Monoamine Oxidase and Dopamine β-Hydroxylase Inhibitors from the Fruits of Gardenia jasminoides

Abstract

This research was designed to determine what components of Gardenia jasminoides play a major role in inhibiting the enzymes related antidepressant activity of this plant. In our previous research, the ethyl acetate fraction of G. jasminosides fruits inhibited the activities of both monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B), and oral administration of the ethanolic extract slightly increased serotonin concentrations in the brain tissues of rats and decreased MAO-B activity. In addition, we found through in vitro screening test that the ethyl acetate fraction showed modest inhibitory activity on dopamine-β hydroxylase (DBH). The bioassay-guided fractionation led to the isolation of five bio-active compounds, protocatechuic acid (1), geniposide (2), 6'-O-trans-p-coumaroylgeniposide (3), 3,5-d-ihydroxy-1,7-bis (4-hydroxyphenyl) heptanes (4), and ursolic acid (5), from the ethyl acetate fraction of G. jasminoides fruits. The isolated compounds showed different inhibitory potentials against MAO-A, -B, and DBH. Protocatechuic acid showed potent inhibition against MAO-B (IC50 300 μmol/L) and DBH (334 μmol/L), exhibiting weak MAO-A inhibition (2.41 mmol/L). Two iridoid glycosides, geniposide (223 μmol/L) and 6'-O-trans-p-coumaroylgeniposide (127μmol/L), were selective MAO-B inhibitor. Especially, 6'-O-trans-p-coumaroylgeniposide exhibited more selective MAO-B inhibition than deprenyl, well-known MAO-B inhibitor for the treatment of early-stage Parkinson’s disease. The inhibitory activity of 3,5-di-hydroxy-1,7-bis (4-hydroxyphenyl) heptane was strong for MAO-B (196 μmol/L), modest for MAO-A (400 μmol/L), and weak for DBH (941 μmol/L). Ursolic acid exhibited significant inhibition of DBH (214 μmol/L), weak inhibition of MAO-B (780 μmol/L), and no inhibition against MAO-A. Consequently, G. jasminoides fruits are considerable for development of biofunctional food materials for the combination treatment of depression and neurodegenerative disorders.

Phytochemistry, Pharmacological Activities and Intellectual Property Landscape of Gardenia jasminoides Ellis: a Review

“…17 Genipin induced cell apoptosis in hepatoma cells and PC3 human prostate cancer cells due to increased significantly in the phosphorylated c-Jun NH(2)-terminal kinase (JNK) protein, phospho-Jun protein, p53 protein and bax protein which led to the accumulation of bax protein, further induced cell apoptotic death eventually. 106 Anti-proliferative activity of genipin in MDA-MB-231 exerted human breast cancer cells 22 by similar mechanism in the previous studies. 17,106 Genipin suppressed the constitutive STAT3 activation in U266 and U937 cells and stimulated Src homology 2 domain-containing phosphatase 1 (SHP-1), which dephosphorylates and inactivates STAT3 by blocking STAT3 activation via repressing the activation of c-Src, but ROHAN SHARADANAND PHATAK: Phytochemistry, Pharmacology and IP of Gardenia jasminoides Ellis not Janus kinase 1 (JAK1) and also down regulated the expression of STAT3 target genes including Bcl-2, Bcl-x(L), Survivin, Cyclin D1, and VEGF.…”

Rapid Antidepressant Activity of Ethanol Extract ofGardenia jasminoidesEllis Is Associated with Upregulation of BDNF Expression in the Hippocampus

“…Geniposide is a hallmark compound enriched in GJ. A number of studies suggest its antidepressant efficacy, which may contribute to rapid antidepressant of GJ [ 20 , 21 ]. We found there was no significant effect on the immobility time in TST at 24 h after a single administration of variable concentration of geniposide (ANOVA, F (5,71) = 0.662, P = 0.654, and n = 12) ( Figure 8 ).…”

“…A previous study reported that geniposide contributed to antidepressant-like effects of Zhi-Zi-Hou-Pu decoction [ 28 ]. The antidepressant potential of geniposide is evidenced as it has monoamine oxidase inhibitory effect [ 20 ]. However, we did not observe the rapid antidepressant-like activity of geniposide after a single administration.…”

Synthesis and Antitumor Evaluation in Vitro of NO‐Donating Ursolic Acid‐Benzylidene Derivatives

“…eu-azarolus MAIRE, Ixora coccinea L. (Rubiaceae), Ligustrum lucidum and Eriobotrya japonica. [1][2][3][4][5] Previous study showed that UA is responsible for many biological activities, such as antioxidant, anti-inflammatory, antibacterial, antitumor and hepatoprotection. [6] Recently, UA is of great concern because of its outstanding antitumor activity.…”