Inhibition of key enzymes linked to type 2 diabetes by compounds isolated from Aframomum melegueta fruit.
BACKGROUND
The use of Aframomum melegueta K. Schum. (Zingiberaceae) fruit for treatment of diabetes has recently been established in Nigeria. However, compounds responsible for the antidiabetic action have not been identified.


OBJECTIVE
The present study carried out the bioassay-guided isolation of possible bioactive compounds responsible for the antidiabetic action of A. melegueta fruit.


METHODS
The A. melegueta fruit was sequentially extracted using ethyl acetate (EtOAc), ethanol and water, and the most active extract (EtOAc) was subjected to column chromatography on a silica gel column using solvent gradient systems of hexane (HEX):EtOAc and EtOAc:MeOH and the isolation of compounds was guided by α-glycosidase and α-amylase inhibitory activities at various concentrations (30-240 μg/mL).


RESULTS
According to the results, 3 arylalkanes, 6-paradol (1), 6-shogaol (2) and 6-gingerol (3) and a pentacyclic triterpene, oleanolic acid (4) were isolated from A. melegueta fruit. All the compounds exhibited inhibitory effects against α-amylase and α-glucosidase. 6-Gingerol (3) and oleanolic acid (4) showed higher inhibitory activity against α-amylase (IC50: 6-gingerol: 81.78 ± 7.79 μM; oleanolic acid: 91.72 ± 1.63 μM) and α-glucosidase (IC50: 6-gingerol: 21.55 ± 0.45 μM; oleanolic acid: 17.35 ± 0.88 μM) compared to the standard drug, acarbose and other isolated compounds. The kinetics of the enzyme action of the compounds showed a noncompetitive mode of inhibition.


CONCLUSIONS
The data of this study suggest that the 6-gingerol (3) and oleanolic acid (4) showed higher α-amylase and α-glucosidase inhibitory action and therefore could be responsible for the antidiabetic activity of A. melegueta fruit.
a Department of Biochemistry , School of Life Sciences, University of KwaZulu-Natal , Durban , South Africa.|b Department of Biochemistry, Faculty of Science , Ahmadu Bello University , Zaria , Nigeria.
Aminu
A
Mohammed
c Department of Chemistry , School of Chemistry and Physics, University of KwaZulu-Natal , Durban , South Africa.
Victoria Awolola
VA
Gbonjubola
c Department of Chemistry , School of Chemistry and Physics, University of KwaZulu-Natal , Durban , South Africa.
Neil Anthony
NA
Koorbanally
a Department of Biochemistry , School of Life Sciences, University of KwaZulu-Natal , Durban , South Africa.
Md Shahidul
MS
Islam
D020909:Acarbose / Q000494:pharmacology; D001681:Biological Assay; D002396:Catechols / Q000302:isolation & purification / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000302:isolation & purification / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry*; D065089:Glycoside Hydrolase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007700:Kinetics; D009828:Oleanolic Acid / Q000302:isolation & purification / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D012997:Solvents / Q000737:chemistry; D030521:Zingiberaceae / Q000737:chemistry*; D000516:alpha-Amylases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002396:Catechols; D005233:Fatty Alcohols; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D012997:Solvents; D009828:Oleanolic Acid; C007845:gingerol; D000516:alpha-Amylases; D020909:Acarbose
Antidiabetic; kinetics; α-amylase; α-glucosidase