In Vitro and in Silico Human Monoamine Oxidase Inhibitory Potential of Anthraquinones, Naphthopyrones, and Naphthalenic Lactones from Cassia obtusifolia Linn Seeds

Pradeep Paudel; Su Hui Seong; Srijan Shrestha; Hyun Ah Jung; Jae Sue Choi

doi:10.1021/acsomega.9b02328

In Vitro and in Silico Human Monoamine Oxidase Inhibitory Potential of Anthraquinones, Naphthopyrones, and Naphthalenic Lactones from Cassia obtusifolia Linn Seeds

ACS Omega. 2019 Sep 18;4(14):16139-16152. doi: 10.1021/acsomega.9b02328. eCollection 2019 Oct 1.

Authors

Pradeep Paudel¹, Su Hui Seong¹, Srijan Shrestha^{1

2}, Hyun Ah Jung³, Jae Sue Choi¹

Affiliations

¹ Department of Food and Life Science, Pukyong National University, Busan 48513, Republic of Korea.
² Discipline of Pharmacology, School of Medicine, Faculty of Health Science, The University of Adelaide, Adelaide, South Australia 5005, Australia.
³ Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, Republic of Korea.

Abstract

In recent years, Cassia seed extract has been reported as a neuroprotective agent in various models of neurodegeneration, mainly via an antioxidant mechanism. However, no one has previously reported the effects of Cassia seed extract and its phytochemicals on human monoamine oxidase (hMAO) enzyme activity. The seed methanol extract, the solvent-soluble fractions, and almost all isolated compounds displayed selective inhibition of hMAO-A isozyme activity. Interestingly, compounds obtusin (3), alaternin (8), aloe-emodin (9), questin (12), rubrofusarin (13), cassiaside (15), toralactone 9-O-β-gentiobioside (26), and (3S)-9,10-dihydroxy-7-methoxy-3-methyl-1-oxo-3,4-dihydro-1H-benzo[g]isochromene-3-carboxylic acid 9-O-β-d-glucopyranoside (38) showed the most promising inhibition of the hMAO-A isozyme with IC₅₀ values of 0.17-11 μM. The kinetic study characterized their mode of inhibition and molecular docking simulation predicted interactions with Ile-335 and Tyr-326 in support of the substrate/inhibitor selectivity in respective isozymes. These results demonstrate that Cassia seed extract and its constituents inhibit hMAO-A enzyme activity with high selectivity and suggest that they could play a preventive role in neurodegenerative diseases, especially anxiety and depression.