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

ABSTRACT: Hepatocellular carcinoma (HCC) is the fourth main reason of cancer-related death. Codonopsis pilosula is a commonly used traditional Chinese medicine (TCM) for patients with HCC. However, its potential mechanism for treatment of HCC remains unclear. Here, we used transcriptomics and network pharmacology to explore the potential molecular mechanisms of Codonopsis pilosula. In our study, twelve differentially expressed genes (DEGs) (5 upregulated and 7 downregulated) of Codonopsis pilosula treating HepG2 cells (a kind of HCC cell) were identified. Among the 12 DEGs, HMOX1 may play an essential role. Codonopsis pilosula mainly affects the mineral absorption pathway in HCC. We acquired 2957, 1877, and 255 targets from TCMID, SymMap, and TCMSP, respectively. Codonopsis pilosula could upregulate HMOX1 via luteolin, capsaicin, and sulforaphane. Our study provided new understanding of the potential pharmacological mechanisms of Codonopsis pilosula in treating HCC and pointed out a direction for further experimental research.

SUBMITTER: Liu Z

PROVIDER: S-EPMC8977304 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Liu Zhili Z Sun Yuzhe Y Zhen Hefu H Nie Chao C

Evidence-based complementary and alternative medicine : eCAM 20220327

Hepatocellular carcinoma (HCC) is the fourth main reason of cancer-related death. Codonopsis pilosula is a commonly used traditional Chinese medicine (TCM) for patients with HCC. However, its potential mechanism for treatment of HCC remains unclear. Here, we used transcriptomics and network pharmacology to explore the potential molecular mechanisms of Codonopsis pilosula. In our study, twelve differentially expressed genes (DEGs) (5 upregulated and 7 downregulated) of Codonopsis ...[more]

PMID: 35388300

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Project description:PurposeThis 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.MethodsThe 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.ResultsA 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.ConclusionCodonopsis 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.

Project description:BackgroundsIt has been regarded as an essential treatment option for diabetic nephropathy (DN) in Traditional Chinese medicine. Previous studies have demonstrated the anti-DN efficacy of Schisandra chinensis Fruit Mixture (SM); however, a comprehensive chemical fingerprint is still uncertain, and its mechanism of action, especially the potential therapeutic targets of anti-DN, needs to be further elucidated.ObjectivePotential mechanisms of SM action on DN were explored through network pharmacology and experimental validation.MethodsThe chemical composition of SM was analyzed using UPLC-ESI-MS/MS technology. Active bioactive components and potential targets of SM were identified using TCMSP, SwissDrugDesign, and SymMap platforms. Differentially expressed genes were determined using microarray gene data from the GSE30528 dataset. Related genes for DN were obtained from online databases, which include GeneCards, OMIM and DisGeNET. PPI networks and compound-target-pathway networks were constructed using Cytoscape. Functional annotation was performed using R software for GO enrichment and KEGG pathway analysis. The DN model was built for experimental validation using a high-sugar and high-fat diet combined with STZ induction. Hub targets and critical signaling pathways were detected using qPCR, Western blotting and immunofluorescence.ResultsUtilizing the UPLC-ESI-MS/MS coupling technique, a comprehensive analysis identified 1281 chemical components of SM's ethanol extract, with 349 of these components recognized as potential bioactive compounds through network pharmacology. Through this analysis, 126 shared targets and 15 HUB targets were pinpointed. Of these, JAK2 is regarded as the most critical gene. Enrichment analysis revealed that SM primarily operates within the PI3K/AKT signaling pathway. In vivo experiments confirmed that SM improved pathological injury and renal function in rats with DN while improving mitochondrial morphology and function and modulating the expression of proteins linked to apoptosis (cleaved-caspase-3, Bax, and Bcl-2) and pro-inflammatory factors (IL-6 and TNF-α). Mechanistically, SM alleviates DN primarily by suppressing the PI3K/AKT/mTOR and JAK2/STAT3 signaling pathways to fulfill the energy needs of renal tissues. Furthermore, molecular docking analysis provided direct validation of these findings.ConclusionThe findings of this study offer initial indications of the active component and robust anti-inflammatory and anti-apoptotic characteristics of SM in the mitigation of DN, along with its capacity to safeguard the integrity and functionality of mitochondria. This research unequivocally validates the favorable anti-DN effects of SM, indicating its potential as a viable pharmaceutical agent for the management of DN.

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

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Network Pharmacology Integrated with Transcriptomics Deciphered the Potential Mechanism of <i>Codonopsis pilosula</i> against Hepatocellular Carcinoma.

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