Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway / 中国天然药物
Chinese Journal of Natural Medicines (English Ed.)
; (6): 122-130, 2019.
Article
ي En
| WPRIM
| ID: wpr-776901
المكتبة المسؤولة:
WPRO
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.
Key words
النص الكامل:
1
الفهرس:
WPRIM
الموضوع الرئيسي:
Pharmacology
/
Phosphorylation
/
Molecular Structure
/
Signal Transduction
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Chemistry
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Gene Expression Regulation
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Cytokines
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Enzyme Inhibitors
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Allergy and Immunology
/
STAT3 Transcription Factor
نوع الدراسة:
Diagnostic_studies
المحددات:
Animals
اللغة:
En
مجلة:
Chinese Journal of Natural Medicines (English Ed.)
السنة:
2019
نوع:
Article