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Molecules 2017, 22(9), 1392; doi:10.3390/molecules22091392

Spasmolytic Mechanism of Aqueous Licorice Extract on Oxytocin-Induced Uterine Contraction through Inhibiting the Phosphorylation of Heat Shock Protein 27

1
Department of Complex Prescription of TCM, Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China
2
Divsion of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, BMC box 574, S-751 23 Uppsala, Sweden
3
Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Road, Taiyuan 030006, China
4
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
These two authors equally contributed to the current work.
*
Authors to whom correspondence should be addressed.
Received: 29 July 2017 / Accepted: 21 August 2017 / Published: 29 August 2017
(This article belongs to the Section Natural Products)
View Full-Text   |   Download PDF [8033 KB, uploaded 29 August 2017]   |  

Abstract

Licorice derived from the roots and rhizomes of Glycyrrhiza uralensis Fisch. (Fabaceae), is one of the most widely-used traditional herbal medicines in China. It has been reported to possess significant analgesic activity for treating spastic pain. The aim of this study is to investigate the spasmolytic molecular mechanism of licorice on oxytocin-induced uterine contractions and predict the relevant bioactive constituents in the aqueous extract. The aqueous extraction from licorice inhibited the amplitude and frequency of uterine contraction in a concentration-dependent manner. A morphological examination showed that myometrial smooth muscle cells of oxytocin-stimulated group were oval-shaped and arranged irregularly, while those with a single centrally located nucleus of control and licorice-treated groups were fusiform and arranged orderly. The percentage of phosphorylation of HSP27 at Ser-15 residue increased up to 50.33% at 60 min after oxytocin stimulation. Furthermore, this increase was significantly suppressed by licorice treatment at the concentration of 0.2 and 0.4 mg/mL. Colocalization between HSP27 and α-SMA was observed in the myometrial tissues, especially along the actin bundles in the oxytocin-stimulated group. On the contrary, the colocalization was no longer shown after treatment with licorice. Additionally, employing ChemGPS-NP provided support for a preliminary assignment of liquiritigenin and isoliquiritigenin as protein kinase C (PKC) inhibitors in addition to liquiritigenin, isoliquiritigenin, liquiritin and isoliquiritin as MAPK-activated protein kinase 2 (MK2) inhibitors. These assigned compounds were docked with corresponding crystal structures of respective proteins with negative and low binding energy, which indicated a high affinity and tight binding capacity for the active site of the kinases. These results suggest that licorice exerts its spasmolytic effect through inhibiting the phosphorylation of HSP27 to alter the interaction between HSP27 and actin. Furthermore, our results provide support for the prediction that potential bioactive constituents from aqueous licorice extract inhibit the relevant up-stream kinases that phosphorylate HSP27. View Full-Text
Keywords: licorice; uterine contraction; HSP27 phosphorylation; ChemGPS-NP prediction; molecular docking licorice; uterine contraction; HSP27 phosphorylation; ChemGPS-NP prediction; molecular docking
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MDPI and ACS Style

Yang, L.; Chai, C.-Z.; Yan, Y.; Duan, Y.-D.; Henz, A.; Zhang, B.-L.; Backlund, A.; Yu, B.-Y. Spasmolytic Mechanism of Aqueous Licorice Extract on Oxytocin-Induced Uterine Contraction through Inhibiting the Phosphorylation of Heat Shock Protein 27. Molecules 2017, 22, 1392.

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