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As a type of contact dermatitis (CD), irritant CD (ICD) is an acute skin inflammation caused by external irritants, such as soap, water and chemicals. Humulus japonicus (HJ) is a herbal medicine widely distributed in Asian countries and has anti-inflammatory, antimicrobial and antioxidant effects. The current study aimed to investigate the anti-dermatitis effect of HJ on ICD and determine the molecular basis of this effect using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermatitis mice models and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Mice were orally administered HJ and luteolin, the major compound in HJ, and topically administered TPA on the right ear to induce dermatitis. Topical application of TPA induced ear redness, oedema and increased infiltration of neutrophils and macrophages, which ameliorated following HJ and luteolin administration. The gene expression levels of inflammatory cell migrating chemokines, chemokine ligand 3 (CCL3) and chemokine (C-X-C motif) ligand 2 (CXCL2), and pro-inflammatory cytokine, IL-1ß, were reduced in the ears of HJ- and luteolin-treated mice. HJ and luteolin also inhibited the gene expression of chemokines, CCL3 and CXCL2, and pro-inflammatory cytokines, IL-1ß, IL-6 and TNF-α, in LPS-stimulated RAW264.7 cells. Moreover, HJ and luteolin decreased the expression levels of two key inflammatory enzymes, cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS), and total and active phosphorylation of NF-κB p65. These results suggest that HJ could have a protective effect against ICD by suppressing inflammatory responses; therefore, HJ is a promising therapeutic strategy for ICD treatment.
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Humulus japonicus (HJ) is a traditional herbal medicine that exhibits antiinflammatory, antimicrobial and antitumor effects that is used for the treatment of hypertension, pulmonary disease and leprosy. Recently, it has also been reported that HJ demonstrates neuroprotective properties in animal models of neurodegenerative diseases. The current study hypothesised that the administration of HJ would exhibit therapeutic effects in autism spectrum disorder (ASD), a neurodevelopmental disorder with lifelong consequences. The BTBR T+ Itpr3tf/J mouse model of ASD was used to investigate the antiautistic like behavioural effects of HJ. Chronic oral administration of the ethanolic extract of HJ significantly increased social interaction, attenuated repetitive grooming behaviour and improved novelobject recognition in BTBR mice. Antiinflammatory effects of HJ in the brain were analysed using immunohistochemistry and reversetranscription quantitative PCR analysis. Microglia activation was markedly decreased in the striatum and hippocampus, and proinflammatory cytokines, including CC Motif Chemokine Ligand 2, interleukin (IL)1ß and IL6, were significantly reduced in the hippocampus following HJ treatment. Moreover, HJ treatment normalised the phosphorylation levels of: NmethylDaspartate receptor subtype 2B and calcium/calmodulindependent protein kinase type II subunit α in the hippocampus of BTBR mice. The results of the present study demonstrated that the administration of HJ may have beneficial potential for ameliorating behavioural deficits and neuroinflammation in ASD.
Assuntos
Transtorno Autístico/tratamento farmacológico , Humulus/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno Autístico/genética , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Hipocampo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Fosforilação/efeitos dos fármacosRESUMO
Obesity is a medical condition in which excess body fat has accumulated to a serious extent. It is a chronic disease that can lead to dyslipidemia, insulin resistance, and type 2 diabetes. In the present study, we investigated the anti-obesity effects of Sicyos angulatus (SA) extract on a high-fat diet (HFD)-induced C57BL/6J obese mice. The mice were divided into vehicle and three SA groups (25, 50, and 100 mg/kg body weight). The mice were fed a HFD with or without SA for 12 weeks. The oral administration of SA reduced body and adipose tissue weight in HFD-fed mice compared to those in the vehicle group (p<0.05). Adipocyte size and inflammation significantly decreased in the SA-administered groups in a dose-dependent manner. In particular, adipocytes larger than 5000 µm2 were remarkably reduced by around 50% in the SA-treated groups (p<0.05). In addition, SA contributes towards reducing insulin resistance (measured as the HOMA-IR index) and glucose intolerance in HFD-induced obese mice (p<0.05; Vehicle 21.5±3.1 vs. SA100 4.7±0.4). These beneficial effects of SA on obesity may be linked to the suppression of lipogenesis and stimulating energy metabolism in white adipose tissue and muscle. In white adipose tissue and muscle, the administration of SA activated AMPK pathway, leading to the inhibition of the development of pathophysiological conditions associated with obesity, including lipogenesis and inflammation. These findings suggest that SA may prevent obesity through inhibiting fat accumulation in HFD-induced obese mice. Therefore, SA is able to exert metabolic benefits in the prevention of obesity and insulin resistance.
Assuntos
Cucurbitaceae/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/patologia , Resistência à Insulina/genética , Lipogênese/efeitos dos fármacos , Camundongos , Camundongos Obesos , Obesidade/etiologia , Obesidade/patologia , Extratos Vegetais/químicaRESUMO
Humulus japonicus (HJ) is a widely used herbal medicine in Asia with antioxidative, antimicrobial, and antiinflammatory effects. We investigated the potential therapeutic effects of HJ in rheumatoid arthritis (RA) using a mouse model of collageninduced arthritis (CIA) and a lipopolysaccharidestimulated murine macrophage cell line (RAW 264.7). The CIA mice were administered 300 mg/kg HJ orally starting 3 days prior to second immunization. The clinical and histopathological findings were assessed in the paw of CIA mice. The levels of autoantibodies and inflammatory markers were determined in the plasma and cell culture supernatant, respectively. The expression at mRNA and protein levels was analyzed by reverse transcription quantitativePCR and western blot analysis, respectively. HJ significantly decreased the gross arthritic scores and paw swelling in CIA mice. Furthermore, synovial inflammation, cartilage destruction, and bone erosion were markedly reduced by HJ. It also decreased the expression of inflammatory enzymes in both the paw of mice and RAW 264.7 cells. Moreover, the expression of genes related to all macrophages and proinflammatory M1 macrophage were significantly decreased, whereas the expression of antiinflammatory M2 macrophage marker was markedly increased in the paw of HJtreated CIA mice. In addition, HJ suppressed the levels of plasma antitype II collagen antibody following the decreased expression of T helper type 1 (Th1) and Th2 cellassociated surface markers and cytokines in the paw. HJ also significantly inhibited the expression of IL6 both in vitro and in vivo, followed by reduced STAT3 phosphorylation and expression in the paw of CIA mice. Finally, the expression of osteoclastrelated genes was decreased in the paw of HJtreated CIA mice. These findings suggest that HJ can play a role in suppressing the development of CIA by overall regulation of articular inflammation. This study should provide new insights into the use of HJ as a therapeutically effective natural product against RA.
Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Humulus , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Modelos Animais de Doenças , Humulus/química , Inflamação/tratamento farmacológico , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Masculino , Camundongos , Extratos Vegetais/química , Células RAW 264.7RESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Recently, the inhibitory effects of flavone glycosides isolated from Sicyos angulatus extract on hepatic lipid accumulation in vitro were demonstrated. However, the effects of S. angulatus extract and its major flavonoid glycoside on in vivo hepatic steatosis induced by a high-fat diet have not yet been established. HYPOTHESIS/PURPOSE: The aim of this study was to investigate the effects of S. angulatus extract and its major flavonoid glycoside, kaempferol 3-O-[α-l-rhamnopyranosyl-(1â6)]-ß-d-glucopyranosyl-7-O-α-l-rhamnopyranoside, on hepatic steatosis in high-fat diet-fed mice, which serves as a model of NAFLD. In addition, attempts have been made to chemically profile the metabolites involved in the activity of the S. angulatus extract. METHODS: C57BL/6â¯J mice were divided into vehicle, total extract of S. angulatus (SA; 50, 100 and 200â¯mg/kg) and major active component (20â¯mg/kg) groups. The mice were fed a high-fat diet (HFD) with or without S. angulatus extract or its major single compound for 10 weeks. Chemical identification was carried out using ultra-high-pressure liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-qTOF-MS/MS) and then quantified by HPLC-DAD. RESULTS: Administration of S. angulatus extract significantly lowered plasma ALT and AST levels in HFD-fed mice compared to those of the vehicle group. The hepatic lipid content, as evidenced by oil-red O staining and quantification, was significantly lower in the S. angulatus-administered group, and the effect was dose dependent. These beneficial effects of S. angulatus extract were related to the decreased expression of hepatic genes involved in fatty acid (ACC1, FAS and SCD1) and triglyceride (DGAT) synthesis. The expression levels of two key transcription factors regulating lipogenesis, SREBP-1c and PPARγ, were significantly suppressed in the liver by administration of S. angulatus extract with HFD. Treatment of the HFD-fed mice with the major compound isolated from S. angulatus extract resulted in improved liver function along with an anti-steatotic effect similar to the results seen with S. angulatus extract. For the standardization of the S. angulatus extract, 23 compounds were identified based on MS/MS fragmentation and UV spectroscopy. Quantitative analysis of the major compound showed that the major component was present in 15.35 ± 0.01â¯mg/g of total extract. CONCLUSION: These findings suggest that S. angulatus extract and its major component have the potential to improve liver function and hepatic steatosis in diet-induced obese mice.
Assuntos
Cucurbitaceae/química , Glicosídeos/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Glicosídeos/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Extratos Vegetais/química , Espectrofotometria Ultravioleta , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Espectrometria de Massas em TandemRESUMO
Humulus japonicus is an annual plant belonging to the Cannabacea family, and it has been traditionally used to treat pulmonary tuberculosis, dysentery, chronic colitis, and hypertension. We investigated the active components against Parkinson's disease from H. japonicus fraction (HJF) using high performance liquid chromatography (HPLC) coupled with quadruple-time-of-flight mass spectroscopy (qTOF-MS) and NMR. Fourteen compounds were isolated from HJF, including one new compound, using HPLC-qTOF-MS and NMR. The major compounds of HJF were luteolin-7-O-glucoside and apigenin-7-O-glucoside, and there was approximately 12.57- and 9.68-folds increase in the contents of these flavonoids compared to those of the 70% EtOH extract. Apigenin and luteolin exhibited the strongest inhibitory effects on monoamine oxidase (MAO) B enzyme activity. In animal studies, limb-use behavior was significantly reduced by unilateral 6-OHDA lesion and ipsilateral rotations. These results indicated that oral administration of 300 mg/kg HJF resulted in the improvement of motor asymmetry and motor impairment in unilateral 6-OHDA-lesioned mice. HJF, including active components leads to an improvement of motor behavior in a Parkinson's disease mouse model.
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Humulus/química , Atividade Motora/efeitos dos fármacos , Doença de Parkinson Secundária/tratamento farmacológico , Extratos Vegetais/química , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Flavonas/administração & dosagem , Flavonas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/administração & dosagem , Glucosídeos/química , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Monoaminoxidase/genética , Atividade Motora/genética , Oxidopamina/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/genética , Doença de Parkinson Secundária/patologia , Extratos Vegetais/administração & dosagem , Espectrometria de Massas em TandemRESUMO
Ultralow power chemical sensing is essential toward realizing the Internet of Things. However, electrically driven sensors must consume power to generate an electrical readout. Here, a different class of self-powered chemical sensing platform based on unconventional photovoltaic heterojunctions consisting of a top graphene (Gr) layer in contact with underlying photoactive semiconductors including bulk silicon and layered transition metal dichalcogenides is proposed. Owing to the chemically tunable electrochemical potential of Gr, the built-in potential at the junction is effectively modulated by absorbed gas molecules in a predictable manner depending on their redox characteristics. Such ability distinctive from bulk photovoltaic counterparts enables photovoltaic-driven chemical sensing without electric power consumption. Furthermore, it is demonstrated that the hydrogen (H2 ) sensing properties are independent of the light intensity, but sensitive to the gas concentration down to the 1 ppm level at room temperature. These results present an innovative strategy to realize extremely energy-efficient sensors, providing an important advancement for future ubiquitous sensing.
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OBJECTIVE: We aimed to investigate the effect of Sicyos angulatus (SA) ethanolic extracts as antioxidants and potential treatments for liver disease. METHODS: To establish a mouse model of liver injury, C57BL/6 male mice were injected via the caudal vein with a single dose of concanavalin A (Con A, 15â mgâ kg-1). SA extracts were administered once by oral gavage 30â min before Con A injection. RESULTS: In vitro studies showed that SA decreased tert-butyl hydroperoxide (t-BHP)-induced reactive oxygen species (ROS) production. SA administration reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, as well as hepatic ROS levels, in a dose-dependent manner. Moreover, SA increased the activities of the hepatic antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner. Furthermore, SA treatment reduced pro-apoptotic protein levels. Con A-mediated cytosolic release of Smac/DIABLO and apoptosis-inducing factor (AIF), which are markers of necrosis, were dramatically decreased in HepG2 cells treated with SA. CONCLUSION: SA ameliorated liver injury and might be a good strategy for the treatment of liver injury.
Assuntos
Antioxidantes/metabolismo , Fígado/efeitos dos fármacos , Fígado/lesões , Loranthaceae/química , Extratos Vegetais/farmacologia , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , terc-Butil Hidroperóxido/metabolismoRESUMO
Melicope ptelefolia has been traditionally used to treat rheumatism and fever. The present study aimed to investigate the therapeutic effect of 3,5diCßDglucopyranosyl phloroacetophenone (ßGP), a main component of M. ptelefolia, on rheumatoid arthritis (RA). A model of collageninduced arthritis (CIA) was established in mice using the RAW 264.7 murine macrophage cell line and mouse embryonic fibroblasts (MEFs). The clinical scores of arthritis, swelling, histopathological findings, and microcomputed tomography in CIA mouse paws were assessed. The levels of antitype II collagen antibody and cytokines were determined in the plasma and cell culture supernatant, respectively. Protein and gene expression levels were analyzed by western blot and reverse transcriptionquantitative polymerase chain reaction analyses. ßGP significantly decreased the gross arthritic scores of CIA mice and joint swelling, and decreased articular inflammation, cartilage degradation and bone erosion. However, ßGP did not exert any effect on antitype II collagen immunoglobulin G plasma levels or inflammatory cytokine expression in macrophages. ßGP significantly suppressed the expression of interleukin6 and leukemia inhibitory factor and decreased the phosphorylation of signal transducer and activator of transcription 3, and expression of receptor activator of nuclear factorκB ligand in tumor necrosis factorαstimulated MEFs and in CIA mouse paws. Osteoclastrelated gene expression was significantly reduced in CIA mouse paws. Taken together, ßGP suppressed the development of RA by regulating the activation of synovial fibroblasts.
Assuntos
Acetofenonas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/efeitos dos fármacos , Glucosídeos/uso terapêutico , Acetofenonas/química , Animais , Anti-Inflamatórios/química , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Citocinas/análise , Fibroblastos/patologia , Glucosídeos/química , Masculino , Camundongos , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Células RAW 264.7 , Rutaceae/química , Microtomografia por Raio-XRESUMO
Histone acetylation is a key regulatory factor for gene expression in cells. Modulation of histone acetylation by targeting of histone acetyltransferases (HATs) effectively alters many gene expression profiles and synaptic plasticity in the brain. However, the role of HATs on L-DOPA-induced dyskinesia of Parkinson's disease (PD) has not been reported. Our aim was to determine whether HAT inhibitors such as anacardic acid, garcinol, and curcumin from natural plants reduce severity of L-DOPA-induced dyskinesia using a unilaterally 6-hydroxydopamine (6-OHDA)-lesioned PD mouse model. Anacardic acid 2 mg/kg, garcinol 5 mg/kg, or curcumin 100 mg/kg co-treatment with L-DOPA significantly reduced the axial, limb, and orofacial (ALO) score indicating less dyskinesia with administration of HAT inhibitors in 6-OHDA-lesioned mice. Additionally, L-DOPA's efficacy was not altered by the compounds in the early stage of treatment. The expression levels of c-Fos, Fra-2, and Arc were effectively decreased by administration of HAT inhibitors in the ipsilateral striatum. Our findings indicate that HAT inhibitor co-treatment with L-DOPA may have therapeutic potential for management of L-DOPA-induced dyskinesia in patients with PD.
Assuntos
Ácidos Anacárdicos/uso terapêutico , Antiparkinsonianos/toxicidade , Curcumina/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Histona Acetiltransferases/antagonistas & inibidores , Levodopa/toxicidade , Transtornos Parkinsonianos/tratamento farmacológico , Terpenos/uso terapêutico , Ácidos Anacárdicos/farmacologia , Animais , Curcumina/farmacologia , Proteínas do Citoesqueleto/biossíntese , Proteínas do Citoesqueleto/genética , Avaliação Pré-Clínica de Medicamentos , Discinesia Induzida por Medicamentos/etiologia , Discinesia Induzida por Medicamentos/genética , Inibidores Enzimáticos/farmacologia , Antígeno 2 Relacionado a Fos/biossíntese , Antígeno 2 Relacionado a Fos/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Código das Histonas/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Oxidopamina/toxicidade , Proteínas Proto-Oncogênicas c-fos/biossíntese , Proteínas Proto-Oncogênicas c-fos/genética , Organismos Livres de Patógenos Específicos , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Terpenos/farmacologiaRESUMO
Gymnema sylvestre (Retz.) R.Br. ex Sm. (Asclepiadaceae) is a well-known Ayurvedic anti-sweet plant for the treatment of type 2 diabetes mellitus. Although it was previously proposed that G. sylvestre exhibits chemical variation based on geography, most research on G. sylvestre has used material originating from India. Morphological and anatomical descriptions, ITS1-5.8S-ITS2 DNA sequencing, and acid hydrolysis analyses showed that G. sylvestre samples from Vietnam are distinguishable from those of Indian origin and thus suggest a dissimilarity among G. sylvestre samples with different geographic distributions. An LC-MS-guided strategy targeting 3ß-glucuronide oleane-triterpenes in the Vietnamese G. sylvestre variety led to the isolation of four known compounds and nine previously undescribed compounds, named gymnemosides ND1-ND9. None of the isolated compounds were reported in the Indian sample, further supporting the geo-diversity of G. sylvestre. Three compounds, gymnemosides ND7-9, exerted significant stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells and thus have potential as lead molecules for anti-diabetes agents.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Gymnema sylvestre/genética , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/química , Desoxiglucose/análogos & derivados , Desoxiglucose/química , Hipoglicemiantes , Índia , Ácido Oleanólico/química , Extratos Vegetais/química , Folhas de Planta/química , Saponinas/química , VietnãRESUMO
Soy-leaf extracts exert their cardioprotective effects by inducing endothelium-dependent vasodilation in the arteries, and they favorably modulate the serum lipid profile. In this study, we investigated the atheroprotective effects of an ethanol extract of soy leaf (ESL) in human umbilical vein endothelial cells (HUVECs) and high-cholesterol diet (HCD)-fed low-density lipoprotein receptor deficient (LDLR-/-) mice. ESL induced the expression of Krüppel-like factor 2 (KLF2), an endothelial transcription factor, and endothelial nitric oxide synthase (eNOS), and suppressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) through moderate inflammatory signal activation, not only in tumor necrosis factor-α (TNF-α)-stimulated HUVECs but also in 7-ketocholesterol (7-KC)-stimulated HUVECs. ESL supplementation reduced aortic lesion formation in Western diet-fed LDLR-/- mice by 46% (p < 0.01) compared to the HCD group. ESL also markedly decreased the aortic expression levels of VCAM-1, ICAM-1, monocyte chemotactic protein-1 (MCP-1), TNF-α, IL-6, IL-1ß, matrix metallopeptidase 9 (MMP-9), and fractalkine, while the expression of KLF2 was significantly increased. These results suggest that ESL supplementation has potential for preventing HCD-induced atherosclerosis effectively.
Assuntos
Moléculas de Adesão Celular/metabolismo , Glycine max/química , Fatores de Transcrição Kruppel-Like/metabolismo , Extratos Vegetais/farmacologia , Folhas de Planta/química , Substâncias Protetoras/farmacologia , Animais , Aorta/metabolismo , Aorta/patologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/genética , Masculino , Camundongos , Camundongos Knockout , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Receptores de LDL/deficiência , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Humulus japonicus (HJ), popularly known as Japanese hops, is a traditional herbal medicine widely used for the treatment of pulmonary disease, skin disease, and hypertension in Korea. HJ exerts scavenging effects against reactive oxygen species (ROS), such as superoxide radical, hydroxyl radical, and hydrogen peroxide. Moreover, dysfunction and damage of mitochondria elicited by ROS are of critical importance in the pathogenesis of Parkinson's disease (PD). The present study aimed to examine neuroprotective potential of extracts of HJ using in vitro and in vivo 6-hydroxydopamine (6-OHDA) models. SH-SY5Y cells were cultured to explore the mechanisms for the neuroprotective effect of HJ in vitro. Unilateral 6-OHDA-induced mouse model of PD was established to investigate the neuroprotective effect of HJ on dopaminergic neurons in substantia nigra pars compacta (SNc) and striatum in vivo. Methanol extract of HJ (HJM) significantly attenuated cytotoxicity and the mitochondrial apoptosis pathway caused by 6-OHDA in SH-SY5Y cells. In addition, HJM significantly increased glutathione levels and decreased phosphorylation of ERK1/2 in SH-SY5Y cells exposed to 6-OHDA. In the in vivo study, the administration of methanol or ethanol extract of HJ improved the motor dysfunction and notably reduced dopaminergic cell death and fiber loss in the SNc and striatum caused by 6-OHDA. Our findings demonstrate that HJ may have therapeutic potential to protect dopaminergic neuron degeneration in Parkinson's disease.
Assuntos
Morte Celular/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Humulus/química , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Dopamina/metabolismo , Neurônios Dopaminérgicos/citologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxidopamina/efeitos adversos , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Humulus japonicus Siebold & Zucc. (HJ) has traditionally been administered to patients with pulmonary disease, skin disease and hypertension in Korea, and it is considered to exert anti-inflammatory, antioxidant, antimicrobial and antimycobacterial effects. However, its effects against Alzheimer's disease (AD) have yet to be explored. Thus, this study was carried out to investigate whether HJ has a beneficial effect on the progression of AD in an animal model. A methanolic extract of HJ (500 mg/kg/day) was intragastrically administered to 5-month-old APP/PS1 transgenic (Tg-APP/PS1) mice for 2.5 months. Novel object recognition and Y-maze alteration tests were used to assess cognitive function, and an immunohistochemical assay was performed to assess amyloid ß (Aß)deposition, tau phosphorylation and gliosis. An in vitro assay using a microglial cell line was also performed to investigate the anti-inflammatory effects of HJ. Our results revealed that HJ significantly decreased the mRNA and protein expression levels of tumor necrosis factor-α (TNFα), interleukin (IL)-1ß, IL-6 and inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide in the microglial cell line. The administration of HJ for 2 months improved the cognitive function of Tg-APP/PS1 mice. HJ notably reduced the area occupied by Aß and neurofibrillary tangles, and the number of activated astrocytes and microglia in the cortex of Tg-APP/PS1 mice. The findings of our study suggest that HJ has the therapeutic potential to inhibit the progression of AD and to improve cognitive deterioration in Tg-APP/PS1 mice.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Progressão da Doença , Humulus/química , Extratos Vegetais/uso terapêutico , Presenilina-1/genética , Doença de Alzheimer/fisiopatologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Linhagem Celular , Cognição/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Humanos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Insulisina , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Óxido Nítrico/biossíntese , Fosforilação/efeitos dos fármacos , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas tau/metabolismoRESUMO
Humulus japonicus (HJ) is used as a traditional medicine in Korea owing to its multiple properties including anti-mycobacterial, antioxidant and antihypertensive effects. The present study aimed to examine the antiinflammatory and anti-atherogenic effects of a methanol extract of HJ. In lipopolysaccharide-stimulated RAW 264.7 cells, HJ significantly suppressed the mRNA expression and secretion of pro-inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1ß and IL-6)], and the release of inflammatory mediators such as nitrite and prostaglandin E2, together with a concomitant decrease in the mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. To examine whether HJ is capable of inhibiting experimental atherogenesis in an animal model, we randomly divided apolipoprotein E-deficient (apoE-/-) mice into three groups: mice fed an atherogenic diet plus vehicle (0.5% carboxymethyl cellulose) as the control vehicle group, and mice fed an atherogenic diet plus either 100 (HJ100) or 500 mg/kg (HJ500) of HJ as the experimental groups. After 12 weeks of HJ administration, lipid accumulation and the formation of atherosclerotic lesions in the aorta (en face) and the aortic sinus markedly decreased in the HJ500 group compared with the corresponding values in the vehicle control group. Moreover, monocyte and macrophage infiltration in the aortic sinus was markedly reduced in the HJ500 group. Reverse transcription-quantitative polymerase chain reaction analysis of the whole aorta showed that the mRNA levels of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, CD68 and IL-18 were significantly decreased in the HJ500 group. Collectively, these findings suggest that HJ may suppress atherosclerosis by inhibiting lipid accumulation and the expression of pro-atherogenic factors, and it may be effective at preventing the development of atherosclerosis.
Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/tratamento farmacológico , Humulus/química , Extratos Vegetais/uso terapêutico , Animais , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Citocinas/metabolismo , Dinoprostona/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Monócitos/efeitos dos fármacos , Monócitos/patologia , Nitritos/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Seio Aórtico/efeitos dos fármacos , Seio Aórtico/patologiaRESUMO
The use of computed tomography (CT) for vascular imaging is critical in medical emergencies requiring urgent diagnostic decisions, such as cerebral ischemia and many cardiovascular diseases. Small-molecule iodinated contrast media are often injected intravenously as radiopaque agents during CT imaging to achieve high contrast enhancement of vascular systems. The rapid excretion rate of these agents is overcome by injecting a significantly high dose of iodine, which can have serious side effects. Here we report a simple method to prepare blood-pool contrast agents for CT based on dendrimers for the first time using tetraiodobenzene derivatives as potent radiopaque moieties. Excellent in vivo safety has been demonstrated for these small (13-22nm) unimolecular water-soluble dendritic contrast agents, which exhibit high contrast enhancement in the blood-pool and effectively extend their blood half-lives. Our method is applicable to virtually any scaffold with suitable surface groups and may fulfill the current need for safer, next-generation iodinated CT contrast agents.
Assuntos
Meios de Contraste/química , Dendrímeros/química , Iodobenzenos/química , Nylons/química , Tomografia Computadorizada por Raios X , Animais , Meios de Contraste/efeitos adversos , Meios de Contraste/farmacocinética , Dendrímeros/efeitos adversos , Dendrímeros/farmacocinética , Células HeLa , Humanos , Iodobenzenos/efeitos adversos , Iodobenzenos/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Nylons/efeitos adversos , Nylons/farmacocinéticaRESUMO
This study investigated the molecular mechanisms underlying the antidiabetic effect of an ethanol extract of soy leaves (ESL) in db/db mice. Control groups (db/+ and db/db) were fed a normal diet (ND), whereas the db/db-ESL group was fed ND with 1% ESL for 8 weeks. Dietary ESL improved glucose tolerance and lowered plasma glucose, glycated hemoglobin, HOMA-IR, and triglyceride levels. The pancreatic insulin content of the db/db-ESL group was significantly greater than that of the db/db group. ESL supplementation altered pancreatic IRS1, IRS2, Pdx1, Ngn3, Pax4, Ins1, Ins2, and FoxO1 expression. Furthermore, ESL suppressed lipid accumulation and increased glucokinase activity in the liver. ESL primarily contained kaempferol glycosides and pheophorbides. Kaempferol, an aglycone of kaempferol glycosides, improved ß-cell proliferation through IRS2-related FoxO1 signaling, whereas pheophorbide a, a product of chlorophyll breakdown, improved insulin secretion and ß-cell proliferation through IRS1-related signaling with protein kinase A in MIN6 cells. ESL effectively regulates glucose homeostasis by enhancing IRS-mediated ß-cell insulin signaling and suppressing SREBP-1-mediated hepatic lipid accumulation in db/db mice.
Assuntos
Clorofila/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glycine max/química , Glicosídeos/administração & dosagem , Células Secretoras de Insulina/efeitos dos fármacos , Quempferóis/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Animais , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Folhas de Planta/químicaRESUMO
Six known triterpenoid compounds, 3-oxoolean-12-en-27-oic acid (1), gypsogenic acid (2), 3α-hydroxyolean-12-en-27-oic acid (3), 3ß-hydroxyolean-12-en-27-oic acid (4), aceriphyllic acid A (5), and oleanolic acid (6), were isolated from the roots of Aceriphyllum rossii. Their chemical structures were determined by comparison with available (1)H-NMR and (13)C-NMR data on known compounds. All the isolated compounds were evaluated for inhibitory activity against human diacylglycerol acyltransferases 1 and 2. Most of the isolates exhibited a better inhibitory activity against diacylglycerol acyltransferase 2 (IC50: 11.6-44.2 µM) than against diacylglycerol acyltransferase 1 (IC50: 22.7-119.5 µM). In particular, compounds 1 and 5 showed strong inhibition efficacy towards diacylglycerol acyltransferases 1 and 2, and appeared to act competitively against oleoyl-CoA in vitro. The results also indicated that both compounds reduced newly synthesized triacylglycerol in HuTu80 and HepG2 cells. Oral administration of compound 1 significantly reduced postprandial triacylglycerol in mice following an oral lipid challenge. In conclusion, the current study indicates that compound 1 suppresses both de novo triacylglycerol biosynthesis and resynthesis through the inhibition of diacylglycerol acyltransferase activity, and therefore may be a useful agent for treating diseases associated with a high triacylglycerol level.
Assuntos
Diacilglicerol O-Aciltransferase/sangue , Inibidores Enzimáticos/farmacologia , Ácido Oleanólico/farmacologia , Extratos Vegetais/farmacologia , Saxifragaceae/química , Triglicerídeos/sangue , Acil Coenzima A/metabolismo , Animais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Células Hep G2 , Humanos , Camundongos , Estrutura Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Extratos Vegetais/química , Raízes de PlantasRESUMO
During a search for SIRT1 activators originating in nature, three new dammarane triterpenes, 6α,20(S)-dihydroxydammar-3,12-dione-24-ene (1), 6α,20(S),24(S)-trihydroxydammar-3,12-dione-25-ene (2), and 6α,20(S),25-trihydroxydammar-3,12-dione-23-ene (3), as well as two known triterpenes, dammar-20(22),24-diene-3ß,6α,12ß-triol (4) and 20(S)-ginsenoside Rg3 (5), were isolated from Panax ginseng leaves. Compounds 1 and 3-5 showed potential as SIRT1 activators, as analyzed by in vitro enzyme-based SIRT1-NAD/NADH and SIRT1-p53 luciferase cell-based assays. They were also found to increase the level of NAD(+)/NADH ratio in HEK293 cells. This study presents a new class of chemical entities that may be able to be developed as SIRT1 activators for antiaging and treatment of age-associated diseases.
Assuntos
Panax/química , Sirtuína 1/efeitos dos fármacos , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Ginsenosídeos/química , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Estereoisomerismo , Triterpenos/química , DamaranosRESUMO
This study was performed to investigate the effect of scoparone on the differentiation of 3T3-L1 preadipocytes. Scoparone inhibited triglyceride (TG) accumulation in the mature adipocytes, evidenced by Oil-red O staining and intracellular quantification. Real time-PCR analysis showed that scoparone significantly down-regulated the mRNA expression of key adipogenic transcription factors, PPARγ, C/EBPα, compared with mature adipocytes. Scoparone appeared to reduce mRNA expression of SREBP1c and FAS being related to the late stage of adipogenesis. Furthermore, aP2 and CD36/FAT, as adipocyte-specific genes, were decreased in mature adipocytes by scoparone treatment. Moreover, scoparone inhibited the up-regulated expression of PPARγ target genes by rosiglitazone to near that observed in cells treated with GW9662. The luciferase assay revealed that scoparone negatively regulates the transcriptional activity of PPARγ. Chromatin immunoprecipitation assay also showed that participation of scoparone in the regulation of PPARγ. Collectively, scoparone has a PPARγ antagonic effect and suppresses differentiation through down-regulation of adipogenic genes by PPARγ inhibition in 3T3-L1 preadipocytes.