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      Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway

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          Abstract

          Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin (HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12 (HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1 (Arg-1), interleukin-10 (IL-10), transforming growth factor β (TGF- β) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase (iNOS) was down-regulated in LPS- and IFN- γ-treated (M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490 (inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN- γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.

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          Author and article information

          Journal
          CJNM
          Chinese Journal of Natural Medicines
          Elsevier
          1875-5364
          20 February 2019
          : 17
          : 2
          : 122-130
          Affiliations
          1 The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
          2 The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
          3 The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei 230032, China
          4 Institute for Liver Diseases, Anhui Medical University, Hefei 230032, China
          5 Anhui Provincial Hospital, Hefei 230001, China
          6 School of Pharmacy, The Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China
          Author notes
          *Corresponding author: LI Jun, Tel/Fax: 86-551-65161001, E-mail: lj@ 123456ahmu.edu.cn

          These authors have no conflict of interest to declare.

          Article
          S1875-5364(19)30014-7
          10.1016/S1875-5364(19)30014-7
          Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funding
          Funded by: Key Fund Project of Anhui Education Department
          Award ID: KJ2016A364
          Funded by: National Natural Science Foundation of China
          Award ID: 81473268
          This work was supported by the Key Fund Project of Anhui Education Department (No. KJ2016A364) and National Natural Science Foundation of China (No. 81473268).

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