Effect of Lippia alba essential oil administration on obesity and T2DM markers in Wistar rats / Efecto de la administración del aceite esencial de Lippia alba sobre la obesidad y los marcadores T2DM en ratas wistar

SUMMARY Introduction: Lippia alba (Mill) N.E. Brown (Verbenaceae) is an aromatic plant from Central America, South America, and the Caribbean, it is traditionally used by the Colombian population to treat various diseases such as diabetes and hypertension. The purpose of this research was to evaluate the metabolic effects of Lippia alba essential oil (EO) oral administration on obesity and diabetes markers in Wistar rats. Methods: control and Streptozotocin (STZ) diabetes induced rats were used to evaluate the EO metabolic effects. Glucose and triglycerides were measured using commercial colorimetric kits, the animals' weight was followed for 21 days treatment and TNF-α and adiponectin concentration was determined with ELISA technique. Results: The consumption of EO shows body weight gain regulation, lower glucose and cholesterol levels in normal rats and lower TNF- α in comparison with the Glibenclamide treated rats between the STZ diabetic groups. No toxic effects were founded. Conclusions: The EO exerts a benefical metabolic effect in rats, therefore it is interesting to be evaluate a future in human beings with T2DM or overweight.

RESUMEN Introducción: Lippia alba (Mill) N.E. Brown (Verbenaceae) más conocida como pronto alivio, es una planta aromática de Centro, Sur América y el Caribe que se utiliza tradicionalmente en Colombia para el tratamiento de diversas enfermedades, como la diabetes e hipertensión. El objetivo del trabajo fue evaluar el efecto metabólico del aceite esencial de Lippia alba (Mill), administrado oralmente, sobre moléculas relacionadas con obesidad y diabetes en ratas Wistar. Métodos: Se pesaron los animales diariamente. Después de 21 días de tratamiento con el AE se determinó en plasma la glucosa, triglicéridos con kits comerciales y las adipocitoquinas (adiponectina y factor de necrosis tumoral alfa (TNFα) marcadores de resistencia a la acción de la insulina) por la técnica de ELISA. Resultados: El consumo de AE mostró una regulación en la ganancia de peso corporal y disminución en los niveles de glucosa y triglicéridos en los animales normales que recibieron el AE. Dentro de los grupos con diabetes inducida, el grupo tratado con AE mostró menores valores de TNF-α comparado con el grupo tratado con glibenclamida. Conclusiones: El AE ejerce un efecto benéfico en el metabolismo de los animales, por lo tanto, es interesante para ser evaluado en seres humanos con diabetes o sobrepeso.

Aceites esenciales, obesidad y diabetes tipo 2 / Essential oils, obesity and type 2 diabetes

RESUMEN El incremento de la obesidad en la sociedad se ha hecho evidente en los últimos años. Estadísticas recientes de entidades oficiales la ubican dentro de las enfermedades más prevalentes en el mundo. La obesidad es una enfermedad crónica proinflamatoria, que cursa con un desbalance en la actividad endocrina del tejido adiposo generando un cambio en el patrón de producción de determinadas adipocitoquinas relacionadas con el incremento en la resistencia a la acción de la insulina y el consecuente aumento de la glucemia, característicos de la diabetes mellitus tipo 2. El tratamiento de estos desórdenes está orientado a disminuir la glucemia y reducir el peso del individuo que los padece. Los medicamentos utilizados para tratar ambas enfermedades comúnmente tienen efectos secundarios indeseables, lo que ha hecho que los farmacólogos estén en constante búsqueda de nuevos medicamentos. El objetivo de esta publicación es hacer una revisión del estado del arte en las dos enfermedades, tomando como punto de partida el hecho de que las dos tienen en común la inflamación sistémica leve y alteración del sistema inmune que desemboca en resistencia a la acción de la insulina y, además, señalar la actividad de algunos aceites esenciales estudiados hasta el momento en ratas y ratones como posibles alternativas terapéuticas en el control de la obesidad y la diabetes mellitus tipo 2.

Summary The increase of obesity in our society has become evident nowadays. Recent statistics from official entities place it within the most prevalent diseases in the world. Obesity is a chronic pro-inflammatory disease that causes an imbalance in endocrine activity of adipose tissue, changing the production pattern of certain adipocytokines related to insulin resistance, consequently there is an increase of glycemia characteristic in type 2 diabetes mellitus. The treatment for these disorders is aimed to lower blood sugar levels and reduce the weight of those who suffer it. The medicines used to treat both diseases usually have undesirable side effects, which have made pharmacologists be in constant search for new drugs. The aim of this publication is to review the state of the art on these two diseases, starting from the fact that both have in common mild systemic inflammation and immunological alterations that lead to resistance to insulin action, and additionally to describe the activity of some essential oils studied so far in rats and mice as possible therapeutic alternatives in controlling obesity and type 2 diabetes mellitus.

Essential oils with insecticidal activity against larvae of Aedes aegypti (Diptera: Culicidae).

Insecticidal activity of the essential oils (EOs) isolated from Tagetes lucida, Lippia alba, Lippia origanoides, Eucalyptus citriodora, Cymbopogon citratus, Cymbopogon flexuosus, Citrus sinensis, Swinglea glutinosa, and Cananga odorata aromatic plants, grown in Colombia (Bucaramanga, Santander), and of a mixture of L. alba and L. origanoides EOs were evaluated on Aedes (Stegomyia) aegypti Rockefeller larvae. The EOs were extracted by microwave-assisted hydrodistillation and characterized by gas chromatography-mass spectrometry (GC-MS). The main components of the EOs were identified using their linear retention indices and mass spectra. The lethal concentrations (LCs) of the EOs were determined between the third and fourth instar of A. aegypti. LC50 was determined by probit analysis using mortality rates of bioassays. All essential oils tested showed insecticidal activity. The following values were obtained for C. flexuosus (LC50 = 17.1 ppm); C. sinensis (LC50 = 20.6 ppm); the mixture of L. alba and L. origanoides (LC50 = 40.1 ppm); L. alba (LC50 = 42.2 ppm); C. odorata (LC50 = 52.9 ppm); L. origanoides (LC50 = 53.3 ppm); S. glutinosa (LC50 = 65.7 ppm); T. lucida (LC50 = 66.2 ppm); E. citriodora (LC50 = 71.2 ppm); and C. citratus (LC50 = 123.3 ppm). The EO from C. flexuosus, with citral (geranial + neral) as main component, showed the highest larvicidal activity.

Tissue distribution and expression of paraoxonases and chemokines in mouse: the ubiquitous and joint localisation suggest a systemic and coordinated role.

A vicious cycle between oxidation and inflammation leads to complications in a growing number of disease states. Knowledge on tissue distribution of chemokines, mediators of inflammatory response, and paraoxonases, with antioxidant and anti-inflammatory actions, may be relevant. Using immunohistochemistry and quantitative real-time PCR we have investigated the distribution of PON1, 2 and 3, CCL2, 7, 8 and 12 and the chemokine receptor CCR2 protein and mRNA in 23 tissues from C57BL/6J mice. As expected, PON1, 2 and 3, CCL2, 7, 8 and 12 and CCR2 proteins were present in the vast majority of tissues investigated. Surprisingly, mRNA for these proteins was also expressed in most of these tissues suggesting local production and the ability to respond in situ to inflammatory stimuli. The wide distribution and expression of mRNA for paraoxonases and CC-chemokines suggest a systemic, probably coordinated, role in the overall inflammatory response.

Infection with HIV and HCV enhances the release of fatty acid synthase into circulation: evidence for a novel indicator of viral infection.

BACKGROUND: Fatty acid synthase (FASN) is an enzyme synthesized by the liver and plays an important role in lipogenesis. The present study aimed to investigate whether serum FASN concentration may provide a direct link between HIV and/or HCV viral infections and lipid metabolic disorders commonly observed in HIV/HCV-infected patients. METHODS: We evaluated serum FASN concentration in 191 consecutive HIV-infected patients in the absence or presence of HCV co-infection. For comparison, 102 uninfected controls were included. Metabolic and inflammatory phenotype was also compared with respect to the presence of HCV co-infection. RESULTS: Serum FASN concentration was significantly higher in HIV-infected patients than in healthy participants and HCV co-infected patients showed higher levels than those without co-infection. Levels were also affected by treatment regimen, but marginally influenced by virological variables. Insulin concentration was the sole variable among metabolic parameters that demonstrated a significant correlation with serum FASN concentrations. Serum alanine aminotransferase (ALT) values correlated significantly with serum FASN concentration and provided the best discrimination with respect to the presence or absence of HCV co-infection. In multivariate analysis, only ALT, monocyte chemoattractant protein-1 (MCP-1) and the presence of antiretroviral treatment regimen significantly contributed to explain serum FASN concentration in HIV/HCV co-infected patients. CONCLUSION: Serum FASN concentration is significantly increased in HIV-infected individuals. The release of FASN into the circulation is further enhanced in patients who are co-infected with HCV. Subsequent studies should explore the usefulness of this indicator to monitor the effect of viral infections on disease progression and survival.

Host-pathogen interactions in the development of metabolic disturbances and atherosclerosis in HIV infection: the role of CCL2 genetic variants.

BACKGROUND: Circulating CCL2 concentration has been implicated in promoting atherosclerosis in patients infected with HIV. We evaluated whether CCL2 gene variants are associated with metabolic disturbances and plasma CCL2 levels in HIV-infected patients. METHODS AND RESULTS: CCL2 genotypes and estimated haplotypes, plasma CCL2 levels and indicators of metabolic status in HIV-infected patients were compared with a representative group of the general population. We also performed a carotid/femoral artery ultrasonography to detect sub-clinical atherosclerosis in these patients. Six haplotypes were estimated in more than the 5% of individuals, and accounted for more than 98% of the population. In HIV-infected patients, carriers of H1, H2 and H5 haplotypes had higher CCL2 concentration than carriers of H3, H4 and H6 haplotypes. However, only carriers of H1 and H5 haplotypes presented higher insulin resistance as well as higher proportion of patients affected with sub-clinical. Conversely, carriers of H2 haplotype, which also showed high plasma CCL2 concentration, were associated with less deleterious metabolic disturbances. CONCLUSIONS: Our data are consistent with the hypothesis that the genetic background of the host is involved in CCL2 production and that this chemokine is implicated in promoting metabolic disturbances and sub-clinical atherosclerosis in HIV-infected patients.

Differential response of two models of genetically modified mice fed with high fat and cholesterol diets: relationship to the study of non-alcoholic steatohepatitis.

Research on the molecular basis of the hepatic alterations associated to obesity is dependent on the availability of suitable animal models. Apolipoprotein E deficient mice (ApoE(-/-)) and LDL-receptor deficient mice (LDLr(-/-)) develop steatosis and steatohepatitis when given pro-atherogenic diets. However, previous data suggest that these two models are not completely interchangeable, and that their metabolic phenotype may partially differ in response to nutrient stimuli. The present study further investigates this question, by comparing changes in hepatic inflammation, lipoprotein metabolism, and their related gene expressions. LDLr(-/-) mice were more susceptible to the development of obesity and hepatic steatosis, while the ApoE(-/-) model increased the amount of macrophages and inflammatory nodules in the liver. These changes were accompanied by a differential expression of selected members of the MAPK family and PPARs in the liver.

Human immunodeficiency virus-infection induces major changes in high-density lipoprotein particle size distribution and composition: the effect of antiretroviral treatment and disease severity.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with abnormal high-density lipoprotein (HDL) particles. We evaluated whether HIV infection and antiretroviral treatment promotes changes in cholesterol distribution among subpopulations of HDL particles of defined sizes. METHODS: HDL particles were isolated from 78 HIV infected patients and fractionated by gel permeation chromatography to obtain five subpopulations. Thirty-six patients were antiretroviral treatment naïve, while 42 patients were treated with efavirenz or protease inhibitors. Uninfected individuals were also included as controls. RESULTS: The distribution of cholesterol across HDL particle sizes was affected by HIV infection itself. Antiretroviral therapy reduced these alterations; only minor changes in small and very small HDL particles were observed in treated patients (p=0.01). Untreated patients with low CD4+ T cell counts had less cholesterol in medium (p=0.006), small (p=0.04) and very small (p=0.03) HDL particles. Treated patients with high CD4+ T cell counts had less cholesterol in the largest HDL particles (p=0.04), with overall particle distributions resembling those observed in uninfected participants. CONCLUSIONS: HIV infection itself may promote major changes in cholesterol distribution among HDL subpopulations that could be partially attenuated by current antiretroviral treatments. Further studies in larger populations are necessary to confirm the impact of HIV on lipoprotein composition and distribution.

Expression of cytokine genes in the aorta is altered by the deficiency in MCP-1: effect of a high-fat, high-cholesterol diet.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) facilitates the recruitment of monocytes/macrophages into vascular intima, and it is probably involved in the regulation of other signaling pathways relevant to the pathogenesis of arteriosclerosis and metabolic disturbances. However, chemokines are redundant. Consequently, the protective effect of MCP-1 deficiency may be mediated by changes in other cytokine signals. METHODS AND RESULTS: Changes in the pattern of gene expression in the aorta were evaluated in LDLr(-/-) and MCP-1(-/-) LDLr(-/-) mice fed either chow or Western-style diet. Functional analyses were used to characterize the pathways affected and to identify biological processes in which MCP-1 may play an additional role. Some data also suggest that MCP-5 may act as a surrogate for MCP-1 deletion. Arteriosclerosis lesion and plaque composition are associated with enrichment in the cytokine-cytokine receptor interaction pathway. CONCLUSIONS: There is a complex network of interactions linking MCP-1 and other cytokines. The lack of MCP-1 limits the aortic response to atherogenic stimuli, but does not completely protect against neointima formation. Activation of alternative inflammatory pathways in the vascular wall in response to MCP-1 deficiency should be considered to fully understand the actual role of this chemokine.