Inhibition of key enzymes linked to type 2 diabetes by compounds isolated from Aframomum melegueta fruit

Abstract

Context: 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.

Materials and 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.

Conclusion: 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.

Keywords:

• Antidiabetic
• α-amylase
• α-glucosidase
• kinetics

Acknowledgements

This study was supported by a competitive research grant from the Research Office, University of KwaZulu-Natal (UKZN), Durban; an incentive grant for rated researchers and a grant support for women and young researchers from the National Research Foundation (NRF), Pretoria, South Africa. The first author was awarded a PhD study fellowship by the Ahmadu Bello University, Zaria, Nigeria. Authors would like to thank Mr. Olusola Bodede and Mr. Olumuyiwa Ogunlaja for their assistance during the study.

Disclosure statement

We declare that we have no conflict of interest.

Additional information

Funding

This study was supported by a competitive research grant from the Research Office, University of KwaZulu-Natal (UKZN), Durban; an incentive grant for rated researchers and a grant support for women and young researchers from the National Research Foundation (NRF), Pretoria, South Africa.