ReferenceID 3935
Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages
Free Radic Biol Med
Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the firs
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- Reference Id
- 3935
- Evidence Id
- 20525
- Core Evidence Id
- 20525
- Source Reference Id
- 1136
- Herb2 Reference Id
- HBREF001919
- Subject Paper Key
- HBIN041294_28690198
- Pubmed Id
- 28690198
- Doi
- 10.1016/j.freeradbiomed.2017.06.014
- Paper Title
- Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages
- Paper Abstract
- Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC50 value of 1.04μM. Results from NPOI further showed that the Kon and Koff of PUN-PTP1B complex were 3.38e2M-1s-1 and 4.13e-3s-1, respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation. Moreover, inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and enhanced anti-inflammatory cytokines expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfα, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases.
- Journal
- Free Radic Biol Med
- Publish Year
- 2017
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Inflammation
- Paper Title Cn
- Paper Title En
- Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages
- Bilingual Status
- semi_complete