title: In vitro and in vivo effects of standardized extract and fractions of Phaleria macrocarpa fruits pericarp on lead carbohydrate digesting enzymes.
abstract: BACKGROUND
  One vital therapeutic approach for the treatment of type 2 diabetes mellitus is the use of agents that can decrease postprandial hyperglycaemia by inhibiting carbohydrate digesting enzymes. The present study investigated the effects of bioassay-guided extract and fractions of the dried fruit pericarp of Phaleria macrocarpa, a traditional anti-diabetic plant, on α-glucosidase and α-amylase, in a bid to understand their anti-diabetic mechanism, as well as their possible attenuation action on postprandial glucose increase.
  
  
  METHODS
  Methanol extract (ME), obtained by successive solvent extraction, its most effective liquid-liquid n-butanol fraction (NBF) and the flash column chromatographic sub-fraction (SFI), were evaluated for in vitro α-glucosidase (yeast) and α-amylase (porcine) activity inhibition. Furthermore, confirmatory in vivo tests were carried out in streptozotocin-induced diabetic rats (SDRs) using oral glucose, sucrose and starch tolerance tests.
  
  
  RESULTS
  At the highest concentration employed (100 μg/ml), NBF showed highest inhibition against α-glucosidase (75%) and α-amylase (87%) in vitro (IC50 = 2.40 ± 0.23 μg/ml and 58.50 ± 0.13 μg/ml, respectively) in a dose-dependent fashion; an effect found to be about 20% higher than acarbose (55%), a standard α-glucosidase inhibitor (IC50 = 3.45 ± 0.19 μg/ml). The ME and SFI also inhibited α-glucosidase (IC50 = 7.50 ± 0.15 μg/ml and 11.45 ± 0.28 μg/ml) and α-amylase (IC50 = 43.90 ± 0.19 μg/ml and 69.80 ± 0.25 μg/ml), but to a lesser extent. In in vivo studies with diabetic rats, NBF and SFI effectively reduced peak blood glucose (PBG) by 15.08% and 6.46%, and the area under the tolerance curve (AUC) by 14.23% and 12.46%, respectively, after an oral sucrose challenge (P < 0.05); thereby validating the observed in vitro action. These reduction effects on PBG and AUC were also demonstrated in glucose and starch tolerance tests, but to a lesser degree.
  
  
  CONCLUSIONS
  These findings reveal that P. macrocarpa can attenuate hyperglycaemia in both in vitro and in vivo conditions by potently inhibiting carbohydrate hydrolysing enzymes, making it a viable plant for sourcing natural compounds for the management of type 2 diabetes mellitus.
authors: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
authors: Rabyah B
authors: RB
authors: Ali
authors: Item J
authors: IJ
authors: Atangwho
authors: Navneet
authors: N
authors: Kuar
authors: Mariam
authors: M
authors: Ahmad
authors: Roziahanim
authors: R
authors: Mahmud
authors: Mohd Z
authors: MZ
authors: Asmawi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004040:Dietary Carbohydrates / Q000378:metabolism*; D004063:Digestion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005638:Fruit; D065089:Glycoside Hydrolase Inhibitors; D006943:Hyperglycemia / Q000378:metabolism / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000378:metabolism; D029645:Thymelaeaceae; D000516:alpha-Amylases / Q000037:antagonists & inhibitors*
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D013395:Sucrose; D000516:alpha-Amylases