From:  Immunomodulation: scope and limitations in promoting diabetic foot ulcer healing

 Therapeutic agents promoting M2 macrophage polarization and wound healing in diabetes.

Macrophage polarizationStudyModelStrategyMechanisms/Outcome
HumansADSCs mediated macrophage polarization [52]Bioinformatics analysis of GSE134431 and GSE80178 datasets of human origin30 macrophage polarization-associated differentially expressed genes (MA-DEGs) were identified and analyzed.ADSCs regulate EREG and CSTA expression to promote M2 macrophage polarization.
ON101 cream, a phase 3 randomized clinical trial [53]Human patientsTwice-daily applications of ON101 or an absorbent dressing were changed once daily or 2 to 3 times a week for 16 weeks, with a 12-week follow-up.ON101 exhibited better healing efficacy.
ON101 regulates macrophage polarization.
Animal model and in vitroMDSC-dependent macrophage polarization [54]DFU mouse modelMCC950 was injected every other day into the wound in C57BL/6 diabetic mice.MCC950 increased M2 macrophages and decreased pro-inflammatory genes. MCC950 recruits MDSCs and significantly accelerates diabetic wound healing.
Resveratrol effects on macrophage polarization and wound healing [55]Diabetic mice model
THP1 cells		Diabetes was induced with STZ in C57BL/6 mice.
THP1 cells were used to evaluate the effects of resveratrol on polarization and the secretion of pro-inflammatory factors.		Resveratrol significantly increased diabetic wound healing.
Resveratrol reduces TNF-α, iNOS, and IL-1β secretion and promotes M2 macrophage polarization.
Puerarin [56]Male C57BL/6 mice
RAW264.7 cells		Diabetes was induced using streptozotocin in mice.
Puerarin (120 mg/kg i.p.) was administered daily to the mice		Induces M2 macrophage polarization.
The effects of puerarin on macrophage polarization are related to NF-κB and MAPK signaling pathways.
Puerarin promotes diabetic wound healing.
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ADSCs: adipose-derived stem cells; MDSCs: myeloid-derived suppressor cells; TNF-α: tumor necrosis factor alpha; iNOS: inducible nitric oxide synthase; IL: interleukin; NF-κB: nuclear factor kappa beta; MAPK: mitogen-activated protein kinase.