title: (Z)-3-butylidenephthalide from Ligusticum porteri , an α-glucosidase inhibitor.
abstract: An extract from the roots of Ligusticum porteri, orally administered to groups of normal and diabetic mice, showed significant hypoglycemic and antihyperglycemic effects. Experimental type-II DM was achieved by treating mice with streptozotocin 15 min after an injection of β-nicotinamide adenine dinucleotide. (Z)-6,6',7,3'α-diligustilide (1), (Z)-ligustilide (2), 3-(Z)-butylidenephthalide (3), myristicin (4), and ferulic acid (5) were isolated from the active extract. When tested In Vivo, compounds 1-3 showed antihyperglycemic activity, with 3 being the most active. Compound 3 (56.2 mg/kg) decreased blood glucose levels in NAD-STZ-diabetic mice after an oral sucrose load, suggesting that its antihyperglycemic effect is due to inhibition of α-glucosidase at the intestinal level. Furthermore, 3 inhibited the activity of yeast-α-glucosidase (IC(50) 2.35 mM) in a noncompetitive fashion with a K(i) of 4.86 mM. Docking analysis predicted that 3 binds to the enzyme in a pocket close to the catalytic site, but different from that for acarbose, with a K(i) of 11.48 mM. Compounds 1 and 2 did not affect α-glucosidase In Vivo, but altered glucose absorption by a mechanism yet to be determined. The stimulatory effect of 5 on insulin secretion, present in high amounts in the extract, has been demonstrated in previous investigations. The present study provides scientific support of the use of L. porteri in Mexican folk medicine for the treatment of diabetes.
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, México.
authors.forename: Fernando
authors.initials: F
authors.lastname: Brindis
authors.forename: Rogelio
authors.initials: R
authors.lastname: Rodríguez
authors.forename: Robert
authors.initials: R
authors.lastname: Bye
authors.forename: Martn
authors.initials: M
authors.lastname: González-Andrade
authors.forename: Rachel
authors.initials: R
authors.lastname: Mata
mesh_terms: D020909:Acarbose / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D030004:Ligusticum / Q000737:chemistry*; D008519:Medicine, Traditional; D008800:Mexico; D051379:Mice; D010796:Phthalic Anhydrides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013237:Stereoisomerism; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D010796:Phthalic Anhydrides; D013311:Streptozocin; C026105:butylidenephthalide; D020909:Acarbose