Orthosiphon aristatus leaf extracts as α-glucosidase and soybean lipoxygenase inhibitors and their toxicity: in-vitro and in-silico approaches

Ahda, Mustofa and Ahmed, Qamar Uddin and Utami, Dwi and Mahfudh, Nurkhasanah and Syahputra, Ryan and Anwar, Muslih and Hernawan, Hernawan and Hanifah, Dini and Zainal Fithri, Helmi Husaini and Abdul Hamid, Azzmer Azzar and Rofiee, Mohd Salleh and Jaswir, Irwandi and Khatib, Alfi and Helal Uddin, A.B.M. (2025) Orthosiphon aristatus leaf extracts as α-glucosidase and soybean lipoxygenase inhibitors and their toxicity: in-vitro and in-silico approaches. Revista Brasileira de Farmacognosia, 35 (6). pp. 1468-1482. ISSN 0102-695X E-ISSN 1981-528X

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Abstract

An in silico approach for identifying potential bioactive compounds in Orthosiphon aristatus (Blume) Miq., Lamiaceae, leaf extracts presents a cost-effective strategy for early-stage drug discovery. This study aimed to profile selected compounds from O. aristatus leaf extracts using LC-HRMS analysis and evaluated their inhibitory potential against α-glucosidase and soybean lipoxygenase (sLOX). The aqueous extract exhibited stronger α-glucosidase inhibition compared to the ethanolic extract. Both extracts showed notable inhibitory activity against sLOX, supported by findings from in vitro and in silico assays. Molecular docking revealed that compounds such as eupatorin (ΔG−8.9 kcal/mol), 3,5-dihydroxy-4′,7-dimethoxyflavone (ΔG−8.3 kcal/mol), aurantioobtusin (ΔG−8.3 kcal/mol), rosmarinic acid (ΔG−8.6 kcal/mol), 5β-cholestane-3α,7α,12α,26- tetrol (ΔG−9.0 kcal/mol), and kukoamine A (ΔG−7.8 kcal/mol) interacted with the catalytic residues of α-glucosidase via hydrogen bonding. Compounds inhibiting sLOX, including aurantioobtusin (ΔG−9.4 kcal/mol), 3,5-dihydroxy-4′,7- dimethoxyflavone (ΔG−9.8 kcal/mol), rosmarinic acid (ΔG−9.6 kcal/mol), and kukoamine A (ΔG−8.8 kcal/mol), were predicted to bind within the quercetin-binding region of the enzyme’s allosteric site. Furthermore, ADME predictions suggested favourable pharmacokinetic profiles, including high absorption, good water solubility, and low toxicity. Toxicity assessment indicated that the aqueous extract was less toxic, containing only one identified toxic compound. Nevertheless, zebrafish embryo exposure at 800 µg/ml resulted in developmental abnormalities, such as reduced pigmentation, yolk sac edema, spinal curvature, and cardiac edema. Overall, the study demonstrates that in silico methods effectively complement in vitro analyses in profiling bioactive compounds from O. aristatus, reinforcing the plant’s therapeutic potential as a natural source of α-glucosidase and sLOX inhibitors.

Item Type:	Article (Journal)
Uncontrolled Keywords:	α-Glucosidase inhibitors, Chemical profiling, Lipoxygenase inhibitor, Toxicity property
Subjects:	Q Science > QD Chemistry
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	International Institute for Halal Research and Training (INHART) Kulliyyah of Pharmacy Kulliyyah of Pharmacy > Department of Pharmaceutical Chemistry Kulliyyah of Science Kulliyyah of Science > Department of Biotechnology
Depositing User:	Prof. Dr. Irwandi Jaswir
Date Deposited:	10 Dec 2025 15:57
Last Modified:	10 Dec 2025 15:57
Queue Number:	2025-12-Q691
URI:	http://irep.iium.edu.my/id/eprint/125461

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