo , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Lipoproteínas HDL/biossíntese , Extratos Vegetais/farmacologia , Zingiber officinale , Animais , Valva Aórtica/metabolismo , Colesterol/análise , Cricetinae , Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/metabolismo , Lipídeos/sangue , Receptores X do Fígado/genética , Masculino , Mesocricetus , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/genética , Sirtuína 1/genéticaRESUMO
BACKGROUND: Stearoyl CoA desaturases (SCD) are enzymes that convert saturated to monounsaturated fatty acids and have increased activity in hepatic steatosis. PURPOSE: We aimed to investigate the potential of ginger extract (GIN) to modulate the liver SCD1 expression and activity in hyperlipidemic (HL) conditions, in order to lower lipid accumulation in the steatotic liver. STUDY DESIGN/METHODS: Male Golden Syrian hamsters were divided in three groups: (i) fed with standard chow (N), (ii) fed with standard chow plus 3% cholesterol and 15% butter for 21 weeks (HL), (iii) HL treated with GIN (800⯵g/kg body weight/day) in the last 5 weeks of fat diet (HL-GIN). Cholesterol (C), triglycerides (TG), non-esterified fatty acids (NEFA), SCD1 estimated activity (C16:1n7/C16:0; C18:1n9/C18:0) and gene expression, acetyl-CoA carboxylase (ACC), thiobarbituric acid reactive substances (TBARS), paraoxonase1 (PON1) and myeloperoxidase (MPO) were determined in the plasma and liver of all hamsters. We measured protein expression of endoplasmic reticulum stress (ERS) markers, gene and protein expression of liver X receptor α/ß (LXRα/ß), peroxisome proliferator-activated receptor γ (PPARγ), ATP-binding cassette sub-family G member 5/8 (ABCG5/G8) and 7α-hydroxylase1 (CYP7A1) in all hamsters' livers. RESULTS: In plasma, in HL-GIN versus HL hamsters, SCD1 estimated activity was lower (27%; 15%, pâ¯<â¯0.05), NEFA levels decreased by 91%, pâ¯<â¯0.001, while C and TG levels did not vary; the oxidative stress expressed as MPO and TBARS levels decreased (15%; 11%, pâ¯<â¯0.01), while PON1 protein increased (75%, pâ¯<â¯0.05). In the liver of HL-GIN versus HL, C, TG, NEFA, MPO and TBARS levels decreased (8-40%, pâ¯<â¯0.05) and PON1 protein levels increased (30%, pâ¯<â¯0.05), SCD1 estimated activity decreased (8%; 9%, pâ¯<â¯0.05), in parallel with the reduced gene expression of SCD1 and ACC (70-80%, pâ¯<â¯0.05). The protein expression of the ERS sensors decreased (30-65%, pâ¯<â¯0.05), while that of ABCG5/G8, CYP7A1, LXRα/ß and PPARγ increased in HL-GIN (20-30%, pâ¯<â¯0.05) versus HL liver. CONCLUSION: GIN reduces SCD1 estimated activity and expression, as well as the lipids accumulated in the livers of HL hamsters. This is achieved through a mechanism involving the decrease of the oxidative and ERS, and the enhancement of cholesterol efflux.