Exploration of the Potential Mechanism of Qi Yin San Liang San Decoction in the Treatment of EGFRI-Related Adverse Skin Reactions Using Network Pharmacology and In Vitro Experiments.
Exploration of the Potential Mechanism of Qi Yin San Liang San Decoction in the Treatment of EGFRI-Related Adverse Skin Reactions Using Network Pharmacology and In Vitro Experiments.
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DOI：
10.3389/fonc.2022.790713
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发表时间：
2022
影响因子：
4.7
通讯作者：
Hua Q
中科院分区：
文献类型：
--
作者：
Wang Y;Zhang Y;Ding C;Jia C;Zhang H;Peng T;Cheng S;Chen W;Tan Y;Wang X;Liu Z;Wei P;Wang X;Jiang M;Hua Q
皮肤不良反应是表皮生长因子受体抑制剂（EGFRIs）治疗癌症最常见的副作用，显著影响患者的生存率和生活质量。芪茵三凉散来自民间，目前临床上用于治疗EGFRIs引起的皮肤不良反应。然而，其治疗机制仍不清楚。采用网络药理学和实验研究方法，探讨芪愈生灵胶囊治疗EGFR抑制所致皮肤不良反应的可能机制。首先，我们使用模型小鼠在体内验证QYSLS的有效性。其次，利用GEO数据库预测EGFR抑制相关皮肤不良反应的相关靶点，并利用中药系统药理学数据库和Batman-TCM数据库分析清瘀生脉方的有效成分和预测靶点。通过Bioconductor（R）V3.8生物信息学软件进行基因本体和京都基因百科全书和基因组途径分析。分子对接研究验证了选定的关键成分和靶标。最后，通过体外实验验证了网络药理学的结果。在小鼠体内模型中，QYSLS有效地减少了皮肤副作用的发生。网络药理学研究结果表明，活性成分毛地黄黄酮、槲皮素、甘草查尔酮a、山奈酚以及有效靶点蒲公英素-内过氧化物合成酶2（PTGS 2）、基质金属肽酶9（MMP 9）、C-C基序趋化因子配体2（CCL 2）均与白细胞介素-17（IL-17）和肿瘤坏死因子（TNF）通路相关。随后，使用HaCaT细胞作为体外不良反应模型验证了相关活性化合物和靶标。结果表明，木犀草素和槲皮素可增加吉非替尼处理的HaCaT细胞PTGS 2和MMP 9的表达，降低CCL 2的表达。结果表明，芪愈生脉散通过多靶点、多途径作用机制，有效治疗EGFRI相关的皮肤不良反应。木犀草素和槲皮素可能是QYSLS治疗EGFRI相关皮肤不良反应的核心活性成分，其治疗作用可能通过IL-17和TNF信号通路中的PTGS 2、CCL 2和MMP 9介导。
Adverse skin reactions are the most common side effects of epidermal growth factor receptor inhibitors (EGFRIs) in the treatment of cancer, significantly affecting the survival rate and quality of life of patients. Qi Yin San Liang San Decoction (QYSLS) comes from folk prescription and is currently used in the clinical treatment of adverse skin reactions caused by EGFRIs. However, its therapeutic mechanism remains unclear. To explore the potential mechanism of QYSLS in the treatment of adverse skin reactions caused by EGFR inhibition using network pharmacology and experimental research. First, we verified the effectiveness of QYSLS in vivo using model mice. Second, the related targets of adverse skin reactions associated with EGFR inhibition were predicted by the Gene Expression Omnibus (GEO) database, and effective components and predictive targets of QYSLS were analyzed by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Batman-TCM databases. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed via the Bioconductor (R) V3.8 bioinformatics software. Molecular docking studies verified the selected key ingredients and targets. Finally, the results of network pharmacology were verified by in vitro experiments. In the in vivo mouse model, QYSLS effectively reduced the occurrence of skin side effects. Network pharmacological results showed that the active ingredient luteolin, quercetin, licochalcone a, and kaempferol and the effective targets prostaglandin-endoperoxide synthase 2 (PTGS2), matrix metallopeptidase 9 (MMP9), and C–C motif chemokine ligand 2 (CCL2) were related to the interleukin-17 (IL-17) and tumor necrosis factor (TNF) pathway. Subsequently, the related active compounds and targets were verified using HaCaT cells as an in vitro adverse reaction model. The results showed that luteolin and quercetin increased the expression of PTGS2 and MMP9 and reduced the expression of CCL2 in HaCaT cells treated with gefitinib. The results revealed that QYSLS effectively treats EGFRI-related adverse skin reactions through multi-target and multi-pathway mechanisms. Luteolin and quercetin may be the core active ingredients of QYSLS in the treatment of EGFRI-related adverse skin reactions, and their therapeutic effects are potentially mediated through PTGS2, CCL2, and MMP9 in the IL-17 and TNF signaling pathway.
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影响因子：
0.3
作者：
Hassel, Jessica C.;Kripp, Melanie;Hofheinz, Ralf-Dieter
通讯作者：
Hofheinz, Ralf-Dieter
DOI：
10.1073/pnas.2109972118
发表时间：
2021-12-14
影响因子：
11.1
作者：
Alam, Muhammad S.;Otsuka, Shizuka;Ashwell, Jonathan D.
通讯作者：
Ashwell, Jonathan D.
影响因子：
4.6
作者：
Seiser S;Janker L;Zila N;Mildner M;Rakita A;Matiasek J;Bileck A;Gerner C;Paulitschke V;Elbe-Bürger A
通讯作者：
Elbe-Bürger A
DOI：
10.4103/0973-7847.194044
发表时间：
2016-07
期刊：
Pharmacognosy reviews
影响因子：
--
作者：
Anand David AV;Arulmoli R;Parasuraman S
通讯作者：
Parasuraman S
影响因子：
4.2
作者：
Hashemzaei M;Delarami Far A;Yari A;Heravi RE;Tabrizian K;Taghdisi SM;Sadegh SE;Tsarouhas K;Kouretas D;Tzanakakis G;Nikitovic D;Anisimov NY;Spandidos DA;Tsatsakis AM;Rezaee R
通讯作者：
Rezaee R