The Identification of the Biomarkers of Sheng-Ji Hua-Yu Formula Treated Diabetic Wound Healing Using Modular Pharmacology.

The Identification of the Biomarkers of Sheng-Ji Hua-Yu Formula Treated Diabetic Wound Healing Using Modular Pharmacology.
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模块化药理学鉴定生肌化瘀方治疗糖尿病伤口愈合的生物标志物

DOI:
10.3389/fphar.2021.726158
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发表时间:
2021
影响因子:
5.6
通讯作者:
Kuai L
Kuai L
中科院分区:
医学2区
文献类型:
--
作者:
Jiang JS;Zhang Y;Luo Y;Ru Y;Luo Y;Fei XY;Song JK;Ding XJ;Zhang Z;Yang D;Yin SY;Zhang HP;Liu TY;Li B;Kuai L

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生肌化瘀方在我们以往的临床试验中已被证明能减轻糖尿病伤口愈合的严重程度,且无明显不良反应。然而,基于多靶点特性,草药、成分和枢纽基因之间的调控网络仍有待阐明。本研究旨在确定SJHY配方治疗糖尿病伤口愈合的生物标志物。首先,使用网络药理学构建SJHY配方的组分和靶标的网络。其次,使用QuantiterONE算法构建模块化网络,并沿着核心途径识别枢纽基因沿着。第三,我们通过分子对接来验证核心靶标以选择枢纽基因。此外,通过在糖尿病伤口愈合小鼠模型中的动物实验验证了SJHY配方的生物标志物。结果显示,SJHY方下调Cxcr 4、Oprd 1和Htr 2a的mRNA表达,上调Adrb 2、Drd、Drd 4和Hrh 1的mRNA表达。此外,SJHY配方上调糖尿病伤口愈合小鼠模型的皮肤组织匀浆中的核心通路、神经活性配体-受体相互作用和cAMP信号通路。总之,本研究确定了潜在的靶点和核心通路,为临床应用SJHY配方治疗糖尿病伤口愈合提供了额外的证据。
Sheng-Ji Hua-Yu (SJHY) formula has been proved to reduce the severity of diabetic wound healing without significant adverse events in our previous clinical trials. However, based on multi-target characteristics, the regulatory network among herbs, ingredients, and hub genes remains to be elucidated. The current study aims to identify the biomarkers of the SJHY formula for the treatment of diabetic wound healing. First, a network of components and targets for the SJHY formula was constructed using network pharmacology. Second, the ClusterONE algorithm was used to build a modular network and identify hub genes along with kernel pathways. Third, we verified the kernel targets by molecular docking to select hub genes. In addition, the biomarkers of the SJHY formula were validated by animal experiments in a diabetic wound healing mice model. The results revealed that the SJHY formula downregulated the mRNA expression of Cxcr4, Oprd1, and Htr2a, while upregulated Adrb2, Drd, Drd4, and Hrh1. Besides, the SJHY formula upregulated the kernel pathways, neuroactive ligand–receptor interaction, and cAMP signaling pathway in the skin tissue homogenate of the diabetic wound healing mice model. In summary, this study identified the potential targets and kernel pathways, providing additional evidence for the clinical application of the SJHY formula for the treatment of diabetic wound healing.
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