Network Pharmacology Integrated with Transcriptomics Deciphered the Potential Mechanism of Codonopsis pilosula against Hepatocellular Carcinoma

Liu, Zhili; Sun, Yuzhe; Zhen, Hefu; Nie, Chao

doi:10.1155/2022/1340194

Cited by 8 publications

(8 citation statements)

References 64 publications

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“…Recently, Liu et al published a report on the application of network pharmacology to analyze the effects of Codonopsis pilosula on HCC. 41 In this report, Liu et al mainly used transcriptomics and network pharmacology to explore the potential molecular mechanisms of Codonopsis pilosula in the treatment of HCC. 41 In our investigation, in addition to the application of network pharmacology to explore the mechanism of Codonopsis pilosula in the treatment of HCC, we further constructed a risk prediction model of Codonopsis pilosula for treating HCC with hub genes.…”

Section: Discussionmentioning

confidence: 99%

“… 41 In this report, Liu et al mainly used transcriptomics and network pharmacology to explore the potential molecular mechanisms of Codonopsis pilosula in the treatment of HCC. 41 In our investigation, in addition to the application of network pharmacology to explore the mechanism of Codonopsis pilosula in the treatment of HCC, we further constructed a risk prediction model of Codonopsis pilosula for treating HCC with hub genes. Simultaneously, luteolin, an active ingredient of Codonopsis pilosula , was also used to verify its anti-cancer effects.…”

Section: Discussionmentioning

confidence: 99%

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Integrating Network Pharmacology and Bioinformatics to Explore the Effects of Dangshen (Codonopsis pilosula) Against Hepatocellular Carcinoma: Validation Based on the Active Compound Luteolin

Yu¹,

Ding²,

Xu³

et al. 2023

DDDT

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Purpose This study aimed to explore the pharmacological mechanism of Dangshen ( Codonopsis pilosula ) against hepatocellular carcinoma (HCC) based on network pharmacology and bioinformatics, and to verify the anticancer effect of luteolin, the active ingredient of Codonopsis pilosula , on HCC cells. Methods The effective compounds and potential targets of Codonopsis pilosula were established using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The genes related to HCC were obtained through the GeneCards database. The interactive genes were imported into the Visualization and Integrated Discovery database for Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal enrichment, and the hub genes were screened out. The Cancer Genome Atlas database was used to construct a prognosis model, and the prognosis and clinicopathological correlation were analyzed. In in vitro experiments, we verified the effects of luteolin, an active compound of Codonopsis pilosula , on the proliferation, cell cycle, apoptosis and migration of HCC cells. Results A total of 21 effective compounds of Codonopsis pilosula and 98 potential downstream target genes were screened through the TCMSP database, and 1406 HCC target genes were obtained through the GeneCards database. Finally, 53 interacting genes between the two databases were obtained, among which, the 10 key node genes were CASP3, TP53, MDM2, AKT1, ESR1, BCL2L1, MCL1, HSP90AA1, CASP9 , and CCND1 , involving 77 typical GO terms and 72 KEGG signals. The Kaplan–Meier survival curve of the model group showed that the overall survival of the low-risk group was significantly higher than that of the high-risk group. Luteolin significantly inhibited the proliferation and migration of HCC cells, induced apoptosis, and increased the G2/M phase ratio. Mechanistically, luteolin significantly inhibited the phosphorylation of MAPK-JNK and Akt (Thr308) and subsequently led to upregulation of ESR1. Pharmacological inhibition of ESR1 with fulvestrant enhanced cell viability and migration and attenuated apoptosis. Conclusion Codonopsis pilosula has potential for clinical development due to its anti-HCC properties. Luteolin, the effective component of Codonopsis pilosula , plays anti-HCC role through AKT- or MAPK-JNK signaling mediated ESR1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrating Network Pharmacology and Bioinformatics to Explore the Effects of Dangshen (Codonopsis pilosula) Against Hepatocellular Carcinoma: Validation Based on the Active Compound Luteolin

Yu¹,

Ding²,

Xu³

et al. 2023

DDDT

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“…Moreover, oral drug administration exacerbates the metabolic burden in the liver, which might result in metabolic disturbances and thereby increasing the susceptibility to carcinogenesis [ 86 ]. Issues regarding hepatotoxicity have been resolved by the promoted liver regeneration by BT [ 87 ], PP [ 88 ], BD [ 89 ], CH [ 90 , 91 ], LC [ 92 , 93 ], SK [ 94 ], and CWT [ 95 ]. ③ IBD patients are susceptible to malnutrition including anemia, amino acid, and vitamin deficiency [ 96 ], which could be rescued by PP [ 97 ] due to its hematopoiesis-promoting effect [ 98 – 100 ] and by the addition of pearl that is produced from shellfish mollusks which contain 20 amino acids and Fe and Mg elements [ 101 ].…”

Section: Discussionmentioning

confidence: 99%

Validation of the Anticolitis Efficacy of the Jian-Wei-Yu-Yang Formula

Yan

Tang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Inflammatory bowel disease (IBD) is a major cause of morbidity and mortality due to its repetitive remission and relapse. The Jian-Wei-Yu-Yang (JW) formula has a historical application in the clinic to combat gastrointestinal disorders. The investigation aimed to explore the molecular and cellular mechanisms of JW. Methods. 2% dextran sodium sulfate (DSS) was diluted in drinking water and given to mice for 5 days to establish murine models of experimental colitis, and different doses of JW solution were administered for 14 days. Network pharmacology analysis and weighted gene co-expression network analysis (WGCNA) were utilized to predict the therapeutic role of JW against experimental colitis and colitis-associated colorectal cancer (CAC). 16S rRNA sequencing and untargeted metabolomics were conducted using murine feces. Western blotting, immunocytochemistry, and wound healing experiments were performed to confirm the molecular mechanisms. Results. (1) Liquid chromatography with mass spectrometry was utilized to confirm the validity of the JW formula. The high dose of JW treatment markedly attenuated DSS-induced experimental colitis progression, and the targets were enriched in inflammation, infection, and tumorigenesis. (2) The JW targets were related to the survival probability in patients with colorectal cancer, underlying a potential therapeutic value in CRC intervention. (3) Moreover, the JW therapy successfully rescued the decreased richness and diversity of microbiota, suppressed the potentially pathogenic phenotype of the gut microorganisms, and increased cytochrome P450 activity in murine colitis models. (4) Our in vitro experiments confirmed that the JW treatment suppressed caspase3-dependent pyroptosis, hypoxia-inducible factor 1α (HIF1α), and interleukin-1b (IL-1b) in the colon; facilitated the alternative activation of macrophages (Mφs); and inhibited tumor necrosis factor-α (TNFα)-induced reactive oxygen species (ROS) level in intestinal organoids (IOs). Conclusion. The JW capsule attenuated the progression of murine colitis by a prompt resolution of inflammation and bloody stool and by re-establishing a microbiome profile that favors re-epithelization and prevents carcinogenesis.

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“…Alzheimer’s disease (AD) is a gradual progressive neurological disorder, and CP can be used to improve nerve cell function and reduce neurodegeneration, which helps to slow down the development of Alzheimer’s disease ( Xie et al, 2024 ). Colon cancer ( Cao Y. et al, 2019 ), gastric precancerous lesions ( He et al, 2022 ), liver cancer ( Liu Z. et al, 2022 ; Li N. et al, 2024 ), hepatitis ( Zeng et al, 2023 ), and colitis ( Li F. et al, 2024 ) are malignant tumors or inflammatory diseases of the digestive system, and CP plays an important role in preventing and treating these diseases play an important role. Interestingly, CP can also regulate the immune function of sepsis ( Choi et al, 2023 ), rheumatoid arthritis ( Wang Y.-J.…”

Section: Subsections Relevant For the Subjectmentioning

confidence: 99%

A systematic review of the mechanism of action and potential medicinal value of codonopsis pilosula in diseases

Guo,

Lou,

Hou

et al. 2024

Front. Pharmacol.

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As a traditional Chinese medicinal herb with a long history, Codonopsis pilosula (CP) has attracted much attention from the medical community in recent years. This review summarizes the research progress of CP in the medical field in the past 5 years. By searching and analyzing the literature, and combining with Cytoscape software, we comprehensively examined the role and mechanism of action of CP in individual application, combination drug application, and the role and mechanism of action of codonopsis pilosula’s active ingredients in a variety of diseases. It also analyzes the medicinal use of CP and its application value in medicine. This review found that CP mainly manifests important roles in several diseases, such as cardiovascular system, nervous system, digestive system, immune system, etc., and regulates the development of many diseases mainly through the mechanisms of inflammation regulation, oxidative stress, immunomodulation and apoptosis. Its rich pharmacological activities and diverse medicinal effects endow CP with broad prospects and application values. This review provides valuable reference and guidance for the further development of CP in traditional Chinese medicine.

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Network Pharmacology Integrated with Transcriptomics Deciphered the Potential Mechanism of Codonopsis pilosula against Hepatocellular Carcinoma

Cited by 8 publications

References 64 publications

Integrating Network Pharmacology and Bioinformatics to Explore the Effects of Dangshen (Codonopsis pilosula) Against Hepatocellular Carcinoma: Validation Based on the Active Compound Luteolin

Integrating Network Pharmacology and Bioinformatics to Explore the Effects of Dangshen (Codonopsis pilosula) Against Hepatocellular Carcinoma: Validation Based on the Active Compound Luteolin

Validation of the Anticolitis Efficacy of the Jian-Wei-Yu-Yang Formula

A systematic review of the mechanism of action and potential medicinal value of codonopsis pilosula in diseases

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