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. 2023 Sep 5;15(18):3866. doi: 10.3390/nu15183866

Figure 2.

Figure 2

Schematic representation of metabolism pathway and toxicity mechanisms of liquorice and its derivatives. After oral intake, liquorice is converted to GL in the gut and this is hydrolyzed to GA by the β-glucuronidases of gut microbiota. GA is later absorbed in the blood stream and carried by serum albumin. In the liver, GA is converted to GA3S by SULT2A1. GA3S is excreted with the bile and enter the enterohepatic circulation. In tissues, GA and its metabolites inhibit 11β-HSD2 thus blocking the constitutive degradation of cortisol to cortisone. Available cortisol binds and activates MR cascade and their downstream effectors. In the kidneys, this event causes a potent increase in Na and H2O absorption combined with K excretion, via ROMKs, ENaCs and AQP2s channels. In blood vessels, GL metabolites boost contractile responses to pressor hormones and reduce endothelial NO production, concurring to AH. GL: Glycyrrhizin; GA: Glycyrrhetinic acid; GA3S: 18β-glycyrrhetyl-3-O-sulfate; SULT2A1: sulfotransferase 2A1; 11β-HSD2: 11-β-hydroxysteroid-dehydrogenase type II; CL: cortisol; CE: cortisone; MR: mineralocorticoid receptor; K: potassium; Na: sodium; H2O: water; ROMK: renal outer medullary potassium channel; ENaC: epithelial Na-channels; AQP2: acquaporine-2; OAT: organic anion transporter; NO: nitric oxide; AH: arterial hypertension.