桃仁红花治疗增生性疤痕的作用机制：基于网络药理分析和体外实验的研究,Chemical Biology & Drug Design

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桃仁红花治疗增生性疤痕的作用机制：基于网络药理分析和体外实验的研究
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2023-12-06 , DOI: 10.1111/cbdd.14412
Xixi Li ₁ , Zhipeng Huang ₂ , Hua Chao ₂ , Xunxun Lin ₂

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传统医学认为，增生性疤痕（HS）属于“瘀血”范畴。中医治疗热射病多选用活血化瘀、通经止痛的中药。桃仁 (SP) 和红花 (FC) 均被证实对治疗 HS 有效。临床上，SP和FC常联合使用。然而，SP-FC治疗HS的药效机制和分子靶点仍不清楚。因此，本研究拟通过网络药理学结合体外细胞和分子生物学实验，探讨SP-FC治疗HS的机制和靶点。SP-FC的靶基因从中药系统药理学数据库与分析平台（TCMSP）中获取，并从Disgenet和GeneCards等数据库中检索HS相关疾病的靶点。根据搜索到的目标，绘制维恩图，获取SP-FC-HS的常见目标。接下来，使用STRING 11.0对常见目标进行蛋白质-蛋白质相互作用（PPI）网络分析；cytoscape 3.9.0用于PPI连接关系分析并绘制“药物-成分-靶标”网络图。此外，采用改良的外植体培养方法分离原代肥厚性疤痕成纤维细胞（HSF）；MTT法检测SP-FC处理24小时后HSF的细胞活力；Annexin V-FITC/PI双染结合流式细胞术检测细胞凋亡；Western blot检测p53蛋白表达水平；实时荧光定量PCR测定p53 mRNA水平。网络药理学分析中，从数据库中筛选出269个SP药理靶点、449个FC药理靶点、2569个HS相关疾病靶点。绘制维恩图后，获得了 SP-FC-HS 的 116 个常见目标。体外实验表明HSF中p53的表达降低。SP-FC 显着降低 HSF 的活力，增加 HSF 中的 p53 水平，并促进细胞凋亡。SP-FC可以通过促进p53表达来减少疤痕形成。

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The mechanism of Semen Persicae-Flos Carthami in treating hypertrophic scar: A study based on network pharmacological analysis and in vitro experiments

Traditional medicine believes that hypertrophic scar (HS) falls into the category of “blood stasis”. Chinese herbs for promoting blood circulation and removing blood stasis, activating meridians, and relieving pain are usually selected to treat HS by traditional Chinese medicine (TCM). Both Semen Persicae (SP) and Flos Carthami (FC) are confirmed to be effective for HS. Clinically, SP and FC are often used in combination with each other. However, the pharmacodynamic mechanism and molecular target of SP-FC in the treatment of HS are still unclear. Therefore, this study is intended to explore the mechanism and target of SP-FC in the treatment of HS through network pharmacology combined with in vitro cell and molecular biology experiments. Target genes of SP-FC were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and targets of HS-related diseases were searched from databases such as Disgenet and GeneCards. Based on the targets searched and obtained, a Venn diagram was plotted to acquire common targets of SP-FC-HS. Next, STRING 11.0 was employed for protein–protein interaction (PPI) network analysis of common targets; and cytoscape 3.9.0 for connection relationship analysis of PPI and plotting of a “drug-component-target” network diagram. Besides, a modified explant culture method was applied to separate primary hypertrophic scar fibroblasts (HSFs); MTT assay to detect cell viability of HSFs after treatment by SP-FC for 24 h; Annexin V-FITC/PI double staining combined with flow cytometry to test apoptosis; western blot to check the protein expression level of p53; and real-time fluorescence quantitative PCR to determine mRNA level of p53. In the analysis of network pharmacology, 269 pharmacological targets of SP, 449 pharmacological targets of FC, and 2569 targets of HS-related diseases were screened from the databases. After plotting the Venn diagram, 116 common targets of SP-FC-HS were acquired. In vitro experiments showed that the expression of p53 in HSFs was decreased. SP-FC significantly reduces the viability of HSFs, increases p53 levels in HSFs, and promotes apoptosis. SP-FC can reduce scar formation by promoting p53 expression.

更新日期：2023-12-06

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