Abstract
Low progesterone level is always linked with pre-term birth. Therefore, maintaining of progesterone level is vital during pregnancy. Aldo-keto reductase family one member C1 (AKR1C1) catalyzes the reduction of progesterone to its inactive form of 20-alpha-hydroxy-progesterone and thus limits the biological effect of progesterone. In our effort to identify the natural compound that would specifically inhibit AKR1C1, liquiritin was found to be a selective and potent inhibitor of AKR1C1. Kinetic analyses in the S-(+)-1,2,3,4-tetrahydro-1-naphthol (s-tetralol) catalyzed by AKR1C1 in the presence of the inhibitors suggest that liquiritin is a competitive inhibitor by targeting the residues Ala-27, Val-29, Ala-25, and Asn-56 of AKR1C1. In HEC-1-B cells, treatment with liquiritin results in 85.00% of reduction in progesterone metabolism, which is mediated by AKR1C1 enzymatic activity. Overall, our study not only identify liquiritin as an inhibitor against AKR1C1, but also reveal that liquiritin may be served as a potential intervention strategy for preventing pre-term birth caused by low progesterone level.
Highlights
Progesterone, a natural female hormone, is essential for pregnancy maintenance (Csapo et al, 1971; Spencer and Bazer, 2002; Romero et al, 2014)
We designed the study of finding Aldo-keto reductase family 1 member C1 (AKR1C1) inhibitor based on purification of AKR1C1 enzymes from E. coli followed by conducting enzymatic assay, which is a classic method in screening inhibitors of AKR1C1 (El-Kabbani et al, 2010; Zheng et al, 2018)
Cellular tests reveal that liquiritin treatment significantly reduces the progesterone metabolism mediated by AKR1C1, suggesting that liquiritin is capable of interfering with progesterone level in cells
Summary
Progesterone, a natural female hormone, is essential for pregnancy maintenance (Csapo et al, 1971; Spencer and Bazer, 2002; Romero et al, 2014). As metabolite of progesterone has Liquiritin Inhibits Progesterone Metabolism a quite low affinity for the progesterone receptors, AKR1C1 plays a critical role in controlling the cellular progesterone concentration, which is an essential hormone impeccable for maintenance of pregnancy (Ji et al, 2004; Lewis et al, 2004; Piekorz et al, 2005). These studies indicate that inhibition of progesterone metabolism mediated by AKR1C1 is a promising strategy for preventing pre-term birth. We propose AKR1C1 as a new potential therapeutic target in pregnancy maintenance
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