RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from M. officinalis L. (Labiatae; lemon balm) has an anti-angiogenic activity, we hypothesized that ALS-L1023 could inhibit adipogenesis and adipocyte hypertrophy. MATERIALS AND METHODS: ALS-L1023 was prepared by a two-step organic solvent fractionation from M. officinalis. The effects of ALS-L1023 on adipogenesis in 3T3-L1 adipocytes and adipocyte hypertrophy in high fat diet (HFD)-fed obese mice were measured using in vivo and in vitro approaches. RESULTS: ALS-L1023 inhibited angiogenesis in a dose-dependent manner in the HUVEC tube formation assay in vitro. Treatment of cells with ALS-L1023 inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or MDI differentiation mix. ALS-L1023 reduced mRNA expression of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9) in differentiated cells. In contrast, mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) increased. Protease activity, as measured by zymography, showed that activity of MMP-2 and MMP-9 decreased in ALS-L1023-treated cells. ALS-L1023 also inhibited MMP-2 and MMP-9 reporter gene expression in the presence of the MMP inducer phorbol 12-myristate 13-acetate. An in vivo study showed that ALS-L1023 not only decreased adipose tissue mass and adipocyte size, but also reduced mRNA levels of adipose tissue angiogenic factors and MMPs in HFD-fed obese mice. CONCLUSIONS: These results suggest that the anti-angiogenic herbal extract ALS-L1023 suppresses adipogenesis and adipocyte hypertrophy, and this effect may be mediated by inhibiting angiogenesis and MMP activities. Thus, by curbing adipogenesis, anti-angiogenic ALS-L1023 yields a possible therapeutic choice for the prevention and treatment of human obesity and its associated conditions.
Asunto(s)
Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Hipertrofia/tratamiento farmacológico , Melissa/química , Extractos Vegetales/farmacología , Células 3T3-L1 , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Inductores de la Angiogénesis/metabolismo , Animales , Línea Celular , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Hipertrofia/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/inducido químicamente , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Extractos Vegetales/química , ARN Mensajero/metabolismoRESUMEN
It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.
Asunto(s)
Tejido Adiposo/patología , Inhibidores de la Angiogénesis/farmacología , Melissa/química , Extractos Vegetales/farmacología , Adipocitos/efectos de los fármacos , Tejido Adiposo/irrigación sanguínea , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/enzimología , Animales , Peso Corporal/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Dieta Alta en Grasa , Células Endoteliales de la Vena Umbilical Humana , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Ratones Endogámicos C57BL , Ratones Obesos , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , PPAR alfa/genética , PPAR alfa/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Aumento de Peso/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Adipocyte lipid accumulation due to impaired fatty acid oxidation causes adipocyte hypertrophy and adipose tissue increment, leading to obesity. The aim of this study was to determine the antiobesity effects of the herbal composition Gambigyeongsinhwan (4) (GGH(4)) composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata. MATERIALS AND METHODS: The effects of GGH(4) and the individual components on lipid accumulation in 3T3-L1 adipocytes and body weight gain in Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined using Oil red O staining, hematoxylin and eosin staining, quantitative real-time PCR, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay. RESULTS: GGH(4), individual components, and an active principle of Curcuma longa curcumin inhibited lipid accumulation and mRNA levels of adipocyte-specific genes (PPARγ, aP2, and C/EBPα) in 3T3-L1 adipocytes compared with control cells. Treatment with GGH(4), the individual components or curcmumin increased mRNA levels of mitochondrial (CPT-1, MCAD, and VLCAD) and peroxisomal (ACOX and thiolase) PPARα target genes. GGH(4) and the individual components also increased PPARα reporter gene expression compared with control cells. These effects were most prominent in GGH(4)-treated cells. However, the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on adipogenesis. An in vivo study showed that GGH(4) decreased body weight gain, adipose tissue mass, and visceral adipocyte size with increasing mRNA levels of adipose tissue PPARα target genes in OLETF rats. CONCLUSIONS: These results demonstrate that GGH(4) has an antiobesity effects through the inhibition of adipocyte lipid accumulation, and this process may be mediated in part through adipose PPARα activation.
Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Obesidad/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Preparaciones de Plantas/uso terapéutico , Células 3T3-L1 , Alnus , Animales , Fármacos Antiobesidad/farmacología , Proteínas Potenciadoras de Unión a CCAAT/genética , Curcuma , Medicamentos Herbarios Chinos/farmacología , Proteínas de Unión a Ácidos Grasos/genética , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Medicina Tradicional Coreana , Ratones , Obesidad/metabolismo , Oxazoles/farmacología , PPAR alfa/antagonistas & inhibidores , PPAR gamma/genética , Fitoterapia , Extractos Vegetales/farmacología , Preparaciones de Plantas/farmacología , ARN Mensajero/metabolismo , Ratas Endogámicas OLETF , Triglicéridos/metabolismo , Tirosina/análogos & derivados , Tirosina/farmacología , Aumento de Peso/efectos de los fármacosRESUMEN
We investigated the effect of essential oil from the flower of Chrysanthemum boreale Makino (CBMEO) on growth of human keratinocytes (HaCaTs) and explored a possible mechanism for this response. CBMEO was extracted using the steam distillation method. CBMEO contained a total of 33 compounds. CBMEO stimulated HaCaT proliferation (EC50, 0.028 µg/mL) and also induced phosphorylation of Akt and ERK1/2 in HaCaTs (EC50, 0.007 and 0.005 µg/mL, for phosphorylated Akt and ERK1/2, respectively). Moreover, CBMEO promoted wound closure in the dorsal side skin of rat tail. This study demonstrated that CBMEO can stimulate growth of human skin keratinocytes, probably through the Akt and ERK1/2 pathways. Therefore, CBMEO may be helpful in skin regeneration and wound healing in human skin, and may also be a possible cosmetic material for skin beauty.
Asunto(s)
Chrysanthemum/química , Queratinocitos/efectos de los fármacos , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Regeneración/efectos de los fármacos , Piel/efectos de los fármacos , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Flores/química , Humanos , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Cicatrización de Heridas/efectos de los fármacosRESUMEN
CONTEXT: Chrysanthemum boreale Makino (Compositae) (CBM) is a traditional medicine that has been used for the prevention or treatment of various disorders; it has various properties including antioxidation, anti-inflammation, and antitumor. OBJECTIVE: The present study was designed to explore the in vitro effect of CBM flower floral water (CBMFF) on atherosclerosis-related responses in rat aortic smooth muscle cells (RASMCs). MATERIALS AND METHODS: CBMFF was extracted from CBM flower by steam distillation and analyzed using gas chromatography-mass spectrometry. The anti-atherosclerosis activity of CBMFF was tested by estimating platelet-derived growth factor (PDGF)-BB (10 ng/mL)-induced proliferation and migration levels and intracellular kinase pathways in RASMCs at CBMFF concentrations of 0.01-100 µM and analyzing ex vivo aortic ring assay. RESULTS: Gas chromatography-mass spectrometry showed that the CBMFF contained a total of seven components. The CBMFF inhibits PDGF-BB-stimulated RASMC migration and proliferation (IC50: 0.010 µg/mL). Treatment of RASMCs with PDGF-BB induced PDGFR-ß phosphorylation and increased the phosphorylations of MAPK p38 and ERK1/2. CBMFF addition prevented PDGF-BB-induced phosphorylation of these kinases (IC50: 008 and 0.018 µg/mL, for p38 MAPK and ERK1/2, respectively), as well as PDGFR-ß (IC50: 0.046 µg/mL). Treatment with inhibitors of PDGFR, P38 MAPK, and ERK1/2 decreased PDGF-BB-increased migration and proliferation in RASMCs. Moreover, the CBMFF suppressed PDGF-BB-increased sprout outgrowth of aortic rings (IC50: 0.047 µg/mL). DISCUSSION AND CONCLUSION: These results demonstrate that CBMFF may inhibit PDGF-BB-induced vascular migration and proliferation, most likely through inhibition of the PDGFR-ß-mediated MAPK pathway; therefore, the CBMFF may be promising candidate for the development of herbal remedies for vascular disorders.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Chrysanthemum , Músculo Liso Vascular/efectos de los fármacos , Extractos Vegetales/farmacología , Factor de Crecimiento Derivado de Plaquetas/farmacología , Animales , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Flores , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Extractos Vegetales/aislamiento & purificación , Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Agua/farmacologíaRESUMEN
Artemisia montana Pampan (Compositae) (AMP) contains various compounds, including phenolic acids, alkaloids, and essential oil. It has been widely used in oriental medicine due to a variety of biological effects. However, the biological activity of the essential oil from AMP (AMPEO) on skin has not been investigated. In the present study, AMPEO was evaluated for its composition and its effect on cellular events (migration and proliferation) related to skin regeneration using normal human keratinocytes (HaCats). AMPEO, which was extracted by steam distillation, contained 42 components. AMPEO increased proliferation in HaCats in a dose-dependent manner (EC 50, 8.5 ng/mL) and did not affect migration. AMPEO also enhanced the phosphorylation of Akt and ERK 1/2 and induced the synthesis of type IV collagen, but not type I collagen in HaCats. In addition, AMPEO promoted wound closure in the dorsal side skin of rat tail. These results demonstrated that AMPEO extracted by steam distillation induced proliferation and synthesis of type IV collagen in human skin keratinocytes, and may thereby exert positive effects on skin regeneration and wound healing in human skin.