EP_095. In silico discovery of α-glucosidase inhibitors from Mitragyna speciosa for antidiabetic therapy

Siti Norain Mat Rasid¹, Alfi Khatib^2*, Dendi Noventri Nando³, Hussam Abdeljabar Ahmad Mizher¹, Mohd Hamzah Mohd Nasir⁴, Mohd Hafiz Arzmi⁵

1. Department of Basic Medical Sciences, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200, Kuantan, Pahang, Malaysia

2. Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200, Kuantan, Pahang, Malaysia

3. Department of Food Science and Biotechnology, Faculty of Agricultural Technology, Universitas Brawijaya, Kota Malang, Jawa Timur 65145, Indonesia

4. Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia, 25200, Kuantan, Pahang, Malaysia

5. Department of Fundamental Dental and Medical Sciences, Kulliyyah of Dentistry, International Islamic University Malaysia, 25200, Kuantan, Pahang, Malaysia

*Corresponding author: Alfi Khatib. This email address is being protected from spambots. You need JavaScript enabled to view it.

ABSTRACT

INTRODUCTION: Mitragyna speciosa (kratom) is a medicinal plant known for its richness in phytochemicals with potential antidiabetic activity. α-glucosidase is an enzyme that plays a key role in carbohydrate hydrolysis. The inhibition of α-glucosidase activity represents a validated therapeutic approach to manage postprandial hyperglycaemia in type 2 diabetes. This study investigates the potential of M. speciosa leaf extract as an α-glucosidase inhibitor.

OBJECTIVE(S): To identify bioactive compounds in M. speciosa ethanolic leaf extract that inhibit α-glucosidase and to evaluate their interaction with the enzyme through in silico molecular docking.

MATERIALS & METHODS: Phytochemical profiling of the 95% ethanolic extract of M. speciosa leaf was performed using LC-MS QTOF. In vitro α-glucosidase inhibition assay was conducted to determine the IC₅₀ value of the extract. Selected compounds were subjected to molecular docking analysis using AutoDock software against α-glucosidase enzyme (PDB ID: 3A4A), and key binding interactions were analysed.

RESULTS: A total of 16 putative bioactive compounds were identified from the extract. The extract exhibited α-glucosidase inhibitory activity with an IC₅₀ of 21.64 µg/mL. In the molecular docking analysis, Rhyncophylline showed strong binding to α-glucosidase (ΔG = -8.8 kcal/mol), comparable to standard inhibitors. Its interaction with ASP352, a known catalytic residue, suggests that Rhyncophylline may act as a potential α-glucosidase inhibitor.

CONCLUSION: The ethanolic leaf extract of M. speciosa exhibits α-glucosidase inhibitory activity. Rhyncophylline, identified via in silico docking, is a promising lead compound for future antidiabetic drug development.

KEYWORDS: Mitragyna speciosa, α-Glucosidase, Molecular Docking, Rhyncophylline