RESUMO
Endometriosis is a chronic inflammatory disorder caused by abnormal adhesion of endometrial tissue to the outside of the uterus. The combination of surgery, non-steroidal anti-inflammatory drugs, and hormone treatment is well established therapy for endometriosis, however, case reports have showed that high rates of relapse and unpleasant side effect. For these reasons, recently, the studies have been focused on the Warburg-like metabolic shift of endometriosis. Prunella vulgaris is one of traditionally used herbal medicine for inflammatory disease and the anti-estrogenic effects of P. vulgaris is well-established. Therefore, in this work, we evaluated water-extracted P. vulgaris (PV) as a potential treatment for endometriosis. To this, we artificially induced endometriosis in ovarectomized mice by intra-peritoneal inoculation of uterus extracts. PV was orally administered, and PV significantly alleviated endometriosis, particularly the growth of ectopic endometrial lesions in artificially endometriosis-induced mice. For the mechanism study of anti-endometriosis by PV, we designed an in vitro study using human normal endometrial stromal cells (T-HESCs) and human endometrial cell (12Z) obtained from patients with endometriosis. PV strongly induced the apoptosis of 12Z cells rather than T-HESCs by control the activity or expression of aerobic glycolysis enzymes, such as lactate dehydrogenase A (LDHA), pyruvate dehydrogenase A, and pyruvate dehydrogenase kinase 1/3. In addition, lactate production was enhanced, and oxygen consumption rate was suppressed in 12Z cells upon PV treatment. These changes in aerobic glycolysis eventually caused mitochondrial damage following decreased mitochondrial membrane potential and excessive mitochondrial ROS production. Especially, ulsolic acid (UA), one of the compounds in PV considerably led 12Z cell apoptosis with inhibition of LDHA activity. Therefore, UA could be a major active substance of PV in terms of endometriosis inhibitors. In conclusion, this study provides the evidence that the beneficial efficacy of PV for the prevention/treatment of endometriosis.
RESUMO
Cornus officinalis, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells. We standardized C. officinalis 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment.
Assuntos
Cornus/química , Fator de Transcrição E2F1/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Extratos Vegetais/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Próstata/metabolismo , Androgênios/metabolismo , Animais , Biomarcadores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Humanos , Masculino , Extratos Vegetais/química , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/etiologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Testosterona/metabolismo , Testosterona/farmacologiaRESUMO
A hypernomic reaction or an abnormal inflammatory process could cause a series of diseases, such as cardiovascular disease, neurodegeneration, and cancer. Additionally, oxidative stress has been identified to induce severe tissue injury and inflammation. Carpesium cernuum L. (C. cernuum) is a Chinese folk medicine used for its anti-inflammatory, analgesic, and detoxifying properties. However, the underlying molecular mechanism of C. cernuum in inflammatory and oxidative stress conditions remains largely unknown. The aim of this study was to examine the effects of a methanolic extract of C. cernuum (CLME) on lipopolysaccharide- (LPS-) induced RAW 264.7 mouse macrophages and a sepsis mouse model. The data presented in this study indicated that CLME inhibited LPS-induced production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 cells. CLME treatment also reduced reactive oxygen species (ROS) generation and enhanced the expression of heme oxygenase-1 (HO-1) protein in a dose-dependent manner in the LPS-stimulated RAW 264.7 cells. Moreover, CLME treatment abolished the nuclear translocation of nuclear factor-κB (NF-κB), enhanced the activation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), and reduced the expression of extracellular signal-related kinase (ERK) and ERK kinase (MEK) phosphorylation in LPS-stimulated RAW 264.7 cells. These outcomes implied that CLME could be a potential antioxidant and anti-inflammatory agent.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Asteraceae/metabolismo , Lipopolissacarídeos/metabolismo , Extratos Vegetais/farmacologia , Sepse/metabolismo , Animais , Dinoprostona/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Heme Oxigenase-1/metabolismo , Inflamação , Macrófagos/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Metanol , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Células RAW 264.7 , Espécies Reativas de Oxigênio , Sais de Tetrazólio/química , Tiazóis/químicaRESUMO
Obesity is one of major health challenges in the industrial world. Although rice hull has been reported to show various bioactivities, no studies have evaluated its anti-obesity effect. We hope to demonstrate the anti-obesity effect of rice hull extract (RHE) and the underlying mechanism in high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Serum lipid profiles were determined by enzymatic methods. Histological analysis of liver and epididymis fat tissues was carried out with hematoxylin and eosin stain. The mRNA expression of adipogenic markers was analyzed with qRT-PCR and western blotting. Oral administration of RHE reduced body weight gain and fat accumulation in HFD-fed mice. RHE also reduced lipid accumulation by inhibiting the mRNA expression of adipogenic-related genes in HFD-fed obese mice and differentiated preadipocytes. The downregulation of adipogenesis by RHE was mediated through the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, RHE induced the phosphorylation of c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinases (ERK) in liver and epididymis adipose tissues of HFD-fed obese mice. Taken together, these findings indicate that RHE could inhibit the differentiation of adipose cell and prevent HFD-induced obesity, suggesting its potential in the prevention of obesity and metabolic syndrome and related-disorders.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Obesidade/prevenção & controle , Oryza , Extratos Vegetais/farmacologia , Sementes , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Adipogenia/genética , Animais , Fármacos Antiobesidade/isolamento & purificação , Modelos Animais de Doenças , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Obesidade/sangue , Obesidade/patologia , Obesidade/fisiopatologia , Oryza/química , Fosforilação , Extratos Vegetais/isolamento & purificação , Sementes/química , Transdução de Sinais , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Recently, it has been noted that natural herbal medications may be effective in treating obesity. Tongbi-san (TBS) is a traditional medicine usually used for dysuria (i.e., painful urination), containing three herbs, Cyperus rotundus L., Citrus unshiu Markovich, and Poria cocos. In this study, we aimed to examine whether TBS can inhibit high-fat diet (HFD)-induced adipogenesis in the liver and epididymal adipose tissue of obese mice. METHODS: Male C57BL/6 N mice were fed a normal diet, an HFD, an HFD plus orlistat 10 or 20 mg/kg, or an HFD plus TBS 50 or 100 mg/kg for 11 weeks. Body weight was checked weekly and histological tissue examinations were investigated. An expression of genes involved in adipogenesis was also assessed. RESULTS: Oral administration of TBS significantly reduced body weight and decreased epididymal and visceral white adipose tissue (WAT) weight. In addition, we found that TBS enhanced the expression of the adenosine monophosphate-activated protein kinase (AMPK) and inhibited the expression of transcription factors, such as CCAAT/enhancer-binding proteins (C/EBPs), sterol regulatory element-binding protein 1 (SREBP1), and peroxisome proliferator-activated receptor γ (PPARγ) in the liver and epididymal WAT as measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). CONCLUSION: These findings demonstrate that the anti-obesity effects of TBS may be linked to the activation of AMPK.
Assuntos
Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos ObesosRESUMO
Although Aster glehni is a common dietary herb that has various bioactivities, including anti-diabetic, anti-adipogenic, and anti-inflammatory effects, A. glehni has not been studied in colon cancer. Therefore, we hypothesized the chemopreventive effects of an ethanol extract of A. glehni (AG) on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer (CAC) in mice. In this study, we found that treatment with AG significantly attenuated the AOM/DSS-induced enlargement of the spleen and shortening of the colon. In addition, colonic tumor formation, colonic damage, and increased muscle thickness were significantly reduced in AOM/DSS-induced mice fed AG. Treatment with AG also reduced intestinal interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α production and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein expression in mice with AOM/DSS-induced CAC. Furthermore, AG reduced nuclear factor (NF)-κB activation via phosphorylation and degradation of inhibitor of kappa Bα (IκBα), leading to inhibition of NF-κB p65 nuclear translocation. It also downregulated the expression of NF-κB-related proteins, including the B-cell lymphoma 2 (Bcl-2) family and inhibitors of apoptosis proteins (IAPs), in mice with AOM/DSS-induced CAC. Taken together, these findings suggest that the treatment with AG inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly mediated by suppression of the NF-κB signaling pathway, indicating that AG could be a promising protective agent against CAC.
Assuntos
Anticarcinógenos/uso terapêutico , Aster , Colite/complicações , Colo/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Inflamação/complicações , Fitoterapia , Animais , Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Azoximetano , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Sulfato de Dextrana , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Interleucinas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Baço/efeitos dos fármacos , Baço/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Although Aster glehni has been reported to prevent diabetes mellitus, hypercholesterolemia, insomnia, and cardiovascular disease, the anti-inflammatory effect of Aster glehni in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of an ethanol extract of Aster glehni (AG) in mice with dextran sulfate sodium (DSS)-induced colitis. AG significantly attenuated DSS-induced DAI scores, which implied that it suppressed diarrhea, gross bleeding, and the infiltration of immune cells. AG administration also effectively prevented shortening of the colon length and enlargement of the spleen size. Histological examinations indicated that AG suppressed colonic damage and the thickness of the muscle layer induced by DSS. In addition, AG inhibited the production of pro-inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, and the protein expression of COX-2 and iNOS in mice with DSS-induced colitis. Administration with AG suppressed the activation of nuclear factor-κB (NF-κB) including the nuclear translocation of the p65 NF-κB subunit, phosphorylation and degradation of IκB-α. Taken together, these findings suggest that the anti-inflammatory effects of AG are mainly related to the inhibition of the expressions of inflammatory mediators via NF-κB inactivation, and support its possible therapeutic application in colitis.
Assuntos
Anti-Inflamatórios/administração & dosagem , Aster/química , Colite/tratamento farmacológico , NF-kappa B/imunologia , Extratos Vegetais/administração & dosagem , Animais , Colite/induzido quimicamente , Colite/genética , Colite/imunologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , NF-kappa B/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Benign prostatic hyperplasia (BPH) is a pathological condition that affects the majority of men above the age of 50 years. Pharmacological agents are typically used to treat BPH; however, there are currently no pharmacological agents that are able to completely cure BPH without causing adverse side effects. As a result of these side effects, there is a great interest in developing effective herbal medicines that are able to inhibit the progression of BPH and are safe for long-term use. Ga-Gam-Nai-Go-Hyan (GGN) is a traditional Korean herbal medicine that has been widely used to treat BPH; however, no biological studies have been performed to elucidate the efficacy of GGN. The aim of the present study was to evaluate the efficacy of GGN as a treatment for BPH. GGN administration was demonstrated to significantly decrease prostate weight (P<0.001), the relative prostate weight ratio (P<0.001) and the ratio of prostate weight to body weight (P<0.001). In addition, GGN treatment was revealed to suppress testosterone and dihydrotestosterone serum levels (P<0.001) and the growth of prostatic tissue. GGN also decreased the levels of the two inflammatory proteins (P<0.05), inducible nitric oxide synthase and cyclooxygenase-2, decreased the levels of the two apoptotic suppressors (P<0.05) B-cell lymphoma (Bcl)-2 and Bcl-xL and increased the levels of the pro-apoptotic factors (P<0.05) Bcl-2-associated X protein, caspase-3, caspase-8, Fas, Fas ligand and Fas-associated protein with death domain. The results of the present study suggested that GGN may have suppressive effects on the development of BPH and therefore have the potential to be used for treating BPH.
RESUMO
Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disorder of the colon. Although UC is generally treated with anti-inflammatory drugs or immunosuppressants, most of these treatments often prove to be inadequate. Rosmarinic acid (RA) is a phenolic ester included in various medicinal herbs such as Salvia miltiorrhiz and Perilla frutescens. Although RA has many biological and pharmacological activities, the anti-inflammatory effect of RA in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and underlying molecular mechanism of RA in mice with dextran sulphate sodium (DSS)-induced colitis. In the DSS-induced colitis model, RA significantly reduced the severity of colitis, as assessed by disease activity index (DAI) scores, colonic damage, and colon length. In addition, RA resulted in the reduction of the inflammatory-related cytokines, such as IL-6, IL-1ß, and IL-22, and protein levels of COX-2 and iNOS in mice with DSS-induced colitis. Furthermore, RA effectively and pleiotropically inhibited nuclear factor-kappa B and signal transducer and activator of transcription 3 activation, and subsequently reduced the activity of pro-survival genes that depend on these transcription factors. These results demonstrate that RA has an ameliorative effect on colonic inflammation and thus a potential therapeutic role in colitis.
Assuntos
Cinamatos/uso terapêutico , Colo/patologia , Depsídeos/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Cinamatos/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/enzimologia , Colite/patologia , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Depsídeos/farmacologia , Sulfato de Dextrana , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos ICR , Óxido Nítrico Sintase Tipo II/metabolismo , Peroxidase/metabolismo , Baço/patologia , Ácido RosmarínicoRESUMO
BACKGROUND: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects. METHODS: We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR-/-) mice fed a high-cholesterol diet for 13 weeks. Mice were randomized in to 6 groups: ND (normal diet) group, HCD (high-cholesterol diet) group, and treatment groups fed HCD and treated with simvastatin (10 mg/kg, p.o.) or HVC1 (10, 50, or 250 mg/kg, p.o.). RESULTS: HVC1 regulated the levels of total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol in mouse serum. In addition, it regulated the transcription level of the peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding proteins (SREBP)-2, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, lipoprotein lipase (LPL), apolipoprotein B (apo B), liver X receptor (LXR), and inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Furthermore, HVC1 activated 5' adenosine monophosphate-activated protein kinase (AMPK). CONCLUSION: Our results suggest that HVC1 might be effective in preventing high-cholesterol diet-induced hyperlipidemia by regulating the genes involved in cholesterol and lipid metabolism, and inflammatory responses.
Assuntos
Anti-Inflamatórios/farmacologia , Colesterol/sangue , Medicamentos de Ervas Chinesas/farmacologia , Hiperlipidemias , Hipolipemiantes/farmacologia , Inflamação , Fitoterapia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Apolipoproteínas B/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Citocinas/metabolismo , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas/uso terapêutico , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/etiologia , Hipolipemiantes/uso terapêutico , Inflamação/sangue , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Knockout , Receptores de LDL/sangue , Receptores de LDL/deficiência , Receptores de LDL/genética , Fatores de Transcrição/metabolismo , Triglicerídeos/sangueRESUMO
OBJECTIVE: To evaluate the efficacy of Bawu Decoction (, BWD, Palmul-tang in Korean) against benign prostatic hyperplasia (BPH). METHODS: Twenty-four male Wistar rats were divided into 4 groups, with 6 rats in each group. The 4 study groups included sham-operated group (CON), BPH model group, fifinasteride-treated group, and BWD-treated group. All the groups except CON group received a subcutaneous injection of 10 mg/kg of testosterone, while CON group received saline. Finasteride at a dose of 5 mg/kg was administered to the finasteride-treated group for a period of 4 weeks. BWD group received BWD at a dose of 200 mg/kg for 4 weeks. The prostatic weight, prostate weight to body weight ratio, relative prostate weight ratio, serum testosterone and dihydrotestosterone (DHT) level, and histological analysis of prostatic tissue were analyzed. RESULTS: Compared to BPH model group, BWD administration was associated with reductions in prostatic weight, prostate and relative prostate weight ratio weight to body weight ratio (P<0.05). The concentration of serum testosterone and DHT were higher in BPH group compared with CON group (P<0.05). Administration of finasteride and BWD suppressed the elevation of serum testosterone and DHT levels signifificantly (both P<0.05). In addition, BWD suppressed the growth of prostatic tissue (P<0.05). CONCLUSION: BWD has suppressant effects on development of BPH through inhibition of serum testosterone and DHT.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Di-Hidrotestosterona/sangue , Epitélio/efeitos dos fármacos , Epitélio/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/patologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Ratos Wistar , Testosterona/sangueRESUMO
Bee venom (BV) has been widely used in the treatment of certain immune-related diseases. It has been used for pain relief and in the treatment of chronic inflammatory diseases. Despite its extensive use, there is little documented evidence to demonstrate its medicinal utility against obesity. In this study, we demonstrated the inhibitory effects of BV on adipocyte differentiation in 3T3-L1 cells and on a high fat diet (HFD)-induced obesity mouse model through the inhibition of adipogenesis. BV inhibited lipid accumulation, visualized by Oil Red O staining, without cytotoxicity in the 3T3-L1 cells. Male C57BL/6 mice were fed either a HFD or a control diet for 8 weeks, and BV (0.1 mg/kg or 1 mg/kg) or saline was injected during the last 4 weeks. BV-treated mice showed a reduced body weight gain. BV was shown to inhibit adipogenesis by downregulating the expression of the transcription factors CCAAT/enhancer-binding proteins (C/EBPs) and the peroxisome proliferator-activated receptor gamma (PPARγ), using RT-qPCR and Western blotting. BV induced the phosphorylation of AMP-activated kinase (AMPK) and acetyl-CoA carboxylase (ACC) in the cell line and in obese mice. These findings demonstrate that BV mediates anti-obesity/differentiation effects by suppressing obesity-related transcription factors.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Venenos de Abelha/uso terapêutico , Obesidade/tratamento farmacológico , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Animais , Fármacos Antiobesidade/farmacologia , Venenos de Abelha/farmacologia , Diferenciação Celular/efeitos dos fármacos , Dieta Hiperlipídica , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Alternative medicine is a widely accepted therapeutic approach for the management of various diseases. The Korean medicine, musulju (MSJ), has been traditionally used to improve vital energy in men with reduced physical strength and a weakened urinary system. The present study determined the mechanisms underlying the protective effect of MSJ against benign prostatic hyperplasia (BPH), a common disorder in elderly men that involves inflammationmediated imbalance between cell proliferation and death. MSJ treatment was demonstrated to decrease prostate weight, cell proliferation, and the protein expression of proliferating cell nuclear antigen in a rat model of BPH. In addition, MSJ markedly reduced serum testosterone levels, 5αreductase2 mRNA expression and BPHassociated upregulation of inflammatory proteins, inducible nitric oxide synthase and cyclooxygenase 2. Furthermore, MSJ induced apoptosis by regulating Bcell lymphoma (Bcl)2 protein expression and the Bcl2:Bax ratio, leading to caspase 3 activation. Taken together, MSJ demonstrated antiproliferative effects in BPH model rats by regulating the expression levels of proteins involved in inflammation and apoptosis. The effects of MSJ may be attributed to its alternative therapeutic properties.
Assuntos
Apoptose/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/patologia , Medicina Tradicional Coreana , Extratos Vegetais/farmacologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Inflamação/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Ratos , Testosterona/sangue , Testosterona/metabolismoRESUMO
HVC1, a novel formation containing four herbs, was developed and its hypolipidemic effects in rats with high cholesterol diet (HCD)induced hyperlipidemia were investigated. The rats were given a HCD for 8 weeks. The HVC1treated groups were orally administered HVC1 at doses of 10, 50 or 250 mg/kg, respectively, and the simvastatin group was treated at a dose of 10 mg/kg. The normal diet and HCD control groups were administered with physiological saline. Oral administration of HVC1 (10, 50 or 250 mg/kg) significantly reduced the body weight of rats with hyperlipidemia and regulated the total cholesterol, lowdensity lipoprotein cholesterol and highdensity lipoprotein cholesterol levels in the serum. In addition, tissue analysis revealed that lipid accumulation in the liver and aorta was reduced by HVC1 administration. Furthermore, HVC1 significantly reduced the mRNA expression of peroxisome proliferatoractivated receptorγ, 3hydroxy3methylglutarylCoA reductase and lowdensity lipoprotein receptor, as well as the protein level of 5' adenosine monophosphateactivated protein kinase in the liver. The results clearly demonstrate that HVC1 has a potent hypolipidemic effect, and suggest that HVC1 should be evaluated as a potential treatment for hyperlipidemia.
Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Medicina Tradicional Coreana , Extratos Vegetais/uso terapêutico , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Colesterol/sangue , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hipolipemiantes/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , PPAR gama/genética , Extratos Vegetais/química , Plantas Medicinais/química , Polygonaceae/química , RNA Mensageiro/genética , Ranunculaceae/química , Ratos , Ratos Sprague-Dawley , Receptores de LDL/genética , Rosaceae/químicaRESUMO
Even though rice hull has various physiological functions with high antioxidant potential, the molecular mechanism(s) underlying the effects of rice hull on benign prostatic hyperplasia (BPH) have not been evaluated. The aim of this study was to determine the protective effect of rice hull water extract (RHE) against BPH, which is a common disorder in elderly men and involves inflammation that induces an imbalance between cell proliferation and cell death. In this study, RHE-treated mice exhibited lower prostate weights and ratios of prostate weight to body weight compared to those for the BPH-induced group. In addition, RHE-treated mice had lower serum levels of dihydrotestosterone, mRNA expression of 5α-reductase2, and protein expressions of proliferating cell nuclear antigen (PCNA). Furthermore, RHE treatment significantly decreased cell proliferation by regulating the expression levels of inflammatory-related proteins (iNOS and COX-2) and apoptosis-associated proteins (Fas, FADD, procaspase-8, -3, and Bcl-2 family proteins). These results suggest that RHE could protect against the development of BPH through its anti-inflammatory and apoptotic properties and has good potential as a treatment for BPH.
Assuntos
Proliferação de Células/efeitos dos fármacos , Inflamação/sangue , Oryza , Fitoterapia , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/patologia , Inibidores de 5-alfa Redutase/farmacologia , Inibidores de 5-alfa Redutase/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Di-Hidrotestosterona/sangue , Hiperplasia , Inflamação/tratamento farmacológico , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/uso terapêutico , Antígeno Nuclear de Célula em Proliferação/sangue , Próstata/patologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/tratamento farmacológico , Ratos Sprague-Dawley , SementesRESUMO
Benign prostatic hyperplasia (BPH) is a urologic disease that affects most of men over the age 50. But until now there is no such perfect cure without side effects. Because of diverse adverse effects, it is desirable to develop effective and long term-safety-herbal medicines to inhibit the progress of BPH. In spite of garlic's large use and a wide spectrum of studies, including anti-hyperlipidemic, cardio-protective, and anti-inflammatory activities, there was none to prove efficacy for BPH. In this study, we evaluated the efficacy of garlic to prove its suppressing effects on BPH. Garlic administration decreased relative prostate weight ratio, suppressed mRNA expression level of AR, DHT serum levels, and the growth of prostatic tissue in BPH-induced rats. Moreover, garlic administration decreased the levels of inflammatory proteins, iNOS, and COX-2 in prostatic tissue. Further investigation showed that garlic induced accumulation of death-inducing signal complex and activation of AMPK and decreased the levels of anti-apoptotic proteins, such as Bcl-2, Bcl-xL, and survivin. These results suggest that garlic may have suppressing effects on BPH and it has great potential to be developed as treatment for BPH. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Proliferação de Células/efeitos dos fármacos , Alho , Fitoterapia , Hiperplasia Prostática/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Di-Hidrotestosterona/sangue , Masculino , Próstata/efeitos dos fármacos , Próstata/patologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Ratos , Ratos WistarRESUMO
Benign prostatic hyperplasia (BPH), which is a common disorder in aging men, involves inflammation that is associated with an imbalance between cell proliferation and cell death. Because current BPH drug treatments have undesirable side effects, the development of well-tolerated and effective alternative medicines to treat BPH is of interest. Bee venom (BV) has been used in traditional medicine to treat conditions, such as arthritis and rheumatism, and pain. Although inflammation has been associated with BPH and BV has strong anti-inflammatory effects, the effects of BV on BPH are not fully understood. Therefore, in this study, we evaluated the efficacy of BV against testosterone-induced BPH in rats. BV decreased prostate weight compared to the untreated group. In addition, BV suppressed serum dihydrotestosterone concentration levels and the levels of proliferating cell nuclear antigen in the histological analysis. Furthermore, BV significantly decreased the levels of the apoptotic suppressors, Bcl-2 and Bcl-xL, and increased the levels of the proapoptotic factors, Bax and caspase-3 activation. These results suggested that BV suppressed the development of BPH and has good potential as a treatment for BPH.
Assuntos
Apoptose/efeitos dos fármacos , Venenos de Abelha/uso terapêutico , Inflamação/tratamento farmacológico , Hiperplasia Prostática/tratamento farmacológico , Animais , Western Blotting , Di-Hidrotestosterona/sangue , Masculino , Tamanho do Órgão/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/sangue , Próstata/efeitos dos fármacos , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Hiperplasia Prostática/fisiopatologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Testosterona/farmacologiaRESUMO
Solanum tuberosum L. cv Jayoung (JY) is a potato with dark purple flesh and contains substantial amounts of polyphenols. In this study, we evaluated the therapeutic effects of S. tuberosum L. cv JY in a mouse model of Dermatophagoides farinae body (Dfb)-induced atopic dermatitis (AD). The ethanol extract of the peel of JY (EPJ) ameliorated Dfb-induced dermatitis severity, serum levels of immunoglobulin E (IgE) and thymus and activation-regulated chemokine. Histological analysis of the skin also revealed that EPJ treatment significantly decreased mast cell infiltration. The suppression of dermatitis by EPJ treatment was accompanied by a decrease in the skin levels of type 2 helper T-cell cytokines such as interleukin (IL)-4, IL-5, and IL-13. The induction of thymic stromal lymphopoietin, which leads to a systemic Th2 response, was also decreased in the skin by EPJ. Nuclear translocation of nuclear factor-κB p65 was decreased by EPJ in Dfb-induced NC/Nga mice. The protein expression of filaggrin in the AD-like skin lesions was restored by EPJ treatment. These results suggested that EPJ may be a potential therapeutic tool for the treatment of AD.
Assuntos
Dermatite Atópica/tratamento farmacológico , Ácaros , Fitoterapia , Extratos Vegetais/uso terapêutico , Pele/efeitos dos fármacos , Solanum tuberosum/química , Equilíbrio Th1-Th2/efeitos dos fármacos , Animais , Antígenos , Citocinas/sangue , Dermatite Atópica/etiologia , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Proteínas Filagrinas , Proteínas de Filamentos Intermediários/metabolismo , Masculino , Camundongos , Epiderme Vegetal , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Pele/metabolismo , Pele/patologia , Linfócitos T Auxiliares-Indutores/metabolismo , Células Th1/metabolismo , Células Th2/metabolismoRESUMO
BACKGROUND: Sam-Hwang-Sa-Sim-Tang (SHSST) is a traditional Oriental medication that has been commonly used in Korea for the treatment of hypertension, insomnia, and chest pain. In addition, some studies reported that administration of SHSST results suppression of hyperlipidemia in rats or lowering lipid plasma level such as total cholesterol (TC). Those results made us find and demonstrate positive effect of SHSST much more. The aim of the current study was to examine whether SHSST exerts an effect against hepatic steatosis and two type of SHSST has different efficacy on liver steatosis. METHODS: Total 40 mice were divided randomly and equally into 4 groups: a normal diet (CON) group, high-cholesterol diet (HC) group, and treatment groups fed a high-cholesterol diet (HCD) with a 30% or 80% ethanol extract of SHSST (SHSST-L and SHSST-H, respectively). The HCD was given for 9 weeks. The SHSST-treated groups were orally administered SHSST at a dose of 150 mg/kg, whereas the other groups received physiological saline. RESULTS: SHSST administration to mice resulted in a decline in serum levels of total cholesterol and low-density lipoprotein. Histological examination showed that lipid droplets were smaller in the SHSST-treated group than in the HC group. At the protein level, expression of sterol regulatory element-binding protein 2 (SREBP-2) was suppressed by SHSST. In addition, the mRNA expression of cholesterol metabolism-related molecules such as SREBP-2, liver X receptor (LXR), low-density lipoprotein receptor (LDLR), and 3-hydroxy-3methylglutary-CoA (HMG-CoA) was also suppressed in SHSST-treated groups in the liver. In the aorta tissue, SHSST decreased the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), transforming growth factor (TGF)-ß1, and fibronectin. CONCLUSIONS: The present study indicates that SHSST protects against liver steatosis and protects vessels against inflammation arising from excessive ingestion of cholesterol. These findings may also suggest that SHSST could be used as an adjuvant remedy for protection against liver steatosis.