RESUMO
Post-menopause, there is an increase in body weight, visceral adiposity, and risk of developing non-alcoholic fatty liver disease (NAFLD), which leads to various cardiovascular diseases (CVDs). Some natural products have proven useful for counteracting the detrimental effects of menopause. The rhizome of Ligusticum chuanxiong Hort. (LC) is a well-known medicinal herb widely used in Chinese communities for the treatment of CVDs. The hepatic and vascular protective effects of LC ethanolic extract under postmenopausal conditions were investigated on ovariectomized (OVX) rats supplemented with or without LC ethanolic extract (600 mg/kg body weight/day, p.o.) or 17ß-estradiol (1 mg/kg body weight/day, p.o.) for 12 weeks. The current findings demonstrated that consumption of LC ethanolic extract could reduce the body weight gain, improve serum lipid profile (lowering low density lipoprotein cholesterol but raising high density lipoprotein cholesterol), combat NAFLD, and protect vascular endothelium in the OVX rats. The beneficial effects of LC may be associated with its antioxidant or vasorelaxant compounds, which enhance the levels of hepatic antioxidant enzymes and up-regulate endothelial nitric oxide synthase mRNA expression, respectively. Taken together, LC may be a promising natural supplement for postmenopausal women to prevent NAFLD and CVDs.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Pós-Menopausa/efeitos dos fármacos , Rizoma , Animais , Antioxidantes , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/patologia , Endotélio Vascular/patologia , Estradiol/farmacologia , Estrogênios/farmacologia , Fígado Gorduroso , Feminino , Ligusticum , Lipídeos/sangue , Fígado/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Hepatopatia Gordurosa não Alcoólica , Ovariectomia , Ratos , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacosRESUMO
OBJECTIVE: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in postmenopausal women. Danshen, the dried root of Salvia miltiorrhiza Bunge, has been used clinically in China to treat CVD and dyslipidemia in postmenopausal women, and its major active ingredients have been found to have an estrogenic effect. The aim of this study was to elucidate the underlying mechanism of danshen's protective effects on vascular function in an ovariectomized (OVX) hyperlipidemic rat model. METHODS: Thirty-five 6-month-old female Sprague-Dawley rats were randomly divided into five groups: sham-operated rats with low-fat control diet + vehicle, sham-operated rats with high-fat diet (HFD) + vehicle, OVX rats with HFD + vehicle, OVX rats with HFD + 17ß-estradiol (1 mg kg d, PO), and OVX rats with HFD + danshen aqueous extract (600 mg kg d, PO). After 12 weeks of treatment, gains in body weight and serum lipid profile levels in rats were measured and histological examination of livers was carried out. Vascular function was evaluated by measuring relaxation responses. Molecular mechanisms were also analyzed in isolated aorta. RESULTS: Treatment with danshen aqueous extract reduced body weight gain, improved serum lipid profiles, and prevented formation of fatty liver induced by HFD and OVX. In addition, danshen could increase endothelial-dependent vasorelaxation and displayed vasoprotection in OVX rats fed with HFD, primarily by stimulating nitric oxide (NO) production, up-regulating the mRNA expression of endothelial NO synthase, and down-regulating the mRNA expression of tumor necrosis factor α, intercellular cell adhesion molecule-1, and vascular cell adhesion molecule-1 in the isolated aortas. CONCLUSIONS: We conclude for the first time that danshen aqueous extract could protect OVX rats fed with HFD from endothelial dysfunction. Its effect may be related to its abilities to normalize serum lipid profiles and enhance NO availability in the vascular system. Our findings indicate that danshen aqueous extract could be a promising natural supplement for postmenopausal women for preventing CVD.
Assuntos
Dieta Hiperlipídica , Medicamentos de Ervas Chinesas/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Ovariectomia , Fenantrolinas/uso terapêutico , Salvia miltiorrhiza/química , Animais , Aorta Torácica/metabolismo , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Endotélio Vascular/fisiopatologia , Fígado Gorduroso/etiologia , Fígado Gorduroso/prevenção & controle , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/genética , Lipídeos/sangue , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo III/genética , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Molécula 1 de Adesão de Célula Vascular/genética , Vasodilatação/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacosRESUMO
Ischemic heart disease is a major cause of death in the world. Common therapies, such as primary coronary angioplasty and thrombolysis, are applied to restore blood supply to the heart, limit infarct size and reduce mortality. However, the restoration of blood supply would generate reactive oxygen species in damaged sites of the myocardium, intensifying the damage to the cardiac tissues. Radix Scutellariae baicalensis (Huangqin) is a well-known herb in traditional Chinese medicine with high antioxidant power. In this study, extract of the dry root of Scutellaria baicalensis Georgi (Sb) was confirmed to have a high content of flavonoids and phenolic compounds. The cardioprotective effects of the Sb extracts (3, 30 and 300 mg/kg) were evaluated in myocardial ischemia-reperfusion injuried rats. The results showed that animals that had received five-day pretreatment of the Sb extract (30 mg/kg) had a significant reduction in myocardial infarct size and a marked increase in the activity of catalase in the liver. The Sb extract could additionally enhance acetylcholine-induced vasorelaxation. It was proposed that the Sb extract exerted its cardioprotection by stimulating the catalase activity and improving vascular elasticity.
Assuntos
Cardiotônicos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fitoterapia , Extratos Vegetais/uso terapêutico , Polifenóis/uso terapêutico , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Cardiotônicos/análise , Cardiotônicos/farmacologia , Catalase/metabolismo , Fígado/metabolismo , Masculino , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas , Polifenóis/análise , Polifenóis/farmacologia , Ratos , Ratos Sprague-Dawley , Scutellaria baicalensis/químicaRESUMO
We evaluated the vasorelaxation effects of formononetin, an isoflavone/phytoestrogen found abundantly in Astragalus mongholicus Bunge, on rat isolated aorta and the underlying mechanisms involved. Cumulative administration of formononetin, genistein, daidzein and biochanin A relaxed phenylephrine-preconstricted aorta. Formononetin and biochanin A caused a similar magnitude of relaxation whereas daidzein was least potent. Mechanical removal of endothelium, L-NAME (100 microM) and methylene blue (10 microM) suppressed formononetin-induced relaxation. Formononetin increased endothelial nitric oxide (NO) synthase (eNOS), but not inducible NO synthase, activity with an up-regulation of eNOS mRNA and p-eNOS(Ser1177) protein expression. In endothelium-denuded preparations, formononetin-induced vasorelaxation was significantly reduced by glibenclamide (3 microM) and iberiotoxin (100 nM), and a combination of glibenclamide (3 microM) plus iberiotoxin (100 nM) abolished the relaxation. In contrast, formononetin-elicited endothelium-independent relaxation was not altered by ICI 182,780 (10 microM, an estrogen receptor (ER alpha/ER beta) antagonist) or mifepristone (10 microM, a progesterone receptor antagonist). In single aortic smooth muscle cells, formononetin caused opening of iberiotoxin-sensitive Ca(2+)-activated K(+) (BK(Ca)) channels and glibenclamide-sensitive adenosine triphosphate (ATP)-dependent K(+) (K(ATP)) channels. Thus, our results suggest that formononetin caused vascular relaxation via endothelium/NO-dependent mechanism and endothelium-independent mechanism which involves the activation of BK(Ca) and K(ATP) channels.
Assuntos
Aorta Torácica , Endotélio Vascular/fisiologia , Isoflavonas/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Concentração Osmolar , Fitoestrógenos/farmacologia , Fitoterapia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Rheum officinale Baill. (Da Huang) is one of the herbs commonly used in traditional Chinese medicine formulae against cancer. The traditional decoction is similar to the water extract used in the present study. AIM OF THE STUDY: The water extract of Da Huang was investigated to see if it possesses anticancer effects through apoptotic pathways. MATERIALS AND METHODS: Human lung adenocarcinoma A549 and human breast cancer MCF-7 cell lines were treated with different concentrations of Da Huang water extract at different time intervals. Growth inhibition was detected by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] and colony formation assays; apoptosis was detected by cell morphologic analysis, DNA fragmentation analysis and COMET assay. RESULTS: Da Huang water extract was found to have significant growth inhibitory effects on both A549 and MCF-7 cell lines with IC(50) values 620+/-12.7 and 515+/-10.1 microg/ml, respectively. Growth inhibitory effects were dose- and time-dependent. A significant decrease in cell number, DNA fragmentation and single DNA strand breakages were observed in the Da Huang water extract treated A549 and MCF-7 cells. CONCLUSIONS: This suggests that the water extract of Da Huang exerts potential anticancer activity through growth inhibition and apoptosis on MCF-7 and A549 cells lines.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fitoterapia , Rheum , Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Sais de Tetrazólio , TiazóisRESUMO
Hypercholesterolemia is a major risk factor for the development and progression of cardiovascular diseases including atherosclerosis. A major active ingredient, scutellarin, from the plant Erigeron breviscapus was investigated for its hypocholesterolemic and atheroscleroprotective effects (30 and 100 mg/kg/day, P. O.). The serum lipid profile (total cholesterol, triglycerides, high density lipoprotein cholesterol and low density lipoprotein cholesterol) was monitored and aortic functions in Sprague-Dawley rats fed with normal diet, atherogenic diet or atherogenic diet plus oral administration of either scutellarin or simvastatin (a positive control) were tested. It was found that scutellarin markedly attenuated the increased serum total cholesterol induced by atherogenic diet. It caused a significant reduction in the atherogenic index. In addition, scutellarin administration could significantly enhance acetylcholine-induced nitrate/nitrite production, increase the gene expression of endothelial nitric oxide synthase and improve acetylcholine-induced endothelium-dependent vasorelaxation in rat isolated aortas. These data revealed that scutellarin could reduce the atherogenic properties of dietary cholesterol in rats. However, whether scutellarin's atheroscleroprotective potential targets endothelial function directly or indirectly on its antioxidative activity remains to be determined.