scholarly journals Comparison and Analysis on the Existing Single-Herbal Strategies against Viral Myocarditis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yu Cao ◽  
Yang Liu ◽  
Tian Zhang ◽  
Jing Pan ◽  
Wei Lei ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Target Genes ◽  
Viral Myocarditis ◽  
Herbal Medicines ◽  
Heart Tissue ◽  
Discovery Studio ◽  
Radix Bupleuri ◽  
Natural Components ◽  
Spatholobus Suberectus

Purpose. Herbal medicine is one of crucial symbols of Chinese national medicine. Investigation on molecular responses of different herbal strategies against viral myocarditis is immeasurably conducive to targeting drug development in the current international absence of miracle treatment. Methods. Literature retrieval platforms were applied in the collection of existing empirical evidences for viral myocarditis-related single-herbal strategies. SwissTargetPrediction, Metascape, and Discovery Studio coordinating with multidatabases investigated underlying target genes, interactive proteins, and docking molecules in turn. Results. Six single-herbal medicines consisting of Huangqi (Hedysarum Multijugum Maxim), Yuganzi (Phyllanthi Fructus), Kushen (Sophorae Flavescentis Radix), Jianghuang (Curcumaelongae Rhizoma), Chaihu (Radix Bupleuri), and Jixueteng (Spatholobus Suberectus Dunn) meet the requirement. There were 11 overlapped and 73 unique natural components detected in these herbs. SLC6A2, SLC6A4, NOS2, PPARA, PPARG, ACHE, CYP2C19, CYP51A1, and CHRM2 were equally targeted by six herbs and identified as viral myocarditis-associated symbols. MCODE algorithm exposed the hub role of SRC and EGFR in strategies without Jianghuang. Subsequently, we learned intermolecular interactions of herbal components and their targeting heart-tissue-specific CHRM2, FABP3, TNNC1, TNNI3, TNNT2, and SCN5A and cardiac-myocytes-specific IL6, MMP1, and PLAT coupled with viral myocarditis. Ten interactive characteristics such as π-alkyl and van der Waals were modeled in which ARG111, LYS253, ILE114, and VAL11 on cardiac troponin (TNNC1-TNNI3-TNNT2) and ARG208, ASN106, and ALA258 on MMP1 fulfilled potential communicating anchor with ellagic acid, 5α, 9α-dihydroxymatrine, and leachianone g via hydrogen bond and hydrophobic interaction, respectively. Conclusions. The comprehensive outcomes uncover differences and linkages between six herbs against viral myocarditis through component and target analysis, fostering development of drugs.

scholarly journals Chronoeffects of the Herbal Medicines Puerariae radix and Coptidis rhizoma in Mice: A Potential Role of REV-ERBα

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinming Liu ◽  
Haiman Xu ◽  
Li Zhang ◽  
Shuai Wang ◽  
Danyi Lu ◽  
...  
Keyword(s):  
Drug Target ◽  
Potential Role ◽  
Target Genes ◽  
Herbal Medicines ◽  
Time Dependent ◽  
Dependent Manner ◽  
Active Constituent ◽  
Puerariae Radix ◽  
Coptidis Rhizoma

Identifying drugs with dosing time-dependent effects (chronoeffects) and understanding the underlying mechanisms would help to improve drug treatment outcome. Here, we aimed to determine chronoeffects of the herbal medicines Puerariae radix (PR) and Coptidis rhizoma (CR), and investigate a potential role of REV-ERBα as a drug target in generating chronoeffects. The pharmacological effect of PR on hyperhomocysteinemia in mice was evaluated by measuring total homocysteine, triglyceride levels and lipid accumulation. PR dosed at ZT10 generated a stronger effect on hyperhomocysteinemia than drug dosed at ZT2. Furthermore, PR increased the expression levels of REV-ERBα target genes Bhmt, Cbs and Cth (encoding three key enzymes responsible for homocysteine catabolism), thereby alleviating hyperhomocysteinemia in mice. Moreover, CR attenuated chronic colitis in mice in a dosing time-dependent manner based on measurements of disease activity index, colon length, malondialdehyde/myeloperoxidase activities and IL-1β/IL-6 levels. ZT10 dosing generated a stronger anti-colitis effect as compared to ZT2 dosing. This was accompanied by lower production of colonic inflammatory cytokines (i.e., Nlrp3, IL-1β, IL-6, Tnf-α and Ccl2, REV-ERBα target genes) in colitis mice dosed at ZT10. The diurnal patterns of PR and CR effects were respectively consistent with those of puerarin (a main active constituent of PR, a REV-ERBα antagonist) and berberine (a main active constituent of CR, a REV-ERBα agonist). In addition, loss of Rev-erbα in mice abolished the dosing time-dependency in PR and CR effects. In conclusion, the therapeutic effects of PR and CR depend on dosing time in mice, which are probably attributed to diurnal expression of REV-ERBα as the drug target. Our findings have implications for improving therapeutic outcomes of herbal medicines with a chronotherapeutic approach.

scholarly journals ADAR1p150 Forms a Complex with Dicer to Promote miRNA-222 Activity and Regulate PTEN Expression in CVB3-Induced Viral Myocarditis

2019 ◽  
Vol 20 (2) ◽  
pp. 407 ◽  
Author(s):  
Xincai Zhang ◽  
Xiangting Gao ◽  
Jun Hu ◽  
Yuxin Xie ◽  
Yuanyi Zuo ◽  
...  
Keyword(s):  
Target Genes ◽  
Viral Infections ◽  
Cultured Cells ◽  
Viral Myocarditis ◽  
Pten Expression ◽  
Pten Protein ◽  
Adenosine Deaminases ◽  
Potential Binding ◽  
Potential Binding Site

Adenosine deaminases acting on RNA (ADAR) are enzymes that regulate RNA metabolism through post-transcriptional mechanisms. ADAR1 is involved in a variety of pathological conditions including inflammation, cancer, and the host defense against viral infections. However, the role of ADAR1p150 in vascular disease remains unclear. In this study, we examined the expression of ADAR1p150 and its role in viral myocarditis (VMC) in a mouse model. VMC mouse cardiomyocytes showed significantly higher expression of ADAR1p150 compared to the control samples. Coimmunoprecipitation verified that ADAR1p150 forms a complex with Dicer in VMC. miRNA-222, which is involved in many cardiac diseases, is highly expressed in cardiomyocytes in VMC. In addition, the expression of miRNA-222 was promoted by ADAR1p150/Dicer. Among the target genes of miRNA-222, the expression of phosphatase-and-tensin (PTEN) protein was significantly reduced in VMC. By using a bioinformatics tool, we found a potential binding site of miRNA-222 on the PTEN gene’s 3′-UTR, suggesting that miRNA-222 might play a regulatory role. In cultured cells, miR-222 suppressed PTEN expression. Our findings suggest that ADAR1p150 plays a key role in complexing with Dicer and promoting the expression of miRNA-222, the latter of which suppresses the expression of the target gene PTEN during VMC. Our work reveals a previously unknown role of ADAR1p150 in gene expression in VMC.

scholarly journals Mitigated viral myocarditis in A/J mice by the immunoproteasome inhibitor ONX 0914 depends on inhibition of systemic inflammatory responses in CoxsackievirusB3 infection

2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Carl Christoph Goetzke ◽  
Nadine Althof ◽  
Hannah Louise Neumaier ◽  
Arndt Heuser ◽  
Ziya Kaya ◽  
...  
Keyword(s):  
Troponin I ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Acute Myocarditis ◽  
Viral Myocarditis ◽  
Heart Tissue ◽  
Preclinical Model ◽  
Cardiac Inflammation ◽  
The Impact

AbstractA preclinical model of troponin I-induced myocarditis (AM) revealed a prominent role of the immunoproteasome (ip), the main immune cell-resident proteasome isoform, in heart-directed autoimmunity. Viral infection of the heart is a known trigger of cardiac autoimmunity, with the ip enhancing systemic inflammatory responses after infection with a cardiotropic coxsackievirusB3 (CV). Here, we used ip-deficient A/J-LMP7−/− mice to investigate the role of ip-mediated effects on adaptive immunity in CV-triggered myocarditis and found no alteration of the inflammatory heart tissue damage or cardiac function in comparison to wild-type controls. Aiming to define the impact of the systemic inflammatory storm under the control of ip proteolysis during CV infection, we targeted the ip in A/J mice with the inhibitor ONX 0914 after the first cycle of infection, when systemic inflammation has set in, well before cardiac inflammation. During established acute myocarditis, the ONX 0914 treatment group had the same reduction in cardiac output as the controls, with inflammatory responses in heart tissue being unaffected by the compound. Based on these findings and with regard to the known anti-inflammatory role of ONX 0914 in CV infection, we conclude that the efficacy of ip inhibitors for CV-triggered myocarditis in A/J mice relies on their immunomodulatory effects on the systemic inflammatory reaction.

scholarly journals Chronoefficacy of the herbal medicines Puerariae radix and Coptidis rhizoma in mice: A potential role of REV-ERBα

2021 ◽  
Author(s):  
Jinming Liu ◽  
Haiman Xu ◽  
Li Zhang ◽  
Shuai Wang ◽  
Danyi Lu ◽  
...  
Keyword(s):  
Drug Target ◽  
Potential Role ◽  
Target Genes ◽  
Herbal Medicines ◽  
Chronic Colitis ◽  
Active Constituent ◽  
Circadian Time ◽  
Coptidis Rhizoma ◽  
Underlying Mechanisms

Abstract Background Identifying drugs with circadian time-dependent efficacy (chronoefficacy) and understanding the underlying mechanisms would help to improve drug treatment outcome. Here, we aimed to determine chronoefficacy of the herbal medicines Puerariae radix (PR) and Coptidis rhizoma (CR), and investigate a potential role of REV-ERBα as a drug target in generating chronoefficacy. Materials and methods PR and CR efficacy were assessed based on the diseases hyperhomocysteinemia and chronic colitis, respectively. The efficacy of PR against hyperhomocysteinemia in mice was evaluated by measuring total homocysteine, triglyceride levels and lipid accumulation. The efficacy of CR against chronic colitis in mice was evaluated by measuring disease activity index, colon length, malondialdehyde/myeloperoxidase activities and IL-1β/IL-6 levels. The underlying mechanisms related to REV-ERBα target genes were analyzed by qPCR. Puerarin in PR and berberine in CR were analyzed by UPLC-QTOF/MS. Results PR dosed at ZT10 generated a better efficacy against hyperhomocysteinemia than drug dosed at ZT2. Furthermore, PR increased the expressions of REV-ERBα target genes Bhmt, Cbs and Cth (encoding three key enzymes responsible for homocysteine catabolism), thereby alleviating hyperhomocysteinemia in mice. Moreover, CR attenuated chronic colitis in mice in a circadian time-dependent manner. ZT10 dosing generated a better anti-colitis efficacy as compared to ZT2 dosing. This was accompanied by lower production of colonic inflammatory cytokines (i.e, Nlrp3, IL-1β, IL-6, Tnf-α and Ccl2, REV-ERBα target genes) in colitis mice at ZT10 dosing. The circadian patterns of PR and CR effects were respectively consistent with those of puerarin (a main active constituent of PR, a REV-ERBα antagonist) and berberine (a main active constituent of CR, a REV-ERBα agonist). Conclusion The therapeutic effects of PR and CR depend on dosing time in mice, which are probably attributed to circadian expression of REV-ERBα as the drug target. Our findings have implications for improving therapeutic outcomes of herbal medicines with a chronotherapeutics approach.

MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target

2020 ◽  
Vol 26 ◽  
Author(s):  
Yini Ma ◽  
Xiu Cao ◽  
Guojuan Shi ◽  
Tianlu Shi
Keyword(s):  
Digestive System ◽  
Target Genes ◽  
Malignant Neoplasm ◽  
Vital Role ◽  
Diagnostic Biomarkers ◽  
Cellular Processes ◽  
Promising Therapeutic Target ◽  
Direct Target ◽  
Potential Strategy

: MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles for cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as valuable biomarkers for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

The Effects of Herbal Medicines on Women Sexual Dysfunction: A Systematic Review

2020 ◽  
Vol 17 ◽  
Author(s):  
Tahereh Molkara ◽  
Maliheh Motavasselian ◽  
Farideh Akhlaghi ◽  
Mohammad Arash Ramezani ◽  
Hamideh Naghedi Baghdar ◽  
...  
Keyword(s):  
Sexual Dysfunction ◽  
Herbal Medicine ◽  
Sexual Health ◽  
Sexual Function ◽  
Psychological Health ◽  
Health Management ◽  
Herbal Medicines ◽  
Physical And Psychological Health ◽  
Female Sexual Response

: Sexual health plays an important role in the women’s health and quality of life. Sexual health management is a prerequisite for physical and psychological health of women. Sexual desire, arousal, and orgasm are three factors of female sexual response. So far many different methods has been known for the treatment of female sexual dysfunction, however none of them are not an efficacious therapy. Generally, use of herbal medicine is a safe and effective therapeutic method in the treatment of women with sexual dysfunction. The role of herbal and nutritional supplementation in female sexual function has attracted researchers’ interest in recent years. This study aimed to the evaluation of the studies focusing on the herbal medicine on women sexual function and the assessment of its effectiveness.

Bioinformatics Analysis and Validation of Differentially Expressed MicroRNAs with Their Target Genes Involved in GLP-1RA Facilitated Osteogenesis

2020 ◽  
Vol 15 ◽  
Author(s):  
Na Wang ◽  
Yukun Li ◽  
Sijing Liu ◽  
Liu Gao ◽  
Chang Liu ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Differentially Expressed ◽  
Functional Study ◽  
Regulation Network ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled ◽  
Lower Expression

Background: Recent studies revealed that the hypoglycemic hormone, glucagon-like peptide-1 (GLP-1), acted as an important modulator in osteogenesis of bone marrow derived mesenchymal stem cells (BMSCs). Objectives: The aim of this study was to identify the specific microRNA (miRNA) using bioinformatics analysis and validate the presence of differentially expressed microRNAs with their target genes after GLP-1 receptor agonist (GLP-1RA) administration involved in ostogenesis of BMSCs. Methods: MiRNAs were extracted from BMSCs after 5 days’ treatment and sent for high-throughput sequencing for differentially expressed (DE) miRNAs analyses. Then the expression of the DE miRNAs verified by the real-time RT-PCR analyses. Target genes were predicted, and highly enriched GOs and KEGG pathway analysis were conducted using bioinformatics analysis. For the functional study, two of the target genes, SRY (sex determining region Y)-box 5 (SOX5) and G protein-coupled receptor 84 (GPR84), were identified. Results: A total of 5 miRNAs (miRNA-509-5p, miRNA-547-3p, miRNA-201-3p, miRNA-201-5p, and miRNA-novel-272-mature) were identified differentially expressed among groups. The expression of miRNA-novel-272-mature were decreased during the osteogenic differentiation of BMSCs, and GLP-1RA further decreased its expression. MiRNA-novel-272-mature might interact with its target mRNAs to enhance osteogenesis. The lower expression of miRNA-novel-272-mature led to an increase in SOX5 and a decrease in GPR84 mRNA expression, respectively. Conclusions: Taken together, these results provide further insights to the pharmacological properties of GLP-1RA and expand our knowledge on the role of miRNAs-mRNAs regulation network in BMSCs’ differentiation.

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