Astragalus polysaccharide improves diabetic ulcers by promoting M2-polarization of macrophages to reduce excessive inflammation via the ß-catenin/ NF-κB axis at the late phase of wound-healing.

Ethnopharmacological relevance: Astragalus polysaccharide (APS), the most biologically active ingredient of Astragali Radix, is used to treat diabetes mellitus (DM)-related chronic wounds in traditional Chinese medicine for several decades. This herb possesses an anti-inflammatory effect. Our study proved that APS can reduce excessive inflammation at the late phase of wound-healing in diabetic ulcers. Aim of the study: To clarify the molecular mechanism of APS in promoting wound-healing via reducing excessive inflammation in diabetic ulcers during the late stages of wound-healing. Methods and materials: The rat model of the diabetic ulcers was established via intraperitoneal injection of streptozocin (60 mg/kg). We detected the regulation of APS on diabetic ulcers by measuring wound-healing rates. Bioinformatics was used to predict the target genes of APS, and autodocking was used to predict the combination of APS and target genes. Immunohistochemistry, Enzyme-linked immunosorbent assay, Western blot, immunofluorescence staining, flow cytometry, and flow cytometric sorting were investigated. Results: The results demonstrated that APS promoted wound-healing and inhibited excessive inflammation at the late phase of wound-healing in diabetic rats. Mechanistic findings showed that APS promoted the expression of ß-catenin and Rspo3 while inhibiting the expression of NF-KB and GSK-3ß, which leads to the transformation of M1-type macrophages into M2-type macrophages and thus reducing excessive inflammation at the late phase of wound-healing in diabetic ulcers. Conclusion: We found an interesting finding that APS promoted the polarization of macrophages towards M2-type through the ß-catenin/NF-κB axis to reduce excessive inflammation at the late phase of wound-healing. Therefore, APS may be a promising drug for treating diabetic ulcers in clinic.

Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis / 国际口腔科学杂志·英文版

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.