RESUMO
AIM OF THE STUDY: To identify pongamol and karanjin as lead compounds with antihyperglycemic activity from Pongamia pinnata fruits. MATERIAL AND METHODS: Streptozotocin-induced diabetic rats and hyperglycemic, hyperlipidemic and hyperinsulinemic db/db mice were used to investigate the antihyperglycemic activity of pongamol and karangin isolated from the fruits of Pongamia pinnata. RESULTS: In streptozotocin-induced diabetic rats, single dose treatment of pongamol and karanjin lowered the blood glucose level by 12.8% (p<0.05) and 11.7% (p<0.05) at 50mg /kg dose and 22.0% (p<0.01) and 20.7% (p<0.01) at 100mg/kg dose, respectively after 6h post-oral administration. The compounds also significantly lowered blood glucose level in db/db mice with percent activity of 35.7 (p<0.01) and 30.6 (p<0.01), respectively at 100mg/kg dose after consecutive treatment for 10 days. The compounds were observed to exert a significant inhibitory effect on enzyme protein tyrosine phosphatase-1B (EC 3.1.3.48). CONCLUSION: The results showed that pongamol and karangin isolated from the fruits of Pongamia pinnata possesses significant antihyperglycemic activity in Streptozotocin-induced diabetic rats and type 2 diabetic db/db mice and protein tyrosine phosphatase-1B may be the possible target for their activity.
Assuntos
Benzofuranos/farmacologia , Benzopiranos/farmacologia , Frutas/química , Hipoglicemiantes/farmacologia , Millettia/química , Células 3T3-L1 , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Camundongos , Fosfoproteínas Fosfatases/antagonistas & inibidores , Extratos Vegetais/análise , Proteína Fosfatase 2C , Ratos , Ratos Sprague-Dawley , EstreptozocinaRESUMO
The hybrid congeners 62-90 of 6- and 7-hydroxyflavones with aminopropanol have been synthesized and evaluated for their antidiabetic activity in sucrose-challenged low-dosed streptozotocin (STZ)-induced diabetic rats and db/db mice. The optical enantiomers 70a, 70b, 90a, and 90b of two congeners 70 and 90 exhibiting consistent antidiabetic and antidyslipidemic activities were also prepared, and their antidiabetic activity results indicate its association mainly with S isomers. These compounds also lower cholesterol and TG profiles while improving high-density lipoprotein cholesterol to CHOL ratio in db/db mice. The bioavailability of compound 70 and its isomer varies between 27 and 29% whereas that of the more polar compound 90a is poor as determined in rat by oral and intraperitoneal administrations.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Flavonas/síntese química , Hipoglicemiantes/síntese química , Hipolipemiantes/síntese química , Animais , Disponibilidade Biológica , Colesterol/sangue , Cricetinae , Relação Dose-Resposta a Droga , Flavonas/química , Flavonas/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Insulina/sangue , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Estereoisomerismo , Estreptozocina , Relação Estrutura-Atividade , Triglicerídeos/sangueRESUMO
A new steroidal saponin, chloragin (1), was isolated and characterised from the aerial part of Chlorophytum nimonii. The structure of chloragin (1) was established as tigogenin-3-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 4)-beta-D-xyloopyranoside on the basis of detailed chemical and spectral evidence. The saponin showed potent antihyperglycaemic and antidyslipidaemic activities in albino rats.
Assuntos
Glicemia/efeitos dos fármacos , Clorófitas/química , Hipoglicemiantes , Saponinas/química , Esteroides/química , Animais , Cricetinae , Diabetes Mellitus Experimental/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Masculino , Mesocricetus , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
PTPases are considered to be involved in the etiology of diabetes mellitus and neural diseases, such as Alzheimer's disease and Parkinson's disease. Therefore, PTPase inhibitors should be useful tools to study the role of PTPases in these diseases and other biological phenomena, and which can be developed into chemotherapeutic agents. In the present study, we have synthesized novel benzofuran isoxazolines 13-21 via 1,3-dipolar cycloaddition reaction using karanjin (1) and kanjone (2), isolated from Pongamia pinnata fruits. All the synthesized compounds were evaluated against PTPase enzyme. Compounds 19 and 20 displayed significant inhibitory activity with IC50 values 76 and 81 microM, respectively.
Assuntos
Inibidores Enzimáticos/síntese química , Hipoglicemiantes/síntese química , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Benzofuranos/síntese química , Benzofuranos/farmacologia , Benzopiranos/química , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/farmacologia , Isoxazóis/síntese química , Isoxazóis/farmacologia , Millettia/química , Modelos Químicos , Oxazolona/análogos & derivados , Oxazolona/síntese química , Oxazolona/farmacologia , Ligação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 1RESUMO
A series of 5-[(5-aryl-1H-pyrazol-3-yl)methyl]-1H-tetrazoles 3a-h have been synthesized and evaluated for their in vivo antihyperglycemic activity. Some of the synthesized compounds have shown significant glucose lowering activity in male Sprague-Dawley rats in sucrose loaded model. These compounds were also evaluated for their peroxisome proliferator activated receptor gamma agonistic property, but none of them displayed any significant activity.
Assuntos
Hipoglicemiantes/síntese química , Pirazóis/síntese química , Tetrazóis/síntese química , Administração Oral , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Hipoglicemiantes/farmacologia , Masculino , Pirazóis/farmacologia , Ratos , Ratos Sprague-Dawley , Sacarose/administração & dosagem , Tetrazóis/farmacologiaRESUMO
A series of aryloxypropanolamines (5a-r) of different chalcones (3a-e) were synthesized and evaluated for antihyperglycemic activity in sucrose loaded (SLM) and streptozotocin (STZ) induced diabetic animal models. Among them compounds 5a, g, m, o, p and r showed significant reduction in blood glucose levels in both SLM and STZ animal models.
Assuntos
Chalcona/análogos & derivados , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/síntese química , Propanolaminas/síntese química , Propanolaminas/farmacologia , Animais , Glicemia/efeitos dos fármacos , Chalcona/farmacologia , Diabetes Mellitus Experimental , Hipoglicemiantes/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Estreptozocina , Relação Estrutura-Atividade , SacaroseRESUMO
A number of thiazolidine-2,4-diones derivatives having carboxylic ester appendage at N-3 were synthesized and their antihyperglycemic activity was evaluated. Many of these derivatives as well as their corresponding carboxylic acid showed significant improvement on post-prandial hyperglycemia in normal rats, in contrast to their poor agonist activity at PPARgamma.
Assuntos
Hipoglicemiantes/síntese química , Tiazolidinedionas/síntese química , Animais , Linhagem Celular , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Masculino , PPAR gama/metabolismo , Ratos , Tiazolidinedionas/metabolismo , Tiazolidinedionas/farmacologiaRESUMO
Various 3,4,5-triarylpyrroles were synthesized and evaluated for their in vivo antihyperglycemic activity in sucrose-loaded (SLM) and/or streptozotocin-induced (STZ) diabetic rat models. Three of the test compounds, 2-methyl-4,5-diphenyl-3-substituted-phenyl-1H-pyrroles (3c, d and h) showed significant inhibition on postprandial hyperglycemia in normal rats post sucrose loaded. These compounds also showed lowering of plasma glucose level in STZ-induced diabetic rat model.