RESUMO
Excessive alcohol uptake exerts hepatocellular toxicity, ultimately leading to multiple liver diseases such as steatohepatitis and liver cirrhosis. Here, we aimed to explore the effects of mulberry leaf extract (MLE) and its major components chlorogenic acid (CGA) and neochlorogenic acid (nCGA) on alcoholic steatohepatitis. We determined the composition of MLE using liquid chromatography-mass spectrometric (LC-MS) analysis, which showed that MLE consisted of mainly chlorogenic acid derivatives and other polyphenols. Next, we utilized a high alcohol-fed mouse model and demonstrated that MLE alleviated alcohol-induced hepatocellular disorders, resulting in lowered hepatic injury markers and lipid accumulation. In addition, MLE reduced lipid peroxidation and meanwhile elevated hepatic superoxide dismutase (SOD). Immunohistochemical (IHC) staining revealed that MLE elevated the expression of caveolin-1 but reduced the expressions of epidermal growth factor receptor (EGFR), signal transducer and activator of transcription (STAT), inducible nitric oxide synthase (iNOS) and receptor interacting protein (RIP) 1/3. Major components of MLE, CGA and nCGA, not only exerted a similar biological activity as MLE but also inhibited alcohol-induced pro-apoptotic signals. Involvement of caveolin-1 in MLE, CGA and nCGA was demonstrated by using specific small inhibitory RNA. In conclusion, MLE and its chlorogenic derivatives CGA and nCGA upregulate caveolin-1 expression and diminish EGFR/STAT3/iNOS signalling, which may contribute to lowered hepatic lipid accumulation and peroxidation and inhibited pro-apoptotic cascades.
Assuntos
Caveolina 1/genética , Ácido Clorogênico/administração & dosagem , Fígado Gorduroso Alcoólico/tratamento farmacológico , Morus/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Animais , Caveolina 1/metabolismo , Ácido Clorogênico/química , Etanol/efeitos adversos , Fígado Gorduroso Alcoólico/etiologia , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Folhas de Planta/química , Regulação para Cima/efeitos dos fármacosRESUMO
Mulberry has favorable antioxidant ability. Menopause is a major cause of osteoporosis in women, and it is partially associated with oxidative stress. Here, mulberry water extract (MWE) was fed to ovariectomic (OVX) rats to explore the potential effect of MWE on osteoporosis. The results revealed that plasma alkaline phosphatase (ALP) significantly decreased in the OVX rats after MWE administration for 8 weeks. Histological examination showed that the MWE increased the density of trabecular bone in the OVX rats. It also revealed that the MWE increases the expression of Runx2 and decreases that of the receptor activator of nuclear factor κB and its ligand in the OVX rats. This implies that MWE might regulate osteoblast differentiation and osteoclast proliferation. The MWE improved the antioxidant status by lowering the expression of heme oxygenase-1. In addition, the MWE increased the expression of osteocalcin, ALP, and bone morphogenetic protein-2 in an osteoblast cell line, MG-63. The present results imply that MWE has potential to decelerate osteoporosis in an experimental OVX rat model.
Assuntos
Morus/química , Extratos Vegetais/farmacologia , Água/química , Animais , Linhagem Celular , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Ovariectomia , Extratos Vegetais/química , Ratos , Ratos Sprague-DawleyRESUMO
Myrciaria cauliflora is a functional food rich in anthocyanins, possessing antioxidative and anti-inflammatory properties. Our previous results demonstrated M. cauliflora extract (MCE) had beneficial effects in diabetic nephropathy (DN) and via the inhibition of Ras/PI3K/Akt and kidney fibrosis-related proteins. The purpose of this study was to assess the benefit of MCE in diabetes associated with kidney inflammation and glycemic regulation in streptozotocin-nicotinamide (STZ/NA)-induced diabetic mice. Compared with the untreated diabetic group, MCE significantly improved blood glucose and serum biochemical characteristic levels. Exposure to MCE increased antioxidative enzyme activity and diminished reactive oxygen synthesis. Mice receiving MCE supplementation had reduced intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), colony stimulating factor 1 (CSF-1), interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor α (TNF-α) levels compared to the untreated diabetic mice. Inflammatory and fibrotic related proteins such as collagen IV, fibronectin, Janus kinase (JAK), phosphorylated signal transducer and activator of transcription 3 (STAT3), protein kinase C beta (PKC-ß), and nuclear factor kappa B (NF-κB) were also inhibited by MCE treatment in STZ/NA mice. These results suggest that MCE may be used as a hypoglycemic agent and antioxidant in Type 2 diabetic mice.
Assuntos
Myrtaceae , Animais , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Inflamação , Camundongos , Niacinamida , Estresse Oxidativo , Fosfatidilinositol 3-Quinases , Extratos Vegetais , EstreptozocinaRESUMO
Curcumin (CUR) has been shown to possess a preventive effect against various cancers and interfere with multiple-cell signaling pathways. We evaluated the protective effects of CUR in regression of UVB-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers associated with carcinogenesis. Mice irradiated with UVB at 180 mJ/cm(2) twice per week elicited 100% tumor incidence at 20 weeks. Topical application of CUR prior to UVB irradiation caused delay in tumor appearance, multiplicity, and size. Topical application of CUR prior to and immediately after a single UVB irradiation (180 mJ/cm(2)) resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells together with an increase in p53 and p21/Cip1-positive cell population in epidermis. Simultaneously, CUR also significantly inhibited NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels. The results suggest that the protective effect of CUR against photocarcinogenesis is accompanied by downregulation of cell proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, while upregulation of p53 and p21/Cip1 to prevent DNA damage and facilitate DNA repair.
RESUMO
Angiostrongylus cantonensis (A. cantonensis) is the most common cause of parasitic eosinophilic meningitis worldwide. By using an animal model of BALB/c mice infected with A. cantonensis, previous studies indicated that the anthelmintic drug, albendazole, could kill A. cantonensis larvae and prevent further infection. However, the dead larvae will induce severe immune responses targeting at brain tissues. To alleviate the detrimental effects caused by the dead larvae, we administered curcumin, a traditional anti-inflammatory agent, as a complementary treatment in addition to albendazole therapy, to determine whether curcumin could be beneficial for treatment. The results showed that although curcumin treatment alone did not reduce worm number, combined treatment by albendazole and curcumin helped to reduce eosinophil count in the cerebrospinal fluid, better than using albendazole alone. This alleviating effect did not affect albendazole treatment alone, since histological analysis showed similar worm eradication with or without addition of curcumin. Nevertheless, curcumin treatment alone and combined albendazole-curcumin treatment did not inhibit MMP-9 expression in the brain tissue. In conclusion, curcumin, when used as a complementary treatment to albendazole, could help to alleviate eosinophilic meningitis through suppression of eosinophil count in the cerebrospinal fluid.
Assuntos
Albendazol/uso terapêutico , Angiostrongylus cantonensis/efeitos dos fármacos , Anti-Helmínticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Curcumina/uso terapêutico , Eosinofilia/tratamento farmacológico , Meningite/tratamento farmacológico , Infecções por Strongylida/tratamento farmacológico , Albendazol/administração & dosagem , Animais , Anti-Helmínticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/parasitologia , Curcumina/administração & dosagem , Modelos Animais de Doenças , Quimioterapia Combinada , Eosinofilia/líquido cefalorraquidiano , Eosinofilia/parasitologia , Eosinófilos/efeitos dos fármacos , Larva/efeitos dos fármacos , Contagem de Leucócitos , Metaloproteinase 9 da Matriz/biossíntese , Meningite/líquido cefalorraquidiano , Meningite/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Strongylida/líquido cefalorraquidiano , Infecções por Strongylida/parasitologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of Paeonia lactiflora Pall (RPA), a traditional Chinese medicines has been shown to treat cancers. AIM OF THE STUDY: The purpose of this study is to evaluate the anticancer effect of RPA in urinary bladder carcinoma in vitro and in vivo. MATERIALS AND METHODS: The cell viability was analyzed with DAPI. Flow cytometry and Western blot were used to study the apoptosis and cell cycle related mechanism. A rat model of bladder cancer was induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN). Tumors were analyzed with immunohistochemical analysis. RESULTS: Our data suggested that RPA inhibits growth of bladder cancer via induction of apoptosis and cell cycle arrest. Treatment of TSGH-8301 cells with RPA resulted in G2-M phase arrest that was associated with a marked decline in protein levels of cdc2, cyclin B1, cell division cycle 25B (Cdc25B) and Cdc25C. We also reported that RPA-mediated growth inhibition of TSGH-8301 cells was correlated with activation of checkpoint kinase 2 (Chk2). Herein, we further evaluated urinary bladder cancer using a model of bladder cancer induced by OH-BBN. Analysis of tumors from RPA-treated rats showed significant decrease in the expression of Bcl2, cyclin D1, and PCNA, and increase in the expression of p-Chk2 (Thr-68), Bax, and Cip1/p21. CONCLUSION: Our data provide the experimental evidence that RPA could modulate apoptosis in models of bladder cancer.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Paeonia , Fitoterapia , Proteínas Serina-Treonina Quinases/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Butilidroxibutilnitrosamina , Carcinoma/metabolismo , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quinase do Ponto de Checagem 2 , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Masculino , Fosforilação , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Ratos Sprague-Dawley , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/metabolismo , UrotélioRESUMO
Solanum nigrum L. (SN) is a widespread plant and is regarded as a common relish in the east and the south of Taiwan. Our previous study has found that SN water extract (SNWE) alleviated carbon tetrachloride-induced liver damage in rats. However, the effects of SNWE on chemical-induced hepatic injury and hepatocarcinogenesis remain unclear. Therefore, this study aims to investigate the effects of SNWE on hepatic injury and hepatocarcinogenesis by using 2-acetylaminofluorene (AAF) and AAF/NaNO(2) treatment. The serum biomarkers for hepatic injury, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and gamma-glutamyl transferase, and for hepatocarcinogenesis, alpha-fetoprotein, were determined. Our results showed that AAF treatment led to a significant decrease of body weight and an increase of liver/body weight and serum biomarkers for hepatic injury and hepatocarcinogenesis. Interestingly, the SNWE supplement significantly lowered the liver/body weight and the biomarkers but did not affect the body weight. Further investigation revealed that a SNWE supplement increased the expression of glutathione S-transferase-alpha and -mu, the level of transcription factor for protection from oxidative stress, Nrf2, and the level of downstream targets regulated by Nrf2, including glutathione peroxidase, superoxide dismutase-1, and catalase. Moreover, the effects of SNWE on AAF/NaNO(2)-induced hepatoma were also investigated, and the findings revealed that SNWE suppressed the progression of the hepatoma and resulted in a great increase of the survival rate. Our findings indicate that the SNWE supplement significantly alleviated the AAF-induced hepatic injury and early hepatocarcinogenesis as well as the AAF/NaNO(2)-induced lethal hepatoma, which may result from the overexpression of glutathione S-transferases, Nrf2, and antioxidant enzymes.
Assuntos
Antioxidantes/metabolismo , Glutationa Transferase/metabolismo , Neoplasias Hepáticas Experimentais/enzimologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Extratos Vegetais/uso terapêutico , Solanum nigrum/química , 2-Acetilaminofluoreno , Animais , Antioxidantes/análise , Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glutationa Transferase/análise , Fígado/enzimologia , Fígado/patologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Masculino , Fitoterapia , Ratos , Ratos Wistar , Nitrito de SódioRESUMO
Oxidative stress and inflammation are related to several chronic diseases including cancer and atherosclerosis. Hibiscus sabdariffa Linnaeus has been found to possess antioxidant effects. In this study, polyphenols extracted from Hibiscus sabdariffa L. (HPE) were used to detect anti-inflammatory effects on nitrite and prostaglandin E(2) (PGE(2)) in lipopolysaccharide (LPS) treated RAW264.7 cells. Sequentially, an animal model examination was performed to confirm the effects of HPE on LPS-induced hepatic inflammation. The results showed that HPE reduced 94.6% of xanthine oxidase activity in vitro, and decreased nitrite and PGE(2) secretions in LPS-induced cells. In LPS-treated rats, HPE significantly decreased the serum levels of alanine and aspartate aminotransferase. In the liver, lipid peroxidation and liver lesions decreased, and catalase activity and glutathione increased. The study also revealed that down-regulation of cyclooxygenase-2 (COX-2), p-c-Jun N-terminal kinase (p-JNK) and p-P38 might have been involved. In sum, this study found an anti-inflammatory potency of HPE both in vitro and in vivo.
Assuntos
Antioxidantes/metabolismo , Ciclo-Oxigenase 2/metabolismo , Flavonoides/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hibiscus/química , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Fenóis/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Flavonoides/isolamento & purificação , Flavonoides/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fenóis/isolamento & purificação , Fenóis/uso terapêutico , Extratos Vegetais/química , Polifenóis , Ratos , Xantina Oxidase/metabolismoRESUMO
Dried flower Hibiscus sabdariffa L. (HSE) extracts, a local soft drink material and medicinal herb, were studied for their protective effects against liver fibrosis induced using carbon tetrachloride (CCl(4)) in rats. Male Wistar rats were administered CCl(4) by intraperitoneal injection for 7weeks and received a normal diet or normal diet with various HSE doses (1-5%) for 9weeks. HSE significantly reduced the liver damage including steatosis and fibrosis in a dose dependent manner. Moreover, HSE significantly decreased the elevation in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also restored the decrease in glutathione content and inhibited the formation of lipid peroxidative products during CCl(4) treatment. In the primary culture, HSE also significantly inhibited the activation of the hepatic stellate cells. These results suggested that HSE may protect the liver against CCl(4)-induced fibrosis. This protective effect appears due to HSEs antioxidant properties.
Assuntos
Antioxidantes/farmacologia , Hibiscus/química , Cirrose Hepática Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Administração Oral , Alanina Transaminase/metabolismo , Animais , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/metabolismo , Tetracloreto de Carbono/toxicidade , Células Cultivadas , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática Experimental/tratamento farmacológico , Cirrose Hepática Experimental/patologia , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Silimarina/administração & dosagem , Silimarina/farmacologia , Silimarina/uso terapêuticoRESUMO
Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of de-toxication, anti-oxidation and anti-mutation. In this study we first examined the effect of PBL extract on the activity of Glutathione S-transferase (GST) isoforms, and found that it inhibited total GST and the alpha class of GST (GSTA), but not the pi class of GST (GSTP), and the mu class of GST (GSTM), activity in Hep G2 cells. RT-PCR results verified a reduction in the expression of GSTA1. Next, we examined whether PBL extract could increase the sensitivity of Hep G2 cells to anti-cancer drugs. The data showed that the cytotoxicity of cisplatin was significantly enhanced by the presence of PBL extract, accompanied by a reduction in the expression of multidrug resistance protein 2 (MRP2). These effects of PBL extract were compared to its major constitute, eugenol. Although eugenol decreased MRP2 level more effectively than PBL extract, it exhibited less sensitizing effect. In conclusion, we demonstrated that PBL extract was able to increase the sensitivity of Hep G2 cells to cisplatin via at least two mechanisms, reducing the expression of MRP2 and inhibiting the activity of total GST and the expression of GSTA. The data of this study support an application of PBL as an additive to reduce drug resistance.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Inibidores Enzimáticos/farmacologia , Hepatócitos/efeitos dos fármacos , Piper betle , Extratos Vegetais/farmacologia , Fracionamento Celular , Linhagem Celular Tumoral/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas , Eugenol/farmacologia , Fase G2 , Glutationa Transferase/metabolismo , Hepatócitos/enzimologia , Hepatócitos/patologia , Humanos , Isoenzimas , Neoplasias Hepáticas/tratamento farmacológico , Proteínas de Membrana Transportadoras/metabolismo , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Folhas de Planta/químicaRESUMO
Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.
Assuntos
Antocianinas/química , Antocianinas/farmacologia , Apoptose/efeitos dos fármacos , Células HL-60 , Hibiscus/química , Extratos Vegetais/farmacologia , Androstadienos/farmacologia , Antocianinas/isolamento & purificação , Antracenos/farmacologia , Apoptose/fisiologia , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3 , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Caspases/genética , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/efeitos dos fármacos , Citocromos c/metabolismo , DNA Mitocondrial/efeitos dos fármacos , DNA Mitocondrial/metabolismo , Relação Dose-Resposta a Droga , Proteína Ligante Fas , Flavonoides/farmacologia , Flores/química , Humanos , Imidazóis/farmacologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Piridinas/farmacologia , RNA Mensageiro , Fatores de Tempo , Wortmanina , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/farmacologiaRESUMO
Baicalin (BA) is a flavonoid compound purified from Scutellaria baicalensis Georgi that is used as a traditional Chinese herbal medicine. Baicalin was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in rat liver system. Baicalin expressed an antioxidant property by its capacity for quenching the free radicals of 1,1-diphenyl-2-picrylhydrazyl (DPPH). Further investigations using the t-BHP-induced cytotoxicity in rat primary hepatocytes demonstrated that baicalin, at the concentrations of 2-220 microM, significantly decreased the leakages of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and the formation of malondialdehyde (MDA) induced by 30 min treatment of t-BHP(1.5 mM). Baicalin also attenuated the t-BHP-induced depletion of glutathione (GSH) and high level of DNA repaired synthesis. An in vivo study in rats showed that pretreatment with baicalin (i.p.) at concentrations of 0.5 and 5 mg/kg for 5 days before a single i.p. dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of hepatic enzyme markers (ALT and AST) and reduced oxidative stress in the liver. Histopathological evaluation of the rat livers revealed that baicalin reduced the incidence of liver lesions induced by t-BHP including hepatocyte swelling, leukocyte infiltration, and necrosis. Based on the results described above, we speculate that baicalin may play a chemopreventive role via reducing oxidative stress in living systems.
Assuntos
Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Flavonoides/uso terapêutico , Hepatite Animal/prevenção & controle , terc-Butil Hidroperóxido/toxicidade , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Flavonoides/administração & dosagem , Flavonoides/farmacologia , Glutationa/metabolismo , Hepatite Animal/etiologia , Hepatite Animal/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Phenylpropanolamine (PPA) is an appetite suppressant. The mechanism for the anorectic effect of PPA has been attributed to its action on the site of hypothalamic paraventriculum. Neuropeptide Y (NPY) is an appetite stimulant that is widely distributed in the site of hypothalamus. It is not clear whether hypothalamic NPY is involved in the anorectic action of PPA. This study was aimed to investigate the mechanism underlying the involvement of NPY gene in the anorectic action of PPA. Results revealed that PPA treatment in rats could decrease both NPY content and mRNA level in the hypothalamus. In addition, the expression of NPY immunoreactivity following PPA treatment was decreased in areas of hypothalamic arcuate nucleus, paraventricular nucleus and periventricular area using immunohistochemical staining, suggesting an involvement of NPYergic pathway in the action of PPA anorexia. Our results provided immunohistochemical and genomic evidence to suggest that PPA might reduce feeding by altering NPY gene expression.
Assuntos
Depressores do Apetite/farmacologia , Apetite/efeitos dos fármacos , Neuropeptídeo Y/fisiologia , Fenilpropanolamina/farmacologia , Animais , Ingestão de Alimentos/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Hipotálamo/química , Hipotálamo/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Neurônios/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Penta-acetyl geniposide, (Ac)5-GP, the acetylated compound of geniposide, is able to inhibit the growth of rat C6 glioma cells in culture and in the bearing rats. Our recent data indicated that the induction of cell apoptosis and cell cycle arrest at G0/gap phase 1 (G1) by (Ac)5-GP might be associated with the induction of p53 and c-Myc, and mediated via the apoptosis-related bcl-2 family proteins. In this report, we further investigated the mechanism involved in the cell cycle arrest induced by (Ac)5-GP in C6 glioma cells. The inhibitory effect of (Ac)5-GP on the cell cycle progression of C6 glioma cells which arrested cells at the G0/G1 phase was associated with a marked decrease in the protein expression of cyclin D1, and an induction in the content of cyclin-dependent kinase (cdk) inhibitor p21 protein. This effect was correlated with the elevation in p53 levels. Further immunoprecipitation studies found that, in response to the treatment, the formation of cyclin D1/cdk 4 complex declined, preventing the phosphorylation of retinoblastoma (Rb) and the subsequent dissociation of Rb/E2F complex. These results illustrated that the apoptotic effect of (Ac)5-GP, arresting cells at the G0/G1 phase, was exerted by inducing the expression of p21 that, in turn, repressed the activity of cyclin D1/cdk 4 and the phosphorylation of Rb.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Glioma/tratamento farmacológico , Glucosídeos/farmacologia , Iridoides/farmacologia , Piranos/farmacologia , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/metabolismo , Glioma/metabolismo , Glioma/patologia , Glucosídeos Iridoides , Fosforilação , Extratos Vegetais/química , Ratos , Proteína do Retinoblastoma/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Betel quid chewing is a general behavior in Taiwan, India, southeastern Asian and South Africa. In this study, microculture tetrazolium test (MTT) showed that the extract of lime-piper betel quid (LPB) (1.0-20 mg/ml) was toxic to JB6 cells. Cells exposed of LPB (0.1, 0.5, 1.0 mg/ml) for 7 days resulted in changes in cytomorphology with characteristics of carcinogenesis. With a long-term treatment (approximately 30 days) of low doses of LPB (1, 5, 10 microg/ml), the production of H2O2 and the activity of myeloperoxidase (MPO) and ornithine decarboxylase (ODC) were increased in JB6 cells. Cell cycle analysis showed a decrease in the G1 phase and an accumulation in the S phase 48 h after LPB treatment. When treating with 0.5 mg/ml LPB for 15 days as a promoter, type III foci were formed in the JB6 culture. These results demonstrated the tumor promotional effect of LPB in JB6 cells.
Assuntos
Areca/toxicidade , Compostos de Cálcio/toxicidade , Carcinógenos/toxicidade , Citrus aurantiifolia/toxicidade , Óxidos/toxicidade , Piper/toxicidade , Extratos Vegetais/toxicidade , Animais , Testes de Carcinogenicidade , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Fase G1/efeitos dos fármacos , Peróxido de Hidrogênio/química , Camundongos , Ornitina Descarboxilase/metabolismo , Peroxidase/metabolismo , Fase S/efeitos dos fármacos , Sais de Tetrazólio , TiazóisRESUMO
Hibiscus sabdariffa L., a local soft drink material and medicinal herb, is usually used effectively in native medicines against hypertension, pyrexia, and liver disorders. Here, we report an extract, HSE (H. sabdariffa extract), which is designed to exhibit hypolipidemia and antiatherosclerotic effects in rabbits with experimental atherosclerosis. New Zealand White rabbits were fed with a normal diet, high cholesterol (1.3%), lard oil (3%) diet (HCD) with or without 0.5 or 1% HSE for 10 weeks. The levels of triglyceride, cholesterol, and low-density lipoprotein cholesterol (LDL-C) were lower in the serum of rabbits fed HCD plus HSE than in the serum of rabbits fed HCD. Feeding HSE (0.5 and 1% in the diet) to rabbits significantly reduced severe atherosclerosis in the aorta. Histopathological examination showed that HSE reduced foam cell formation and inhibited smooth muscle cell migration and calcification in the blood vessel of rabbits. These results suggest that HSE inhibits serum lipids and shows an antiatherosclerotic activity.
Assuntos
Arteriosclerose/prevenção & controle , Colesterol na Dieta/administração & dosagem , Hibiscus/química , Extratos Vegetais/uso terapêutico , Animais , Aorta Torácica/patologia , Arteriosclerose/induzido quimicamente , Arteriosclerose/patologia , Gorduras na Dieta , Lipídeos/sangue , CoelhosRESUMO
Penta-acetyl geniposide, (Ac)(5)-GP, was produced by acetylation of a glycoside, isolated from an extract of Gardenia fructus. Previously, we have reported that C6 glioma cells could be inhibited in culturing as well as in bearing rats by treating with (Ac)(5)-GP. In this study, the effect and action of (Ac)(5)-GP on inducing cell death was examined in rat C6 glioma cells. Treatment of C6 glioma cells with (Ac)(5)-GP caused cell death, chromatin condensation, and internucleosomal DNA ladder. Also, cell cycle arrest at G(0)/G(1) phase revealed that (Ac)(5)-GP-induced cell death appears to be mediated by apoptosis. In addition, the results also showed that p53 and c-Myc increased due to treatment of (Ac)(5)-GP in a dose-response and time-dependent manner. Concomitant with the expression of p53 and c-Myc, decreased level of Bcl-2 and increased level of Bax protein were observed. These results suggest that cell death caused by (Ac)(5)-GP through apoptosis and cell cycle arrest at G(0)/G(1) may be associated with the induction of p53, c-Myc and may be mediated with apoptosis-related Bcl-2 family proteins.
Assuntos
Apoptose/efeitos dos fármacos , Glioma/patologia , Piranos/farmacologia , Animais , Western Blotting , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Gardenia/química , Estrutura Molecular , Extratos Vegetais/química , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Piranos/química , Ratos , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2RESUMO
Components of betel quid (BQ) have been investigated for genotoxicity, mutagenicity, and animal toxicity. However, little information exists regarding their carcinogenic characteristics. Considerable attention has already been focused on tumor promoters that occur environmentally for human uptake. In this study, the promoting effects of BQ and lime-piper additives (LPA) in BQ on epidermal hyperplasia in CD-1 mouse skin are investigated. In the present study, we found that BQ and LPA at concentrations of 25,50,75 mg/ml caused significant induction of hyperplasia, but only LPA caused an increase of epidermal ornithine decarboxylase (ODC). Treatment of mouse skin with LPA caused remarkable increases in the production of H(2)O(2) by 2.41-, 3.90-, and 3.76-fold (for the above-indicated concentrations respectively); as well as marked increases of myeloperoxidase (MPO) by 1.43-, 2.70-, and 2.29-fold. Application of LPA or BQ (50,100,150 mg/ml) also caused induction of protein kinase C-alpha (PKC-alpha) and NF-kappaB. LPA exhibited more significant effect than BQ. Thus, LPA might make a major contribution to the BQ-induced expression of PKC and NF-kappaB. These results indicated that BQ has the potential of being promoting agents, and that LPA should play a major role in increasing the effects of BQ-caused skin hyperplasia and inflammation. The promoting effects of BQ and LPA on mouse skin were associated with the induction of the expressions of PKC and NF-kappaB.