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Bioinformatics and Chemoinformatics Analysis Explored the Role of Linum usitatissimum in Diabetic Heart Conditions:
Kamran Safavi1, Fatemeh Hajibabaie2,3, Navid Abedpoor3
1Department of Plant Biotechnology, Medicinal Plants Research Centre, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran.
Insights
Linum usitatissimum (LiU) extract reduces inflammation and boosts antioxidant defenses in diabetic heart failure (DHF) models. This study highlights LiU
Area of Science:
- Cardiovascular Research
- Pharmacology
- Biochemistry
Background:
- Inflammation and cytokine storms are key drivers of heart failure (HF).
- Bioactive compounds from complementary medicine offer anti-inflammatory properties.
- Linum usitatissimum (LiU) exhibits antioxidant and anti-inflammatory activities.
Purpose of the Study:
- To identify druggable targets for diabetic heart failure (DHF) using bioinformatics.
- To investigate the therapeutic potential of Linum usitatissimum (LiU) in DHF.
- To evaluate the effects of LiU on key inflammatory and antioxidant pathways.
Main Methods:
- Bioinformatic analysis of the GSE26887 dataset to identify differentially expressed genes in DHF.
- Protein-protein interaction network construction to pinpoint key targets like Interleukin-6 (IL-6).
- In vitro induction of DHF in H9c2 cell lines, followed by gene expression analysis (RT-PCR) and IL-6 quantification (ELISA) after LiU treatment.
Main Results:
- Bioinformatic analysis identified IL-6 as a high-scoring, druggable target in DHF.
- LiU treatment significantly altered the expression of SMAD7, STAT3, and NRF2.
- LiU administration markedly reduced IL-6 concentration in DHF models.
Conclusions:
- Linum usitatissimum (LiU) effectively modulates inflammation and enhances antioxidant defense mechanisms in HF.
- LiU demonstrates significant potential for managing and preventing diabetic heart failure (DHF).
- IL-6 is a promising therapeutic target for DHF, with LiU showing efficacy in targeting it.
Background:
Cytokine storms and inflammation lead to heart failure (HF). Bioactive compounds, as complementary medicine, can be the primary source of compounds with anti-inflammatory properties. Linum usitatissimum (LiU) has antioxidant capacity and anti-inflammatory activity. Here, candidate hugeness was selected based on the in silico studies, bio-cheminformatics, and bioinformatic analysis for excremental validation.
Methods:
We selected the vital genes with differential expression from the GSE26887 dataset. Based on the bioinformatics analysis, several parameters are determined to choose switchable genes involved in diabetic HF (DHF). We designed the protein-protein interactions network to consider the nodes' degree, modularity, and betweenness centrality. Hence, we selected the interleukin (IL)-6 protein as a target for drug design and discovery to reduce diabetes complications in the heart. Here, H9c2 cell lines of rat embryonic cardiomyocytes induce HF using hyperglycemic and hyperlipidemic conditions. Real-time polymerase chain reaction evaluated the relative expression of SMAD7/NRF-2/STAT3. Furthermore, we assessed the concentration of IL-6 using the enzyme-linked immunosorbent assay technique.
Results:
Based on the bioinformatic analysis, we found that IL-6 with the highest network parameters score might be presented as a druggable protein in the DHF. Bioactive compounds and phytochemicals have potential strategies to manage DHF. LiUs decreased the expression level of the SMAD7 (P <0.0001) and STAT3 (P < 0.0001), and increased the expression level of the NRF2 (P < 0.0001). In addition, LiUs significantly reduced the concentration of IL-6 (P < 0.0001).
Conclusion:
Our data proposed that LiUs regulated inflammation and triggered the antioxidant defense in HF. Moreover, LiUs could have potential approaches to managing and preventing DHF.
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