Role of statins in regulating molecular pathways following traumatic brain injury: A system pharmacology study

Mahmoudi, Alireza; Heydari, Sahar; Markina, Yuliya V.; Barreto, George E.; Sahebkar, Amirhossein

doi:10.1016/j.biopha.2022.113304

Cited by 7 publications

(3 citation statements)

References 167 publications

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“…Virtual screening based on systems biology methodology has recently garnered interest in target deconvolution studies and the exploration of therapeutic targets in various diseases [ 41 , 42 , 43 , 44 ].…”

Section: Introductionmentioning

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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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: Introductionmentioning

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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“…In recent years, many attempts to discover new and more specific pharmacological therapies to alleviate TBI damage have been explored [ 18 , 30 , 31 ]. Causes of secondary brain injury, such as inflammation and neuronal death, can also be treated with natural compounds [ 32 , 33 , 34 , 35 ] obtained from plants; they are used in treating many diseases due to their potent antioxidant effects [ 33 , 36 , 37 ] neutralizing reactive oxygen and nitrogen species (ROS/RNS), hence mitigating inflammation.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Antioxidant Capacity and Network Pharmacology of Phloretin and Phlorizin against Neuroinflammation in Traumatic Brain Injury

2023

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Neuroinflammation is a hallmark of traumatic brain injury (TBI)’s acute and chronic phases. Despite the medical and scientific advances in recent years, there is still no effective treatment that mitigates the oxidative and inflammatory damage that affects neurons and glial cells. Therefore, searching for compounds with a broader spectrum of action that can regulate various inflammatory signaling pathways is of clinical interest. In this study, we determined not only the in vitro antioxidant capacity of apple pomace phenolics, namely, phlorizin and its metabolite, phloretin, but we also hypothesize that the use of these bioactive molecules may have potential use in TBI. We explored the antioxidant effects of both compounds in vitro (DPPH, iron-reducing capacity (IRC), and Folin–Ciocalteu reducing capacity (FCRC)), and using network pharmacology, we investigated the proteins involved in their protective effects in TBI. Our results showed that the antioxidant properties of phloretin were superior to those of phlorizin in the DPPH (12.95 vs. 3.52 mg ascorbic acid equivalent (AAE)/L), FCRC (86.73 vs. 73.69 mg gallic acid equivalent (GAE)/L), and iron-reducing capacity (1.15 vs. 0.88 mg GAE/L) assays. Next, we examined the molecular signature of both compounds and found 11 proteins in common to be regulated by them and involved in TBI. Meta-analysis and GO functional enrichment demonstrated their implication in matrix metalloproteinases, p53 signaling, and cell secretion/transport. Using MCODE and Pearson’s correlation analysis, a subcluster was generated. We identified ESR1 (estrogen receptor alpha) as a critical cellular hub being regulated by both compounds and with potential therapeutic use in TBI. In conclusion, our study suggests that because of their vast antioxidant effects, probably acting on estrogen receptors, phloretin and phlorizin may be repurposed for TBI treatment due to their ease of obtaining and low cost.

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“…In a recent investigation, virtual screening based on a bioinformatics method has played an important role in the deconvolution and examination of the relationship of medications and diseases [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Role of Curcumin in Diabetes: An Analysis Based on Bioinformatic Findings

et al. 2022

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Background: Diabetes is an increasingly prevalent global disease caused by the impairment in insulin production or insulin function. Diabetes in the long term causes both microvascular and macrovascular complications that may result in retinopathy, nephropathy, neuropathy, peripheral arterial disease, atherosclerotic cardiovascular disease, and cerebrovascular disease. Considerable effort has been expended looking at the numerous genes and pathways to explain the mechanisms leading to diabetes-related complications. Curcumin is a traditional medicine with several properties such as being antioxidant, anti-inflammatory, anti-cancer, and anti-microbial, which may have utility for treating diabetes complications. This study, based on the system biology approach, aimed to investigate the effect of curcumin on critical genes and pathways related to diabetes. Methods: We first searched interactions of curcumin in three different databases, including STITCH, TTD, and DGIdb. Subsequently, we investigated the critical curated protein targets for diabetes on the OMIM and DisGeNET databases. To find important clustering groups (MCODE) and critical hub genes in the network of diseases, we created a PPI network for all proteins obtained for diabetes with the aid of a string database and Cytoscape software. Next, we investigated the possible interactions of curcumin on diabetes-related genes using Venn diagrams. Furthermore, the impact of curcumin on the top scores of modular clusters was analysed. Finally, we conducted biological process and pathway enrichment analysis using Gene Ontology (GO) and KEGG based on the enrichR web server. Results: We acquired 417 genes associated with diabetes, and their constructed PPI network contained 298 nodes and 1651 edges. Next, the analysis of centralities in the PPI network indicated 15 genes with the highest centralities. Additionally, MCODE analysis identified three modular clusters, which highest score cluster (MCODE 1) comprises 19 nodes and 92 edges with 10.22 scores. Screening curcumin interactions in the databases identified 158 protein targets. A Venn diagram of genes related to diabetes and the protein targets of curcumin showed 35 shared proteins, which observed that curcumin could strongly interact with ten of the hub genes. Moreover, we demonstrated that curcumin has the highest interaction with MCODE1 among all MCODs. Several significant biological pathways in KEGG enrichment associated with 35 shared included the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, PI3K-Akt signaling pathway, TNF signaling, and JAK-STAT signaling pathway. The biological processes of GO analysis were involved with the cellular response to cytokine stimulus, the cytokine-mediated signaling pathway, positive regulation of intracellular signal transduction and cytokine production in the inflammatory response. Conclusion: Curcumin targeted several important genes involved in diabetes, supporting the previous research suggesting that it may have utility as a therapeutic agent in diabetes.

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Role of statins in regulating molecular pathways following traumatic brain injury: A system pharmacology study

Cited by 7 publications

References 167 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

Comparison of Antioxidant Capacity and Network Pharmacology of Phloretin and Phlorizin against Neuroinflammation in Traumatic Brain Injury

Therapeutic Role of Curcumin in Diabetes: An Analysis Based on Bioinformatic Findings

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