Transcriptome Analysis Reveals the Anti-cancerous Mechanism of Licochalcone A on Human Hepatoma Cell HepG2

Hepatocellular carcinoma is a malignancy with a low survival rate globally, and there is imperative to unearth novel natural phytochemicals as effective therapeutic strategies. Licochalcone A is a chalcone from Glycyrrhiza that displayed various pharmacological efficacy. A globally transcriptome analysis was carried out to reveal the gene expression profiling to explore Licochalcone A's function as an anti-cancer phytochemical on HepG2 cells and investigate its potential mechanisms. Altogether, 6,061 dysregulated genes were detected (3,414 up-regulated and 2,647 down-regulated). SP1 was expected as the transcription factor that regulates the functions of most screened genes. GO and KEGG analysis was conducted, and the MAPK signaling pathway and the FoxO signaling pathway were two critical signal pathways. Protein-protein interaction (PPI) network analysis based on STRING platform to discover the hub genes (MAPK1, ATF4, BDNF, CASP3, etc.) in the MAPK signaling pathway and (AKT3, GADD45A, IL6, CDK2, CDKN1A, etc.) the FoxO signaling pathway. The protein level of essential genes that participated in significant pathways was consistent with the transcriptome data. This study will provide an inclusive understanding of the potential anti-cancer mechanism of Licochalcone A on hepatocellular, signifying Licochalcone A as a promising candidate for cancer therapy.

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The oxygenated products of cryptotanshinone by biotransformation with Cunninghamella elegans exerting anti-neuroinflammatory effects by inhibiting TLR 4-mediated MAPK signaling pathway

10.21203/rs.3.rs-19324/v1 ◽

2020 ◽

Author(s):

Jing-Shuai Wu ◽

Qin-Yu Meng ◽

Xiao-Hui Shi ◽

Zhen-Kun Zhang ◽

Hua-Shi Guan ◽

...

Keyword(s):

Signaling Pathway ◽

Transcriptome Analysis ◽

Salvia Miltiorrhiza ◽

Underlying Mechanism ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Mitogen Activated Protein Kinase ◽

Cunninghamella Elegans ◽

Chinese Medicinal Herb ◽

Oxygenated Products

Abstract Background: Neuroinflammatory processes are critical in the development and progression of Alzheimer's disease (AD). The potent anti-neuroinflammatory inhibitors are expected as the candidates to treat AD. Cryptotanshinone (1), a major bioactive constituent in the traditional Chinese medicinal herb Dan-Shen Salvia miltiorrhiza Bunge, has been reported to possess remarkable pharmacological activities, especially anti-oxidation and anti-inflammation. Methods: Cryptotanshinone (1) was biotransformed with the fungus Cunninghamella elegans AS3.2028 to improve its bioactivities and physicochemical properties. The structures of transformed products were elucidated by comprehensive spectroscopic analysis including HRESIMS, NMR and ECD data. Their anti-neuroinflammatory activities were assessed by ELISA, transcriptome analysis, western blot, and immunofluorescence methods. Results: Three oxygenated products (2–4) at C-3 of cryptotanshinone (1) were obtained, among them 2 was a new compound. All of the biotransformed products (2–4) were found to inhibit significantly lipopolysaccharide-induced nitric oxide production in BV2 microglia cells with the IC50 values of 0.16‒1.16 μM, approximately 2‒20 folds stronger than the substrate (1). These biotransformed products also displayed remarkably improved inhibitory effects on the production of inflammatory cytokines (IL-1β, IL-6, TNF-α, COX-2 and iNOS) in BV-2 cells via targeting TLR4 compared to substrate (1). The underlying mechanism of 2 was elucidated by comparative transcriptome analysis, which suggested that it reduced neuroinflammatory mainly through mitogen-activated protein kinase (MAPK) signaling pathway. Western blotting results revealed that 2 downregulated LPS-induced phosphorylation of JNK, ERK, and p38 in MAPK signaling pathway. Conclusion: The biotransformed products of cryptotanshinone exhibit potent anti-neuroinflammatory activities. These findings provide a basal material for the discovery of candidates in treating AD.

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Transcriptome analysis of MAPK signaling pathway and associated genes to angiogenesis in chicken erythrocytes on response to thiram-induced tibial lesions

Research in Veterinary Science ◽

10.1016/j.rvsc.2019.10.013 ◽

2019 ◽

Vol 127 ◽

pp. 65-75 ◽

Cited By ~ 3

Author(s):

Ali Raza Jahejo ◽

Sheng Niu ◽

Ding Zhang ◽

Guan-bao Ning ◽

Afrasyab Khan ◽

...

Keyword(s):

Signaling Pathway ◽

Transcriptome Analysis ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Chicken Erythrocytes

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Targeting ERK-Hippo Interplay in Cancer Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms21093236 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3236 ◽

Cited By ~ 2

Author(s):

Karel Vališ ◽

Petr Novák

Keyword(s):

Cancer Therapy ◽

Signaling Pathways ◽

Signaling Pathway ◽

Cross Talk ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Mitogen Activated Protein Kinase ◽

Cancer Therapies ◽

Anti Cancer ◽

Targeted Inhibition

Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. Deregulation of the MAPK signaling occurs under many pathological conditions including neurodegenerative disorders, metabolic syndromes and cancers. Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. We demonstrate the mechanism of cell death induction shared between MAPK/ERK and Hippo/MST signaling pathways and discuss the potential of combination targeting of these pathways in the development of more effective anti-cancer therapies.

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Combined Effect of Deoxynivalenol (DON) and Porcine Circovirus Type 2 (Pcv2) on Inflammatory Cytokine mRNA Expression

Toxins ◽

10.3390/toxins13060422 ◽

2021 ◽

Vol 13 (6) ◽

pp. 422

Author(s):

Chao Gu ◽

Xiuge Gao ◽

Dawei Guo ◽

Jiacai Wang ◽

Qinghua Wu ◽

...

Keyword(s):

Mrna Expression ◽

Signaling Pathway ◽

Porcine Circovirus Type ◽

Mapk Signaling ◽

Porcine Circovirus Type 2 ◽

Mapk Signaling Pathway ◽

Porcine Circovirus ◽

Signal Pathways ◽

Dependent Manner

A host’s immune system can be invaded by mycotoxin deoxynivalenol (DON) poisoning and porcine circovirus type 2 (PCV2) infections, which affect the host’s natural immune function. Pro-inflammatory cytokines, IL-1β and IL-6, are important regulators in the process of natural immune response, which participate in inflammatory response and enhance immune-mediated tissue damage. Preliminary studies have shown that DON promotes PCV2 infection by activating the MAPK signaling pathway. Here, we explored whether the mRNA expression of IL-1β and IL-6, induced by the combination of DON and PCV2, would depend on the MAPK signaling pathway. Specific pharmacological antagonists U0126, SP600125 and SB203580, were used to inhibit the activities of ERK, JNK and p38 in the MAPK signaling pathway, respectively. Then, the mRNA expression of IL-1β and IL-6 in PK-15 cells was detected to explore the effect of the MAPK signaling pathway on IL-1β and IL-6 mRNA induced by DON and PCV2. The results showed that PK-15 cells treated with DON or PCV2 induced the mRNA expression of IL-1β and IL-6 in a time- and dose-dependent manner. The combination of DON and PCV2 has an additive effect on inducing the mRNA expression of IL-1β and IL-6. Additionally, both DON and PCV2 could induce the mRNA expression of IL-1β and IL-6 via the ERK and the p38 MAPK signal pathways, while PCV2 could induce it via the JNK signal pathway. Taken together, our results suggest that MAPKs play a contributory role in IL-1β and IL-6 mRNA expression when induced by both DON and PCV2.

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Network Pharmacology Study Reveals the Mechanism of Astragali Radix in Treatment of Diabetic Nephropathy

10.21203/rs.3.rs-42374/v1 ◽

2020 ◽

Author(s):

Chongmei Tian ◽

Jing-bai Chen ◽

Xiang Chen ◽

Dao-zong Xia

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathway ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Network Pharmacology ◽

Signal Pathways ◽

Therapeutic Effects ◽

Disease Network ◽

Astragali Radix ◽

Target Disease

Abstract Background Diabetic nephropathy (DN), a unique complication of diabetes, could contribute to an increase in mortality. In this study, we predicted and proved the molecular pharmacological mechanism concerning the protective effects of Astragali Radix on DN. Methods The same potential target genes from Astragali Radix and DN were analyzed and constructed the protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment-related major targets and signal pathways were performed. The drug-ingredients-target-disease network was visually built using Cytoscape 3.6.1. The beneficial pharmacological activities of quercetin from Astragali Radix were confirmed by CCK-8 assay, determination of antioxidant parameters and Western blotting analysis. Results There are 12 bioactive components from Astragali Radix and 56 same targets between Astragali Radix and DN. The GO analysis results showed that the biological processes mainly included protein homodimerization activity. KEGG analysis indicate that the screened targets were most closely linked to the mitogen-activated protein kinase (MAPK) signaling pathway. The drug-ingredients-target-disease network results revealed that the therapeutic effects of Astragali Radix mainly included oxidative stress, inflammatory reaction and apoptosis. During the verification process, quercetin from Astragali Radix could attenuate cytotoxicity, enhance catalase (CAT) and superoxide dismutase (SOD) activities and suppress MAPK signaling pathway. Conclusions In the current study, network pharmacology with experimental analysis predicted and proved the therapeutic function of Astragali Radix by improving antioxidant capacity and suppressing MAPK signaling pathway, these investigations could provide a new perspective for further exploration of Astragali Radix on DN treatment.

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C-Phycocyanin exerts anti-cancer effects via the MAPK signaling pathway in MDA-MB-231 cells

Cancer Cell International ◽

10.1186/s12935-018-0511-5 ◽

2018 ◽

Vol 18 (1) ◽

Cited By ~ 32

Author(s):

Liangqian Jiang ◽

Yujuan Wang ◽

Guoxiang Liu ◽

Huihui Liu ◽

Feng Zhu ◽

...

Keyword(s):

Signaling Pathway ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Anti Cancer

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MAPK: A Key Player in the Development and Progression of Stroke

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200613223018 ◽

2020 ◽

Vol 19 (4) ◽

pp. 248-256

Author(s):

Yangmin Zheng ◽

Ziping Han ◽

Haiping Zhao ◽

Yumin Luo

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Complex Disease ◽

Therapeutic Targets ◽

Cell Types ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Effective Prevention ◽

Prevention And Treatment ◽

Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

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