RESUMO
Pigeon pea (Cajanus cajan (L.) Millsp.) is a legume crop consumed as an indigenous vegetable in the human diet and a traditional medicinal plant with therapeutic properties. The current study highlights the cholesterol-modulating effect and underlying mechanisms of the methanol extract of Cajanus cajan L. leaves (MECC) in HepG2 cells. We found that MECC increased the LDLR expression, the cell-surface LDLR levels and the LDL uptake activity in HepG2 cells. We further demonstrated that MECC suppressed the proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA and protein expression, but not affected the expression of other cholesterol or lipid metabolism-related genes including inducible degrader of LDLR (IDOL), HMG-CoA reductase (HMGCR), fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC1), and liver X receptor-α (LXR-α) in HepG2 cells. Furthermore, we demonstrated that MECC down-regulated the PCSK9 gene expression through reducing the amount of nuclear hepatocyte nuclear factor-1α (HNF-1α), a major transcriptional regulator for activation of PCSK9 promoter, but not that of nuclear sterol-responsive element binding protein-2 (SREBP-2) in HepG2 cells. Finally, we identified the cajaninstilbene acid, a main bioactive stilbene component in MECC, which significantly modulated the LDLR and PCSK9 expression in HepG2 cells. Our current data suggest that the cajaninstilbene acid may contribute to the hypocholesterolemic activity of Cajanus cajan L. leaves. Our findings support that the extract of Cajanus cajan L. leaves may serve as a cholesterol-lowering agent.
Assuntos
Cajanus/química , Colesterol/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Biomarcadores , Genes Reporter , Células Hep G2 , Humanos , Lipogênese/efeitos dos fármacos , Folhas de Planta/química , Regiões Promotoras Genéticas , Pró-Proteína Convertase 9/metabolismo , RNA Mensageiro/genética , Receptores de LDL/metabolismo , Ativação TranscricionalRESUMO
Angelica radix (Danggui in Chinese) used in China and Japan is derived from two species of Angelica, namely Angelica sinensis and Angelica acutiloba, respectively. The differences in quality between A. sinensis radix (ASR) and A. acutiloba radix (AAR) should be therefore investigated to guide the medicinal and dietary applications of these two species. Secondary metabolites and carbohydrates have been demonstrated to be the two major kinds of bioactive components of Danggui. However, previously, quality comparison between ASR and AAR intensively concerned secondary metabolites but largely overlooked carbohydrates, thus failing to include or take into consideration an important aspect of the holistic quality of Danggui. In this study, untargeted/targeted metabolomics and glycomics were integrated by multiple chromatography-based analytical techniques for qualitative and quantitative characterization of secondary metabolites and carbohydrates in Danggui so as to comprehensively evaluate and compare the quality of ASR and AAR. The results revealed that not only secondary metabolites but also carbohydrates in ASR and AAR were different in type and amount, which should collectively contribute to their quality difference. By providing more comprehensive chemical information, the research results highlighted the need to assess characteristics of both carbohydrates and secondary metabolites for overall quality evaluation and comparison of ASR and AAR.
Assuntos
Angelica sinensis/química , Angelica/química , Medicamentos de Ervas Chinesas/química , Angelica/metabolismo , Angelica sinensis/metabolismo , Carboidratos/química , Cromatografia , Glicômica , Metabolômica , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Controle de Qualidade , Metabolismo SecundárioRESUMO
Baicalein (BE) extracted from Scutellaria baicalensis Georgi is able to alleviate various cardiovascular and inflammatory diseases. However, the effects of BE on pulmonary arterial hypertension (PAH) remain unknown. Therefore, the present study aimed to examine whether BE ameliorates pneumonectomy and monocrotaline-induced PAH in rats and further investigate the underlying molecular mechanisms. Administration of BE greatly attenuated the development of PAH as evidenced by an improvement of its characteristic features, including elevation of right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling. Moreover, the increased protein expression of endothelin-1 (ET-1) and ETA receptor (ETAR), superoxide overproduction, and activation of Akt/ERK1/2/GSK3[Formula: see text]/[Formula: see text]-catenin pathway that occurred in the lungs of PAH rats were markedly reversed by BE treatment. Compared with the untreated PAH rats, higher expression of endothelial nitric oxide synthase (eNOS), but lower levels of inducible nitric oxide synthase and vWF were observed in BE-treated PAH rats. Collectively, treatment with BE remarkably attenuates the pathogenesis of PAH, and the protection of BE may be associated with suppressing Akt/Erk1/2/GSK3[Formula: see text]/[Formula: see text]-catenin/ET-1/ETAR signaling and preventing endothelial dysfunction. These results suggest that BE is a potential agent for treatment of PAH.
Assuntos
Regulação para Baixo/efeitos dos fármacos , Endotelina-1/metabolismo , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Monocrotalina/efeitos adversos , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Receptor de Endotelina A/metabolismo , Scutellaria baicalensis/química , Animais , Modelos Animais de Doenças , Flavanonas/administração & dosagem , Flavanonas/isolamento & purificação , Hipertensão Pulmonar/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Pneumonectomia , Ratos Sprague-Dawley , Superóxidos/metabolismo , Fator de von Willebrand/metabolismoRESUMO
Asatone is an active component extracted from the Chinese herb Radix et Rhizoma Asari. Our preliminary studies have indicated that asatone has an anti-inflammatory effect on RAW 264.7 culture cells challenged with lipopolysaccharide (LPS). Acute lung injury (ALI) has high morbidity and mortality rates due to the onset of serious lung inflammation and edema. Whether asatone prevents ALI LPS-induced requires further investigation. In vitro studies revealed that asatone at concentrations of 2.5-20[Formula: see text][Formula: see text]g/mL drastically prevented cytotoxicity and concentration-dependently reduced NO production in the LPS-challenged macrophages. In an in vivo study, the intratracheal administration of LPS increased the lung wet/dry ratio, myeloperoxidase activity, total cell counts, white blood cell counts, NO, iNOS, COX, TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 in the bronchoalveolar lavage fluid as well as mitogen-activated protein kinases in the lung tissues. Pretreatment with asatone could reverse all of these effects. Asatone markedly reduced the levels of TNF-[Formula: see text] and IL-6 in the lung and liver, but not in the kidney of mice. By contrast, LPS reduced anti-oxidative enzymes and inhibited NF-[Formula: see text]B activations, whereas asatone increased anti-oxidative enzymes in the bronchoalveolar lavage fluid and NF-[Formula: see text]B activations in the lung tissues. Conclusively, asatone can prevent ALI through various anti-inflammatory modalities, including the major anti-inflammatory pathways of NF-[Formula: see text]B and mitogen-activated protein kinases. These findings suggest that asatone can be applied in the treatment of ALI.
Assuntos
Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/prevenção & controle , Asarum/química , Mediadores da Inflamação/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Anti-Inflamatórios , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lipopolissacarídeos/efeitos adversos , Macrófagos/metabolismo , Masculino , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7RESUMO
Scutellaria baicalensis has been widely used as both a dietary ingredient and traditional herbal medicine in Taiwan to treat inflammation, cancer, and bacterial and viral infections of the respiratory tract and gastrointestinal tract. This paper aims to investigate the in vitro and in vivo anti-inflammatory effects of S. baicalensis. In HPLC analysis, the fingerprint chromatogram of the water extract of S. baicalensis (WSB) was established. The anti-inflammatory effects of WSB were inverstigated using lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) in vitro and LPS-induced lung injury in vivo. WSB attenuated the production of LPS-induced nitric oxide (NO), tumor necrosis factor-alpha (TNF-[Formula: see text], interleukin-[Formula: see text] (IL-1[Formula: see text], and IL-6 in vitro and in vivo. Pretreatment with WSB markedly reduced the LPS-induced histological alterations in lung tissues. Furthermore, WSB significantly reduced the number of total cells and the protein concentration levels in the BALF. WSB blocked protein expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of I[Formula: see text]B-[Formula: see text] protein and MAPKs in LPS-stimulated RAW 264.7 cells and LPS-induce lung injury was also blocked. This study suggests that WSB possesses anti-inflammatory effects in vitro and in vivo, and the results suggested that WSB may be a potential therapeutic candidate for the treatment of inflammatory diseases.
Assuntos
Lesão Pulmonar Aguda/imunologia , Anti-Inflamatórios/farmacologia , Inflamação , Pulmão/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Lesão Pulmonar Aguda/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Técnicas In Vitro , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Lipopolissacarídeos/farmacologia , Pulmão/imunologia , Pulmão/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Inibidor de NF-kappaB alfa/efeitos dos fármacos , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Scutellaria baicalensis , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/imunologiaRESUMO
OBJECTIVE: To study whether the ethanol extract of Phellinus merrillii (EPM) has chemopreventive potential against liver carcinogenesis. METHODS: Thirty male Spraque-Dawley rats were randomly divided into control group, EPM control group, hepatocarcinoma control group, low-dose EPM group and high-dose EPM group, 6 in each group. Using the Solt and Farber protocol in a rat model of hepatocarcinogenesis, the chemopreventive effect of EPM on diethylnitrosamine (DEN)-initiated, 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH)-promoted liver carcinogenesis in rats was evaluated. Basic pathophysiological and histological examinations, together with the serum levels of glutamic oxaloacetic transaminase (sGOT), glutamic pyruvic transaminase (sGPT) and gamma-glutamyl transpeptidase (γ-GT) were measured. RESULTS: Treatment of EPM at the concentration of 2 g/kg body weight in the diet for 8 weeks clearly prevented the development of carcinogenesis and reduced the levels of sGOT, sGPT, and serum γ-GT of rats as compared with the hepatocarcinoma control group (P<0.05 or P<0.01). These phenotypes were accompanied by a significant increase in natural killer cell activity. CONCLUSION: EPM showed a strong liver preventive effect against DEN+2-AAF+PH-induced hepatocarcinogenesis in a rat model.
Assuntos
2-Acetilaminofluoreno , Basidiomycota/química , Dietilnitrosamina , Etanol/química , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Carcinogênese/induzido quimicamente , Citoproteção/efeitos dos fármacos , Masculino , Phellinus , Extratos Vegetais/química , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Hispolon (a phenolic compound isolated from Phellinus linteus) has been shown to possess strong antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. In this study, we investigated the antiproliferative effect of hispolon on human hepatocellular carcinoma NB4 cells using the MTT assay, DNA fragmentation, DAPI (4, 6-diamidino-2-phenylindole dihydrochloride) staining, and flow cytometric analysis. Hispolon inhibited the cellular growth of NB4 cells in a dose-dependent manner through the induction of cell cycle arrest at G0/G1 phase measured using flow cytometric analysis and apoptotic cell death, as demonstrated by DNA laddering. Exposure of NB4 cells to hispolon-induced apoptosis-related protein expressions, such as the cleavage form of caspase 3, caspase 8, caspase 9, poly (ADP ribose) polymerase, and the proapoptotic Bax protein. Western blot analysis showed that the protein levels of extrinsic apoptotic proteins (Fas and FasL), intrinsic related proteins (cytochrome c), and the ratio of Bax/Bcl-2 were increased in NB4 cells after hispolon treatment. Hispolon-induced G0/G1-phase arrest was associated with a marked decrease in the protein expression of p53, cyclins D1, and cyclins E, and cyclin-dependent kinases (CDKs) 2, and 4, with concomitant induction of p21waf1/Cip1 and p27Kip1. We conclude that hispolon induces both of extrinsic and intrinsic apoptotic pathways in NB4 human leukemia cells in vitro.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Catecóis/farmacologia , Catecóis/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Leucemia/tratamento farmacológico , Leucemia/patologia , Fitoterapia , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Antineoplásicos Fitogênicos/química , Catecóis/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Genes Neoplásicos/genética , Humanos , Leucemia/genética , Leucemia/prevenção & controle , Phellinus , Extratos Vegetais , Polissacarídeos/químicaRESUMO
Dioscorea japonica Thunb. var. pseudojaponica (DP) is consumed as food and widely used in traditional Chinese medicine in Taiwan. The aims of this study are to investigate the antioxidant and anti-inflammatory effects of ethanol extract of DP (EDP) and its reference compounds. Fingerprint chromatogram from HPLC indicated that EDP contains gallic acid and vanillic acid. EDP was evaluated for its antioxidant effects and LPS-induced nitrite oxide (NO) production in RAW264.7 cells. EDP decreased the LPS-induced NO production and expressions of iNOS and COX-2 in RAW264.7 cells. In-vivo anti-inflammatory activities of EDP were assessed in mouse paw oedema induced by λ-carrageenan (Carr). We investigated the antioxidant mechanism of EDP via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the oedematous paw. The results showed that EDP might be a natural antioxidant and anti-inflammatory agent.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Dioscorea/química , Edema/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Catalase/genética , Catalase/metabolismo , Edema/imunologia , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Macrófagos/imunologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , TaiwanRESUMO
Hispolon, an active ingredient in the fungi Phellinus linteus was evaluated with analgesic and anti-inflammatory effects. Treatment of male ICR mice with hispolon (10 and 20 mg/kg) significantly inhibited the numbers of acetic acid-induced writhing response. Also, our result showed that hispolon (20 mg/kg) significantly inhibited the formalin-induced pain in the later phase (P<.01). In the anti-inflammatory test, hispolon (20 mg/kg) decreased the paw edema at the fourth and fifth hour after λ-carrageenin (Carr) administration, and increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRx) in the liver tissue. We also demonstrated that hispolon significantly attenuated the malondialdehyde (MDA) level in the edema paw at the fifth hour after Carr injection. Hispolon (10 and 20 mg/kg) decreased the nitric oxide (NO) levels on both the edema paw and serum level at the fifth hour after Carr injection. Also, hispolon (10 and 20 mg/kg) diminished the serum TNF-α at the fifth hour after Carr injection. The anti-inflammatory mechanisms of hispolon might be related to the decrease in the level of MDA in the edema paw by increasing the activities of SOD, GPx and GRx in the liver. It probably exerts anti-inflammatory effects through the suppression of TNF-α and NO.
RESUMO
Crossostephium chinensis (L.) (CC) Makino is a common traditional Chinese medicinal plant used to dehumidify and cure rheumatism and arthralgia. The water and methanol extracts of C. chinensis (CCW and CCM) were evaluated for their antioxidant and antiproliferative activities. The antioxidant activities of CC were evaluated by using ABTS radical scavenging, DPPH radical scavenging, nitric oxide scavenging and superoxide scavenging methods. Iron chelating activity, lipid peroxidation, total polyphenol contents, total flavonoid contents and total flavonol contents were also detected. In all the tested models, both CCW and CCM showed their ability to scavenge the free radicals in a does-dependent manner. CCW had higher antioxidant and antiproliferative activities than CCM. In LC-MS-MS analysis, the chromatograms of CCW with good antioxidant activities were established. Rutin might be an important bioactive compound in CCW. The antiproliferative activities of CCW and CCM were also studied in vitro by using human hepatoma HepG2 cells. CCW exhibited good antiproliferative activity. These results indicated that CCW might be used as a potential source of natural antioxidants and as an anti-tumor agent.
Assuntos
Antioxidantes/farmacologia , Asteraceae/química , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antioxidantes/química , Compostos de Bifenilo/química , Linhagem Celular Tumoral , Cromatografia Líquida , Relação Dose-Resposta a Droga , Flavonoides/análise , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Quelantes de Ferro/química , Quelantes de Ferro/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Espectrometria de Massas , Metanol/química , Óxido Nítrico/química , Fenóis/análise , Picratos/química , Extratos Vegetais/química , Superóxidos/química , Água/químicaRESUMO
In the present study, we investigated the hepatoprotective and antioxidant capacities of ethanol extract of Phellinus merrillii (PM) on carbon tetrachloride-induced hepatotoxicity. In high-performance liquid chromatography (HPLC) analysis, the finger print chromatogram of PM was established. Both hispolon and PM showed a similar peak at the retention time of 6 min. This implied that PM did contain the active ingredient of hispolon. Treatment with PM (0.5, 1 and 2 g/kg) prior to the administration of carbon tetrachloride (1.5 ml/kg in olive oil, 20%) significantly prevented the increased serum alanine aminotransferase (s-GOT) and serum aspartate aminotransferase (s-GPT) in a dose-dependent manner. We also found that the incidences of ballooning degeneration, necrosis and portal triaditis were lowered in the group pretreated with PM. Carbon tetrachloride induces up-regulation of antioxidant enzymes, including superoxide dismutase (SOD) (86.6%), catalase (58.8%) and glutathione peroxidase (GPx)(64.7%) in the liver. Pretreatment with PM significantly reduced the all these antioxidant enzyme activities. Therefore, we verified that ethanol extract of PM has the hepatoprotective and antioxidant capacities on rats.