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

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.

Reveals of New Candidate Active Components in Hemerocallis Radix and Its Anti-Depression Action of Mechanism Based on Network Pharmacology Approach

“…Though human MAO and mouse MAO have 92% sequence identity, differential sensitivity to phentermine inhibition suggests that structural and functional differences exist between them. That is to say, the type of MAO enzyme must be the reason for these inconsistent findings [33]. Consistent with our study, anthraquinone can down-regulate MAOA and MAOB, and all the gene data we used were set at Homo sapiens.…”

Emodin Derivatives as Multi-Target-Directed Ligands Inhibiting Monoamine Oxidase and Antagonizing Vasopressin V1A Receptors

“…From our recent study on metabolites from C. obtusifolia Linn seeds, we identified the anthraquinones as selective hMAO-A inhibitors. 42 Likewise, major protein targets of hMAO active anthraquinones were predicted via proteocheminformatics modeling (PCM), and the prediction result was validated via a GPCRs cell-based functional assay. 43 From the PCM, we predicted human V 1A R as a prime target and human dopamine D 3 R within a list of top enriched targets.…”

“…It was less potent at hMAO-B inhibition (IC 50 : 54.67 ± 0.74 μM). 42 However, the additional 7-hydroxy group in the EM structure (=alaternin) increased the potency of hMAO-A inhibition by 4 times and the potency of hMAO-B inhibition by 14 times. The 7-OHEM (=alaternin) was equally potent in hMAO inhibition.…”

Novel Diels–Alder Type Adducts from Morus alba Root Bark Targeting Human Monoamine Oxidase and Dopaminergic Receptors for the Management of Neurodegenerative Diseases

“…The potential of the test compounds for human MAO inhibition was evaluated via a chemiluminescence technique using the MAO-Glo kit (Promega, Madison, WI, USA). Detailed experimental conditions and procedures were reported previously [64,65]. The test compounds were evaluated at a concentration of 6, 30, and 120 µM.…”