RESUMEN

The aim of the present study was to identify the active principle from Catharanthus roseus leaf using larvicidal bioassay against three mosquito species viz. Aedes aegypti, Culex quinquefasciatus, and Anopheles stephensi. Preliminary studies of the three successive extracts such as hexane, chloroform, and methanol against Ae. aegypti larvae showed that the chloroform extract was more active with LC50 and LC90 values of 40.09 ppm and 189.15 ppm respectively. Bioassay guided fractionation of the active chloroform extract resulted in the isolation of a triterpenoid (ursolic acid) as the active constituent. Three derivatives acetate, formate, and benzoate were prepared using this, and they were tested for their larvicidal activity against three mosquito species. The acetyl derivative was highly active against all the three species compared to the parent compound ursolic acid; the activities of benzoate and formate were higher than ursolic acid when tested against Cx. quinquefasciatus. This is the first report related to ursolic acid from C. roseus with mosquito larvicidal activity. The pure compound could be considered for medicinal and other pharmacological applications in future.

Asunto(s)

Aedes , Anopheles , Catharanthus , Culex , Insecticidas , Animales , Larva , Cloroformo , Insecticidas/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta , Ácido Ursólico

RESUMEN

Mosquitoes are important vectors responsible for spreading a number of diseases affecting both humans and animals. Many diseases as dengue, chikungunya, yellow fever, malaria, filariasis and Japanese encephalitis are spread by mosquitoes. There are many reports of plant extracts and their active constituents showing anti-mosquito activities as larvicidal, pupicidal, ovicidal and adulticidal activities. Persea americana Mill. (Lauraceae), known as avocado, has been reported to show many pharmacological and antimicrobial activities. In this communication, the mosquito larvicidal activities of the three-active constituents, avocadene, avocadyne and avocadenol-A, from the methanolic extract of the unripe fruit peel are presented. The three mosquito species studied were Aedes aegypti, Culex quinquefasciatus and Anopheles stephensi. All three compounds showed the highest larvicidal activity against An. stephensi, LC50 values being 2.80ppm for avocadene, 2.33ppm for avocadyne and 2.07ppm for avocadenol-A. Avocadene showed larvicidal activity of 3.73ppm against Ae. aegypti and 5.96ppm against Cx. quinquefasciatus. The LC50 value of avocadyne was 5.35ppm against Ae. aegypti and 3.98ppm against Cx. quinquefasciatus. Similarly, avocadenol-A showed 6.56ppm against Ae. aegypti and 2.35ppm against Cx. quinquefasciatus. The active constituents were isolated by bioactivity-guided fractionation by silica gel column chromatography and RP HPLC. The compounds were identified by physical and spectroscopic data and compared with literature values already reported.

Asunto(s)

Culex , Insecticidas , Persea , Humanos , Animales , Mosquitos Vectores , Frutas , Insecticidas/química , Larva , Extractos Vegetales/química , Hojas de la Planta/química

RESUMEN

Embelin was isolated from the chloroform extract of Embelia ribes (Burm.f.) fruits; its derivative compounds 6-bromoembelin and vilangin were prepared, and they were evaluated for mosquitocidal activities against the third instar larvae and pupae of Aedes aegypti L. and Culex quinquefasciatus Say. (Diptera: Culicidae). The concentrations used were 0.5, 1.0, 1.5, and 2.0 ppm. Embelin recorded LC50 values of 5.79 and 5.54 ppm against the larvae of Ae. aegypti and Cx. quinquefasciatus, respectively. Similarly, the LC50 values of embelin were 10.23 and 6.93 ppm against the pupae of Ae. aegypti and Cx. quinquefasciatus, respectively. Of the two derivatives tested, vilangin showed the highest larvicidal activity with LC50 values of 1.38 and 1.28 ppm against the larvae of Ae. aegypti and Cx. quinquefasciatus, respectively. Similarly, the LC50 values of vilangin were 1.60 and 1.43 ppm against the pupae of Ae. aegypti and Cx. quinquefasciatus, respectively. The LC50 values of 6-bromoembelin were 3.30 and 2.83 ppm against the larvae and 4.40 and 4.30 ppm against the pupae of Ae. aegypti and Cx. quinquefasciatus, respectively. The histopathological results displayed significant damage on cuboidal cells of the midgut (CU) in vilangin treated larvae of Ae. aegypti and Cx. quinquefasciatus at a concentration of 2.0 ppm. Similarly, peritrophic membrane (PM) was completely impaired in vilangin-treated larvae of Cx. quinquefasciatus and midgut content (MC) was very low in vilangin-treated larvae of Cx. quinquefasciatus. In addition, molecular docking and molecular dynamics studies demonstrated the efficacy of vilangin on the inhibition of acetylcholinesterase (AChE1) in Ae. aegypti and Cx. quinquefasciatus. The present results suggest that vilangin could be used to develop a natural active product against mosquito larvae.

Asunto(s)

Aedes , Culex , Acetilcolinesterasa , Animales , Benzoquinonas , Larva , Simulación del Acoplamiento Molecular , Extractos Vegetales/farmacología

RESUMEN

Vector-borne diseases such as filariasis and dengue that contribute significantly to disease burden, death, poverty, and social frailty are still a major public healthcare problem worldwide. Currently, synthetic chemicals have been used in mosquito control programs. However, repeated use of chemical insecticides causes environmental pollution and harmful effects on non-target organisms. Therefore, alternative ecofriendly sources from biological source are urgently needed to manage mosquitoes. In this respect, the present study was aimed to evaluate mosquito larvicidal and pupicidal activities of 22 crude extracts of soil actinomycetes on Culex quinquefasciatus and Aedes aegypti and to identify the active molecule. Briefly, the crude ethyl acetate extract and fractions were tested at 62.5, 125, 250, and 500 ppm and 2.5, 5.0, 7.5, and 10.0 ppm concentrations on larval and pupal stages of Cx. quinquefasciatus and Ae. aegypti. The larval and pupal mortality was assessed after 24 h of treatment. Among the 22 isolates screened, Nonomuraea sp. VAS-16 exhibited significant larvicidal and pupicidal activities against the tested mosquito species. Among the 18 fractions screened, fraction-6 showed strong larvicidal and pupicidal activities with the LC50 and LC90 values of 9.1, 18.7, 9.82, and 22.85 ppm against the larvae and LC50 and LC90 values of 10.5, 23.1, 12.3, and 24.13 ppm against the pupae of Cx. quinquefasciatus and Ae. aegypti, respectively. Fascinatingly, the isolated compound 1,2-benzenedicarboxylic acid from fraction-6 at 0.5, 1.0, 1.5, and 2.0 ppm concentration recorded lower LC50 and LC90 values of 4.27, 14.90, 4.67, and 11.90 ppm against the larvae and LC50 and LC90 values of 4.58, 12.06, 5.36, and 13.07 ppm against the pupae of Cx. quinquefasciatus and Ae. aegypti, respectively. On the other hand, the compound recorded less ovicidal activity of 11.0% and 10.3% at 2 ppm against the eggs of Cx. quinquefasciatus and Ae. aegypti, respectively. The present study clearly shows that the crude extract and the compound from Nonomuraea sp. VAS-16 can be used as an effective biopesticide in integrated mosquito management program.

Asunto(s)

Actinobacteria , Aedes , Anopheles , Culex , Insecticidas , Actinomyces , Animales , Agentes de Control Biológico/análisis , Agentes de Control Biológico/farmacología , Insecticidas/química , Larva , Mosquitos Vectores , Extractos Vegetales/química , Hojas de la Planta/química , Suelo

RESUMEN

The bio-efficacy of crude ethyl acetate extract, fractions and a compound phenyl acetic acid from the ethyl acetate extract of Streptomyces collinus was evaluated on Culex quinquefasciatus Say and Aedes aegypti L. mosquitoes (Diptera: Culicidae). The larvae were exposed to concentrations of 2.5, 5.0, 7.5 and 10.0 ppm for fractions and 0.5, 1.0, 1.5 and 2.0 ppm for compound. After 24 h, the larval mortality was assessed and the LC50 and LC90 values were calculated. Similarly, per cent ovicidal activity was calculated for eggs after 120 h post treatment for phenyl acetic acid. Among the eleven fractions screened, fraction 7 from the ethyl acetate extract of Streptomyces collinus exhibited good larvicidal activity against both mosquito species. The LC50 and LC90 values of fraction 7 were 4.42, 6.23 ppm against Cx. quinquefasciatus larvae and 5.13, 14.51 ppm against Ae. aegypti larvae, respectively. Further, the isolated compound, phenyl acetic acid from fraction 7 recorded 100% larvicidal activity at 2 ppm concentration with LC50 and LC90 values of 2.07, 4.87 ppm on Cx. quinquefasciatus larvae and 3.81, 9.87 ppm on Ae. aegypti larvae, respectively. Phenyl acetic acid presented 50.3% and 42.0% ovicidal activity against Cx. quinquefasciatus and Ae. aegypti eggs at 2 ppm concentration after 120 h post treatment. The compound, phenyl acetic acid could be used in mosquito control programme.

Asunto(s)

Aedes , Culex , Fenilacetatos , Streptomyces/química , Aedes/efectos de los fármacos , Aedes/enzimología , Aedes/crecimiento & desarrollo , Análisis de Varianza , Animales , Bioensayo , Culex/efectos de los fármacos , Culex/enzimología , Culex/crecimiento & desarrollo , Esterasas/antagonistas & inhibidores , Glutatión Transferasa/antagonistas & inhibidores , India , Larva/efectos de los fármacos , Dosificación Letal Mediana , Óvulo/efectos de los fármacos , Fenilacetatos/química , Fenilacetatos/aislamiento & purificación , Fenilacetatos/farmacología

RESUMEN

The present study was aimed to isolate active constituents from Blumea axillaris (Lam.) DC (Asteraceae) against phytopathogenic fungi. Bioactivity guided fractionation of the successive n-hexane, chloroform and methanol extract led to the isolation of the monoterpene ester (4 R,5S)-4-hydroxy-7-tigloyloxycarvotanacetone (1). The compound 1 was converted into acetyl derivative (2). The acetyl derivative (2) and the parent compound 1 were tested again phytopathogenic fungi by using mycelial inhibition and minimal inhibitory concentration values were found out by the broth microdilution method. The acetyl derivative (2) showed the highest antifungal activity against Rhizoctonia solani and Aspergillus niger. Based upon in vitro results, compound 1 was tested against Fusarium oxyporum (wilting disease) and compound 2 was tested against R. solani (leaf blight disease) in vivo using the foliar spray method. Both compounds had no phytotoxicity and also in silico docking study showed that both compounds were binding similarly as commercial fungicide carbendazim.

Asunto(s)

Asteraceae , Fusarium , Antifúngicos/farmacología , Ésteres , Hongos , Simulación del Acoplamiento Molecular , Monoterpenos/farmacología , Enfermedades de las Plantas

RESUMEN

The present study was aimed to check the mosquitocidal activity of intracellular methanol extract fractions and the compound di (2-ethylhexyl) phthalate isolated from Streptomyces rimosus. The isolated compound was also analyzed for its interaction with Acetylcholinesterase (AChE1). The larvae and eggs of Culex quinquefasciatus were exposed to four different concentrations such as 2.5, 5.0, 7.5 and 10 ppm for fractions and 0.5, 1.0, 1.5 and 2.0 ppm for compound. After 24 and 120 h post treatment, the larval mortality and ovicidal activity were recorded. Fractions collected from the intracellular methanol extract were tested for larvicidal activity; among them Fraction 4 was found to be the active fraction. Fraction 4 showed 74% larvicidal activity with LC50 and LC90 values of 6.9 and 17.2 ppm, respectively, in 24 h against the larvae of Cx. quinquefasciatus. Fraction 4 showed 95% ovicidal activity at 10 ppm concentration after 120 h post treatment. The eluted compound di(2-ethylhexyl) phthalate was highly toxic and exhibited promising activity against the eggs of Cx. quinquefasciatus. The compound presented 94% ovicidal activity at 2.0 ppm concentration after 120 h post treatment. The larvae of Cx. quinquefasciatus were exposed to di(2-ethylhexyl) phthalate which showed good activity in a concentration-dependent manner. The compound showed 76% larvicidal activity against the larvae of Cx. quinquefasciatus with LC50 and LC90 values of 1.22 and 3.28 ppm, respectively, at 2 ppm concentration in 24 h. Fraction 4 and the compound were subjected to toxicity study against non-target organism and were found to be nontoxic. The present studies revealed that the treated larvae showed serious damage in the midgut cells. Growth disruption and larval deformities were observed in compound-treated larvae. The compound was highly active and inhibited AChE in a concentration-dependent manner. Computational analysis of the compound had strong interaction with AChE1 of Cx. quinquefasciatus. These results clearly showed that Fraction 4 and the compound isolated from S. rimosus can be used to control the life stages of Cx. quinquefasciatus; it will be a good alternative to synthetic insecticides.

Asunto(s)

Acetilcolinesterasa/metabolismo , Productos Biológicos/farmacología , Culex/efectos de los fármacos , Dietilhexil Ftalato/farmacología , Insecticidas/farmacología , Larva/efectos de los fármacos , Streptomyces rimosus/química , Animales , Inhibidores de la Colinesterasa/farmacología , Culex/enzimología , Culex/crecimiento & desarrollo , Culex/metabolismo , Dosificación Letal Mediana , Mosquitos Vectores/efectos de los fármacos , Mosquitos Vectores/enzimología , Mosquitos Vectores/crecimiento & desarrollo , Mosquitos Vectores/metabolismo , Óvulo/efectos de los fármacos

RESUMEN

The triterpenoid, bauerenol, from Suregada angustifolia (Baill. ex Muell.-Arg.) Airy Shaw (Euphorbiaceae) was screened for anti-cancer property using hepatocellular carcinoma cell line, HepG2. Bauerenol exhibited growth inhibitory and apoptosis inducing potential against HepG2 cancer cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxic assay revealed that bauerenol treatment significantly reduced the growth of HepG2 cells in a time- and dose-dependent manner with 50% growth inhibitory concentration doses of 45 and 25 µg/mL at 24 and 48 h treatments, respectively. Bauerenol-induced cell death reflected apoptotic morphological features, that is, cell membrane blebbing, vacuolization, chromatin condensation, and nuclear fragmentation. In addition, bauerenol treatment diminished the mitochondrial membrane potential, by inducing the efflux of cytochrome c, downregulating the levels of anti-apoptotic Bcl-2 as well as upregulating the levels of pro-apoptotic Bax, and inducing caspase activation and poly (ADP-ribose) polymerase cleavage. Moreover, bauerenol treatment activates p38MAPK and inactivates the anti-apoptotic kinases Akt and ERK1/2 through the induction of reactive oxygen species. Furthermore, bauerenol-mediated S-phase arrest was associated with downregulation of cell cycle-rate-limiting factor (cyclin D1) and upregulation of cyclin-dependent kinase inhibitor p21 and tumor suppressor p53. Interestingly, pre-treatment of cells with reactive oxygen species inhibitor and p38 inhibitor significantly decreases bauerenol-induced cytotoxicity, Bax upregulation, and p38 activation. This study clearly states that bauerenol induces cell cycle arrest and apoptosis through the reactive oxygen species-dependent p38MAPK activation in HepG2 cancer cells.

Asunto(s)

Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Triterpenos/administración & dosificación , Proteínas Quinasas p38 Activadas por Mitógenos/biosíntesis , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Ciclina D1/biosíntesis , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo , Suregada/química , Triterpenos/química , Proteína X Asociada a bcl-2/biosíntesis , Proteínas Quinasas p38 Activadas por Mitógenos/genética

RESUMEN

Mimosa pudica Linn. (Mimosaceae) has been traditionally used for the management of type 2 diabetes mellitus (T2DM) in India. The present study evaluates the therapeutic efficacy of myoinositol (25 and 50mg/kg) isolated from M. pudica stem methanol extract in Triton WR-1339 induced hyperlipidemic and high-fat diet (HFD) fed-streptozotocin (STZ)-induced insulin-resistant diabetic rats. Lipid biomarkers, fasting blood glucose (FBG), changes in body weight, food and water intakes, plasma insulin, HOMA-IR, oral glucose tolerance, intraperitoneal insulin tolerance, urea, creatinine, marker enzymes of liver function, ß-cell function and the expression levels of insulin receptor-induced signaling molecules were studied. Molecular-docking was also carried out to determine the possible interactions of myoinositol into the active sites of insulin-induced signaling markers. In addition, histology of liver, pancreas, kidney, heart and adipose tissues were also performed. In Triton WR-1339 induced hyperlipidemic rats, myoinositol (25 and 50mg/kg) exhibited significant reductions in total cholesterol: 37.5% and 59.73%, triglycerides: 57.75% and 80.14% and LDL-c: 81.44% and 101.75% respectively. HFD fed-STZ receiving myoinositol (25 and 50mg/kg) showed significant reductions in fasting blood glucose: 55.68% and 56.48%, plasma insulin level: 25.45% and 27.06% when compared with diabetic control. It significantly normalized the hyperglycemia induced biochemical abnormalities in insulin-resistant diabetic rats. Furthermore, it demonstrated cytoprotective effects besides increase in the intensity of positive reaction for insulin in pancreas. Myoinositol enhanced the level of PPARγ expression in the adipose tissue of treated rats when compared with rats that did not receive drug treatment; also, it significantly upregulated GLUT4 and IR signaling molecules. Myoinositol had predicted the interactions within the active sites of PPARγ, GLUT4 and IR. These findings suggested that myoinositol could play an effective role in glucose disposal into adipose tissue by insulin-dependent signaling cascade mechanism; hence it could be used in the treatment of obesity-associated T2DM.

Asunto(s)

Diabetes Mellitus Experimental/tratamiento farmacológico , Inositol/uso terapéutico , Receptor de Insulina/metabolismo , Transducción de Señal , Administración Oral , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Dieta Alta en Grasa , Conducta de Ingestión de Líquido/efectos de los fármacos , Ayuno/sangre , Conducta Alimentaria/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Hiperlipidemias/sangre , Hiperlipidemias/complicaciones , Hiperlipidemias/tratamiento farmacológico , Inmunohistoquímica , Inositol/administración & dosificación , Inositol/química , Inositol/farmacología , Insulina/sangre , Resistencia a la Insulina , Riñón/efectos de los fármacos , Riñón/patología , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Simulación del Acoplamiento Molecular , Polietilenglicoles , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Transducción de Señal/efectos de los fármacos

RESUMEN

AIMS: This paper investigates the hypoglycemic activity of two derivatives of embelin (1) viz. 6-bromoembelin (2) and vilangin (3), in high-fat diet - STZ induced diabetic rats. MAIN METHODS: The effects of 6-bromoembelin (2) and vilangin (3) on insulin resistance, ß-cell dysfunction and glucose transport in high-fat diet (HFD) fed-streptozotocin (STZ) (40mg/kg) induced type 2 diabetic rats were evaluated. The binding modes of 6-bromoembelin (2) and vilangin (3) into PPARγ, PI3K, Akt, and GLUT4 were also studied using Autodock 4.2 and ADT 1.5.6 programs. KEY FINDINGS: At the dose of 30mg/kg, the plasma glucose, plasma insulin and body weight were reduced by both embelin derivatives in diabetic rats. Additionally the altered lipid profiles and hexokinase, glucose-6-phosphatase and fructose-1,6-bisphosphatase levels were brought to normal. Compared to diabetic control group, there was a significant increase in the expression of PPARγ in epididymal adipose tissue. Inhibition of adipogenic activity and mild activation of PPARγ levels in the skeletal muscle and liver were observed. In epididymal adipose tissue, the compounds increased the insulin-mediated glucose uptake through the activation and translocation of GLUT4 in PI3K/p-Akt signaling cascade. SIGNIFICANCE: The derivatives of embelin such as 6-bromoembelin (2) and vilangin (3) may be useful in the prevention and treatment of obesity-linked type 2 diabetes mellitus.

Asunto(s)

Benzoquinonas/uso terapéutico , Diabetes Mellitus Experimental/sangre , Dieta Alta en Grasa , Hipoglucemiantes/uso terapéutico , Animales , Peso Corporal , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Lípidos/sangre , Masculino , Simulación del Acoplamiento Molecular , Ratas , Ratas Wistar , Estreptozocina

RESUMEN

Ecbolin A and ecbolin B were isolated from ethyl acetate extract of Ecbolium viride (Forsk.) Alston root and evaluated for larvicidal and growth disturbance activities against Aedes aegypti L. (Diptera: Culicidae). For larvicidal activity, the third instar larvae of A. aegypti were exposed to different concentrations viz., 1.0, 2.5, 5.0 and 10 ppm for each compound. Among the two compounds screened, ecbolin B recorded highest larvicidal activity with LC50 and LC90 values of 0.70 and 1.42 ppm, respectively. In control, the larval behaviour was normal. The active compound ecbolin B was tested for growth disruption activity at sub lethal concentrations viz., 0.5, 1.0 ppm and observed for malformation like larval gut elongation, larval longevity, intermediates, malformed adults, failed adult emergence and compared with methoprene. The results showed significant level of larva-pupa intermediates, pupa-adult intermediates, malformed adult emergence and less adult formation against A. aegypti. The histopathological results revealed a severe damage on the midgut epithelial columnar cells (CC) and cuboidal cells (CU) in ecbolin B treated larvae of A. aegypti. Similarly peritrophic membrane (pM) was also observed to be damaged in the treated larvae. The present results suggest that, ecbolin B could be used as a larvicidal agent against dengue vector A. aegypti.

RESUMEN

In this study, the therapeutic efficacy of gallic acid from Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans was examined against high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats. Molecular-dockings were done to determine the putative binding modes of gallic acid into the active sites of key insulin-signaling markers. Gallic acid (20 mg/kg) given to high-fat diet fed-streptozotocin-induced rats lowered body weight gain, fasting blood glucose and plasma insulin in diabetic rats. It further restored the alterations of biochemical parameters to near normal levels in diabetic treated rats along with cytoprotective action on pancreatic ß-cell. Histology of liver and adipose tissues supported the biochemical findings. Gallic acid significantly enhanced the level of peroxisome proliferator-activated receptor γ (PPARγ) expression in the adipose tissue of treated rat compared to untreated diabetic rat; it also slightly activated PPARγ expressions in the liver and skeletal muscle. Consequently, it improved insulin-dependent glucose transport in adipose tissue through translocation and activation of glucose transporter protein 4 (GLUT4) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (p-Akt) dependent pathway. Gallic acid docked with PPARγ; it exhibited promising interactions with the GLUT4, glucose transporter protein 1 (GLUT1), PI3K and p-Akt. These findings provided evidence to show that gallic acid could improve adipose tissue insulin sensitivity, modulate adipogenesis, increase adipose glucose uptake and protect ß-cells from impairment. Hence it can be used in the management of obesity-associated type 2 diabetes mellitus.

Asunto(s)

Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Ácido Gálico/farmacología , Transportador de Glucosa de Tipo 4/metabolismo , Resistencia a la Insulina , PPAR gamma/agonistas , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/patología , Dieta Alta en Grasa/efectos adversos , Ácido Gálico/administración & dosificación , Ácido Gálico/química , Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4/genética , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Masculino , Modelos Moleculares , PPAR gamma/química , PPAR gamma/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Estreptozocina/toxicidad

RESUMEN

The aim of the present study was to evaluate the mosquitocidal activity of fractions and a compound niloticin from the hexane extract of Limonia acidissima L. leaves on eggs, larvae and pupae of Aedes aegypti L. (Diptera: Culicidae). In these bioassays, the eggs, larvae and pupae were exposed to concentrations of 2.5, 5.0, 7.5 and 10.0ppm for fractions and 0.5, 1.0, 1.5 and 2.0ppm for compound. After 24h, the mortality was assessed and the LC50 and LC90 values were calculated for larvae and pupae. Per cent ovicidal activity was calculated for eggs after 120h post treatment. Among the sixteen fractions screened, fraction 8 from the hexane extract of L. acidissima generated good mosquitocidal activity against Ae. aegypti. The LC50 and LC90 values of fraction 8 were 4.11, 8.04ppm against Ae. aegypti larvae and 4.19, 8.10ppm against Ae. aegypti pupae, respectively. Further, the isolated compound, niloticin recorded strong larvicidal and pupicidal activities. The 2ppm concentration of niloticin showed 100% larvicidal and pupicidal activities in 24h. The LC50 and LC90 values of niloticin on Ae. aegypti larvae were 0.44, 1.17ppm and on pupae were 0.62, 1.45ppm, respectively. Niloticin presented 83.2% ovicidal activity at 2ppm concentration after 120h post treatment and niloticin exhibited significant growth disruption and morphological deformities at sub lethal concentrations against Ae. aegypti. The structure of the isolated compound was identified on the basis of single XRD and spectral data ((1)H NMR and (13)C NMR) and compared with literature spectral data. The results indicate that niloticin could be used as a potential natural mosquitocide.

Asunto(s)

Aedes , Insecticidas , Limoninas/farmacología , Extractos Vegetales/farmacología , Rutaceae/química , Animales , Larva , Estructura Molecular , Control de Mosquitos , Óvulo , Hojas de la Planta/química , Pupa

RESUMEN

The mosquitocidal activity of different fractions and isolated compounds from the ethyl acetate extract of Ecbolium viride root was assessed on larvae and pupae of Culex quinquefasciatus Say (Diptera: Culicidae). The larvae and pupae were exposed to concentrations of 6.125, 12.5, 25 and 50 ppm for fractions and 1, 2.5, 5 and 10 ppm for compound. Among the 12 fractions screened, fraction 6 from the ethyl acetate extract of E. viride was recorded to have the highest larvicidal and pupicidal activities against C. quinquefasciatus. The lethal concentration (LC50 and LC90) values of fraction 6 were 4.26 and 9.0 ppm against C. quinquefasciatus larvae and 6.55 and 12.19 ppm against C. quinquefasciatus pupae, respectively, in 24 h. Fraction 7 was recorded to have moderate activity with LC50 and LC90 values of 11.25 and 25.02 ppm against C. quinquefasciatus larvae and 13.33 and 31.15 ppm against C. quinquefasciatus pupae, respectively, in 24 h. Ecbolin A and ecbolin B were identified from fractions 7 and 6, respectively. The structure of the isolated compounds was identified on the basis of spectral data ((1)H NMR and (13)C NMR) and compared with literature spectral data. Further, the isolated compound, ecbolin B, from fraction 6 was recorded to have strong larvicidal and pupicidal activities than ecbolin A. The LC50 and LC90 values of ecbolin B on C. quinquefasciatus larvae were 1.36 and 2.76 ppm, and on pupae, these were 1.54 and 3.51 ppm, respectively. The present results suggest that ecbolin B could be used as a mosquitocidal agent against C. quinquefasciatus.

Asunto(s)

Culex/efectos de los fármacos , Insecticidas/farmacología , Lignanos/farmacología , Extractos Vegetales/farmacología , Acanthaceae , Animales , Relación Dosis-Respuesta a Droga , Insecticidas/administración & dosificación , Insecticidas/química , Larva/efectos de los fármacos , Dosificación Letal Mediana , Lignanos/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Pupa/efectos de los fármacos

RESUMEN

BACKGROUND: The present study was aimed at isolating an antidiabetic molecule from a herbal source and assessing its mechanism of action. METHODS: Embelin, isolated from Embelia ribes Burm. (Myrsinaceae) fruit, was evaluated for its potential to regulate insulin resistance, alter ß-cell dysfunction and modulate key markers involved in insulin sensitivity and glucose transport using high-fat diet (HFD) fed-streptozotocin (STZ) (40mg/kg)-induced type 2 diabetic rats. Molecular-dockings were performed to investigate the binding modes of embelin into PPARγ, PI3K, p-Akt and GLUT4 active sites. RESULTS: Embelin (50mg/kg b wt.) reduced body weight gain, blood glucose and plasma insulin in treated diabetic rats. It further modulated the altered lipid profiles and antioxidant enzymes with cytoprotective action on ß-cell. Embelin significantly increased the PPARγ expression in epididymal adipose tissue compared to diabetic control group; it also inhibited adipogenic activity; it mildly activated PPARγ levels in the liver and skeletal muscle. It also regulated insulin mediated glucose uptake in epididymal adipose tissue through translocation and activation of GLUT4 in PI3K/p-Akt signaling cascade. Embelin bound to PPARγ; it disclosed stable binding affinities to the active sites of PI3K, p-Akt and GLUT4. CONCLUSIONS: These findings show that embelin could improve adipose tissue insulin sensitivity without increasing weight gain, enhance glycemic control, protect ß-cell from damage and maintain glucose homeostasis in adipose tissue. GENERAL SIGNIFICANCE: Embelin can be used in the prevention and treatment of type 2 diabetes mellitus caused due to obesity.

Asunto(s)

Benzoquinonas/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Transportador de Glucosa de Tipo 4/metabolismo , Glucosa/metabolismo , Hipoglucemiantes/farmacología , PPAR gamma/agonistas , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Benzoquinonas/química , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Embelia/química , Frutas/química , Regulación de la Expresión Génica/efectos de los fármacos , Homeostasis/efectos de los fármacos , Hipoglucemiantes/química , Resistencia a la Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Masculino , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/patología , PPAR gamma/metabolismo , Transporte de Proteínas/efectos de los fármacos , Ratas , Ratas Wistar

RESUMEN

OBJECTIVES: Inula racemosa Hook. f. is indicated for precordial chest pain in Ayurveda. In this study, the effects of a hexane (IrH) and an alcohol extract (IrA) of Inula racemosa on atherosclerosis induced by a high-fat diet in guinea-pigs were investigated. METHODS: After 30 days on a high-fat diet (guinea-pig pellet diet + 0.2% w/w cholesterol) six animals were killed and evaluated for the onset of early atherosclerotic changes in coronary artery, aorta and major organs. The remaining animals were assigned to 5 groups of six animals each and fed for the following 90 days with a pellet diet + 0.15% w/w cholesterol (positive control) along with 100 mg/kg IrA, 100 mg/kg IrH or 10 mg/kg atorvastatin calcium. The normal control group received only the pellet diet. At the end of experimental period, serum lipid levels, heart and liver antioxidant status, area of lipophilic aortic lesions and histopathology of coronary artery were estimated. KEY FINDINGS: IrA decreased total cholesterol, triglycerides, low-density lipoprotein cholesterol and the atherogenic index, and increased high-density lipoprotein cholesterol compared with the positive control. It scavenged thiobarbituric acid reactive substances and increased reduced glutathione in liver, and enhanced superoxide dismutase and glutathione peroxidase in heart. Aortic lesion area and % bodyweight increase was least in the IrA-treated group. Coronary artery changes due to the high-fat diet were reversed by the extracts. The observed effects are presumably mediated by phenolics in IrA and sesquiterpene lactones in IrH. CONCLUSIONS: The results demonstrate the anti-atherogenic effect of I. racemosa, thus validating the cardioprotective and anti-obesity claims in traditional medicine.

Asunto(s)

Aterosclerosis/tratamiento farmacológico , Inula/química , Extractos Vegetales/farmacología , Animales , Aorta/efectos de los fármacos , Aorta/patología , Aterosclerosis/etiología , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/patología , Grasas de la Dieta/efectos adversos , Modelos Animales de Enfermedad , Cobayas , Masculino , Medicina Ayurvédica , Solventes/química , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo

RESUMEN

OBJECTIVES: The liver is often damaged by environmental toxins, poor eating habits, alcohol and over-the-counter drug use that damage and weaken the liver, leading to important public health problems such as hepatitis, cirrhosis, and alcoholic liver diseases. It is cardinal to treat liver disorders, because it affects the biochemistry of the cell directly. Damage to the liver can be prevented by including a balanced diet that includes nutrients and herbs that support a healthy liver. Premna tomentosa (PT) is one such herbal drug used widely in India for the treatment of liver disorders, and we have already reported the hepatoprotective potential and antioxidant property of methanolic extract of PT leaves. Because injury to the liver can promote a variety of reactions with consequent effect on lipids, the present study was designed to elucidate the hypolipidemic effect of PT extract in acetaminophen (AA)-induced hepatotoxicity in rats. DESIGN AND SUBJECTS: Animals were pretreated with PT extract (750 mg/kg, orally) for 15 days and then induced with hepatotoxicity by AA (640 mg/kg, intraperitoneally). RESULTS: PT extract pretreatment significantly inhibited induced alterations in the levels of cholesterol, triglycerides, free fatty acids, phospholipids, serum lipoproteins, and lipid-metabolizing enzymes. CONCLUSIONS: The results indicate that PT extract improves lipid metabolism and has the potential for use in hepatic disorders.

Asunto(s)

Metabolismo de los Lípidos , Hepatopatías/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Verbenaceae , Acetaminofén/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Relación Dosis-Respuesta a Droga , Estrés Oxidativo/efectos de los fármacos , Hojas de la Planta , Ratas , Ratas Wistar , Factores de Tiempo

RESUMEN

The effect of the alcoholic extract of the whole plant of Bacopa monniera (Scrophulariaceae) on morphine withdrawal was evaluated in vitro in guinea-pig ileum. After a 4 min in vitro exposure to morphine, addition of naloxone induced a strong contraction. Addition of various concentrations of the alcoholic extract of B. monniera (100-1000 microg/ml) 15 min before exposure to morphine reduced the naloxone-induced contraction in a dose-dependent manner. The results suggest that B. monniera extract may be useful in reducing the withdrawal symptoms induced by morphine.

Asunto(s)

Bacopa , Etanol/uso terapéutico , Íleon/efectos de los fármacos , Morfina/efectos adversos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Animales , Etanol/farmacología , Cobayas , Íleon/fisiología , Técnicas In Vitro , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Estructuras de las Plantas