Suppression of TGP on myocardial remodeling by regulating the NF-κB pathway

Naveed, Muhammad; Han, Lei; Hasnat, Muhammad; Wang, Wenlu; Mikrani, Reyaj; Liu, Zhiwei; Sembatya, Kiganda Raymond; Xie, Dianyou; Zhou, Xiaohui

doi:10.1016/j.biopha.2018.09.168

Cited by 16 publications

(7 citation statements)

References 64 publications

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“…After that Na-alginate coating was applied on the VI loaded DNA-nanocubes to further solidify by calcification technique to form gastric resistant, polymer-protected nanospheres [ 17 ]. For evaluating the nanospheres for oral enteric sustained release delivery of VI, we used Db–Db mice with similar metabolic status as that of patients suffering from diabetes [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and evaluation of DNA nano-cubes as a core material protected by the alginate coating for oral administration of anti-diabetic drug

Abbas

Naveed

Kassim

et al. 2019

Journal of Food and Drug Analysis

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Poor control towards glycemic levels among diabetic patients may lead to severe micro/ macro-vascular and neuropathic complexities. Proper functioning of alpha-beta cells of pancreases is required to attain long term glycemic control among type 2 diabetics. The recent developments to manage diabetes are focused on controlling the insulin-glucagon secretions from the pancreases. DPP-4 inhibitors class of drugs after elevating GLP-1/GIP (incretins) levels in the blood, not only raise the insulin levels but also suppress the glucagon level. Vildagliptin (VI) is a potent DPP-4 inhibitor with least adverse events compared to other DPP-4 inhibitors. We encapsulated VI into 3D nanocube that gets bind to the DNA due to secondary amine in its chemical structure. DNA-nanocube being negatively charged was incubated with the PLL to attain positive surface. Ultimately VI loaded nanocubes were coated with the negatively charged Na-alginate via electrostatic attraction method to get stable spherical nanospheres for oral delivery of VI. Nanospheres were evaluated physically through native PAGE analysis, DSC, TGA, dissolution testing, XRD and FTIR. We attained uniformed and spherical nanospheres with stable topology, nanoscale size precision (40–150 nm in diameter), Entrapment efficiency (up to 90%), prolonged drug release (13 ± 4 h) at basic pH, and superior oral antidiabetic effects with improved GLP1 and glycemic levels. The formulated nanospheres attained size uniformity and better therapeutic outcomes in terms of reduced adverse events and better control of glycemic levels than previously reported methods with decreased dosage frequency tested in Db/Db mice.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis and evaluation of DNA nano-cubes as a core material protected by the alginate coating for oral administration of anti-diabetic drug

Abbas

Naveed

Kassim

et al. 2019

Journal of Food and Drug Analysis

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“…In addition, cirrhosis not only causes myocardial cell hypertrophy but can also cause myocardial interstitial hyperplasia ( 33 ). In the present study, rats with cirrhosis, myocardial collagen fibers were found to be disordered, which can lead to hyperplasia and stiffness ( 34 ). Therefore, myocardial compliance indicated by the enlargement of left atrium and the decrease of VE/VA ratio in the present study decreased, which caused diastolic dysfunction.…”

Section: Discussionmentioning

confidence: 61%

“…Therefore, myocardial compliance indicated by the enlargement of left atrium and the decrease of VE/VA ratio in the present study decreased, which caused diastolic dysfunction. In addition, an increase in the levels of collagen fibers may interfere with the arrangement, communication and connection of myocardial cells, adversely affecting the production and transmission of force to induce systolic dysfunction ( 34 ). Myocardial fibrosis is an important manifestation of ventricular remodeling and also an intrinsic cause of cardiac insufficiency that can lead to heart failure ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Autonomic regulation of imbalance‑induced myocardial fibrosis and its mechanism in rats with cirrhosis

Sun

Wang

et al. 2021

Exp Ther Med

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The aim of the present study was to investigate the changes in cardiac function and myocardial damage in rats with cirrhosis. In addition, a secondary aim was to explore any potential changes in the expression levels of β1-adrenergic (β1) and muscarinic acetylcholine (M2) receptors . A cirrhotic cardiomyopathy (CCM) rat model was established by CCL4-oil solution for subcutaneous injection into the neck. Pathological changes in the liver and myocardial tissues were detecting by H&E staining and Masson trichrome staining. Furthermore, changes in the levels of myocardial enzymes lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB) and troponin in serum were measured by ELISA. The myocardial samples were homogenized and centrifuged. Subsequently, the supernatant was collected for detecting the expression of interleukins in myocardial tissue. Changes in the levels of inflammatory factors, IL-1, IL-2 and IL-6 both in the serum and myocardial tissue were determined by ELISA. Changes in echocardiographic measurements were evaluated using high-frequency ultrasound and the expression levels of β1 and M2 receptors in myocardial tissues were determined by western blotting. The normal lobular structure in liver tissues was found to be disappeared 8 weeks after modeling, which was replaced by pseudolobules in the rats in the CCM group. In addition, the myocardial cells were observed to be swollen and disorderly arranged. Compared with those in the control group, the left ventricular end-systolic and end-diastolic dimensions, interventricular septal dimension and LAD in rats in the CCM8 group were found to be significantly increased. The levels of myocardial enzymes LDH, CK-MB and cardiac troponin in the serum were also revealed to be significantly increased in the CCM8 group. Additionally, the levels of IL-1 and IL-6 in both serum and myocardial tissues were significantly increased in rats in the CCM8 group. However, the levels of IL-2 in both serum and myocardial tissues were decreased, which were observed alongside reductions in myocardial β1 and M2 receptor protein expression in the myocardial tissues. Taken together, these results indicate that inflammatory factors may be involved in mediating damage to the myocardium in rats with cirrhosis. During cirrhosis-induced cardiac dysfunction, there may exist a mechanism for downregulation of autonomic nerve system.

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“…Previous research had demonstrated the myocardial protective effects of TPG in both isoprenaline-induced myocardial ischemia rat and acute myocardial infarction rat (69,70). TGP also suppressed myocardial remodeling by regulating the NF-κB pathway (71). The effects of TGP on CVD protection in RA patients lack of clinical evidence in RA, which deserves further investigation.…”

Section: Discussionmentioning

confidence: 96%

Network pharmacology-based prediction of inhibiting leukocyte recruitment and angiogenesis of total glucosides of peony against rheumatoid arthritis

Hao¹,

Qi²,

Wang³

et al. 2022

Ann Palliat Med

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Background: Total glucosides of peony (TGP) is extracted from Paeonia lactiflora Pallas, which has been approved for rheumatoid arthritis (RA) treatment. There were approximately 15 monoterpene glycosides identified in TGP. Pervious researches focused on the effects of TGP and the major ingredient paeoniflorin (PF), but the functions of other monoterpene glycosides and their interactions were not clear.Network pharmacology has been one of the new strategies for multi-target drug discovery. In this study, we investigate the functions of all components of TGP and their interactions in RA treatment based on network pharmacology methods. Methods:The components of TGP were searched out the Web of Science, PubMed, China National Knowledge Infrastructure databases; then we identified the potential targets based of chemical similarity in the Similarity Ensemble Approach. The molecular related with RA were obtained from DrugBank, GeneCards, DisGeNET and Online Mendelian Inheritance in Man (OMIM) databases. The componentstargets-disease network was constructed and analyzed with Cytoscape software; Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted with R for function analysis. The hub components-targets interactions were validated with Autodock Vina.Results: Twenty potential targets of TGP were predicted for RA treatment. The major components of TGP, PF and albiflorin (AF) had more predicted targets. Hub targets of TGP were LGALS3/9, VEGFA, FGF1, FGF2, IL-6, IL-2, SELP, PRKCA and ERAP1. These targets ameliorated RA mainly through inhibiting leukocyte recruitment and angiogenesis. Enriched pathways including VEGFR pathway, signaling by interleukins, PI3K-Akt signaling pathway, platelet activation, extracellular matrix organization, and so on. The combination of PF, AF and lactiflorin (LF) with the hub targets was further validated using docking program. Conclusions:We investigated the comprehensive mechanism of TGP for RA treatment. We analyzed the different targets of the components in TGP and predicted the new effects of TGP on inhibiting leukocyte recruitment and angiogenesis. This study provides a better understanding of TGP on the RA treatment.

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Suppression of TGP on myocardial remodeling by regulating the NF-κB pathway

Cited by 16 publications

References 64 publications

Design, synthesis and evaluation of DNA nano-cubes as a core material protected by the alginate coating for oral administration of anti-diabetic drug

Design, synthesis and evaluation of DNA nano-cubes as a core material protected by the alginate coating for oral administration of anti-diabetic drug

Autonomic regulation of imbalance‑induced myocardial fibrosis and its mechanism in rats with cirrhosis

Network pharmacology-based prediction of inhibiting leukocyte recruitment and angiogenesis of total glucosides of peony against rheumatoid arthritis

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