Network Pharmacology and Molecular Docking Technology Analysis of the Mechanism of Lichong Decoction in the Treatment of Uterine Leiomyoma

Background: Uterine Leiomyoma (UL) is one of the most common benign tumors of the female reproductive system. A Traditional Chinese Medicine (TCM) treatment known as Lichong Decoction (LD) can effectively alleviate the clinical symptoms of UL and reduce adverse reactions and complications. Methods: The active ingredients and targets of LD were retrieved in the TCMSP database and related literature, and the action targets of UL were obtained through the DisGeNET, Genecards, and OMIM databases. The intersection of LD and UL targets was extracted by R software, and the “ingredient-target” network was constructed by Cytoscape software. At the same time, a potential target protein interaction network was constructed by means of a protein interaction database (STRING), and information visualization and topology analysis were completed by Cytoscape software. R software was used for GO enrichment analysis and KEGG pathway enrichment analysis of intersection targets. Molecular docking technology was used for docking verification of key ingredients and core targets. Results: A total of 93 LD active ingredients and 143 LD-UL intersecting targets involving 2,660 GO analysis items and 178 KEGG signaling pathways were obtained. It is predicted that the key active ingredients of LD in the treatment of UL may be quercetin, luteolin, hederagenin, bis-demethoxycurcumin, and kaempferol, which mainly involve SRC, TP53, HSP90AA1, AKT1, MAPK1, and other targets, and may play a role in the treatment of UL through multiple KEGG pathways such as PI3K−Akt signaling pathway, AGE-RAGE pathway in diabetic complications, and cancer-related pathway. Molecular docking results indicated that quercetin, luteolin, hederagenin, bis-demethoxycurcumin, and kaempferol had good docking effects with SRC, TP53, HSP90AA1, AKT1, and MAPK1, respectively. Conclusions: This study analyzed the key ingredients, core targets and related pathways of LD in the treatment of UL, confirmed the therapeutic effect of LD in the treatment of UL, and provided a reference for subsequent clinical practice and basic research in traditional Chinese medicine.

[1]  Zhi-min Wang,et al.  [Quality evaluation of Galli Gigerii Endothelium Corneum based on HPLC fingerprints and content determination of nucleosides]. , 2023, Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.

[2]  T. G. Singh,et al.  Mechanistic insights and perspectives involved in nfeuroprotective action of quercetin. , 2021, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[3]  S. As-Sanie,et al.  Epidemiology and management of uterine fibroids , 2020, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[4]  Xue-Ting Deng,et al.  Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[5]  B. Salehi,et al.  Kaempferol: A Key Emphasis to Its Anticancer Potential , 2019, Molecules.

[6]  Xin Xiao,et al.  HSP90AA1-mediated autophagy promotes drug resistance in osteosarcoma , 2018, Journal of Experimental & Clinical Cancer Research.

[7]  Amirhosein Sahebkar,et al.  Promising anti‐tumor properties of bisdemethoxycurcumin: A naturally occurring curcumin analogue , 2018, Journal of cellular physiology.

[8]  Dale R. Nyholt,et al.  Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis , 2017, Human reproduction.

[9]  Zhaoxia Ding,et al.  Mechanistic Study of the Inhibitory Effect of Kaempferol on Uterine Fibroids In Vitro , 2016, Medical science monitor : international medical journal of experimental and clinical research.

[10]  J. Donnez,et al.  Uterine fibroid management: from the present to the future , 2016, Human reproduction update.

[11]  A. Mahdi,et al.  PI3K/Akt/mTOR signaling & its regulator tumour suppressor genes PTEN & LKB1 in human uterine leiomyomas , 2016, The Indian journal of medical research.

[12]  Iman H Hewedi,et al.  Diagnostic value of progesterone receptor and p53 expression in uterine smooth muscle tumors , 2012, Diagnostic Pathology.

[13]  Ravi Iyengar,et al.  Network analyses in systems pharmacology , 2009, Bioinform..

[14]  S. Karmakar,et al.  Unique roles of p160 coactivators for regulation of breast cancer cell proliferation and estrogen receptor-alpha transcriptional activity. , 2009, Endocrinology.

[15]  U. Banerji,et al.  Heat Shock Protein 90 as a Drug Target: Some Like It Hot , 2009, Clinical Cancer Research.

[16]  Yong Lin,et al.  Luteolin, a flavonoid with potential for cancer prevention and therapy. , 2008, Current cancer drug targets.

[17]  M. López-Lázaro Distribution and biological activities of the flavonoid luteolin. , 2009, Mini reviews in medicinal chemistry.