基于精确网络药理学的升脂化瘀方靶向PI3K/Akt信号通路的糖尿病创面愈合新单体配方

IF 5.4 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2025-03-26 Epub Date: 2025-02-17 DOI:10.1016/j.jep.2025.119509

Sheng Hu , Fang Shen , Ning Jia , Caiyun Zhang , Xinxin Wu , Wencheng Jiang , Bin Li , Qilong Chen

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引用次数: 0

摘要

民族药理学相关性：生脂化瘀方已被临床用于糖尿病溃疡的治疗。转录谱分析显示，PI3K/Akt信号通路在糖尿病创面愈合中起关键作用。然而，SJHY在糖尿病伤口治疗中的作用和潜在机制往往具有挑战性。目的：通过体内和体外实验，探讨SJHY治疗糖尿病创面的新单体配方和作用机制。材料与方法：建立糖尿病创面小鼠模型，评价SJHY对糖尿病溃疡的治疗效果。采用转录谱法鉴定SJHY治疗的糖尿病创面小鼠的差异表达基因（DEGs）。利用构建的PPI网络和KEGG-target网络识别核心通路和相关靶点。采用高效液相色谱-质谱联用法对复方进行成分鉴别。通过分子对接和体外实验，筛选哪些单体调控糖尿病创面的核心通路。最后，提出了一种用于糖尿病创面愈合的新型单体配方。结果：体内实验表明，SJHY方能显著促进糖尿病创面愈合。转录组学和网络分析显示，PI3K/Akt信号通路的存在与SJHY治疗糖尿病创面高度相关。HPLC-MS和分子对接显示，Calycosin （Cal）和Dehydromiltirone （DHT）对Itga6和Thbs1具有强烈的靶向作用。mRNA和蛋白水平表明，Itga6和Thbs1是糖尿病创面PI3K/Akt信号通路的重要上游调控因子，体外实验显示，Cal、DHT及其配方可显著提高MGO诱导的HaCaT细胞中Itga6、Thbs1、PI3K和Akt的水平。结论：SJHY方对糖尿病创面愈合具有一定的治疗效果，Cal和DHT可能是通过调节Itga6和Thbs1激活PI3K/Akt信号通路减轻炎症的重要单体。我们的研究表明Cal和DHT形成了一个新的单体配方，这可能是SJHY配方促进糖尿病伤口愈合的关键策略之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Novel monomers recipe derived from Shengji-Huayu formula targeting PI3K/Akt signaling pathway for diabetic wound healing based on accurate network pharmacology

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Novel monomers recipe derived from Shengji-Huayu formula targeting PI3K/Akt signaling pathway for diabetic wound healing based on accurate network pharmacology

Ethnopharmacological relevance

Shengji-Huayu (SJHY) formula has been used clinically for diabetic ulcer (DU) treatment. The transcriptional profiles analysis revealed the PI3K/Akt signaling pathway plays a critical role for diabetic wound healing. However, the effects and underlying mechanisms of SJHY are often challenging in diabetic wound treatment.

Aim of the study

To explore the novel monomers recipe and mechanism of SJHY treated diabetic wound via the in vivo and in vitro experiments.

Materials and methods

The diabetic wound mice model was established to evaluate the therapeutic efficacy of SJHY treated diabetic ulcer. The transcriptional profile was implemented to identify the differentially expressed genes (DEGs) of SJHY treated diabetic wound mice. The constructed PPI network and KEGG-target network were used to identify the core pathway and related targets. The HPLC-MS method was used to identify the ingredients of SJHY formula. The molecular docking and in vitro experiment was used to screen which monomers regulated core pathway in diabetic wound. Finally, a novel monomers recipe was performed for diabetic wound healing.

Results

The in vivo experiment demonstrated SJHY formula significantly promoted diabetic wound healing. Transcriptomic and network analysis revealed the existence of PI3K/Akt signaling pathway was high correlated with SJHY treated diabetic wound. The HPLC-MS and molecular docking revealed that Calycosin (Cal) and Dehydromiltirone (DHT) were strongly targeting Itga6 and Thbs1. The mRNA and protein levels suggested that Itga6 and Thbs1 acted as important upstream regulators of PI3K/Akt signaling pathway in diabetic wound, and the in vitro experiments revealed Cal, DHT and their recipe were significantly increased the levels of Itga6, Thbs1, PI3K and Akt in MGO induced HaCaT cells.

Conclusions

SJHY formula has therapeutic efficiency for diabetic wound healing, and Cal and DHT may be a part of the important monomers that alleviate inflammation via activating the PI3K/Akt signaling pathway by regulated Itga6 and Thbs1. Our study demonstrated Cal and DHT formed a novel monomers recipe, which may be one of the critical strategies of SJHY formula promote diabetic wound healing.

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.