title: Xanthones as α-glucosidase inhibitors from the antihyperglycemic extract of Securidaca inappendiculata.
abstract: BACKGROUND
  Securidaca inappendiculata Hassk. (SI) is used to cure fractures and rheumatoid arthritis in China. Also, it is a potential antidiabetes drug; however, there are no reports on this.
  
  
  OBJECTIVE
  The study was designed to evaluate the antihyperglycemic activities of fractions and compounds from SI, and attempt to explore the mechanism.
  
  
  METHODS
  Antihyperglycemic activities were evaluated by the suppression on serum glucose levels in vivo and α-glucosidase inhibition assays in vitro. Fractions were given to mice by gastric intubation for 8 d. The high, medium, and low doses of fractions were equal to 10, 5, and 2.5 g/kg of the herb [SID (dichloromethane fraction) and SIE (ethyl acetate fraction) were doubled]. The serum glucose was monitored at 1 and 12 h after feeding. The silica gel and LH-20 chromatography were used to isolate active compounds. Structure-activity relationship analysis was based on IC50s and structures.
  
  
  RESULTS
  The IC50s of SID, SIE, SIA (acetone fraction), SIM (methanol fraction), and acarbose were 712, 446, 1123, 1418, and 735 μg/mL. The postprandial and fasting serum glucose levels of SID, SIE, SIA, and SIM (high dose) were 5.5, 5.9, 6.2, 6.3 and 3.7, 3.5, 4.0, 5.0 mmol/L, while those of vehicle control were 7.5 and 5.6 mmol/L. Eleven xanthones isolated all exhibited inhibitory activities, mainly in a non-competitive reversible manner. The IC50s varied from 3.2 to 77.3 μg/mL. Structure-activity relationship analysis exhibited free hydroxyls contributed the most importance to the activity.
  
  
  CONCLUSIONS
  The results indicated that xanthones from SI were powerful agents for antidiabetes.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine , China and.
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.forename: Cong-Lan
authors.initials: CL
authors.lastname: Ji
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Chen
mesh_terms: D020909:Acarbose / Q000494:pharmacology; D000085:Acetates / Q000737:chemistry; D000096:Acetone / Q000737:chemistry; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008752:Methylene Chloride / Q000737:chemistry; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology; D018547:Plant Stems / Q000737:chemistry; D031802:Securidaca / Q000737:chemistry*; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000085:Acetates; D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D044004:Xanthones; D000096:Acetone; D008752:Methylene Chloride; C007650:ethyl acetate; D020909:Acarbose
keywords: Activity screening; antidiabetes; material base; structure–activity relationship analysis