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CHOLINESTERASE INHIBITORY ACTIVITY AND ANTIOXIDANT POTENTIALS OF THE FOUR SPECIES OF ARTOCARPUS SPP.

YASIR ULLAH 1, ERLINDA ROHMATUL LAILI 2, HAMIZAH HAULA 3, TEOW CHONG TEOH 1, ATY WIDYAWARUYANTI 2,3,4, NITRA NUENGCHAMNONG 5, SUCIATI SUCIATI 2,6,7*

1 Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
2 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia
3 Centre for Natural Product Medicine Research and Development, Institute of Tropical Diseases, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia.
4 Inter-University Centre of Excellence (IUCoE) of Health Autonomy-Drug Discovery, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia
5 Science Laboratory Centre, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand
6 Natural Product Drug Discovery and Development Research Group, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia
7 Skin and Cosmetic Technology Centre of Excellent, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia

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This study evaluated the potential of four Artocarpus species as antioxidants and cholinesterase inhibitors for Alzheimer’s disease drug development. Extract activity was tested by colorimetric assays against AChE and BChE, while antioxidant capacity was assessed using DPPH and ABTS methods. The chemical composition of the most active extract was analysed by LC-MS/MS, followed by in silico molecular docking. The stem extract of A. rigidus showed the strongest AChE inhibition (IC₅₀ = 12.35 μg/mL), while the leaf extract exhibited moderate BChE inhibition (IC₅₀ = 26.52 μg/mL). All four extracts demonstrated antioxidant activity ranging from strong to moderate. LC-MS/MS analysis of the A. rigidus stem extract identified 19 flavonoids and one xanthone. Docking studies suggested that phenolic compounds contribute to cholinesterase inhibition, with artorigidin C (-8.8885 kcal/mol) and artoindonesianin V (-9.2980 kcal/mol) showing notable predicted interactions with AChE and BChE, respectively. These values compared favorably with reference drugs galantamine (-7.7266 kcal/mol) and tacrine (-5.7573 kcal/mol). Overall, the findings highlight A. rigidus as a promising source of bioactive compounds with antioxidant and cholinesterase inhibitory properties, supporting its potential in the development of anti-Alzheimer’s therapies.