RESUMO
The purpose of this study was to examine whether Limonium tetragonum, cultivated in a smart-farming system with LED lamps, could increase exercise capacity in mice. C57BL/6 male mice were orally administered vehicle or Limonium tetragonum water extract (LTE), either 30 or 100 mg/kg, and were subjected to moderate intensity treadmill exercise for 4 weeks. Running distance markedly increased in the LTE group (100 mg/kg) by 80 ± 4% compared to the vehicle group, which was accompanied by a higher proportion of oxidative fibers (6 ± 6% vs. 10 ± 4%). Mitochondrial DNA content and gene expressions related to mitochondrial biogenesis were significantly increased in LTE-supplemented gastrocnemius muscles. At the molecular level, the expression of PGC-1α, a master regulator of fast-to-slow fiber-type transition, was increased downstream of the PKA/CREB signaling pathway. LTE induction of the PKA/CREB signaling pathway was also observed in C2C12 cells, which was effectively suppressed by PKA inhibitors H89 and Rp-cAMP. Altogether, these findings indicate that LTE treatment enhanced endurance exercise capacity via an improvement in mitochondrial biosynthesis and the increases in the formation of oxidative slow-twitch fibers. Future study is warranted to validate the exercise-enhancing effect of LTE in the human.
Assuntos
Condicionamento Físico Animal , Extratos Vegetais , Plumbaginaceae , Corrida , Animais , DNA Mitocondrial/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Biogênese de Organelas , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Condicionamento Físico Animal/fisiologia , Resistência Física , Extratos Vegetais/farmacologia , Plumbaginaceae/químicaRESUMO
Targeting energy expenditure offers a strategy for treating obesity more effectively and safely. In previous studies, we found that the root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) increased energy metabolism in C2C12 cells. Here, we investigated the effects of ARA on obesity and glucose intolerance by examining energy metabolism in skeletal muscle and brown fat in high-fat diet (HFD) induced obese mice. ARA decreased body weight gain, hepatic lipid levels and serum total cholesterol levels, but did not modify food intake. Fasting serum glucose, serum insulin levels and glucose intolerance were all improved in ARA treated mice. Furthermore, ARA increased peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) expression, and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle tissues, and also prevented skeletal muscle atrophy. In addition, the numbers of brown adipocytes and the expressions of PGC1α and uncoupling protein 1 (UCP1) were elevated in the brown adipose tissues of ARA treated mice. Our results show that ARA can prevent diet-induced obesity and glucose intolerance in C5BL/6 mice and suggests that the mechanism responsible is related to the promotion of energy metabolism in skeletal muscle and brown adipose tissues.
Assuntos
Atractylodes/química , Metabolismo Energético/efeitos dos fármacos , Intolerância à Glucose/metabolismo , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Modelos Animais de Doenças , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Obesidade/etiologia , Obesidade/prevenção & controle , Extratos Vegetais/químicaRESUMO
The cortex of Cinnamomum cassia Presl (Cinnamomi Cortex: CC) has commonly been used for weight control in traditional medicines, but without a scientific basis. Therefore, this study was undertaken to investigate the anti-obesity effect of CC extract in a high-fat diet (HFD)-induced obese mouse model and in C2C12 mouse skeletal muscle cells. Male C57BL/6 mice were fed a normal diet or a HFD for 16 consecutive weeks, and orally administered CC extract (100 or 300[Formula: see text]mg/kg) or metformin (250[Formula: see text]mg/kg; positive control) daily for 16 weeks. CC extract administration significantly decreased body weights, food intakes, and serum levels of glucose, insulin, total cholesterol and ALT levels, prevented oral glucose tolerance and insulin resistance, inhibited the protein expressions of MyHC and PGC1[Formula: see text] and the phosphorylation of AMPK, suppressed lipid accumulation in liver, decreased adipocyte size and increased muscle mass in obese mice. For this in vitro study, C2C12 myoblasts were differentiated into the myotubes for five days, and then treated with CC extract (0.1 or 0.2[Formula: see text]mg/ml) for 24[Formula: see text]h. CC extract significantly increased ATP levels by increasing the mRNA expressions of mitochondrial biogenesis-related factors, such as, PGC1[Formula: see text], NRF-1, and Tfam, and the phosphorylations of AMPK and ACC. Our results suggest CC extract controls weight gain in obese mice by inhibiting lipid accumulation and increasing energy expenditure, and that its action mechanism involves the up-regulation of mitochondrial biogenesis in skeletal muscle cells.
Assuntos
Cinnamomum/química , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Obesidade/tratamento farmacológico , Obesidade/etiologia , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , Células Cultivadas , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias Musculares/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Targeting energy expenditure provides a potential alternative strategy for achieving energy balance to combat obesity and the development of type 2 diabetes mellitus (T2DM). In the present study, we investigated whether atractylenolide III (AIII) regulates energy metabolism in skeletal muscle cells. Differentiated C2C12 myotubes were treated with AIII (10, 20, or 50 µM) or metformin (2.5 mM) for indicated times. The levels of glucose uptake, the expressions of key mitochondrial biogenesis-related factors and their target genes were measured in C2C12 myotubes. AIII significantly increased the glucose uptake levels, and significantly increased the expressions of peroxisome proliferator-activated receptor coactivator-1α (PGC1α) and mitochondrial biogenesis-related markers, such as, nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) and mitochondrial mass and total ATP contents. In addition, AIII significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of sirtuin1 (SIRT1). These results suggest that AIII may have beneficial effects on obesity and T2DM by improving energy metabolism in skeletal muscle.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Metabolismo Energético/efeitos dos fármacos , Lactonas/farmacologia , Músculo Esquelético/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Sirtuína 1/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Atractylodes/química , Glicemia/metabolismo , Linhagem Celular , Proteínas de Ligação a DNA/sangue , Diabetes Mellitus Tipo 2/metabolismo , Proteínas de Grupo de Alta Mobilidade/sangue , Camundongos , Mitocôndrias/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Fator 1 Nuclear Respiratório/sangue , Obesidade/metabolismo , FosforilaçãoRESUMO
Radix Pueraria lobata (RP) has been reported to prevent obesity and improve glucose metabolism; however, the mechanism responsible for these effects has not been elucidated. The mechanism underlying anti-obesity effect of RP was investigated in high-fat diet (HFD) induced obese mice and skeletal muscle cells (C2C12). Five-week-old C5BL/6 mice were fed a HFD containing or not containing RP (100 or 300 mg/kg) or metformin (250 mg/kg) for 16 weeks. RP reduced body weight gain, lipid accumulation in liver, and adipocyte and blood lipid levels. In addition, RP dose-dependently improved hyperglycemia, insulinemia, and glucose tolerance, and prevented the skeletal muscle atrophy induced by HFD. Furthermore, RP increased the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) expression and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle tissues. RP and its main component, puerarin, increased mitochondrial biogenesis and myotube hypertrophy in C2C12 cells. The present study demonstrates that RP can prevent diet-induced obesity, glucose tolerance, and skeletal muscle atrophy in mouse models of obesity. The mechanism responsible for the effect of RP appears to be related to the upregulation of energy metabolism in skeletal muscle, which at the molecular level may be associated with PGC-1α and AMPK activation.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Isoflavonas/farmacologia , Músculo Esquelético/efeitos dos fármacos , Obesidade/prevenção & controle , Extratos Vegetais/farmacologia , Pueraria/química , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Alanina Transaminase/sangue , Animais , Fármacos Antiobesidade/farmacologia , Aspartato Aminotransferases/sangue , Linhagem Celular , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Insulina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosforilação , Raízes de Plantas/química , Triglicerídeos/sangueRESUMO
Obesity is associated with a number of metabolic abnormalities such as type 2 diabetes and has become a major health problem worldwide. In the present study, we investigated the effects of Epimedium koreanum Nakai (Herba Epimedii, HE) and its main constituent icariin on the adipocyte differentiation in 3T3-L1 preadipocytes. HE extract and icariin significantly reduced lipid accumulation and suppressed the expressions of PPARγ, C/EBPα, and SREBP-1c in 3T3-L1 adipocytes. They also inhibited fatty acid synthase (FAS), acyl-Co A synthase (ACS1), and perilipin. Moreover, HE extract and icariin markedly increased the phosphorylation of AMPK. These results indicated that HE extract and icariin can inhibit the adipocyte differentiation through downregulation of the adipogenic transcription factors, suggesting that HE containing icariin may be used as a potential therapeutic agent in the treatment and prevention of obesity.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Epimedium/química , Flavonoides/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Camundongos , PPAR gama/genética , PPAR gama/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismoRESUMO
SCOPE: Diet-induced obesity and consequent insulin resistance are caused, in part, by macrophage polarization and accumulation in peripheral tissues. Here, we examined the effects of endogenously synthesized n-3 PUFAs on macrophage chemotaxis and polarization. METHODS AND RESULTS: Fat-1 mice and wild-type (WT) littermates were fed a 60% calorie high-fat diet (HFD) for 10 weeks. Bone marrow macrophages (BMMs) from fat-1 and WT mice were used in in vitro chemotaxis assays and macrophage polarization studies. WT mice fed a HFD exhibited glucose intolerance, insulin resistance, and lipid accumulation and macrophage infiltration in liver and adipose tissue. However, these metabolic and inflammatory phenotypes were not observed in HFD-fed fat-1 mice. In flow cytometric analysis, M1 macrophage infiltration into adipose tissue was markedly attenuated in fat-1 mice. Consistently, results from in vitro experiments indicated that n-3 PUFAs prevented adipocyte conditioned medium-mediated macrophage chemotaxis, stimulated M2 polarization, and suppressed M1 polarization. The inhibition of macrophage migration by n-3 PUFAs was associated with suppression of multiple kinases, such as IκB kinase, AKT, and focal adhesion kinase. CONCLUSION: Our results indicate that n-3 PUFAs play a crucial role in macrophage polarization and chemotaxis, and thus regulate the development of HFD-induced tissue inflammation and metabolic derangements.
Assuntos
Dieta Hiperlipídica , Macrófagos/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Gorduras na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Inflamação/metabolismo , Resistência à Insulina , Fígado/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Obesidade/metabolismoRESUMO
The root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) is a Traditional Korean Medicine and has been commonly used for weight control. Mitochondrial dysfunction appears to be a key contributor to insulin resistance, and therefore mitochondrial targeting drugs represent an important potential strategy for the treatment of insulin resistance and obesity. In this study, the authors investigated the regulatory effects of ARA on mitochondrial function with respect to the stimulation of glucose and lipid metabolism in C2C12 myotubes. After differentiating C2C12 myotubes, cells were treated with or without different concentrations (0.2, 0.5, and 1.0 mg/mL) of ARA extract. ARA extract significantly increased the expression of peroxisome proliferator-activated receptor coactivator 1 alpha (PGC1α) and the downregulations of its targets, nuclear respiratory factor-1 (NRF-1), transcription factor A (TFAM), and total ATP content in C2C12 myotubes. ARA extract also increased the expressions of PGC1α activator and of the metabolic sensors, AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase and sirtuin (SIRT) 1. Furthermore, it significantly increased glucose uptake by enhancing glucose consumption and subsequently decreased FFA contents and increased carnitine palmitoyltransferase (CPT) 1b expression. Our study indicates that ARA has a potential for stimulating mitochondrial function and energy metabolism in muscle.
RESUMO
SCOPE: In this study, we focus on the effects of n-3 polyunsaturated fatty acids (PUFAs) on tunicamycin-, streptozotocin-, or high fat diet (HFD)-induced ß-cell damage and dysfunction. MATERIALS AND METHODS: Pretreatment with n-3 PUFAs protected RINm5F cells and mouse islets against tunicamycin-induced ß-cell damage through suppression of ER stress and apoptosis induction. This protective effect of n-3 PUFAs on ß-cells was further demonstrated by the normalization of insulin secretion in response to glucose in tunicamycin-treated islets. In multiple low-dose streptozotocin-induced diabetes models, fat-1 mice, which endogenously synthesize n-3 PUFAs from n-6 PUFAs, were fully resistant to the development of diabetes, with normal islet morphology, high insulin immunoreactivity, and decreased apoptotic cells. In HFD-induced diabetes models, fat-1 mice also exhibited improved glucose tolerance and functional ß-cell mass. In both diabetes models, we observed an attenuation of ER stress in fat-1 mice. Interestingly, n-3 PUFAs attenuated the nuclear translocation of lipogenic transcription factors sterol regulatory element-binding protein-1 (SREBP-1) and C/EBPß, induced by tunicamycin or HFD, suggesting that n-3 PUFAs suppress ER stress via modulation of SREBP-1 and C/EBPß. CONCLUSION: Together, these results suggest that n-3 PUFAs block ER stress, thus protecting ß cells against diabetogenic insult; therefore, dietary supplementation of n-3 PUFAs has therapeutic potential for the preservation of functional ß-cell mass.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Insulina/sangue , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Estreptozocina , TunicamicinaRESUMO
OBJECTIVE: Programmed death-ligand 1 (PD-L1) has been shown to negatively regulate immune responses via its interaction with PD-1 receptor. In this study, we investigated the effects of PD-L1-Fc treatment on intestinal inflammation using two murine models of inflammatory colitis induced by dextran sulfate sodium (DSS) and T-cell transfer. DESIGN: The anti-colitis effect of adenovirus expressing Fc-conjugated PD-L1 (Ad/PD-L1-Fc) and recombinant PD-L1-Fc protein was evaluated in DSS-treated wild-type and Rag-1 knockout (KO) mice. We examined differentiation of T-helper cells, frequency of innate immune cells, and cytokine production by dendritic cells (DCs) in the colon from DSS-treated mice after PD-L1-Fc administration. In Rag-1 KO mice reconstituted with CD4 CD45RB(high) T cells, we assessed the treatment effect of PD-L1-Fc protein on the development of colitis. RESULTS: Administration of Ad/PD-L1-Fc significantly ameliorated DSS-induced colitis, which was accompanied by diminished frequency of interleukin (IL)-17A-producing CD4 T cells and increased interferon-γ-producing CD4 T cells in the colon of DSS-fed mice. The anti-colitic effect of PD-L1-Fc treatment was also observed in DSS-treated Rag-1 KO mice, indicating lymphoid cell independency. PD-L1-Fc modulated cytokine production by colonic DCs and the effect was dependent on PD-1 expression. Furthermore, PD-L1-Fc protein could significantly reduce the severity of colitis in CD4 CD45RB(high) T-cell-transferred Rag-1 KO mice. CONCLUSIONS: Based on the protective effect of PD-L1-Fc against DSS-induced and T-cell-induced colitis, our results suggest that PD-1-mediated inhibitory signals have a crucial role in limiting the development of colonic inflammation. This implicates that PD-L1-Fc may provide a novel therapeutic approach to treat inflammatory bowel disease.
Assuntos
Antígeno B7-H1/uso terapêutico , Colite Ulcerativa/prevenção & controle , Fatores Imunológicos/uso terapêutico , Doença Aguda , Adenoviridae/genética , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Antígeno B7-H1/farmacologia , Diferenciação Celular/efeitos dos fármacos , Colite Ulcerativa/etiologia , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colo/imunologia , Citocinas/biossíntese , Células Dendríticas/imunologia , Sulfato de Dextrana , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Vetores Genéticos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Imunidade Inata , Imunidade nas Mucosas , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Fragmentos Fc das Imunoglobulinas/farmacologia , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Fatores Imunológicos/genética , Fatores Imunológicos/metabolismo , Fatores Imunológicos/farmacologia , Mucosa Intestinal/imunologia , Transfusão de Linfócitos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Linfócitos T Auxiliares-Indutores/imunologia , Células Th17/imunologiaRESUMO
The root bark of Lycium barbarum (Lycii radicis cortex, LRC) is used as a cooling agent for fever and night sweats in East Asian traditional medicine. The inhibitory effect of LRC water extract on inflammation is unknown. In this study, the anti-inflammatory effect of LRC was investigated in lipopolysaccharide (LPS)-stimulated mouse macrophage, RAW 264.7 cells. LRC extract significantly decreased the LPS-induced production of inflammatory mediators, nitric oxide (NO), prostaglandin (PG) E2 and pro-inflammatory cytokines, interleukin (IL)-1ß and IL-6 in the cells. In addition, LRC extract inhibited the LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA and protein, and inflammatory cytokines mRNA in the cells. The action mechanism of LRC underlies the blocking of LPS-mediated p38 and Jun N-terminal kinase (JNK), mitogen-activated protein kinases (MAPKs), and the nuclear factor (NF)-κB signaling pathway. These results indicate that LRC extract inhibits the inflammatory response in activated macrophages by down-regulating the transcription levels of inflammatory mediators and blocking the MAPKs and NF-κB pathway.
Assuntos
Anti-Inflamatórios , Lipopolissacarídeos/imunologia , Lycium , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Extratos Vegetais/farmacologia , Animais , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ativação de Macrófagos/genética , Ativação de Macrófagos/imunologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Casca de Planta , Raízes de PlantasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ephedra sinica (Ma Huang) has been used in traditional Chinese medicine for more than 5000 years for treatment of various conditions, including modern-day obesity. Ephedra has been used as a supplement for weight loss and its effects have been reported. The current study investigated the influence of ephedra on the composition of gut microbiota, and its correlation with weight loss. MATERIALS AND METHODS: Clinical data of subjects were measured at pre- and post-intake of ephedra (4g of water extract, roughly equivalent of 24g of crude herb), and analysis of the alteration of gut microbiota was performed simultaneously using 16S rRNA gene based pyrosequencing. RESULTS: Body weight (BW), body mass index (BMI), and body fat percentage of subjects were reduced after intake (p<0.05). In correlation analysis, Subdoligranulum, Oscillibacter, and Akkermansia showed an association with changes of BW and BMI (p<0.05). However, the alteration of gut microbiota varied by indigenous microbiota of each subject, and the dissimilarity between microbiota of subjects at pre- and post-intake were different. CONCLUSIONS: The influences of gut microbiota are unique according to indigenous microbiota and differences in individual sensitivity to ephedra. Alteration of gut microbiota by ephedra intake showed correlation with loss of BW and BMI.
Assuntos
Ephedra sinica/química , Microbiota/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Adulto , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Feminino , Trato Gastrointestinal/microbiologia , Humanos , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , República da Coreia , Redução de Peso/efeitos dos fármacosRESUMO
Lipopolysaccharide (LPS) is known to produce endotoxic shock by triggering systemic inflammatory responses. Here, we evaluated the protective effects of three fermented/re-fermented herbs, Rhizoma Atractylodis Macrocephalae, Massa Medicata Fermentata, and Dolichoris Semen, in an LPS-mediated inflammatory insult, either individually in vitro using RAW264.7 cells or in combination in in vivo using rats. In general, each of the fermented herbs showed appreciable in vitro anti-inflammatory activity, although the degree of this activity varied with the herb used. Moreover, a mixture of fermented herbal extracts in combination with probiotics significantly attenuated the blood endotoxin and CRP levels, as well as the gut permeability, and significantly augmented the intestinal Lactobacillus spp. colonisation in LPS-treated rats. However, these effects were not observed following the administration of the corresponding mixture of unfermented herbal extracts. Thus, our results highlight the beneficial impacts of the use of fermented herb products with probiotics to combat LPS-mediated inflammatory insults.
Assuntos
Anti-Inflamatórios/administração & dosagem , Inflamação/tratamento farmacológico , Lipopolissacarídeos/imunologia , Extratos Vegetais/administração & dosagem , Plantas Medicinais/química , Probióticos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Animais , Anti-Inflamatórios/metabolismo , Bacillus/metabolismo , Linhagem Celular , Fermentação , Humanos , Inflamação/imunologia , Leuconostoc/metabolismo , Masculino , Extratos Vegetais/metabolismo , Plantas Medicinais/metabolismo , Plantas Medicinais/microbiologia , Substâncias Protetoras/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Lipopolysaccharide (LPS) can produce endotoxic shock by triggering the systemic inflammatory response. Here, we evaluated the in vitro and in vivo protective effects of unfermented and fermented Rhizoma coptidis (RC and FRC, respectively) against LPS-insult. In general, RC suppressed the LPS-induced expression of key inflammatory mediators in RAW264.7 cells, in a dose-dependent manner. Notably, FRC at a 20 µg/ml dose in combination with the probiotic used for fermentation showed more potent in vitro anti-inflammatory activities than that exhibited by the corresponding dose of RC. Moreover, oral treatment with FRC in association with the probiotic, but not oral administration of RC, significantly attenuated blood endotoxin and C-reactive protein (CRP) levels, and gut permeability, and significantly augmented the intestinal population of Bifodobacterium spp. and Lactobacillus spp. in LPS-treated animals. Our results demonstrate the beneficial impact of fermented RC in combination with the associated probiotic in combating LPS-insult both in vitro and in vivo.
Assuntos
Anti-Inflamatórios/farmacologia , Coptis/química , Inflamação/tratamento farmacológico , Lipopolissacarídeos/imunologia , Extratos Vegetais/farmacologia , Probióticos/farmacologia , Rizoma/química , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/metabolismo , Linhagem Celular , Coptis/microbiologia , Fermentação , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Humanos , Inflamação/genética , Inflamação/imunologia , Leuconostoc/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Extratos Vegetais/análise , Extratos Vegetais/metabolismo , Probióticos/análise , Probióticos/metabolismo , Ratos , Ratos Sprague-Dawley , Rizoma/microbiologiaRESUMO
The objective of this systematic review was to assess the evidence from rigorous clinical trials evaluating the efficacy of mixed herbal medicine formulations used in traditional Oriental medicines for the treatment of obesity and to describe the safety and types of adverse events reported in such trials. To accomplish this, 14 databases were searched from inception to July 31, 2009. The search terms used were "obesity" or "obese" and "herb," "herbal," or "herbal medicine" without language restriction. All randomized clinical trials using mixed herbal medicines on obese or overweight subjects were considered for inclusion. Of the publications in the identified databases, 1144 results were searched and reviewed, and in total 12 studies were included. Their methodological quality was assessed using the Jadad score. The results of our review provide evidence suggesting that mixed Oriental herbal medicines may be safe and effective for the treatment of obesity when compared with conventional medicine, placebos, or lifestyle control. Many trials also reported improved concomitant conditions including impaired glucose tolerance, hypertension, and inflammation. Small numbers of adverse events were reported, but most were mild or not related to the intervention in itself. No significant mortality was observed in any of the trials. However, the evidence provided by the trials reviewed is not fully convincing because of their poor methodological quality. Therefore, more research and well-designed clinical trials are necessary to address these issues, as well as to assess the safety of mixed Oriental herbal medicines used to treat obesity.
Assuntos
Obesidade/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Fitoterapia , Extratos Vegetais/uso terapêutico , Combinação de Medicamentos , Humanos , Medicina Tradicional do Leste Asiático , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia , Plantas MedicinaisRESUMO
UNLABELLED: We are constructing an ontology for traditional Korean medicine, and we started with medicinal materials to express the relationships between patients' symptoms, diseases and treatments. Biological materials and mineral resources have been used traditionally for patient treatments. The ontology includes various data related to these materials, such as their scientific names, parts of materials used, effectiveness and related oriental organ of the human body. AVAILABILITY: http://tkm.kiom.re.kr/ontology/TraditionalKoreanMedicine.rdf-xml.owl (10-20 s using Internet Explorer.)
Assuntos
Medicina Tradicional Coreana , Doença , Humanos , InternetRESUMO
AIM: To investigate the anti-diabetogenic mechanism of Nardostachys jatamansi extract (NJE). METHODS: Mice were injected with streptozotocin via a tail vein to induce diabetes. Rat insulinoma RINm5F cells and isolated rat islets were treated with interleukin-1beta and interferon-gamma to induce cytotoxicity. RESULTS: Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was confirmed by immunohistochemical staining of the islets. The diabetogenic effects of streptozotocin were completely abolished when mice were pretreated with NJE. Inhibition of streptozotocin-induced hyperglycemia by NJE was mediated by suppression of nuclear factor (NF)-kappaB activation. In addition, NJE protected against cytokine-mediated cytotoxicity. Incubation of RINm5F cells and islets with NJE resulted in a significant reduction in cytokine-induced NF-kappaB activation and downstream events, inducible nitric oxide synthase expression and nitric oxide production. The protective effect of NJE was further demonstrated by the normal insulin secretion of cytokine-treated islets in response to glucose. CONCLUSION: NJE provided resistance to pancreatic beta-cell damage from cytokine or streptozotocin treatment. The beta-cell protective effect of NJE is mediated by suppressing NF-kappaB activation.
Assuntos
Citocinas/antagonistas & inibidores , Citocinas/toxicidade , Diabetes Mellitus Experimental/prevenção & controle , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Nardostachys , Animais , Sequência de Bases , Morte Celular/efeitos dos fármacos , Linhagem Celular , Primers do DNA/genética , Técnicas In Vitro , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/patologia , Células Secretoras de Insulina/fisiologia , Interferon gama/antagonistas & inibidores , Interferon gama/toxicidade , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
We examined the effects of Rhizoma Dioscoreae Tokoronis extracts (RDTEs) on plasma lipids, body weight, and lipogenic enzymes. Mice were administered a standard chow diet, a 60% high-fat diet, or a high-fat diet with RDTE. Mice that were fed a high-fat diet containing RDTE were found to have lower increases in body and epididymal adipose tissue weights and a lessened occurrence of hepatic steatosis than mice that were fed a high-fat diet. The decreased adiposity that was induced by RDTE accounted for lower plasma levels of tumor necrosis factor-alpha, leptin, and glucose and a higher level of adiponectin. RDTE administration also resulted in a significant decrease in triglyceride, total plasma cholesterol, and low-density lipoprotein-cholesterol when compared to the high-fat group. To identify the mechanism by which RDTE induced its antiobesity effect, we investigated the sterol response element binding protein (SREBP) transcription system, which was induced in mice that were fed the high-fat diet. RDTE was found to suppress the expression of SREBP-1 as well as that of fatty acid synthase in adipose and liver tissues in mice provided the high-fat diet. These findings suggest that the antiobesity action of RDTE in mice that are fed a high-fat diet may occur in response to suppression of the SREBP-1-dependent lipogenic pathway.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Fármacos Antiobesidade/uso terapêutico , Dioscorea , Obesidade/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Adiponectina/sangue , Animais , Fármacos Antiobesidade/farmacologia , Glicemia , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Gorduras na Dieta/administração & dosagem , Epididimo/efeitos dos fármacos , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Fígado Gorduroso/prevenção & controle , Expressão Gênica , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/farmacologia , RNA Mensageiro/metabolismo , Rizoma , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Cytokines released by infiltrating inflammatory cells around the pancreatic islets are involved in the pathogenesis of type 1 diabetes. Interleukin (IL)-1beta and interferon (IFN)-gamma are the primary cytokines responsible for stimulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, which leads to beta-cell damage. In addition, nuclear factor-kappaB (NF-kappaB) plays a crucial role in the activation of this pathway. Therefore, suppression of the cytokine-NF-kappaB pathway is considered an effective therapeutic strategy for preventing inflammatory reactions in pancreatic beta-cells. In this study, the effects of Fructus Xanthii extract (FXE) on IL-1beta and IFN-gamma-induced beta-cell damage were examined. Treatment of RINm5F cells with IL-1beta and IFN-gamma reduced cell viability, however, FXE completely protected cells from IL-1beta and IFN-gamma-mediated reduction in viability in a concentration-dependent manner. In addition, incubation with FXE resulted in a significant suppression of IL-1beta and IFN-gamma-induced nitric oxide (NO) production, which correlated with the reduced levels of the inducible form of iNOS mRNA and protein observed. The IL-1beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappaB binding activity and p50 subunit levels in the nucleus, as well as increased IkappaBalpha degradation in cytosol when compared to unstimulated cells, which indicates that the mechanism by which FXE inhibited the iNOS gene involves inhibition of NF-kappaB activation. Furthermore, a protective effect of FXE was demonstrated by reduction in NO generation and iNOS expression, as well as the normal insulin secreting responses to glucose observed in IL-1beta and IFN-gamma-treated islets.
Assuntos
Citocinas/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Xanthium/química , Animais , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Desvio de Mobilidade Eletroforética , Frutas/química , Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Interferon gama/farmacologia , Interleucina-1beta/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Nucleares/metabolismo , Oligonucleotídeos/genética , Oligonucleotídeos/metabolismo , Extratos Vegetais/química , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
In the present study, Flos magnoliae extract (FME) was evaluated to determine if it could protect pancreatic beta-cells against multiple low dose streptozotocin (MLDS) and interleukin-1beta and interferon-gamma. Injection of mice with MLDS resulted in hyperglycemia and hypoinsulinemia, which was confirmed by immunohistochemical staining. However, the induction of diabetes by MLDS was completely prevented when mice were pretreated with FME. FME also effectively protected beta-cells against cytokine toxicity, which was demonstrated by an increase in the viability of rat insulinoma RINm5F cells and by preserved insulin secreting responses to glucose in isolated rat islets. Moreover, cytokine-induced nitric oxide production and iNOS mRNA and protein expression were significantly reduced in RINm5F cells and islets that were preincubated with FME. The molecular mechanism by which FME inhibits iNOS gene expression in in vitro and in vivo appears to involve inhibition of NF-kappaB activation. Taken together, these results reveal the possible therapeutic value of FME for the prevention of type 1 diabetes progression.