Silybin phytosome attenuates cerebral ischemia‐reperfusion injury in rats by suppressing oxidative stress and reducing inflammatory response: In vivo and in silico approaches

Pasala, Praveen Kumar; Uppara, Ramya K; Rudrapal, Mithun; Zothantluanga, James H.; Umar, Abd. Kakhar

doi:10.1002/jbt.23073

Cited by 30 publications

(15 citation statements)

References 40 publications

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“…The structure of α-amylase (PDB ID:4W93), α-glycosidase (PDB ID:3A4A), cyclooxygenase (PDB ID:5F1A), lipoxygenase (PDB ID:6N2W), HIV protease (PDB ID: 5KR0), and epidermal growth factor receptor (PDB ID:1IVO) were retrieved from the database ( https://www.rcsb.org/ ) ( 46 ). Pre-processing of proteins for removal of side chains, identification of the active site, removal of heteroatoms, removal of water and addition of hydrogen atoms was carried out ( 43 , 47 – 49 ). The coordinates of the active binding sites are as follows: α-amylase (x = −12.30, y = 4.25, z = −22.43), α-glycosidase (x = 21.31, y = −7.82, z = 23.30), cyclooxygenase (x = 41.74, y = 24.19, z = 239.73), epidermal growth factor receptor (x = 108.02, y = 66.26, z = 45.17), HIV protease (x = −16.70, y = 12.41, z = −20.16), and lipoxygenase (x = 42.34, y = 20.37, z = 36.35).…”

Section: Methodsmentioning

confidence: 99%

Section: In Silico Studiesmentioning

confidence: 99%

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Valorization of Adhatoda vasica leaves: Extraction, in vitro analyses and in silico approaches

et al. 2023

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Adhatoda vasica (also called Vasaka) is a traditional medicinal herb used traditionally for the relief of cough, asthma, nasal congestion, bronchial inflammation, upper respiratory infections, bleeding disorders, skin diseases, leprosy, tuberculosis, diabetes, allergic conditions, rheumatism, tumor, and many more diseases. The present study aims to investigate the biological activities of vasicine, a potent alkaloid from A. vasica with different biological/ pharmacological assays and in silico techniques. Vasicine showed antimicrobial activity as evidenced fromthe colony-forming unit assay. It showed antioxidant activity in ABTS scavenging assay (IC50 = 11.5 μg/ml), ferric reducing power assay (IC50 = 15 μg/ml), DPPH radical scavenging assay (IC50 = 18.2 μg/ml), hydroxyl radical scavenging assay (IC50 = 22 μg/ml), and hydrogen peroxide assay (IC50 = 27.8 μg/ml). It also showed anti-inflammatory activity in proteinase inhibitory assay (IC50 = 76 μg/ml), BSA method (IC50 = 51.7 μg/ml), egg albumin method (IC50 = 53.2 μg/ml), and lipooxygenase inhibition assay (IC50 = 76 μg/ml). Vasicine showed antidiabetic activity in α-amylase inhibition assay (IC50 = 47.6 μg/ml), α-glucosidase inhibition assay (IC50 = 49.68 μg/ml), and non-enzymatic glycosylation of hemoglobin assay. It showed antiviral activity against HIV-protease (IC50 = 38.5 μg/ml). Vasicine also showed anticancer activity against lung cancer cells (IC50 = 46.5 μg/ml) and human fibroblast cells (IC50 = 82.5 μg/ml). In silico studies revealed that similar to the native ligands, vasicine also showed a low binding energy, i.e., good binding affinity for the active binding sites and interacted with α-amylase (-6.7 kcal/mol), α-glucosidase (-7.6 kcal/mol), cyclooxygenase (-7.4 kcal/mol), epidermal growth factor receptor (-6.4 kcal/mol), lipooxygenase (-6.9 kcal/mol), and HIV-protease (-6.4 kcal/mol). The present study ascertains the potential of vasicine as a bioactive compound isolated from A. vasica having therapeutic usefulness in many human diseases.

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Section: Methodsmentioning

confidence: 99%

Section: In Silico Studiesmentioning

confidence: 99%

Valorization of Adhatoda vasica leaves: Extraction, in vitro analyses and in silico approaches

et al. 2023

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“…The silybin phytosome was also administered to rats with Cerebral Ischemia–Reperfusion (CIR) injury. Rats treated with the silybin phytosome had higher levels of SOD and glutathione and lower levels of monoaldehyde, TNF-α and IL-6 in both the hippocampus and cortex; this demonstrates the neuroprotective action of the silybin phytosome under CIR conditions [ 113 ].…”

Section: Phytosome and Pathologiesmentioning

confidence: 99%

Inflammation, Mitochondria and Natural Compounds Together in the Circle of Trust

Nesci

Spagnoletta

Oppedisano

2023

IJMS

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Human diseases are characterized by the perpetuation of an inflammatory condition in which the levels of Reactive Oxygen Species (ROS) are quite high. Excessive ROS production leads to DNA damage, protein carbonylation and lipid peroxidation, conditions that lead to a worsening of inflammatory disorders. In particular, compromised mitochondria sustain a stressful condition in the cell, such that mitochondrial dysfunctions become pathogenic, causing human disorders related to inflammatory reactions. Indeed, the triggered inflammation loses its beneficial properties and turns harmful if dysregulation and dysfunctions are not addressed. Thus, reducing oxidative stress with ROS scavenger compounds has proven to be a successful approach to reducing inflammation. Among these, natural compounds, in particular, polyphenols, alkaloids and coenzyme Q10, thanks to their antioxidant properties, are capable of inhibiting the activation of NF-κB and the expression of target genes, including those involved in inflammation. Even more, clinical trials, and in vivo and in vitro studies have demonstrated the antioxidant and anti-inflammatory effects of phytosomes, which are capable of increasing the bioavailability and effectiveness of natural compounds, and have long been considered an effective non-pharmacological therapy. Therefore, in this review, we wanted to highlight the relationship between inflammation, altered mitochondrial oxidative activity in pathological conditions, and the beneficial effects of phytosomes. To this end, a PubMed literature search was conducted with a focus on various in vitro and in vivo studies and clinical trials from 2014 to 2022.

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“…Table S1: Common genes between silybin and MI, Table S2: Top 10 Hub gene identification by cytohubba and MCODE algorithm in the Cytoscape, Table S3: Gene ontology (GO) enrichmentin the top 10 Hub genes, Table S4: Target genes in the enrichment of signaling pathways related to TY2DM, Table S5: Binding energy and interactions of silybin on TNF‐α, IL‐6, and AKT1. Additional references cited within the Supporting Information [25–48] …”

Section: Supporting Information Summarymentioning

confidence: 99%

Investigation of Cardioprotective Activity of Silybin: Network Pharmacology, Molecular Docking, and In Vivo Studies

Kumar Pasala,

Donakonda,

Dintakurthi

et al. 2023

ChemistrySelect

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The abundant health benefits of silybin are known to benefit people with myocardial infarction (MI). However, their mechanisms of action are not precise. To address this problem, network pharmacology was used to identify the various components that can be utilized to treat this condition, and an in vivo study was conducted to evaluate the cardioprotective effect in MI rats. Genes associated with silybin and MI targets were extracted, and overlapping genes between silybin‐associated genes and MI targets were identified using Venn diagrams. Using Cytoscape, we built, visualized, and analyzed a network of compounds and genes with pathways. Protein‐protein interaction network (PPI), gene ontology (GO) function enrichment, and Kyoto Encyclopedia of Genes, and Genomes (KEGG) pathway enrichment analyses of the core targets were performed to predict its mechanism. A molecular docking study assessed the affinity between silybin and the top three genes. ECG pattern, serum CK‐MB, LDH, serum and heart tissue antioxidants, SOD and catalase in isoproterenol‐induced MI rats were used to test the cardioprotective effect of silybin. Silybin‐related genes (114) and MI‐related genes (1800) were identified, and 74 genes overlapped, in which the degrees of AKT1, TNF‐α and IL‐6 were higher than those of other targets are the disease target precisely. The enrichment of the gene set‐based indicated that the PI3K‐Akt, TNF‐α, IL‐17, VEGF, and HIF‐1 signaling pathways were significantly involved in the mechanisms of silybin against MI. The QRS complex of the ECG of silybin‐treated MI rats was restored to normal ECG and significantly increased serum (p<0.0001***) and heart tissue (p<0.0001***) SOD and serum (p<0.001**) and heart tissue (p<0.001**) catalase compared to MI rats. This study embodies the complex network relationship of multi‐target and multiple pathways of silybin in the treatment of MI and provides a novel method for further research on the mechanism of silybin. It has been suggested that silybin alleviates the symptoms of MI by improving antioxidant levels through the PI3K‐Akt/HIF‐1 pathway.

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Silybin phytosome attenuates cerebral ischemia‐reperfusion injury in rats by suppressing oxidative stress and reducing inflammatory response: In vivo and in silico approaches

Cited by 30 publications

References 40 publications

Valorization of Adhatoda vasica leaves: Extraction, in vitro analyses and in silico approaches

Valorization of Adhatoda vasica leaves: Extraction, in vitro analyses and in silico approaches

Inflammation, Mitochondria and Natural Compounds Together in the Circle of Trust

Investigation of Cardioprotective Activity of Silybin: Network Pharmacology, Molecular Docking, and In Vivo Studies

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