Identifying cancer-related molecular targets of Nandina domestica Thunb. by network pharmacology-based analysis in combination with chemical profiling and molecular docking studies

Taha, Kamilia F.; Khalil, Marwa Saad M; Abubakr, Marwa S.; Shawky, Eman

doi:10.1016/j.jep.2019.112413

Cited by 30 publications

(16 citation statements)

References 27 publications

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“…A previous study has confirmed the potent anti-apoptotic effect of IQC by demonstrating that it attenuates the hydrogen peroxide-induced upregulation of p53 expression ( 44 ). Additionally, a network pharmacology analysis revealed that IQC has synergistic interactions with the p53 signaling pathway through apoptosis ( 45 ). The current data further demonstrated that IQC exerted its protective effect in ECs stimulated with HG by regulating p53.…”

Section: Discussionmentioning

confidence: 99%

Isoquercitrin protects HUVECs against high glucose‑induced apoptosis through regulating p53 proteasomal degradation

Liu

Huang

et al. 2021

Int J Mol Med

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High glucose (HG)-induced endothelial apoptosis serves an important role in the vascular dysfunction associated with diabetes mellitus (dM). It has been reported that isoquercitrin (IQC), a flavonoid glucoside, possesses an anti-DM effect, but the mechanism requires further investigation. The present study investigated the effect of IQc against HG-induced apoptosis in human umbilical vein endothelial cells (HUVEcs) and explored its molecular mechanism. HUVEcs were treated with 5 or 30 mM glucose for 48 h. Endothelial cell viability was monitored using the cell counting Kit-8 assay. Mitochondrial membrane potential was detected by Jc-1 staining. Apoptosis was observed by TUNEL staining and flow cytometry. Western blotting was used for the analysis of apoptosis-associated proteins Bax, Bcl-2, cleaved (c)-caspase3, total-caspase3, p53 and phosphorylated p53. Reverse transcription-quantitative PcR was used to analyze the mRNA expression levels of Bax, Bcl-2 and p53. Immunofluorescence staining was utilized to detect the expression levels and distribution of p53 and ubiquitin specific peptidase 10 (USP10) in HUVEcs. The results revealed that IQC significantly attenuated HG-induced endothelial apoptosis, as shown by decreased apoptotic cells observed by TUNEL, Jc-1 staining and flow cytometry. Moreover, under HG stress, IQc treatment markedly inhibited the increased expression levels of the pro-apoptotic proteins p53, Bax and c-caspase3, and increased the expression levels of the anti-apoptotic protein Bcl-2 in HUVEcs. However, the anti-apoptotic effect of IQc against HG was partially blunted by increasing p53 protein levels in vitro. IQC influenced the mRNA expression levels of Bax and Bcl-2 in response to HG, but it did not affect the transcription of p53. Notably, IQc inhibited the HG-induced phosphorylation of p53 at Ser15 and the nuclear transport of USP10, destabilizing p53 and increasing the proteasomal degradation of the p53 protein. The current findings revealed that IQC exerted a protective effect against the HG-induced apoptosis of endothelial cells by regulating the proteasomal degradation of the p53 protein, suggesting that IQc may be used as a novel therapeutic compound to ameliorate dM-induced vascular complications.

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Section: Discussionmentioning

confidence: 99%

Isoquercitrin protects HUVECs against high glucose‑induced apoptosis through regulating p53 proteasomal degradation

Liu

Huang

et al. 2021

Int J Mol Med

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“…Generally, negative values of binding energy are associated with the stable conformation of ligand binding to the receptor. If the binding energy is less than −5 kcal/mol, then the ligand and receptor can bind spontaneously; binding energy ≤−7 kcal/mol denotes good binding [ 21 , 22 ]. The flowchart of the experimental procedures of our study is shown in Figure 1 .…”

Section: Methodsmentioning

confidence: 99%

Exploration of the Mechanism of Lianhua Qingwen in Treating Influenza Virus Pneumonia and New Coronavirus Pneumonia with the Concept of “Different Diseases with the Same Treatment” Based on Network Pharmacology

Zhan

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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The 31 main components of Lianhua Qingwen (LHQW) were obtained through a literature and database search; the components included glycyrrhizic acid, emodin, chlorogenic acid, isophoroside A, forsythia, menthol, luteolin, quercetin, and rutin. Sixty-eight common targets for the treatment of novel coronavirus pneumonia (NCP) and influenza virus pneumonia (IVP) were also obtained. A “component-target-disease” network was constructed with Cytoscape 3.2.1 software, and 20 key targets, such as cyclooxygenase2 (COX2), interleukin-6 (IL-6), mitogen-activated protein kinase14 (Mapk14), and tumor necrosis factor (TNF), were screened from the network. The David database was used to perform a Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis and gene ontology (GO) biological process enrichment. Results showed that the key targets of LHQW in the treatment of NCP and IVP mainly involved biological processes, such as immune system process intervention, cell proliferation, apoptosis and invasion, toxic metabolism, cytokine activity, and regulation of the synthesis process. KEGG enrichment analysis revealed that 115 signalling pathways were related to the treatment of LHQW. Amongst them, IL-17, T cell receptor, Th17 cell differentiation, TNF, toll-like receptor, MAPK, apoptosis, and seven other signalling pathways were closely related to the occurrence and development of NCP and IVP. Molecular docking showed that each component had different degrees of binding with six targets, namely, 3C-like protease (3CL), angiotensin-converting enzyme 2 (ACE2), COX2, hemagglutinin (HA), IL-6, and neuraminidase (NA). Rutin, isoforsythiaside A, hesperidin and isochlorogenic acid B were the best components for docking with the six core targets. The first five components with the best docking results were isoforsythiaside, hesperidin, isochlorogenic acid B, forsythin E, and quercetin. In conclusion, LHQW has many components, targets, and pathways. The findings of this work can provide an important theoretical basis for determining the mechanism of LHQW in treating NCP and IVP.

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“…By UPLC-MS/MS analysis, Taha et al [ 145 ] identified 22 compounds in the extracts of the fruits of Nandina domestica Thunb. which have served as a folk medicine in therapies of some types of cancer.…”

Section: Anti-cancer Effects Of Coffeementioning

confidence: 99%

Anti-Cancer Effects of Green Tea Epigallocatchin-3-Gallate and Coffee Chlorogenic Acid

et al. 2020

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Tea and coffee are consumed worldwide and epidemiological and clinical studies have shown their health beneficial effects, including anti-cancer effects. Epigallocatechin gallate (EGCG) and chlorogenic acid (CGA) are the major components of green tea polyphenols and coffee polyphenols, respectively, and believed to be responsible for most of these effects. Although a large number of cell-based and animal experiments have provided convincing evidence to support the anti-cancer effects of green tea, coffee, EGCG, and CGA, human studies are still controversial and some studies have suggested even an increased risk for certain types of cancers such as esophageal and gynecological cancers with green tea consumption and bladder and lung cancers with coffee consumption. The reason for these inconsistent results may have been arisen from various confounding factors. Cell-based and animal studies have proposed several mechanisms whereby EGCG and CGA exert their anti-cancer effects. These components appear to share the common mechanisms, among which one related to reactive oxygen species is perhaps the most attractive. Meanwhile, EGCG and CGA have also different target molecules which might explain the site-specific differences of anti-cancer effects found in human studies. Further studies will be necessary to clarify what is the mechanism to cause such differences between green tea and coffee.

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Identifying cancer-related molecular targets of Nandina domestica Thunb. by network pharmacology-based analysis in combination with chemical profiling and molecular docking studies

Cited by 30 publications

References 27 publications

Isoquercitrin protects HUVECs against high glucose‑induced apoptosis through regulating p53 proteasomal degradation

Isoquercitrin protects HUVECs against high glucose‑induced apoptosis through regulating p53 proteasomal degradation

Exploration of the Mechanism of Lianhua Qingwen in Treating Influenza Virus Pneumonia and New Coronavirus Pneumonia with the Concept of “Different Diseases with the Same Treatment” Based on Network Pharmacology

Anti-Cancer Effects of Green Tea Epigallocatchin-3-Gallate and Coffee Chlorogenic Acid

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