RESUMO
CONTEXT: Cordia dichotoma Forst. (Boraginaceae) has potent pharmacological impact. Meanwhile, its effect on fertility is unclear. OBJECTIVE: This study investigates the effect of Cordia fresh fruits hydroethanolic extract on fertility. MATERIALS AND METHODS: 120 Wistar albino male rats were divided into four groups (n = 30). The first group was negative control, and the second, third, and fourth groups received 125, 250, and 500 mg extract/kg bodyweight for 56 days. After 56 days, Cordia force-feeding stopped, and all groups were kept under laboratory conditions for another month to study the recovering effect. RESULTS: After day 56, extract at 500 mg/kg significantly reduced sperm total count, motility%, and alive%, to 47.60 ± 2.27 × 106 sperm/mL, 43.33% ± 1.49, and 63.67% ± 1.19, respectively, abnormalities% increased considerably (26.67% ± 0.54), compared to the negative control. Also, significant depletion on follicle-stimulating hormone (2.66 ± 0.21 mIU/L), luteinizing hormone (1.07 ± 0.06 mIU/L), and testosterone (2.69 ± 0.13 nmol/L) level was recorded, compared to the negative control. Cordia negative effect showed on histopathological studies of testes, prostate, and seminal vesicles. Fortunately, these adverse effects of Cordia recovered remarkably after stopping administration for one month. CONCLUSIONS: Cordia antifertility effect may be due to its hypocholesterolemic effect, where cholesterol, the steroid cycle precursor, was significantly reduced. This study can be incorporated in clinical research after being repeated on another small experimental animal, their offspring, and one large experimental animal, then going to a clinical study that we plan to do in the future.
Assuntos
Cordia/química , Extratos Vegetais/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/toxicidade , Relação Dose-Resposta a Droga , Hormônio Foliculoestimulante/metabolismo , Frutas , Hormônio Luteinizante/metabolismo , Masculino , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Testículo/patologia , Testosterona/metabolismoRESUMO
Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of Protium heptaphyllum gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS2 and GC-FID/MS identified 13 compounds mainly belonging to ursane, oleanane, and tirucallane groups. Studies on human hepatocytes have revealed how PHE is able to reduce cholesterol production and regulate the expression of proteins involved in its metabolism. (HMGCR, PCSK9, LDLR, FXR, IDOL, and PPAR). Moreover, measuring the inhibitory activity of PHE against HMGR, moderate inhibition was recorded. Finally, molecular docking studies identified acidic tetra- and pentacyclic triterpenoids as the main compounds responsible for this action. In conclusion, our study demonstrates how PHE may be a useful alternative to contrast hypercholesterolemia, highlighting its potential as a sustainable multitarget natural extract for the nutraceutical industry that is rapidly gaining acceptance as a source of health-promoting compounds.
Assuntos
Anticolesterolemiantes/farmacologia , Hidrogênio/química , Gomas Vegetais/química , Resinas Vegetais/química , Triterpenos/farmacologia , Anticolesterolemiantes/isolamento & purificação , Domínio Catalítico/efeitos dos fármacos , Colesterol/metabolismo , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais , Avaliação Pré-Clínica de Medicamentos , Ionização de Chama , Cromatografia Gasosa-Espectrometria de Massas , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lovastatina/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Conformação Proteica , Triterpenos/isolamento & purificaçãoRESUMO
There are abundant natural diterpenoids in the plants of the genus Daphne from the Thymelaeaceae family, featuring a 5/7/6-tricyclic ring system and usually with an orthoester group. So far, a total of 135 diterpenoids has been isolated from the species of the genus Daphne, which could be further classified into three main types according to the substitution pattern of ring A and oxygen-containing functions at ring B. A variety of studies have demonstrated that these compounds exert a wide range of bioactivities both in vitro and in vivo including anticancer, anti-inflammatory, anti-HIV, antifertility, neurotrophic, and cholesterol-lowering effects, which is reviewed herein. Meanwhile, the fascinating structure-activity relationship is also concluded in this review in the hope of providing an easy access to available information for the synthesis and optimization of efficient drugs.
Assuntos
Fármacos Anti-HIV/farmacologia , Anti-Inflamatórios/farmacologia , Anticolesterolemiantes/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Daphne/química , Diterpenos/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anticolesterolemiantes/química , Anticolesterolemiantes/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , HumanosRESUMO
AIMS: This study was designed to select lactic acid bacteria with histamine- and cholesterol-reducing abilities to be used as potential probiotics. METHODS AND RESULTS: Thirty strains of lactic acid bacteria isolated from an artisanal raw milk cheese were screened for their abilities to degrade histamine, reduce cholesterol and hydrolyse bile salts. Strains were also screened for safety and probiotic traits, such as resistance to gastrointestinal conditions, adhesion to Caco-2 cells, resistance to antibiotics and presence of virulence genes. Two Lactobacillus paracasei strains presented high cholesterol- and histamine-lowering abilities, tested negative for the presence of virulence genes and showed susceptibility to most important antibiotics. These strains were also shown to possess desirable in vitro probiotic properties, revealed by tolerance to gastrointestinal conditions and high adhesion to intestinal cells. CONCLUSIONS: Among the screened strains, Lb. paracasei L3C21M6 revealed the best cholesterol and histamine reducing abilities together with desirable probiotic and safety features to be used in food applications. SIGNIFICANCE AND IMPACT OF THE STUDY: The strain L3C21M6 is a good candidate for use as a probiotic with histamine-degrading activity and cholesterol lowering effect. In addition, this strain could be use in dairy foods to prevent histamine food poisoning.
Assuntos
Anticolesterolemiantes/farmacologia , Queijo/microbiologia , Antagonistas dos Receptores Histamínicos/farmacologia , Lactobacillales/fisiologia , Probióticos/farmacologia , Animais , Anticolesterolemiantes/isolamento & purificação , Células CACO-2 , Antagonistas dos Receptores Histamínicos/isolamento & purificação , Humanos , Lactobacillales/isolamento & purificação , Lacticaseibacillus paracasei/isolamento & purificação , Lacticaseibacillus paracasei/fisiologia , Leite/microbiologia , Probióticos/isolamento & purificaçãoRESUMO
BACKGROUND AND AIM: This systematic review and meta-analysis aimed to assess the effects of green coffee bean extract (GCBE) supplementation on lipid profile in adults. METHODS AND RESULTS: The PubMed/Medline, Scopus, Web of sciences, and Google Scholar were systematically searched for randomized controlled trials available in English and published before February 2019. The meta-analysis was conducted using fixed effects models, and between-study heterogeneity was assessed by Cochran's Q test and I2. A total of 17 effect sizes were included in the meta-analysis. Combined effect sizes on serum total cholesterol concentrations revealed significant effects of GCBE supplementation on serum total cholesterol [weighted mean difference (WMD): -4.51 mg/dL, 95% confidence interval (CI): -6.89, -2.12, p < 0.001], low density lipoprotein-cholesterol (LDL-C) (WMD: -4.38 mg/dL, 95% CI: -6.44, -2.31, p < 0.001), and high density lipoprotein-cholesterol (HDL-C) (WMD: 2.63 mg/dL, 95% CI: 2.20, 3.07, p < 0.001) compared to controls. Nevertheless, no significant changes were observed in serum triglycerides levels (WMD: -4.34 mg/dL, 95% CI: -9.00, 0.32, p = 0.068). CONCLUSION: The evidence from available studies suggests that the GCBE supplementation leads to significant reductions in total cholesterol, HDL-C, and LDL-C levels, and has modest, but, non-significant effects on triglycerides levels.
Assuntos
Anticolesterolemiantes/administração & dosagem , Colesterol/sangue , Coffea , Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Sementes , Anticolesterolemiantes/isolamento & purificação , Biomarcadores/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Coffea/química , Dislipidemias/sangue , Dislipidemias/diagnóstico , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Extratos Vegetais/isolamento & purificação , Ensaios Clínicos Controlados Aleatórios como Assunto , Sementes/química , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
BACKGROUND AND AIM: Hypercholesterolemia (HC) is a major risk factor for cardiovascular (CV) diseases, that are the major cause of mortality worldwide. Free radicals mediated oxidative stress is a critical player in HC-associated pathophysiological insults including atherosclerosis. Unwanted side effects associated with statins, COX-2 inhibitors, and other synthetic drugs limit their use. Thus, modulation of oxidative stress during HC using green pharmaceuticals seems an appropriate approach against deleterious CV consequences without noticeable side-effect. In this regard, owing to an abundance of proteins, fiber and optimal ratios of omega 6 PUFA: omega-3 PUFA in Hempseed (HS), we aim to exploit its anti-inflammatory and antioxidant properties to ameliorate HC- associated CV effects. METHODS AND RESULTS: Comparing the antioxidant capacity of protein and lipid fractions of HS using ABTS and DPPH assays, HS was supplemented to high-fat diets (HFD) induced hypercholesterolemic wistar rats. After treatment schedules, lipid profiles, histological and ultrastructural investigations, gene and protein expressions of inflammatory markers, markers of oxidative stress were studied and correlated with biophysical parameters such as ECG and impedance/conductance across the aorta. HS demonstrating in vitro free radical scavenging activity, ameliorated the signs of HC as seen with improved lipid profiles, aortic tissue damage and ECG patterns compared to HFD groups. HS administration also relieved the COX-2 mediated inflammation, which correlated well with the improved redox status in the tissue. CONCLUSIONS: Current study evidently demonstrates that the anti-hypercholesterolemic effects of HS are mediated through redox-sensitive modulation of inflammatory pathways.
Assuntos
Anti-Inflamatórios/farmacologia , Anticolesterolemiantes/farmacologia , Antioxidantes/farmacologia , Cannabis , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Mediadores da Inflamação/sangue , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sementes , Animais , Anti-Inflamatórios/isolamento & purificação , Anticolesterolemiantes/isolamento & purificação , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Cannabis/química , Doenças Cardiovasculares/sangue , Modelos Animais de Doenças , Frequência Cardíaca/efeitos dos fármacos , Hipercolesterolemia/sangue , Oxirredução , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Sementes/químicaRESUMO
Beauverolides (beauveriolides) are abundant, biologically active cyclodepsipeptides produced by many entomopathogenic fungi, including those that are used as biopesticides. Beauverolides act as cholesterol acyltransferase inhibitors in humans; thus, their mode of action has been the subject of pharmacological and clinical research. The cost-effective analytical methods are needed for fast, routine laboratory analysis of beauverolides. We isolated beauverolides from the fungal strain Isaria fumosorosea PFR 97-Apopka and opened the rings of the isolated beauverolides using a pyridine alkaline medium. We separated fractions of cyclic and linearized beauverolides by thin-layer chromatography, and found the chloroform-acetate (9:1, v/v) and chloroform-acetonitrile-acetate (8:1:1, v/v/v) mobile phases, respectively, to be the most efficient. We examined all the fractions by liquid chromatography-mass spectrometry using ion trap and Orbitrap high resolution mass spectrometry. For rapid screening of the contents of cyclic, and, particularly, linearized beauverolides, we developed a novel analytical method that consisted of using capillary electrophoresis coupled with contactless conductivity detection. Furthermore, we improved the separation of the peptides by applying capillary micellar electrokinetic chromatography with the N-cyclohexyl-2-aminoethanesulfonic acid:SDS:NaOH buffer, pH 9.8 as the background electrolyte. The described novel methods allow fast and cost-effective separation of chemically related groups of beauverolides.
Assuntos
Anticolesterolemiantes/isolamento & purificação , Cordyceps/química , Depsipeptídeos/isolamento & purificação , Anticolesterolemiantes/química , Cromatografia Líquida , Depsipeptídeos/química , Humanos , Espectrometria de MassasRESUMO
The aim of this project was to improve the Aspergillus terreus strain and pretreatment of sugarcane bagasse as carrier substrate for bulk production of lovastatin, a cholesterol-lowering drug, in solid state fermentation. Sugarcane bagasse was treated with alkali (1-3% NaOH) for the conversion of complex polysaccharides into simple sugars for better utilization of carrier substrate by microorganism for maximum lovastatin production. Ethidium bromide (time of exposure 30-180 min) was used to induce mutation in Aspergillus terreus and the best mutant was selected on the basis of inhibition zone appeared on petri plates. Fermented lovastatin was quantified by high-performance liquid chromatography. The fermented lovastatin, produced by parent and mutant Aspergillus terreus strain, was checked on body weight, blood glucose and serum cholesterol, ALT, AST, HDL-C, LDL-C, TG and TC levels of rats for their cholesterol lowering capacity. Our results indicate that selected strain along with 2% NaOH treated sugar cane bagasse was best suitable for bulk production of lovastatin by fermentation and fermented lovastatin effectively lower the cholesterol level of rats.
Assuntos
Anticolesterolemiantes , Aspergillus , Colesterol/sangue , Lovastatina , Animais , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/farmacocinética , Anticolesterolemiantes/farmacologia , Aspergillus/genética , Aspergillus/crescimento & desenvolvimento , Celulose/química , Avaliação Pré-Clínica de Medicamentos , Lovastatina/biossíntese , Lovastatina/isolamento & purificação , Lovastatina/farmacocinética , Lovastatina/farmacologia , Masculino , Ratos , Saccharum/químicaRESUMO
Girardinia diversifolia, also known as Himalayan nettle, is a perennial herb used in Nepal to make fiber as well as in traditional medicine for the treatment of several diseases. To date, phytochemical studies and biological assays on this plant are scarce. Thus, in the present work, the G. diversifolia extracts have been evaluated for their potential pharmaceutical, cosmetic and nutraceutical uses. For this purpose, detailed phytochemical analyses were performed, evidencing the presence of phytosterols, fatty acids, carotenoids, polyphenols and saponins. The most abundant secondary metabolites were ß- and γ-sitosterol (11 and 9% dw, respectively), and trans syringin (0.5 mg/g) was the most abundant phenolic. Fatty acids with an abundant portion of unsaturated derivatives (linoleic and linolenic acid at 22.0 and 9.7 mg/g respectively), vitamin C (2.9 mg/g) and vitamin B2 (0.12 mg/g) were also present. The antioxidant activity was moderate while a significant ability to inhibit acetylcholinesterase (AChE), butyrilcholinesterase (BuChE), tyrosinase, α-amylase and α-glucosidase was observed. A cytotoxic effect was observed on human ovarian, pancreatic and hepatic cancer cell lines. The effect in hepatocarcinoma cells was associated to a downregulation of the low-density lipoprotein receptor (LDLR), a pivotal regulator of cellular cholesterol homeostasis. These data show the potential usefulness of this species for possible applications in pharmaceuticals, nutraceuticals and cosmetics.
Assuntos
Anticolesterolemiantes/isolamento & purificação , Antioxidantes/isolamento & purificação , Citotoxinas/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Urticaceae/química , Anticolesterolemiantes/farmacologia , Antioxidantes/farmacologia , Ácido Ascórbico/isolamento & purificação , Ácido Ascórbico/farmacologia , Carotenoides/isolamento & purificação , Carotenoides/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/farmacologia , Inibidores Enzimáticos/farmacologia , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Humanos , Fenilpropionatos/isolamento & purificação , Fenilpropionatos/farmacologia , Compostos Fitoquímicos/farmacologia , Fitosteróis/isolamento & purificação , Fitosteróis/farmacologia , Extratos Vegetais/química , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Receptores de LDL/antagonistas & inibidores , Receptores de LDL/genética , Receptores de LDL/metabolismo , Riboflavina/isolamento & purificação , Riboflavina/farmacologia , Saponinas/isolamento & purificação , Saponinas/farmacologia , Sitosteroides/isolamento & purificação , Sitosteroides/farmacologiaRESUMO
Olive (Olea europaea) processing results in large amounts of by-products that contain valuable molecules such as phenolic compounds and phytosterols. These molecules have demonstrated to reduce blood cholesterol levels. This work proposes the development of a method to obtain simultaneously phenolic compounds and phytosterols from the olive stone using CO2-expanded liquid extraction. Hansen solubility parameters were employed for the theoretical prediction of the most suitable bio-based solvent to extract target compounds. The Box-Behnken experimental design was employed to select the optimal conditions of pressure (8-25 MPa), the molar fraction of CO2 in ethyl acetate (0.15-0.55), and the temperature (40-80 °C). Extracts showing the highest and the lowest reductions of micellar cholesterol solubility capacity were analyzed by gas chromatography coupled to mass spectrometry to find out the compounds responsible for this activity. Different phenolic compounds, free fatty acids, and phytosterols were identified in the extracts. ß-Sitosterol and, especially, tyrosol and hydroxytyrosol were the compounds that primarily contributed to the reduction of micellar cholesterol solubility capacity.
Assuntos
Acetatos/química , Anticolesterolemiantes/isolamento & purificação , Dióxido de Carbono/química , Olea/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Extração Líquido-Líquido/métodosRESUMO
BACKGROUND AND AIMS: The novel nutraceutical combination containing red yeast rice (monacolin K 3.3 mg), Berberis aristata cortex extract (Berberine 531.25 mg) and Morus alba leaves extract (1-deoxynojirimycin 4 mg) is effective in the management of elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The aim of the present study was to investigate the effects of the three components on proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of LDL receptor (LDLR) expression, in hepatocyte cell lines and to compare their effects on LDL cellular uptake. METHODS AND RESULTS: HepG2 and Huh7 cells were incubated with B. aristata cortex extract (BCE), red yeast rice (RYR) and M. alba leaves extract (MLE) alone or in combination for 24 h. RYR (50 µg/mL) increased PCSK9 protein expression (Western blot analysis and ELISA), PCSK9 mRNA (qPCR) and its promoter activity (luciferase reporter assay). BCE (40 µg/mL) reduced instead PCSK9 expression, mRNA levels and promoter activity. MLE determined a concentration-dependent reduction of PCSK9 at the mRNA and protein levels, with a maximal reduction at 1 mg/mL, without significant changes of PCSK9 promoter activity. MLE also downregulated the expression of 3-hydroxy-3-methyl-3-glutaryl coenzyme A reductase and fatty acid synthase mRNA levels. The combination of RYR, BCE and MLE reduced the PCSK9 mRNA and protein levels, as well as the promoter activity. Finally, the single components and their combination induced LDL receptor and LDL uptake by the hepatocytes. CONCLUSION: The positive effect of MLE on PCSK9 supports the rationale of using the nutraceutical combination of RYR, BCE and MLE to control hyperlipidemic conditions.
Assuntos
Anticolesterolemiantes/farmacologia , Berberis/química , Produtos Biológicos/farmacologia , LDL-Colesterol/metabolismo , Hepatócitos/efeitos dos fármacos , Lovastatina/farmacologia , Morus/química , Extratos Vegetais/farmacologia , Pró-Proteína Convertase 9/metabolismo , Anticolesterolemiantes/isolamento & purificação , Relação Dose-Resposta a Droga , Regulação para Baixo , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Regulação Enzimológica da Expressão Gênica , Células Hep G2 , Hepatócitos/enzimologia , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Pró-Proteína Convertase 9/genéticaRESUMO
Mulberry (M. alba L.) has prominent use in traditional Chinese medicine since ancient times but its therapeutic properties have not been sufficiently explored in India. Present study was designed to isolate and identify the polyphenolic constituents present in mulberry leaf (M. latifolia) using HPLC and to evaluate its antihyperglycemic and antihyperlipedemic properties in streptozotocin (STZ) induced diabetic wistar rat models. HPLC analysis identified chlorogenic acid (103mg/100gm), caffeic acid (4.3mg/100gm), coumaric acid (11.61mg/kg), rutin (53mg/100gm) and quercetin (46.19mg/100gm) as the major constituents of crude polyphenolic extracts in M. latifolia. STZ induced diabetic rats administered with mulberry leaf extract at doses 250 and 500mg/kg after 4 weeks of treatment significantly improved their glycemic control (p<0.001). Body weight increased significantly (p<0.001) after administration of BC259 extract at a dose of 500mg/kg. Results also showed that there was a significant decrease in serum urea (p<0.001) and creatinine level (p<0.01). Significant decline was observed in the levels of serum triglycerides (p<0.01), total cholesterol (p<0.001), LDL-cholesterol (p<0.01) and VLDL-cholesterol (p<0.01), while the serum HDL-cholesterol (p<0.01) significantly increased. Results revealed that the leaf extract of M. latifolia (var.BC259) causes significant antidiabetic and antihypercholesterolemic activity. Evidence of identified bioactive polyphenolic compounds present in M. latifolia leaf extract strengthens its antidiabetic property.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Morus , Extratos Vegetais/farmacologia , Folhas de Planta , Polifenóis/farmacologia , Animais , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/farmacologia , Biomarcadores/sangue , Glicemia/metabolismo , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/diagnóstico , Hipoglicemiantes/isolamento & purificação , Masculino , Morus/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Polifenóis/isolamento & purificação , Ratos Wistar , Estreptozocina , Triglicerídeos/sangue , Aumento de Peso/efeitos dos fármacosRESUMO
Obesity and nonalcoholic fatty liver disease (NAFLD) are highly prevalent and cause numerous metabolic diseases. However, drugs for the prevention and treatment of obesity and NAFLD remain unavailable. In this study, we investigated the effects of mogrosides (luo han guo, LH) in Siraitia grosvenorii saponins on high-fat-diet-induced obesity and NAFLD in mice. We found that compared with the negative control, LH reduced body and liver weight. LH also decreased fat accumulation and increased AMP-activated protein kinase (AMPK) phosphorylation (pAMPK) levels in mouse livers. We also found that high-purity mogroside V upregulated pAMPK expression in HepG2 cells. In addition, high-purity mogroside V inhibited reactive oxygen species production and upregulated sequestosome-1 (SQSTM1, p62) expression in THP-1 cells. These results suggest that LH may affect obesity and NAFLD by enhancing fat metabolism and antioxidative defenses. Mogroside V may be a main component of LH. However, the exact molecular mechanisms and active components responsible for the inhibitory effects of LH on obesity and NAFLD require further investigation.
Assuntos
Fármacos Antiobesidade/farmacologia , Anticolesterolemiantes/farmacologia , Momordica/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Triterpenos/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Anticolesterolemiantes/química , Anticolesterolemiantes/isolamento & purificação , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Tamanho do Órgão/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Proteína Sequestossoma-1/agonistas , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Células THP-1 , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
In previous studies, it has not been reported that protein isolated from chia interferes favorably with antibacterial activity, and reduces cholesterol synthesis. The objective of this study was to determine whether commonly used commercial microbial proteases can be utilized to generate chia protein-based antibacterial and hypocholesterolemic hydrolysates/peptides, considering the effects of protein extraction method. Alcalase, Flavourzyme and sequential Alcalase-Flavourzyme were used to produce hydrolysates from chia protein (CF), protein-rich fraction (PRF) and chia protein concentrates (CPC1 and CPC2). These hydrolysates were evaluated for their antimicrobial activity against Gram-positive (G+) and Gram-negative (G-) microorganisms. The protein hydrolysates were purified by ultrafiltration through a membrane with 3 kDa nominal molecular weight, for evaluation of hypocholesterolemic activity. An inhibition zone was observed when the hydrolysate was tested against S. aureus, and minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were obtained. Peptides from chia protein with molecular mass lower than 3 kDa reduced up to 80.7% of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) enzymatic reaction velocity. It was also observed that, independent of the method used to obtain chia proteins, the fractions showed relevant bioactivity. Moreover, the intensity of the bioactivity varied with the method for obtaining the protein and with the enzyme used in the hydrolysis process. This is the first report to demonstrate that chia peptides are able to inhibit cholesterol homeostasis.
Assuntos
Antibacterianos/farmacologia , Anticolesterolemiantes/farmacologia , Peptídeos/farmacologia , Hidrolisados de Proteína/farmacologia , Salvia/química , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/análise , Antibacterianos/isolamento & purificação , Anticolesterolemiantes/análise , Anticolesterolemiantes/isolamento & purificação , Colesterol , Endopeptidases/metabolismo , Hidrólise , Peso Molecular , Peptídeo Hidrolases/metabolismo , Peptídeos/análise , Peptídeos/isolamento & purificação , Hidrolisados de Proteína/análise , Hidrolisados de Proteína/isolamento & purificação , Subtilisinas/metabolismoRESUMO
The elution characteristics of lovastatin were studied by varying the composition of mobile phase in both isocratic and gradient elution modes to comprehend the role of organic modifier and acidifier on the overall analysis time and retention time of individual forms of lovastatin. Acetonitrile has influenced on the overall analysis time, whereas the acidifier determines the retention time of hydroxy acid form of lovastatin and the retention time gap between the individual forms. A combination of acetonitrile and 0.1% trifluoroacetic acid (TFA) (60:40, v/v) in isocratic elution mode eluted both hydroxy acid and lactone forms of lovastatin at 4.5 and 5.4 min, respectively. This appears to be a better approach for the separation of pharmaceutical and clinical lovastatin samples. At isocratic elution mode, a mixture of acetonitrile and either 0.05% TFA or 0.1% H3PO4 of 60:40 (v/v) has eluted both hydroxy acid and lactone forms of lovastatin at 10 ± 0.5 and 17 ± 0.5 min, respectively. This is suitable for the fermentation-derived samples or for the complex mixtures of structural analogs. The fermentation broth (pH not adjusted) extracted with ethyl acetate at a ratio of 1:1 (v/v) at 60°C for 30 min was the optimal extraction condition for lovastatin.
Assuntos
Anticolesterolemiantes/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Lovastatina/isolamento & purificação , Monascus/metabolismo , Anticolesterolemiantes/química , Anticolesterolemiantes/metabolismo , Fermentação , Microbiologia Industrial , Lovastatina/química , Lovastatina/metabolismo , Monascus/químicaRESUMO
CONTEXT: Prunus domestica Linn (Rosaceae) has been considered a functional food, owing to its various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic and anticancer. OBJECTIVE: This placebo-controlled, randomized study was framed to check the beneficial activity of prune essence concentrates (PEC) in corroboration with intestinal function and lipid profile in mildly hypercholesterolemic subjects. MATERIALS AND METHODS: Sixty healthy mild hypercholesterolemic subjects were randomly chosen and segregated into three groups as placebo (consume 50 mL of simulated prune drink), PEC I (consume 50 mL of PEC/day) and PEC II (consume 100 mL of PEC/day) for 4 weeks with 2 weeks of follow-up without PEC consumption. RESULTS: Intake of PEC (I and II) for 4 weeks substantially ameliorated (p < 0.05) the colony number of Bifidobacterium spp. (1.18- and 1.19-fold) and Lactobacillus spp. (1.07- and 1.16-fold), but markedly lowered (p < 0.05) the colony number of Clostridium perfringens (5.97 and 8.35%) and Escherichia coli (6.25 and 9.38%). Meanwhile, the total cholesterol (TC; 5.90 and 6.99%) levels and LDL-c (6.68 and 6.53%) were significantly reduced (p < 0.05), but no change in other lipid parameters. Whereas, the antioxidant capacity was also concomitantly elevated (p < 0.05) upon administration with PEC. DISCUSSION AND CONCLUSION: Overall, the results suggest that the use of PEC may positively regulate the intestinal microflora and thereby effectively lower the TC levels and thus act as a hypocholesterolemic agent.
Assuntos
Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Sucos de Frutas e Vegetais , Fármacos Gastrointestinais/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipercolesterolemia/tratamento farmacológico , Intestinos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Prunus domestica/química , Adolescente , Adulto , Anticolesterolemiantes/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Biomarcadores/sangue , Contagem de Colônia Microbiana , Regulação para Baixo , Fezes/microbiologia , Feminino , Fármacos Gastrointestinais/isolamento & purificação , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Intestinos/microbiologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Índice de Gravidade de Doença , Taiwan , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Functional and health endorsing benefits of various foods are often attributed to their phytochemistry. The bitter gourd holds potential in improving the health of the individuals owing to its incredible versatility in phytochemistry. However, the efficacy of different parts of bitter gourd needs attention of the researchers. In the current exploration, different parts of bitter gourd were evaluated for their cholesterol lowering potential in cholesterol fed Sprague dawley rats. For the purpose, four types of bitter gourd part i.e. whole fruit, seedless fruit, seeds, and seed extracts were used and compared with placebo in hypercholesterolemic rats. In placebo, momentous increase in serum cholesterol, triglycerides and LDL levels was observed. All parts attenuate the cholesterol 18.79 to 40.17% triglycerides 25.97 to 37.01% and LDL 14.49 to 26.09%. However, 1% extract powder was most effective in reducing the cholesterol and triglycerides. From the present study, it is deduced that bitter gourd extract can be supplemented in food products for the management of hypercholesterolemia. However, future studies in human subjects needs to be conducted for meticulousness of the present findings.
Assuntos
Anticolesterolemiantes/farmacologia , Colesterol na Dieta/sangue , Suplementos Nutricionais , Hipercolesterolemia/prevenção & controle , Momordica charantia , Extratos Vegetais/farmacologia , Animais , Anticolesterolemiantes/isolamento & purificação , Biomarcadores/sangue , Modelos Animais de Doenças , Frutas , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Pós , Ratos Sprague-Dawley , Sementes , Fatores de Tempo , Triglicerídeos/sangueRESUMO
Diabetes mellitus (DM) is universal of the hormonal problem and Type II diabetes is foremost obstacle. Accessible management in medicine has numerous contrary paraphernalia. Medical flora shows an essential part in managing diabetes specifically in unindustrialized nations. The present study was done on leaves of Rhazya stricta Decane, Adhatoda zeylanica, Berberis lycium Royle and Olea furrrignea, whose methanolic extracts were used to check their hypoglycemic and hypolipidemic activity by using glucometer and kit method respectively in blood of male and female albino mice Balb C. Results showed that leaves of R. stricta were best for hypoglycemia (125.34±63.79mg/dl, 107.34±18.00mg/dl, 146.00±40.36mg/dl and 178.34±17.03mg/dl), hypocholesterolemia (147.88±21.83mg/dl and 125.89±14.03mg/dl) and triglycerides (103±8.88mg/dl and 89.±43.4mg/dl) in random and fasting conditions, in male and female mice respectively. All plant extract were most effective for hypoglycemia and hypocholesterolemia in female mice as compared to male mice. Moreover statistical analysis revealed that leaves of other plants were also effective but less than leaves of R. stricta. So this plant part and a combination of presently used plants can be used for further studies particularly among females by the purification of active compounds against hyperglycemia and hypercholesterolemia.
Assuntos
Anticolesterolemiantes/farmacologia , Apocynaceae/química , Berberis/química , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Justicia/química , Olea/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Anticolesterolemiantes/isolamento & purificação , Biomarcadores/sangue , Glicemia/metabolismo , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Feminino , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipoglicemiantes/isolamento & purificação , Masculino , Metanol/química , Camundongos Endogâmicos BALB C , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Solventes/química , Estreptozocina , Triglicerídeos/sangueRESUMO
A highly efficient three-phase single drop microextraction (SDME) method is presented by using an organic-aqueous compound droplet. A coupling microdevice is designed to produce compound droplets in different sizes conveniently. In this way, the volume ratio of organic phase to aqueous phase in a compound droplet can be significantly reduced. Good operability and droplet stability were observed during extraction under vigorous stirring conditions. Five statins were used as model compounds and spiked in river water and human serum samples to evaluate the analytical performance of the proposed method. By using a 1.2 µL toluene-aqueous compound droplet (volume ratio 0.2 : 1), a 350 to 1712 fold enrichment of statins was obtained within 4 minutes. The results indicate that the proposed method is a very rapid and efficient sample pretreatment method, and is promising for automated and high-throughput applications.
Assuntos
Anticolesterolemiantes/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Microextração em Fase Líquida/instrumentação , Rios/química , Poluentes Químicos da Água/análise , Anticolesterolemiantes/análise , Anticolesterolemiantes/isolamento & purificação , Desenho de Equipamento , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/análise , Inibidores de Hidroximetilglutaril-CoA Redutases/isolamento & purificação , Limite de Detecção , Microextração em Fase Líquida/economia , Tamanho da Amostra , Tolueno/química , Água/química , Poluentes Químicos da Água/isolamento & purificaçãoRESUMO
Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.