Dataset Information

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

ABSTRACT: 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 ?M, respectively. On hV1AR, emodin and alaternin showed an antagonist effect with IC50 values of 10.25 ± 1.97 and 11.51 ± 1.08 ?M, 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 ?M). 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.

SUBMITTER: Paudel P

PROVIDER: S-EPMC7144155 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Paudel Pradeep P Seong Su Hui SH Fauzi Fazlin Mohd FM Bender Andreas A Jung Hyun Ah HA Choi Jae Sue JS

ACS omega 20200325 13

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 poss ...[more]

PMID: 32280914

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Project description:Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7?-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-? protein was significantly increased while the expression of PPAR-? and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-? protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-? and SREBP-1c, and through normalizing the intestinal dysbiosis and improving the intestinal mucosal barrier function.

Dataset Information

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

Publications

Establishing GPCR Targets of hMAO Active Anthraquinones from <i>Cassia obtusifolia</i> Linn Seeds Using <i>In Silico</i> and <i>In Vitro</i> Methods.

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