title: Antidiabetic effect, antioxidant activity, and toxicity of 3',4'-Di-O-acetyl-cis-khellactone in Streptozotocin-induced diabetic rats.
abstract: Pyranocoumarins are compounds with an important pharmacological profile, such as anti-inflammatory, antioxidant, cytotoxic, antiviral, antibacterial, and hypoglycemic effects. These molecules have a widespread presence as secondary metabolites in medicinal plants used to treat Diabetes Mellitus (DM). The aim of this work was to evaluate antidiabetic activity in Streptozotocin (STZ)-induced diabetic rats and the antioxidant effects of 3',4'-Di-O-acetyl-cis-khellactone (DOAcK), as well as its toxic potential. We obtained DOAcK with an enantiomeric excess of 70% by chemical synthesis. Our results showed that this compound exerts an important antidiabetic effect: blood glucose decreased in groups treated with DOAcK by 60.9% at dose of 15mg/kg (p<0.05) compared with the diabetic control group, and demonstrated a statistically significant increase in weight gain (45.7±9.7 in the group treated with DOAcK vs. -23.0±33.1 in the group with diabetes). In a biochemical profile, DOAcK did not modify lipid metabolism and did not cause damage at the renal level. DOAcK administration increased the activities of Catalase (CAT), Glutathione Peroxidase (GPx), and Super Oxide Dismutase (SOD) to levels near those of the healthy group. Histopathological analysis exhibited morphology similar to that of the healthy group and the group treated with DOAcK. DOAcK is not mutagenic by Ames test for Salmonella typhimurium strains TA98, TA100, or TA102, and is not genotoxic by Micronucleus assay; median lethal dose (LD50) >2000mg/kg and, at this dose, no signs of toxicity or death were reported after 14days of observation. These results indicate that DOAcK can improve glucose metabolism, which may be due to the increased antioxidant activity of CAT, GPx and SOD. In addition, DOAcK is not toxic in the studies tested.
authors.affiliation: Laboratorio de Biología Celular y Productos Naturales, Edificio de Posgrado, Primer Piso, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional, Guillermo Massieu Helguera 239, Col. La Escalera Del. Gustavo A. Madero, 07320 CDMX, Mexico.
authors.forename: Elix Alberto
authors.initials: EA
authors.lastname: Domínguez-Mendoza
authors.affiliation: Laboratorio de Biología Celular y Productos Naturales, Edificio de Posgrado, Primer Piso, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional, Guillermo Massieu Helguera 239, Col. La Escalera Del. Gustavo A. Madero, 07320 CDMX, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cornejo-Garrido
authors.affiliation: Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Col. Santo Tomás, 11340 CDMX, Mexico.
authors.forename: Eleuterio
authors.initials: E
authors.lastname: Burgueño-Tapia
authors.affiliation: Laboratorio de Biología Celular y Productos Naturales, Edificio de Posgrado, Primer Piso, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional, Guillermo Massieu Helguera 239, Col. La Escalera Del. Gustavo A. Madero, 07320 CDMX, Mexico. Electronic address: dra_cynthia@hotmail.com.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ordaz-Pichardo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D009152:Mutagenicity Tests; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013311:Streptozocin / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D003374:Coumarins; D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin; C030123:coumarin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; C520900:khellactone
keywords: 3′,4′-Di-O-acetyl-cis-khellactone; Antidiabetic activity; Antioxidant activity; Diabetes