title: Hypoglycemic properties of some preparations and compounds from Artemisia ludoviciana Nutt.
abstract: BACKGROUND
  Artemisia ludoviciana, commonly known as "estafiate", plays an important role in contemporary Mexico for treating several diseases including diabetes. To establish the preclinical efficacy of Artemisia ludoviciana as hypoglycemic and/or antihyperglycemic agent using well-known animal models.
  
  
  METHODS
  Acute hypoglycemic as well as oral glucose (OGTT) and sucrose (OSTT) tolerance tests were used to demonstrate the value of the plant for treating diabetes. An essential oil (EO), an organic extract (OE) and an infusion (AE) were assayed in normal and NA-STZ-treated mice. The acute toxicity of the three preparations was analyzed by the Lorke method. The infusion was subjected to conventional phytochemical study using chromatographic conventional procedures. Some of the isolates were evaluated using the same pharmacological assays as well as an enzymatic test. The latter was employed to assess their potential inhibitory effect on yeast α-glucosidase.
  
  
  RESULTS
  Oral administration of OE to normal mice significantly decreased blood glucose level only at the dose of 100 mg/kg; in NA-STZ-mice the hypoglycemic effect was observed at the three doses tested (31.6, 100, and 316 mg/kg). The infusion reduced significantly, blood sugar levels only in diabetic mice; the best effect was observed at the dose of 316 mg/kg. The EO was inactive when evaluated in normal mice. Regarding to the antihyperglycemic effect, the best effect was observed with the OE, during the OGTT and OSTT in diabetic mice. The infusion (AE) showed better effects during the OGTT in both normal and diabetic animals at the dose of 100 mg/kg. Finally, the EO was inactive during an OGTT at the three doses tested (31.6, 100, and 316 mg/kg) in diabetic mice. In addition, the results of AE on the enzymatic test using yeast α-glucosidase revealed an inhibition of 45%; this finding was consistent with the results obtained with the same preparation in vivo during an OSTT. Conventional phytochemical analysis of the active AE led to the isolation and characterization of eupatilin (1), jaceosidin (2), arglanin (3), salvinine (4), and 3,5-dicaffeoylquinic acid (5). Biological testing of 1 and 3 revealed their hypoglycemic effect. The hypoglycemic effect of arglanin (3) was attenuated in the presence of nicorandil, which suggested that the lactone behaved as an ATP-K+-channel blocker as glibenclamide. Salvinine (4) turned out to be a mixed α-glucosidase inhibitor, while 3 was inactive.
  
  
  CONCLUSIONS
  Artemisia ludoviciana preparations showed hypoglycemic and antihyperglycemic effects, which could explain its effectiveness for treating diabetes in contemporary Mexico. Some of the active principles of the plant included compounds 1-5. These compounds seem to be acting synergistically on different molecular targets which involved glucose absorption and insulin liberation.
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
authors.forename: Gerardo D
authors.initials: GD
authors.lastname: Anaya-Eugenio
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rivero-Cruz
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Rivera-Chávez
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico. Electronic address: rachel@unam.mx.
authors.forename: Rachel
authors.initials: R
authors.lastname: Mata
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008519:Medicine, Traditional; D008800:Mexico; D051379:Mice; D008813:Mice, Inbred ICR; D009822:Oils, Volatile / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D013311:Streptozocin / Q000633:toxicity; D000520:alpha-Glucosidases / Q000187:drug effects / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009822:Oils, Volatile; D010936:Plant Extracts; D013311:Streptozocin; D000520:alpha-Glucosidases; D005905:Glyburide
keywords: Antihyperglycemic; Arglanin; Artemisia ludoviciana; Eupatilin; Hypoglycemic; Salvinine