Transcriptomics and proteomics analysis of system-level mechanisms in the liver of apigenin-treated fibrotic rats

Qiao, Ming; Yang, Jin; Zhu, Yi Ping; Zhao, Yao; Hu, Junping

doi:10.1016/j.lfs.2020.117475

Cited by 17 publications

(15 citation statements)

References 32 publications

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“…The biological processes analysis of the acquired targets is mainly concerned with oxidative stress regulation, small RNA production, telomerase activity, cell proliferation, and necrotic cell death. In our study, various important pathways were highlighted based on enrichment analysis, and some of them have been widely studied for liver cirrhosis [ 63 , 64 , 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

“…They also showed that the activation of numerous pro-fibrotic pathways including the hedgehog/smoothened pathway was associated with FAK-deficient animals and promoted matrix stiffness independently [ 83 ]. A proteomic and transcriptomic study reported that focal adhesion and actin cytoskeleton pathways were significantly involved in rats with liver fibrosis [ 66 ]. Through the focal adhesion kinase pathway, curcumin may control cellular processes such as migration and proliferation.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study

et al. 2022

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Background: Liver cirrhosis is a life-threatening seqsuel of many chronic liver disorders of varying etiologies. In this study, we investigated protein targets of curcumin in liver cirrhosis based on a bioinformatics approach. Methods: Gene/protein associations with curcumin and liver cirrhosis were probed in drug–gene and gene–diseases databases including STITCH/DGIdb/DisGeNET/OMIM/DISEASES/CTD/Pharos and SwissTargetPrediction. Critical clustering groups (MCODE), hub candidates and critical hub genes in liver cirrhosis were identified, and connections between curcumin and liver cirrhosis-related genes were analyzed via Venn diagram. Interaction of hub genes with curcumin by molecular docking using PyRx-virtual screening tools was performed. Results: MCODE analysis indicated three MCODEs; the cluster (MCODE 1) comprised 79 nodes and 881 edges (score: 22.59). Curcumin database interactions recognized 318 protein targets. Liver cirrhosis genes and curcumin protein targets analysis demonstrated 96 shared proteins, suggesting that curcumin may influence 20 candidate and 13 hub genes, covering 81% of liver cirrhosis critical genes and proteins. Thirteen shared proteins affected oxidative stress regulation, RNA, telomerase activity, cell proliferation, and cell death. Molecular docking analysis showed the affinity of curcumin binding hub genes (Binding affinity: ΔG < −4.9 kcal/mol). Conclusions: Curcumin impacted on several critical liver cirrhosis genes mainly involved in extracellular matrix communication, focal adhesion, and the response to oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study

et al. 2022

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“…ALT and AST are mainly synthesized by liver cells, and their high levels in serum imply the occurrence of liver injury [ 38 ]. ALP and LDH are widely distributed in the liver, skeletal muscle, and kidney, and are therefore also important indices to determine liver injury [ 39 ]. Our results indicate that burn injury induces liver injury, while blended protein supplementation contributes to improving the liver function.…”

Section: Resultsmentioning

confidence: 99%

Effect of blended protein nutritional support on reducing burn-induced inflammation and organ injury

Zhang

Wang

et al. 2022

Nutr Res Pract

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BACKGROUND/OBJECTIVES Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction. MATERIALS/METHODS This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups. RESULTS Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation. CONCLUSIONS In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients.

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“…It can illustrate the underlying mechanisms of HBG in treating LF via using existing is research manifested that apigenin, 3-nbutylphthalide, and kaempferol might be the pivotal compounds in the pharmacological effect of HBG. Our previous research has indicated that apigenin could mitigate liver inflammation and fibrosis in rats by MAPK, PI3K/AKT, HIF-1, and eNOS signaling pathways [24]. Moreover, the preceding study has revealed that 3-n-butylphthalide, aesculetin, and quercetin could decrease the synthesis of the hepatic extracellular matrix (ECM) to alleviate LF via regulating proliferation and apoptosis of hepatic HSCs [17].…”

Section: Discussionmentioning

confidence: 99%

Elucidating the Mechanisms of Hugan Buzure Granule in the Treatment of Liver Fibrosis via Network Pharmacology

Zhu

Qiao

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

Self Cite

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Objective. To holistically explore the latent active ingredients, targets, and related mechanisms of Hugan buzure granule (HBG) in the treatment of liver fibrosis (LF) via network pharmacology. Methods. First, we collected the ingredients of HBG by referring the TCMSP server and literature and filtered the active ingredients though the criteria of oral bioavailability ≥30% and drug-likeness index ≥0.18. Second, herb-associated targets were predicted and screened based on the BATMAN-TCM and SwissTargetPrediction platforms. Candidate targets related to LF were collected from the GeneCards and OMIM databases. Furthermore, the overlapping target genes were used to construct the protein-protein interaction network and “drug-compound-target-disease” network. Third, GO and KEGG pathway analyses were carried out to illustrate the latent mechanisms of HBG in the treatment of LF. Finally, the combining activities of hub targets with active ingredients were further verified based on software AutoDock Vina. Results. A total of 25 active ingredients and 115 overlapping target genes of HBG and LF were collected. Besides, GO enrichment analysis exhibited that the overlapping target genes were involved in DNA-binding transcription activator activity, RNA polymerase II-specific, and oxidoreductase activity. Simultaneously, the key molecular mechanisms of HBG against LF were mainly involved in PI3K-AKT, MAPK, HIF-1, and NF-κB signaling pathways. Also, molecular docking simulation demonstrated that the key targets of HBG for antiliver fibrosis were IL6, CASP3, EGFR, VEGF, and MAPK. Conclusion. This work validated and predicted the underlying mechanisms of multicomponent and multitarget about HBG in treating LF and provided a scientific foundation for further research.

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Transcriptomics and proteomics analysis of system-level mechanisms in the liver of apigenin-treated fibrotic rats

Cited by 17 publications

References 32 publications

Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study

Effect of Curcumin on Attenuation of Liver Cirrhosis via Genes/Proteins and Pathways: A System Pharmacology Study

Effect of blended protein nutritional support on reducing burn-induced inflammation and organ injury

Elucidating the Mechanisms of Hugan Buzure Granule in the Treatment of Liver Fibrosis via Network Pharmacology

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