title: Antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats.
abstract: Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies. Non insulin-dependent diabetic mellitus (NIDDM) rats were treated over a short period (for 10 days) with 60mg/Kg/day of tilianin. After treatment, a biochemical blood profile was determined. Also, adipose and thoracic aortic tissues were used to determine pro-inflammatory profile, adiponectin and adhesion molecules by real-time PCR. In 3T3-L1 cells pretreated with tilianin (10μM), PPARα, PPARγ, GLUT4, FATP-1 and ACSL-1 mRNA expression were measured. In order to explain the potential PPARα interaction with tilianin, a docking study with PPARα was carried out. Thus, intragastric administration of tilianin and metformin induced a decrease in plasma glucose (GLU) in diabetic rats on day 6, and remained significantly lower until the end of the treatment; also blood triacylglycerides (TAG) and cholesterol (CHOL) (p<0.05) were diminished. Moreover, IL-1β and IL-18 expression was significantly decreased in adipose tissue (p<0.05); meanwhile adiponectin was significantly overexpressed (p<0.05). Besides, ICAM-1 expression was significantly reduced in aortic tissue (p<0.05). In 3T3-L1 cells it was found that tilianin increased PPARα and ACSL1 mRNA levels (p<0.05). Finally, tilianin docking studies with PPARα showed polar interactions with Glu269, Tyr314, His 440 and Tyr464 residues. In conclusion, short-term tilianin treatment might exert its antidiabetic and antihyperlipidemic effect by modulating a pro-inflammatory profile, and increasing adiponectin expression. In addition, our results suggest the possible interaction of tilianin with PPARα.
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001 Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico.
authors.forename: Jorge Alberto
authors.initials: JA
authors.lastname: García-Díaz
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001 Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vázquez
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001 Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico.
authors.forename: Sara
authors.initials: S
authors.lastname: García-Jiménez
authors.affiliation: Laboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana-Iztapalapa, Apdo-Postal 55-535, CP 09340, Ciudad de México, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Hidalgo-Figueroa
authors.affiliation: Laboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana-Iztapalapa, Apdo-Postal 55-535, CP 09340, Ciudad de México, Mexico.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Almanza-Pérez
authors.affiliation: Laboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana-Iztapalapa, Apdo-Postal 55-535, CP 09340, Ciudad de México, Mexico.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Alarcón-Aguilar
authors.affiliation: U.I.M. en Bioquímica, Hospital de Especialidades, CMNSXXI, IMSS, Ciudad de México, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Gómez-Zamudio
authors.affiliation: U.I.M. en Bioquímica, Hospital de Especialidades, CMNSXXI, IMSS, Ciudad de México, Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Cruz
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Estado de México 54090, Mexico. Electronic address: maxibarrab@hotmail.com.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Ibarra-Barajas
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001 Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico. Electronic address: enoch@uaem.mx.
authors.forename: Samuel
authors.initials: S
authors.lastname: Estrada-Soto
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005419:Flavonoids / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006027:Glycosides / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D062105:Molecular Docking Simulation; D009536:Niacinamide; D010084:Oxidation-Reduction / Q000187:drug effects; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D005227:Fatty Acids; D005419:Flavonoids; D006027:Glycosides; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; C426884:tilianin; D009536:Niacinamide; D013311:Streptozocin; D008687:Metformin
keywords: Adiponectin; Flavones; NIDDM model; PPARα; Tilianin