Xanthoangelol and 4-Hydroxyderricin Are the Major Active Principles of the Inhibitory Activities against Monoamine Oxidases on Angelica keiskei K

Abstract

Monoamine oxidase inhibitors (MAOI) have been widely used as antidepressants. Recently, there has been renewed interest in MAO inhibitors. The activity-guided fractionation of extracts from Angelica keiskei Koidzumi (A. keiskei K.) led to the isolation of two prenylated chalcones, xanthoangelol and 4-hydroxyderricin and a flavonoid, cynaroside. These three isolated compounds are the major active ingredients of A. keiskei K. to inhibit the MAOs and DBH activities. Xanthoangelol is a nonselective MAO inhibitor, and a potent dopamine β-hydroxylase (DBH) inhibitor. IC50 values of xanthoangelol to MAO-A and MAO-B were calculated to be 43.4 μM, and 43.9 μM. These values were very similar to iproniazid, which is a nonselective MAO inhibitor used as a drug against depression. The IC50 values of iproniazid were 37 μM, and 42.5 μM in our parallel examination. Moreover, IC50 value of xanthoangelol to DBH was calculated 0.52 μM. 4-Hydroxyderricin is a potent selective MAO-B inhibitor and also mildly inhibits DBH activity. The IC50 value of 4-hydroxyderricin to MAO-B was calculated to be 3.43 μM and this value was higher than that of deprenyl (0.046 μM) used as a positive control for selective MAO-B inhibitor in our test. Cynaroside is a most potent DBH inhibitor. The IC50 value of cynaroside to DBH was calculated at 0.0410 μM. Results of this study suggest that the two prenylated chalcones, xanthoangelol and 4-hydroxyderricin isolated from A. keiskei K., are expected for potent candidates for development of combined antidepressant drug. A. keiskei K. will be an excellent new bio-functional food material that has the combined antidepressant effect.

Integration of Biochemometrics and Molecular Networking to Identify Antimicrobials in Angelica keiskei

“…Compound 2 was obtained at 95% purity following three stages of fractionation using both normal-phase flash chromatography and reversed-phase preparative-scale HPLC. The structures of compounds 1 and 2 were confirmed with 1 H and 13 C NMR by comparing to literature data [21] (Supplementary Fig. S4 – S7).…”

Angelica keiskeiKoidzumi Extracts Improve Some Markers of Liver Function in Habitual Alcohol Drinkers: A Randomized Double-Blind Clinical Trial

“…27 The xanthoangelol and 4-hydroxyderricin compounds found in AKE inhibit the monoamine oxidase enzyme, thereby preventing the breakdown of monoamine neurotransmitters and increasing their levels. 28 Monoamine oxidase inhibitors have been used for the treatment of depression, anxiety, and chronic fatigue syndrome. 29 However, we observed no significant effects on fatigue.…”

Quercetin and Related Chromenone Derivatives as Monoamine Oxidase Inhibitors: Targeting Neurological and Mental Disorders

“…Cynaroside showed notable MAO inhibition with IC 50 values MAO-A400 µM and MAO-B 268 µM. Therefore, it is likely that that inhibition of MAO-B exerts antidepressant activity (Figure 5) [44].…”