Network Pharmacology–Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells

Zhang, Yuzhu; Yang, Jiayao; Wu, Ruixian; Chen, Fang; Lu, Hai; Li, Hua-Chao; Li, Dongmei; Zuo, Huali; Ren, Liping; Liu, Xiao‐Yuan; Xu, Rui; Wen, Jiahuai; Huang, Hsien-Da; Hong, Ri; Chen, Qianjun

doi:10.3389/fphar.2021.714628

Cited by 13 publications

(10 citation statements)

References 61 publications

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“…Using the DAVID database, the GO functional and KEGG pathway enrichment analyses were further performed on potential anti-COVID-19 prime targets by keeping the species threshold of “Homo sapiens” ( 49 , 50 ). There are three categories of GO terms: cellular component (CC), biological process (BP), and molecular function (MF).…”

Section: Methodsmentioning

confidence: 99%

Identifying potential pharmacological targets and molecular pathways of Meliae cortex for COVID-19 therapy

Khan

Lee

2023

Front. Immunol.

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Coronavirus disease-19 (COVID-19), caused by SARS-CoV-2, has contributed to a significant increase in mortality. Proinflammatory cytokine-mediated cytokine release syndrome (CRS) contributes significantly to COVID-19. Meliae cortex has been reported for its several ethnomedical applications in the Chinese Pharmacopoeia. In combination with other traditional Chinese medicines (TCM), the Meliae cortex suppresses coronavirus. Due to its phytoconstituents and anti-inflammatory capabilities, we postulated that the Meliae cortex could be a potential therapeutic for treating COVID-19. The active phytonutrients, molecular targets, and pathways of the Meliae cortex have not been explored yet for COVID-19 therapy. We performed network pharmacology analysis to determine the active phytoconstituents, molecular targets, and pathways of the Meliae cortex for COVID-19 treatment. 15 active phytonutrients of the Meliae cortex and 451 their potential gene targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and SwissTargetPrediction website tool, respectively. 1745 COVID-19-related gene targets were recovered from the GeneCards. 104 intersection gene targets were determined by performing VENNY analysis. Using the DAVID tool, gene ontology (GO) and KEGG pathway enrichment analysis were performed on the intersection gene targets. Using the Cytoscape software, the PPI and MCODE analyses were carried out on the intersection gene targets, which resulted in 41 potential anti-COVID-19 core targets. Molecular docking was performed with AutoDock Vina. The 10 anti-COVID-19 core targets (AKT1, TNF, HSP90AA1, IL-6, mTOR, EGFR, CASP3, HIF1A, MAPK3, and MAPK1), three molecular pathways (the PI3K-Akt signaling pathway, the HIF-1 signaling pathway, and the pathways in cancer) and three active phytonutrients (4,8-dimethoxy-1-vinyl-beta-carboline, Trichilinin D, and Nimbolin B) were identified as molecular targets, molecular pathways, and key active phytonutrients of the Meliae cortex, respectively that significantly contribute to alleviating COVID-19. Molecular docking analysis further corroborated that three Meliae cortex’s key active phytonutrients may ameliorate COVID-19 disease by modulating identified targets. Hence, this research offers a solid theoretic foundation for the future development of anti-COVID-19 therapeutics based on the phytonutrients of the Meliae cortex.

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Section: Methodsmentioning

confidence: 99%

Identifying potential pharmacological targets and molecular pathways of Meliae cortex for COVID-19 therapy

Khan

Lee

2023

Front. Immunol.

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“…Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out using the DAVID database for annotation, visualization, and integrated discovery (Version 6.8; https://david.ncifcrf.gov/ , accessed on December 16, 2021) [ 35 – 37 ]. The GO terms were categorized into three types: cellular component (CC), biological process (BP), and molecular function (MF).…”

Section: Methodsmentioning

confidence: 99%

Network pharmacology and molecular docking-based prediction of active compounds and mechanisms of action of Cnidii Fructus in treating atopic dermatitis

Khan

et al. 2022

BMC Complement Med Ther

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Background Atopic dermatitis (AD) is a common inflammatory skin disease that compromises the skin's barrier function and capacity to retain moisture. Cnidii Fructus (CF), the dried fruits of Cnidium monnieri, has long been used to treat atopic dermatitis (AD) in China. However, the anti-AD compounds and mechanisms of CF are not fully understood. In this study, we evaluated the active compounds and molecular targets of CF in treating AD. Methods The Traditional Chinese Medicine Systems Pharmacology database was used to acquire information regarding the compounds that occur in the herb. Targets of these compounds were predicted using the SwissTargetPrediction website tool. AD-related genes were collected from the GeneCards database. Gene ontology (GO) enrichment analysis and KEGG pathway analysis of proteins that are targeted by active compounds of CF and encoded by AD-related genes were performed using Database for Annotation, Visualization, and Integrated Discovery Bioinformatics Resources. A “compound-target” network was constructed and analyzed using Cytoscape Software. Molecular docking was performed using BIOVIA Discovery Studio Visualizer and AutoDock Vina. Results We identified 19 active compounds in CF, 532 potential targets for these compounds, and 1540 genes related to AD. Results of GO enrichment indicated that CF affects biological processes and molecular functions, such as inflammatory response and steroid hormone receptor activity, which may be associated with its anti-AD effects. KEGG pathway analyses showed that PI3K-Akt signaling, calcium signaling, Rap1 signaling, and cAMP signaling pathways are the main pathways involved in the anti-AD effects of CF. Molecular docking analyses revealed that the key active compounds in CF, such as (E)-2,3-bis(2-keto-7-methoxy-chromen-8-yl)acrolein, ar-curcumene, and diosmetin, can bind the main therapeutic targets AKT1, SRC, MAPK3, EGFR, CASP3, and PTGS2. Conclusions Results of the present study establish a foundation for further investigation of the anti-AD compounds and mechanisms of CF and provide a basis for developing modern anti-AD agents based on compounds that occur in CF.

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“…Similarly, Hermawan et al found that naringenin inhibited BCSC mammosphere formation, potentially through the modulation of p53 and ERα mRNA [ 82 ]. Naringenin was also identified as the active compound in the Xihuang pill, a traditional medicine used to treat breast cancer in China [ 156 ]. In vitro, both the Xihuang pill and naringenin inhibited mammosphere formation in triple negative breast cancer cell lines by upregulating NR3C2 expression [ 156 ].…”

Section: Phytoestrogens Targeting Bcscs and Their Mechanisms Of Actionmentioning

confidence: 99%

Targeting Breast Cancer Stem Cells Using Naturally Occurring Phytoestrogens

Nguyen

Osipo

2022

IJMS

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Breast cancer therapies have made significant strides in improving survival for patients over the past decades. However, recurrence and drug resistance continue to challenge long-term recurrence-free and overall survival rates. Mounting evidence supports the cancer stem cell model in which the existence of a small population of breast cancer stem cells (BCSCs) within the tumor enables these cells to evade conventional therapies and repopulate the tumor, giving rise to more aggressive, recurrent tumors. Thus, successful breast cancer therapy would need to target these BCSCs, as well the tumor bulk cells. Since the Women’s Health Initiative study reported an increased risk of breast cancer with the use of conventional hormone replacement therapy in postmenopausal women, many have turned their attention to phytoestrogens as a natural alternative. Phytoestrogens are plant compounds that share structural similarities with human estrogens and can bind to the estrogen receptors to alter the endocrine responses. Recent studies have found that phytoestrogens can also target BCSCs and have the potential to complement conventional therapy eradicating BCSCs. This review summarized the latest findings of different phytoestrogens and their effect on BCSCs, along with their mechanisms of action, including selective estrogen receptor binding and inhibition of molecular pathways used by BCSCs. The latest results of phytoestrogens in clinical trials are also discussed to further evaluate the use of phytoestrogen in the treatment and prevention of breast cancer.

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Network Pharmacology–Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells

Cited by 13 publications

References 61 publications

Identifying potential pharmacological targets and molecular pathways of Meliae cortex for COVID-19 therapy

Identifying potential pharmacological targets and molecular pathways of Meliae cortex for COVID-19 therapy

Network pharmacology and molecular docking-based prediction of active compounds and mechanisms of action of Cnidii Fructus in treating atopic dermatitis

Targeting Breast Cancer Stem Cells Using Naturally Occurring Phytoestrogens

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