Antidiabetic, antidyslipidemic and toxicity profile of ENV-2: A potent pyrazole derivative against diabetes and related diseases.
Diabetes is a major health problem and a predisposition factor for further degenerative complications and, therefore, novel therapies are urgently needed. Currently, cannabinoid receptor 1 (CB1receptor) antagonists have been considered as promissory entities for metabolic disorders treatment. Accordingly, the purpose of this work was the evaluation of the sub-acute antidiabetic, anti-hyperglycemic, antidyslipidemic and toxicological profile of ENV-2, a potent hypoglycemic and antioxidant CB1receptor antagonist. In this study, ENV-2 showed a pronounced anti-hyperglycemic effect even at a dose of 5mg/kg (P<0.05) in a glucose tolerance test on normoglycemic rats. Moreover, after administration of ENV-2 (16mg/kg) to diabetic rats, a prominent antidiabetic activity was observed (P<0.05), which was higher than glibenclamide. Sub-acute treatment (10 days) of ENV-2 resulted in a significant reduction of plasma glucose (P<0.05). Also, the levels of peripheral lipids were improved; blood triacylglycerols (TG) and cholesterol (CHOL) were diminished (P<0.05). In addition, it was found that ENV-2 reduced IL-1β and IL-18 mRNA expression in adipose tissue (P<0.05). Due to the satisfactory outcomes, we were interested in evaluating the toxicity of ENV-2 in both acute and sub-chronic approaches. Regarding the acute administration, the compound resulted to be non-toxic and was grouped in category 5 according to OECD. It was also found that sub-chronic administration did not increase the size of the studied organs, while no structural damage was observed in heart, lung, liver and kidney tissues. Finally, neither AST nor ALT damage hepatic markers were augmented.
Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Ciudad de México 04510, México.
Eduardo
E
Hernández-Vázquez
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, México.
Hugo
H
Ocampo-Montalban
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, México.
Litzia
L
Cerón-Romero
Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México 06720, México.
Miguel
M
Cruz
Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México 06720, México.
Jaime
J
Gómez-Zamudio
Instituto Nacional de Enfermedades Respiratorias, Ciudad de México 14080, México.
Guadalupe
G
Hiriart-Valencia
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla Estado de México 54090, México.
Rafael
R
Villalobos-Molina
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, México.
Angelica
A
Flores-Flores
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Morelos, México. Electronic address: enoch@uaem.mx.
Samuel
S
Estrada-Soto
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D006835:Hydrazones / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000960:Hypolipidemic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats
C000624697:ENV-2 compound; D006835:Hydrazones; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D011720:Pyrazoles; C031280:pyrazole
Antidiabetic; Antidyslipidemic; Cannabinoid receptor 1 antagonist; ENV-2