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Licocoumarone isolated from Glycyrrhiza uralensis selectively alters LPS-induced inflammatory responses in RAW 264.7 macrophages.
Eur J Pharmacol 2017; 801:46-53EJ

Abstract

The effects of licocoumarone (LC) isolated from Glycyrrhiza uralensis were studied in LPS-stimulated RAW 264.7 macrophages. Our study demonstrated that LC dose-dependently attenuated LPS-induced NO production by down-regulating iNOS expression. Additionally, the treatment with LC inhibited LPS-induced expression of cytokines including IL-1β, IL-6 and IL-10, but not TNF-α, at both mRNA and protein levels. Similar suppressive effects of LC were observed on LPS-stimulated murine peritoneal macrophages as well. Furthermore, LC significantly reduced LPS-stimulated NF-κB activation by inhibition of IκBα degradation and p65 phosphorylation. The results from NF-κB-luc reporter gene assay further support the inhibitory effect of LC on NF-κB activation. Further studies showed that LC also interfered with the MAPKs and STAT3 signaling pathways, which are typical inflammatory signaling pathways triggered by LPS. Taken together, these results show that LC attenuates LPS-induced cytokine gene expression in RAW 264.7 macrophages through mechanisms that involve NF-κB, MAPKs and STAT3 signaling pathways, but the pattern of inhibition differs from that of a global immunosuppresant. Our study indicates that LC is a functional constituent of Glycyrrhiza uralensis with potential implications in infectious and immune-related diseases.

Authors+Show Affiliations

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: jiny@ecust.edu.cn.School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: zhangyan_sjtu@sjtu.edu.cn.School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Institute of Chinese Medical Sciences, University of Macau, Macau, SAR, China. Electronic address: yedequan@sjtu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28263754

Citation

Wu, Lehao, et al. "Licocoumarone Isolated From Glycyrrhiza Uralensis Selectively Alters LPS-induced Inflammatory Responses in RAW 264.7 Macrophages." European Journal of Pharmacology, vol. 801, 2017, pp. 46-53.
Wu L, Fan Y, Fan C, et al. Licocoumarone isolated from Glycyrrhiza uralensis selectively alters LPS-induced inflammatory responses in RAW 264.7 macrophages. Eur J Pharmacol. 2017;801:46-53.
Wu, L., Fan, Y., Fan, C., Yu, Y., Sun, L., Jin, Y., ... Ye, R. D. (2017). Licocoumarone isolated from Glycyrrhiza uralensis selectively alters LPS-induced inflammatory responses in RAW 264.7 macrophages. European Journal of Pharmacology, 801, pp. 46-53. doi:10.1016/j.ejphar.2017.02.049.
Wu L, et al. Licocoumarone Isolated From Glycyrrhiza Uralensis Selectively Alters LPS-induced Inflammatory Responses in RAW 264.7 Macrophages. Eur J Pharmacol. 2017 Apr 15;801:46-53. PubMed PMID: 28263754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Licocoumarone isolated from Glycyrrhiza uralensis selectively alters LPS-induced inflammatory responses in RAW 264.7 macrophages. AU - Wu,Lehao, AU - Fan,Yunpeng, AU - Fan,Chao, AU - Yu,Yang, AU - Sun,Lei, AU - Jin,Yu, AU - Zhang,Yan, AU - Ye,Richard D, Y1 - 2017/03/02/ PY - 2016/11/07/received PY - 2017/02/28/revised PY - 2017/02/28/accepted PY - 2017/3/7/pubmed PY - 2017/4/18/medline PY - 2017/3/7/entrez KW - Glycyrrhiza uralensis KW - Licocoumarone KW - MAPKs KW - NF-κB KW - STAT3 SP - 46 EP - 53 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 801 N2 - The effects of licocoumarone (LC) isolated from Glycyrrhiza uralensis were studied in LPS-stimulated RAW 264.7 macrophages. Our study demonstrated that LC dose-dependently attenuated LPS-induced NO production by down-regulating iNOS expression. Additionally, the treatment with LC inhibited LPS-induced expression of cytokines including IL-1β, IL-6 and IL-10, but not TNF-α, at both mRNA and protein levels. Similar suppressive effects of LC were observed on LPS-stimulated murine peritoneal macrophages as well. Furthermore, LC significantly reduced LPS-stimulated NF-κB activation by inhibition of IκBα degradation and p65 phosphorylation. The results from NF-κB-luc reporter gene assay further support the inhibitory effect of LC on NF-κB activation. Further studies showed that LC also interfered with the MAPKs and STAT3 signaling pathways, which are typical inflammatory signaling pathways triggered by LPS. Taken together, these results show that LC attenuates LPS-induced cytokine gene expression in RAW 264.7 macrophages through mechanisms that involve NF-κB, MAPKs and STAT3 signaling pathways, but the pattern of inhibition differs from that of a global immunosuppresant. Our study indicates that LC is a functional constituent of Glycyrrhiza uralensis with potential implications in infectious and immune-related diseases. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/28263754/Licocoumarone_isolated_from_Glycyrrhiza_uralensis_selectively_alters_LPS_induced_inflammatory_responses_in_RAW_264_7_macrophages_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(17)30135-8 DB - PRIME DP - Unbound Medicine ER -