18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models

Abstract

The purpose of this study was to examine the effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, in suppressing prolactin (PRL) hyperactivity and reducing antipsychotic-induced hyperprolactinemia (hyperPRL) and the underlying mechanisms in in vitro and in vivo models. GA treatment for 24 h inhibited PRL synthesis and secretion in MMQ cells and cultured pituitary cells in a dose-dependent fashion; but this effect was not reproduced in GH3 cells that lack the expression of functional dopamine D2 receptors. GA suppressed elevated PRL level and growth hormone, and normalized several sex hormones in a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide. GA also modulated the expression 5-HT1A and 5-HT2A receptors in both in vivo and in vitro models. These results indicate that GA is effective in suppressing PRL hyperactivity caused by the blockade of dopamine D2 receptors. This suppressive effect of GA may be related to its modulation of the serotonergic system. This study provides additional evidence in support of GA as an adjunct for the treatment of hyperPRL.

Modulation of intestinal microbiota by glycyrrhizic acid prevents high-fat diet-enhanced pre-metastatic niche formation and metastasis

“…For pre-metastatic niche formation experiment, Balb/c mice and C57BL/6 mice were fed HFD and treated with GA (10 and 20 mg/kg, i.g., qd × 5 days per w) or vehicle for 12 w, respectively. The doses of GA used in the present study were based on the published studies 44 and our preliminary experiments. The mice in the control group were fed the control diet.…”

18β-Glycyrrhetinic Acid Ameliorates Neuroinflammation Linked Depressive Behavior Instigated by Chronic Unpredictable Mild Stress via Triggering BDNF/TrkB Signaling Pathway in Rats

“…Enoxolone, glycyrrhetin, 3β-hydroxy-11oxo-18β, 20β-olean12-en-29oic acid, uralenic acid, or sub-glycyrrhelinic acid are all names for 18β-glycyrrhetinic acid. 18β-glycyrrhetinic acid have been described to reduce airway inflammation [ 16 , 17 ], alpha-naphthylisothiocyanate-induced cholestasis [ 18 ], D-GalN/LPS-induced acute liver injury [ 19 ], cyclophosphamide-induced hepatotoxicity [ 20 ], prostate tumor [ 21 ], lung cancer [ 22 ], gastric tumor [ 23 ], streptozotocin-induced diabetes [ 24 ], pulmonary arterial hypertension [ 25 ], visceral leishmaniasis [ 26 ], rotavirus replication [ 27 ], bacterial load [ 28 , 29 ], antipsychotic-induced hyperprolactinemia [ 30 ], myocardial infarction [ 31 ], hyperoxia exposure effects in neonatal rats [ 32 ], rheumatoid arthritis [ 33 ], fructose-induced nephropathy [ 34 ], radiation-induced skin damage [ 35 ], cisplatin-induced oxidative intestinal damage [ 36 ].…”

The Effect of SBA-15 Surface Modification on the Process of 18β-Glycyrrhetinic Acid Adsorption: Modeling of Experimental Adsorption Isotherm Data

“…18β-Glycyrrhetinic acid (18β-GA) is a pentacyclic triterpenoid derivative of oleanane type (β-amyrin) that is found in the roots and rhizomes of licorice ( Glycyrrhiza glabra ) [55,56,57]. 18β-GA is an aglycone and active metabolite of glycyrrhizin [55,58]. Figure 1 prevents the chemical structure of 18β-GA.…”

“…18β-GA possesses various beneficial pharmacological properties, including antitumor [55,56], anti-inflammatory [59,60,61], antioxidant [57,58,61], immunomodulatory [56], antiviral [57,58,62], hepatoprotective [57,62,63], antiulcer [56,57,62], and antiallergic [61] activities. Its chemopreventive effect is ascribed to the inhibition of tumorigenesis and the induction of apoptosis in cancer cells [55].…”

“…18β-GA reveals the antileishmanial effect by great reducing the parasite load in experimental visceral leishmaniasis, mainly through nitric oxide upregulation and proinflammatory cytokine expression [56]. Moreover, it was demonstrated to suppress prolactin hyperactivity and reduce antipsychotic-induced hyperprolactinemia [58]. 18β-GA also reveals an antihyperglycemic effect on streptozocin-diabetic rats, which was evidenced by lowered plasma glucose with a simultaneous increase in the insulin secretion [62].…”