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


ABSTRACT:

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 β-catenin and Rspo3 while inhibiting the expression of NF-KB and GSK-3β, 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 β-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.

SUBMITTER: Zhen Z 

PROVIDER: S-EPMC10881534 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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

Zhen Zhang Z   Wei Shan S   Yunfei Wang W   Jie Xing X   Jienan Xu X   Yiting Shen S   Wen Xiao X   Shuyu Guo G   Yue Liang L   Xuanyu Wang W   Yumei Zhong Z   Huafa Que Q  

Heliyon 20240205 4


<h4>Ethnopharmacological relevance</h4>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.<h4>Aim of the study</h4>To clarify the molecular mechanism of APS in promoting wound-hea  ...[more]

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