Establishing GPCR Targets of hMAO Active Anthraquinones from Cassia obtusifolia Linn Seeds Using in Silico and in Vitro Methods

• Published in: ACS Omega
• Main Author: Paudel P.; Seong S.H.; Fauzi F.M.; Bender A.; Jung H.A.; Choi J.S.
• Format: Article
• Language: English
• Published: American Chemical Society 2020
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85082740205&doi=10.1021%2facsomega.0c00684&partnerID=40&md5=5d451b262f860dc8eeb5f8075e4a79ee

The present study examines the effect of human monoamine oxidase active anthraquinones emodin, alaternin (=7-hydroxyemodin), aloe-emodin, and questin from Cassia obtusifolia Linn seeds in modulating human dopamine (HD1R, HD3R, and HD4R), serotonin (h5-HT1AR), and vasopressin (hV1AR) receptors that were predicted as prime targets from proteocheminformatics modeling via in vitro cell-based functional assays, and explores the possible mechanisms of action via in silico modeling. Emodin and alaternin showed a concentration-dependent agonist effect on HD3R with EC50 values of 21.85 ± 2.66 and 56.85 ± 4.59 μM, respectively. On hV1AR, emodin and alaternin showed an antagonist effect with IC50 values of 10.25 ± 1.97 and 11.51 ± 1.08 μM, respectively. Interestingly, questin and aloe-emodin did not have any observable effect on hV1AR. Only alaternin was effective in antagonizing h5-HT1AR (IC50: 84.23 ± 4.12 μM). In silico studies revealed that a hydroxyl group at C1, C3, and C8 and a methyl group at C6 of anthraquinone structure are essential for HD3R agonist and hV1AR antagonist effects, as well as for the H-bond interaction of 1-OH group with Ser192 at a proximity of 2.0 Å. Thus, based on in silico and in vitro results, hV1AR, HD3R, and h5-HT1AR appear to be prime targets of the tested anthraquinones. Copyright © 2020 American Chemical Society.