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.