RESUMEN
Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. To confirm this, we studied its mechanism of action using qPCR and WB in LPS-treated HGF-1 cells and RANKL-induced osteoclasts. We found that MKE suppressed proinflammatory cytokine protein expression by inhibiting the TLR4/NF-κB pathway in LPS-PG-induced HGF-1 cells and blocking ECM degradation by regulating the expression of TIMPs and MMPs. We also confirmed that TRAP activity and multinucleated cell formation were reduced in RANKL-stimulated osteoclasts after exposure to MKE. These results were confirmed by inhibiting TRAF6/MAPK expression, which led to the suppression of NFATc1, CTSK, TRAP, and MMP expression at the gene and protein levels. Our results confirmed that MKE is a promising candidate for the management of periodontal disease based on its anti-inflammatory effects and inhibition of ECM degradation and osteoclastogenesis.
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Smilax sieboldii, a climbing tree belonging to Smilacaceae, has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago. To evaluate the anti-obesity effects of S. sieboldii (Smilacaceae), we screened methylene chloride (CH2Cl2), ethyl acetate (EtOAc), aqueous-saturated n-butanol, and ethanol (EtOH) extracts of the whole plant at various concentrations to inhibit adipogenesis in adipocytes. The 3T3-L1 cell line with Oil red O staining with the help of fluorometry was used as an indicator of anti-obesity activity. Bioactivity-guided fractionation of the EtOH extract and subsequent phytochemical investigation of the active CH2Cl2- and EtOAc-soluble fractions resulted in the isolation of 19 secondary metabolites (1-19), including a new α-hydroxy acid derivative (16) and two new lanostane-type triterpenoids (17 and 18). The structures of these compounds were characterized using various spectroscopic methods. All the isolated compounds were screened for adipogenesis inhibition at a concentration of 100 µM. Of these, compounds 1, 2, 4-9, 15, and 19 significantly reduced fat accumulation in 3T3-L1 adipocytes, especially compounds 4, 7, 9, and 19, showing 37.05 ± 0.95, 8.60 ± 0.41 15.82 ± 1.23, and 17.73 ± 1.28% lipid content, respectively, at a concentration of 100 µM. These findings provide experimental evidence that isolates from S. sieboldii extracts exert beneficial effects regarding the regulation of adipocyte differentiation.
Asunto(s)
Adipogénesis , Smilax , Animales , Ratones , Células 3T3-L1 , Smilax/metabolismo , Extractos Vegetales/química , Adipocitos/metabolismo , Obesidad/metabolismo , Diferenciación Celular , PPAR gamma/metabolismoRESUMEN
Veratrum spp. have traditionally been used in folk medicine to treat various pathologies. In this study, nine compounds, comprising one simple phenolic compound (1), three stilbenoids (2-4), and five flavonoids (5-9), were isolated from the aerial parts of Veratrum versicolor f. viride Nakai. The structures of these compounds were elucidated by spectroscopic analyses and comparison with reported data. Together, all reported compounds were isolated from V. versicolor f. viride for the first time in the study. Among them, two flavone aglycone tricetins (7 and 9) have never been isolated from the genus Veratrum or the family Melanthiaceae. The ethanol extract and isolated compounds were assessed for their inhibitory effects on elastase, tyrosinase, and melanin synthesis. Compounds 5 and 7 inhibited elastase (IC50: 292.25 ± 14.39 and 800.41 ± 5.86 µM, respectively), whereas compounds 2-5 inhibited tyrosinase with IC50 values in the range of 6.42 ~ 51.19 µM, respectively. In addition, compounds 3-6 and 8 exhibited dose-dependent inhibition (70.4% ~ 91.0%) of melanogenesis at a concentration of 100 µM.
RESUMEN
GV1001, a human telomerase reverse transcriptase catalytic subunit-derived 16-mer peptide, has been developed as a novel anticancer vaccine against various cancers including pancreatic cancer. In the current study, we demonstrate the regulatory roles and mechanisms of GV1001 in endothelial cell responses in vitro and microvessel sprouting ex vivo. GV1001 markedly inhibits vascular endothelial growth factor-A (VEGF-A)-stimulated endothelial cell permeability, proliferation, migration, invasion, tube formation as well as microvessel outgrowth from rat aortic rings. These anti-angiogenic effects of GV1001 were associated with the inhibition of VEGF-A/VEGFR-2 signaling pathways, redistribution of vascular endothelial-cadherin to cell-cell contacts, and down-regulation of VEGFR-2 and matrix metalloproteinase-2. Furthermore, GV1001 suppresses the proliferation and invasion of non-small cell lung cancer cells, and the release of VEGF from the cells, suggesting the regulatory role of GV1001 in tumor-derived angiogenesis as well as cancer cell growth and progression. Collectively, our study reports the pharmacological potential of GV1001 in the regulation of angiogenesis, and warrants further evaluation and development of GV1001 as a promising therapeutic agent for a variety of angiogenesis-related diseases including cancer.
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Spiraea prunifolia has been used in Korean traditional medicine to treat malaria, fever, and emetic conditions. Previous investigation reported that several parts of Spiraea prunifolia show various functional effects. However, the effect of Spiraea prunifolia leaves extract (SPE) on anti-obesity remains unclear. Therefore, we used a high-fat diet (HFD)-induced obese mouse model in this study to investigate the effects of SPE on adipogenesis, lipogenesis, and ß-oxidation. Oral administration of SPE in HFD-induced obese mice considerably reduced body weight, serum levels such as total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, adipose tissue weight, and adipocyte cell size. Moreover, SPE significantly decreased protein expression levels of adipogenesis and lipogenesis related genes such as CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, adipocyte protein 2, acetyl-CoA carboxylase, and fatty acid synthase in epididymal adipose tissues. SPE treatment induced the protein expression of carnitine palmitoyl transferase-1, which might have promoted phosphorylated AMP-activated protein kinase-medicated ß-oxidation. The present study reveals an anti-adipogenic, anti-lipogenic, ß-oxidation effects of SPE in vivo and represents AMP-activated protein kinase signaling as targets for SPE.
Asunto(s)
Fármacos Antiobesidad , Spiraea , Proteínas Quinasas Activadas por AMP/metabolismo , Adipogénesis , Animales , Fármacos Antiobesidad/farmacología , Colesterol , Dieta Alta en Grasa/efectos adversos , Lipogénesis , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Spiraea/metabolismoRESUMEN
Tetracera loureiri (T. loureiri) is a woody climber inhabiting open deciduous or evergreen forests in Southeast Asia. A decoction comprising its stem and other herbs is a traditional Thai remedy for fatigue and jaundice, as well as to promote overall health. Anti-inflammatory effects induced by T. loureiri extract have not been reported. In this study, we investigated the anti-inflammatory effect of an ethanol extract of T. loureiri (ETL) on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 macrophages. We found that ETL treatment inhibited the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells, without affecting cell viability. The effect of ETL on the expression of various pro-inflammatory mediators was analyzed using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). We observed that ETL inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels and decreased the production of prostaglandin E2 (PGE2) by COX-2 in RAW264.7 macrophages. ETL dose-dependently reduced the production of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in LPS-induced RAW264.7 cells, in a dose-dependent manner. Furthermore, ETL suppressed the LPS-induced nuclear translocation of the nuclear factor, NF-κB. Additionally, ETL was found to inhibit the activation of mitogen-activated protein kinases (MAPK), such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and p38 MAPK. In conclusion, our findings demonstrate that ETL inhibits the expression of pro-inflammatory mediators and cytokines, thereby downregulating NF-κB and MAPK signaling pathways in LPS-stimulated macrophages, Consequently, ETL is a potential therapeutic agent for the treatment of inflammatory diseases.
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In the present study, we demonstrate the regulatory effects and mechanism of broussonin A and B, diphenylpropane derivatives isolated from Broussonetia kazinoki, on vascular endothelial growth factor-A (VEGF-A)-stimulated endothelial cell responses in vitro and microvessel sprouting ex vivo. Treatment with broussonin A or B suppressed VEGF-A-stimulated endothelial cell proliferation by regulating the expression of cell cycle-related proteins and the phosphorylation status of retinoblastoma protein. In addition, treatment with broussonin A or B abrogated VEGF-A-stimulated angiogenic responses including endothelial cell migration, invasion, tube formation and microvessel formation from rat aortic rings. These anti-angiogenic activities of broussonin A and B were mediated through inactivation of VEGF-A-stimulated downstream signalling pathways, localization of vascular endothelial-cadherin at cell-cell contacts, and down-regulation of integrin ß1 and integrin-liked kinase. Furthermore, treatment with broussonin A or B inhibited proliferation and invasion of non-small cell lung cancer and ovarian cancer cells. Taken together, our findings suggest the pharmacological potential of broussonin A and B in the regulation of angiogenesis, cancer cell growth and progression.
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Alcanos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Fenoles , Alcanos/metabolismo , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Movimiento Celular , Proliferación Celular , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Integrina beta1 , Neoplasias Pulmonares/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Fenoles/metabolismo , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia-a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.
Asunto(s)
Amomum/química , Carbohidratos/efectos adversos , Dislipidemias/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Plantas Medicinales/química , Zingiberaceae/química , Tejido Adiposo/efectos de los fármacos , Animales , Dieta/efectos adversos , Dislipidemias/metabolismo , Lipoproteínas LDL/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Triglicéridos/metabolismoRESUMEN
In our search for novel plant-derived inhibitors of nitric oxide (NO) with potential for treating inflammatory diseases, the phytochemicals of Amomum tsao-ko fruits were investigated, leading to the isolation of one bicyclic nonane (1), three menthene skeleton monoterpenoids (2-4), and two acyclic monoterpenoids (5 and 6). Their structures were identified using one- and two-dimensional nuclear magnetic resonance spectroscopy, and mass spectrometry. To the best of our knowledge, compounds 2-5 were obtained from the genus Amomum for the first time. All isolates were tested for their ability to inhibit lipopolysaccharide-stimulated NO overproduction in RAW264.7 cells. Compound 4 was found to inhibit NO production. Western blotting analysis indicated that active compound 4 can regulate inducible NO synthase expression. In addition, lipopolysaccharide-induced interleukin 1 beta and interleukin-6 overproduction was reduced in a concentration-dependent manner.
RESUMEN
In the present study the effects and molecular mechanisms of wheat bran (WB), the hard outer layer of the wheat kernel used in food ingredients, on mast cell-mediated allergic responses in vitro and in vivo were investigated. The water extract of WB inhibited degranulation and expression of allergic and inflammatory mediators such as tumor necrosis factor-α, cyclooxygenase-2 and inducible nitric oxide synthase in antigen-stimulated RBL-2H3 cells. These anti-allergic activities of WB were mediated by the inactivation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, which play important roles in degranulation and expression of various allergic and inflammatory molecules. In agreement with its in vitro effects, WB inhibited immunoglobulin E (IgE)/antigen-induced and compound 48/80-induced anaphylactic reactions in vivo. Taken together, these findings suggest the pharmacological potential of WB in the regulation of allergic diseases, including allergic rhinitis, atopic dermatitis, asthma and anaphylaxis.
Asunto(s)
Fibras de la Dieta/farmacología , Hipersensibilidad/patología , Mastocitos/patología , Extractos Vegetales/farmacología , Animales , Antígenos/inmunología , Degranulación de la Célula/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Inmunoglobulina E/metabolismo , Mediadores de Inflamación/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mastocitos/efectos de los fármacos , Mastocitos/fisiología , Ratones Endogámicos BALB C , Anafilaxis Cutánea Pasiva/efectos de los fármacos , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , beta-N-Acetilhexosaminidasas/metabolismo , p-Metoxi-N-metilfenetilamina/farmacologíaRESUMEN
Angiogenesis plays important roles in pathological conditions such as cancer and inflammation as well as normal tissue development and homeostasis. Here, we investigated the effects and molecular mechanisms of α-viniferin, an oligostilbene isolated from Caragana sinica, on human umbilical vein endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. α-viniferin treatment inhibited mitogen-induced HUVEC proliferation by retinoblastoma protein hypophosphorylation. In addition, α-viniferin suppressed mitogen-induced HUVEC adhesion, migration, invasion, and microvessel outgrowth. These anti-angiogenic activities of α-viniferin might be mediated through downregulation of cell cycle-related proteins, vascular endothelial growth factor receptor-2 (VEGFR-2), and matrix metalloproteinase-2. Furthermore, inactivation of VEGFR-2/p70 ribosomal S6 kinase signaling pathway was found to be involved in α-viniferin-mediated modulation of endothelial cell responses. Our results demonstrate the pharmacological functions and molecular mechanisms of α-viniferin in regulating angiogenesis, suggesting the therapeutic potential of α-viniferin to treat and prevent various angiogenesis-related diseases.
Asunto(s)
Benzofuranos/uso terapéutico , Neovascularización Patológica/tratamiento farmacológico , Extractos Vegetales/química , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Animales , Benzofuranos/farmacología , Técnicas de Cultivo de Célula , Movimiento Celular , Proliferación Celular , Humanos , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.
Asunto(s)
Combretum/química , Dermatitis Atópica/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Extractos Vegetales/farmacología , Piel/efectos de los fármacos , Piel/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/etiología , Dermatitis Atópica/patología , Modelos Animales de Enfermedad , Inmunohistoquímica , Mediadores de Inflamación/metabolismo , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/química , Piel/patologíaRESUMEN
In this study, we investigated the effects and molecular mechanisms of 2-phenylbenzimidazole-5-sulphonic acid (PBSA), an ultraviolet B protecting agent used in sunscreen lotions and moisturizers, on ovarian cancer cell responses and tumour angiogenesis. PBSA treatment markedly blocked mitogen-induced invasion through down-regulation of matrix metalloproteinase (MMP) expression and activity in ovarian cancer SKOV-3 cells. In addition, PBSA inhibited mitogen-induced cell proliferation by suppression of cyclin-dependent kinases (Cdks), but not cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. These anti-cancer activities of PBSA in ovarian cancer cell invasion and proliferation were mediated by the inhibition of mitogen-activated protein kinase kinase 3/6-p38 mitogen-activated protein kinase (MKK3/6-p38MAPK ) activity and subsequent down-regulation of MMP-2, MMP-9, Cdk4, Cdk2 and integrin ß1, as evidenced by treatment with p38MAPK inhibitor SB203580. Furthermore, PBSA suppressed the expression and secretion of vascular endothelial growth factor in SKOV-3 cells, leading to inhibition of capillary-like tubular structures in vitro and angiogenic sprouting ex vivo. Taken together, our results demonstrate the pharmacological effects and molecular targets of PBSA on modulating ovarian cancer cell responses and tumour angiogenesis, and suggest further evaluation and development of PBSA as a promising chemotherapeutic agent for the treatment of ovarian cancer.
Asunto(s)
Imidazoles/farmacología , Neovascularización Patológica/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Piridinas/farmacología , Adipatos/farmacología , Animales , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Femenino , Fase G1/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Neovascularización Patológica/metabolismo , Neoplasias Ováricas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Succinatos/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Atopic dermatitis (AD) is a chronic inflammatory skin disease. Korean red ginseng is a Korean traditional medicine. In this study, we estimated the effects of Korean red ginseng water extract (RGE) in the 1-chloro-2,4-dinitrobenzene (DNCB)-induced BALB/c mouse model which develops AD-like lesions. After RGE administration (100, 200, and 400 mg/kg) to DNCB-induced mice there were improvements in the dermatitis score and skin pH, a decrease in trans-epidermal water loss, and improved skin hydration. RGE also significantly inhibited eosinophil infiltration, increased filaggrin protein levels, and decreased serum IgE levels, epidermal thickness, mast cell infiltration, and ceramidase release. Compared with that in DNCB-induced mice, RGE effectively decreased the mRNA expression levels of interleukin-6 (IL-6), thymic stromal lymphopoietin (TSLP), and tumor necrosis factor-α (TNF-α), as well as the protein level of thymus and activation-regulated chemokine (TARC). These inhibitory RGE effects are mediated by inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Furthermore, we confirmed that RGE suppresses interferon-γ (IFN-γ) and TNF-α-induced expression of macrophage-derived chemokine (MDC) and TARC genes in human keratinocyte (HaCaT) cells. Taken together, these results demonstrate that RGE may exert anti-atopic related to responses by suppression the expression of inflammatory mediators, cytokines, and chemokines via downregulation of MAPK signaling pathways, suggesting that RGE may be an effective therapeutic approach for prevention of AD-like disease.
Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/enzimología , Inflamación/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas , Panax/química , Extractos Vegetales/uso terapéutico , Agua/química , Animales , Supervivencia Celular/efectos de los fármacos , Quimiocinas/metabolismo , Dermatitis Atópica/patología , Dinitroclorobenceno , Modelos Animales de Enfermedad , Proteínas Filagrina , Humanos , Inflamación/patología , Mediadores de Inflamación/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacos , Extractos Vegetales/farmacología , Piel/efectos de los fármacos , Piel/patología , Pérdida Insensible de Agua/efectos de los fármacosRESUMEN
The ethanolic extract obtained from the stems of Glycosmis pentaphylla was found to suppress antigen-mediated degranulation of rat basophilic leukemia (RBL-2H3) cells. Four new geranylated 2-quinolone alkaloids, named glycopentanolones A-D (1-4), and 12 known metabolites (5-16) were isolated from the ethanolic extract from the stems of G. pentaphylla using bioassay-guided fractionation. Their structures were elucidated by a combination of 1D and 2D NMR, and HRESI-MS. The inhibitory effects of the isolated constituents on ß-hexosaminidase release from RBL-2H3 cells were examined, and compounds 1, 5, 8 and 11 exhibited potent inhibitory activity with IC50 values between 0.05 and 4.28⯵M.
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Alcaloides/farmacología , Antineoplásicos Fitogénicos/farmacología , Quinolonas/farmacología , Rutaceae/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Quinolonas/química , Quinolonas/aislamiento & purificación , Ratas , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Ligularia fischeri, indigenous to eastern Asia, has been used as a traditional herbal medicine. Ligularia fischeri reportedly possesses a number of biological activities such as antimutagenic, antioxidant, antigenotoxic, and anti-inflammation. This study demonstrated the effects of ethanol extracts of Ligularia fischeri (ELF) on a high-carbohydrate diet (HCD)-induced hyperlipidemia in C57BL/6 mice. The mice were divided into six groups (n = 7/group) as follows: normal diet, HCD, or HCD+ELF (100, 200, 400, and 800 mg/kg/day), which were orally administered daily for 12 weeks. Various lipid parameters and histological changes in liver and fat tissue were compared among the treatment and control groups. ELF remarkably reduced body weight gain and attenuated hyperlipidemia by improving the plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, atherogenic index, and cardiac risk factor. Moreover, ELF decreased the HCD-induced hepatic accumulation of lipid droplets and adipocyte hypertrophy. These regulatory effects of ELF appeared to be mediated through the phosphorylation of AMP-activated protein kinase, acetyl-CoA carboxylase, sterol regulatory element-binding protein-1c, and expression of fatty acid synthase. Taken together, these findings indicate a functional role for ELF in the regulation of HCD-induced obesity and hyperlipidemia.
Asunto(s)
Fármacos Antiobesidad/administración & dosificación , Asteraceae/química , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/administración & dosificación , Obesidad/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Proteínas Quinasas Activadas por AMP/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Fármacos Antiobesidad/química , Peso Corporal/efectos de los fármacos , Colesterol/metabolismo , Carbohidratos de la Dieta/efectos adversos , Carbohidratos de la Dieta/metabolismo , Humanos , Hiperlipidemias/etiología , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Hipolipemiantes/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Obesidad/genética , Obesidad/metabolismo , Extractos Vegetales/química , Triglicéridos/metabolismoRESUMEN
Kummerowia striata (K. striata) is used as a traditional medicine for inflammation-related therapy. To determine whether it has beneficial anti-melanogenic and anti-oxidant activities, we investigated the biological activities of the ethanol extract of Kummerowia striata (EKS) using a variety of in vitro and cell culture model systems. The anti-melanogenic activity was assessed in B16F10 melanoma cells in terms of melanin synthesis and in vitro tyrosinase inhibitory activity. The anti-oxidant assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS). EKS showed strong anti-oxidant activities in DPPH and ABTS assays. The mRNA transcription levels and protein expression levels of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor decreased in a dose-dependent manner with EKS treatment. Additionally, EKS did not affect cell viability at different concentrations used in this study, indicating that the mechanism of action of EKS-mediated inhibition of melanin synthesis does not involve cytotoxicity. Also, we confirmed that p-coumaric acid and quercetin are important compounds for anti-melanogenesis and antioxidant properties of EKS. Collectively, our findings demonstrate for the first time that EKS possesses anti-melanogenic and anti-oxidant activities. Further evaluation and development of EKS as a functional supplement or cosmetic may be useful for skin whitening and reducing wrinkles.
RESUMEN
Coix lachryma-jobi L. var. ma-yuen has been a source of food and traditional folk medicine in some parts of Asia for thousands of years; however, the roots of this plant have not been phytochemically investigated. Herein, we report the isolation of a new benzoxazinoid glycoside, coixlachryside B (1), along with ten known compounds (2-11), from the roots of C. lachryma-jobi var. ma-yuen using a variety of chromatographic methods. Among the known compounds, the absolute configuration of compound 4 was determined. The structures of all compounds were elucidated by interpreting NMR spectroscopic data, and experimental and calculated electronic circular dichroism spectra.
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Benzoxazinas/aislamiento & purificación , Coix/química , Glicósidos/aislamiento & purificación , Benzoxazinas/química , Dicroismo Circular , Glicósidos/química , Imagen por Resonancia Magnética , Raíces de Plantas/químicaRESUMEN
Kobophenol A (KPA) is a biologically active natural compound isolated from the roots of Caragana sinica (Buc'hoz) Rehder (C. sinica). However, the anti-inflammatory effects of KPA have not been reported. This study aims to find out whether KPA isolated from roots of C. sinica can act as a potential substance on inflammation and analyze the molecular mechanism using the lipopolysaccharide (LPS)-stimulated J774â¯A.1 macrophage cell line. We showed that KPA treatment significantly suppressed the production of nitric oxide (NO) by inhibiting inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner without cytotoxicity. In the KPA also inhibited pro-inflammatory cytokine gene expression and production, such as interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in LPS-stimulated J774â¯A.1 cells. As continuing study on the mechanisms involved, we confirmed that these effects of KPA were related to the inhibition of nuclear factor-κB (NF-κB) pathway including the suppression of IκB kinase α/ß (IKKα/ß) phosphorylation and translocation of NF-κB into the nucleus. Taken together, the present study is the first to demonstrate that KPA isolated from C. sinica suppresses the expression of inflammatory mediators and cytokines by inhibiting NF-κB nuclear translocation in LPS-stimulated J774â¯A.1 macrophages. KPA may be a potential candidate for the treatment of inflammatory diseases in the future.