Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats

Wahba, Mariam Gamal Fahmy; Messiha, Basim Anwar Shehata; Abo-Saif, Ali A.

doi:10.1016/j.ejphar.2015.08.026

Cited by 43 publications

(17 citation statements)

References 84 publications

(58 reference statements)

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“…Price et al demonstrated in a rodent model of rheumatoid arthritis (RA) that TNF-α release and subsequent knee joint swelling were significantly inhibited by the application of ACE inhibitors [19]. Other groups confirmed these findings, revealing beneficial anti-arthritic effects of ACE inhibitors and angiotensin II receptor type 1 blockers (ARBs) by reducing inflammation, neutrophil recruitment, hypernociception, disease activity, oxidative stress levels, and ultimately joint destruction [20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Moreover, renal injury models revealed that inhibition or reduction of AngII actions via ACE inhibitors or ARBs reduced proteinuria, recruitment of pro-inflammatory cells, fibrosis, and catabolic gene expression [34][35][36].…”

Section: Introductionmentioning

confidence: 89%

Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells

Saravi¹,

Li²,

Pfannkuche³

et al. 2020

Preprint

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Our recent study detected the expression of a tissue Renin-Angiotensin System (tRAS) in human intervertebral discs (IVDs). The present study sought to investigate the impact of angiotensin II receptor type 1 (AGTR1) antagonist losartan on human nucleus pulposus (NP) cell inflammation and degeneration induced by tumor necrosis factor-α (TNF-α). Human NP cells (4 donors, Pfirrmann grade 2-3, 30-37 years old, male) were isolated and expanded. TNF-α (10 ng/mL) was used to induce inflammation and degeneration. We examined the impact of losartan supplementation and measured gene expression of tRAS, anabolic, catabolic, and inflammatory markers in NP cells after 24 h and 72 h of exposure, respectively. T0070907, a PPAR-gamma antagonist, was applied to examine the regulatory pathway of losartan. Losartan (1 mM) significantly impaired TNF-α induced increase of pro-inflammatory (nitric oxide and TNF-α), catabolic (matrix metalloproteinases), and tRAS (AGTR1a and Angiotensin Converting Enzyme) markers. Further, losartan maintained the NP cell phenotype by upregulating aggrecan and downregulating collagen type I expression. In summary, losartan showed anti-inflammatory, anti-catabolic, and positive phenotype modulating effects on human NP cells. These results indicate that tRAS signaling plays an important role in IVD degeneration, and tRAS modulation with losartan could represent a novel therapeutic approach.

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Section: Introductionmentioning

confidence: 89%

Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells

Saravi¹,

Li²,

Pfannkuche³

et al. 2020

Preprint

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show abstract

“…Arab and El-Sawalhi (2013) pointed out that as a potential anti-arthritic drug, Carvedilol may be effect on the reduction of leukocyte migration. Fahmy Wahba et al (2015) provided us a clue that Ramipril may represent a new promising strategy against RA because of its anti-inflammatory effect on rats. In short, it is very feasible to apply the conserved disease modules found by our method to drug repositioning research.…”

Section: Resultsmentioning

confidence: 99%

Conserved Disease Modules Extracted From Multilayer Heterogeneous Disease and Gene Networks for Understanding Disease Mechanisms and Predicting Disease Treatments

Yao

Gao

et al. 2019

Front. Genet.

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Disease relationship studies for understanding the pathogenesis of complex diseases, diagnosis, prognosis, and drug development are important. Traditional approaches consider one type of disease data or aggregating multiple types of disease data into a single network, which results in important temporal- or context-related information loss and may distort the actual organization. Therefore, it is necessary to apply multilayer network model to consider multiple types of relationships between diseases and the important interplays between different relationships. Further, modules extracted from multilayer networks are smaller and have more overlap that better capture the actual organization. Here, we constructed a weighted four-layer disease-disease similarity network to characterize the associations at different levels between diseases. Then, a tensor-based computational framework was used to extract Conserved Disease Modules (CDMs) from the four-layer disease network. After filtering, nine significant CDMs were reserved. The statistical significance test proved the significance of the nine CDMs. Comparing with modules got from four single layer networks, CMDs are smaller, better represent the actual relationships, and contain potential disease-disease relationships. KEGG pathways enrichment analysis and literature mining further contributed to confirm that these CDMs are highly reliable. Furthermore, the CDMs can be applied to predict potential drugs for diseases. The molecular docking techniques were used to provide the direct evidence for drugs to treat related disease. Taking Rheumatoid Arthritis (RA) as a case, we found its three potential drugs Carvedilol, Metoprolol, and Ramipril. And many studies have pointed out that Carvedilol and Ramipril have an effect on RA. Overall, the CMDs extracted from multilayer networks provide us with an impressive understanding disease mechanisms from the perspective of multi-layer network and also provide an effective way to predict potential drugs for diseases based on its neighbors in a same CDM.

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“…Group 1 (normal) received vehicle only. Group 2 (arthritic control) received three s.c. doses of 0.4 ml CFA on days 1, 4, and 7 in the flank of different limbs to reduce the risk of ulceration ( Hawkins et al, 2015 , Wahba et al, 2015 ). Groups 3 and 4 were kept as reference treatment groups and received methotrexate (1 mg/kg/week; i.p.)…”

Section: Methodsmentioning

confidence: 99%

Aliskiren, tadalafil, and cinnamaldehyde alleviate joint destruction biomarkers; MMP-3 and RANKL; in complete Freund's adjuvant arthritis model: Downregulation of IL-6/JAK2/STAT3 signaling pathway

Azouz

Saleh

Abo-Saif

2020

Saudi Pharmaceutical Journal

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Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, which is accompanied by progressive joint damage and disability. The intolerability of conventional antirheumatic drugs by some patients necessitates the search for effective antirheumatic agents having better tolerability. In the current work, we aimed to investigate the efficacy of cinnamaldehyde, tadalafil, and aliskiren as potential antirheumatic candidates and to explore their modulatory effects on joint destruction, inflammatory response, and intracellular signaling. Arthritis was induced in female Wistar rats by complete Freund's adjuvant (CFA) 0.4 ml s.c. on days 1, 4, and 7. Treated groups received their respective drugs, starting from day 13, daily for 3 weeks. Methotrexate and prednisolone were the standard antirheumatic drugs, while cinnamaldehyde, tadalafil, and aliskiren were the test agents. Treatment with cinnamaldehyde, tadalafil, or aliskiren reduced serum levels of rheumatoid factor, and pro-inflammatory cytokines; tumor necrosis factor-alpha and interleukin-6 (IL-6), along with elevated level of IL-10 which is an anti-inflammatory cytokine. Besides, cartilage and bone destruction biomarkers; matrix metalloproteinase-3 (MMP-3) and receptor activator of nuclear factor-kappa B ligand (RANKL); were significantly reduced after treatment with the test agents, which was further confirmed by histopathological investigation. The elevated protein expressions of phosphorylated-Janus kinase 2 (p-JAK2), phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), and inducible nitric oxide synthase (iNOS) in articular tissue were markedly attenuated after treatment with cinnamaldehyde, tadalafil, or aliskiren, while that of endothelial nitric oxide synthase (eNOS) was greatly enhanced. In addition, oxidative stress and inflammatory markers such as malondialdehyde, nitric oxide, and myeloperoxidase were reduced in joint tissue after treatment with the test agents, while glutathione content was elevated. Furthermore, the renin inhibitor aliskiren produced effects close to those of the normal and methotrexate, the gold standard antirheumatic drug, in most of the measured parameters. Collectively, these findings led to the assumption that the downregulation of IL-6/JAK2/STAT3 signaling by cinnamaldehyde, tadalafil, and aliskiren could alleviate joint destruction by MMP-3 and RANKL, reduce iNOS, and enhance eNOS expressions. Moreover, aliskiren could be a promising therapeutic agent for RA, because of its ability to normalize most of the measured parameters after CFA-induced arthritis.

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Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats

Cited by 43 publications

References 84 publications

Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells

Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells

Conserved Disease Modules Extracted From Multilayer Heterogeneous Disease and Gene Networks for Understanding Disease Mechanisms and Predicting Disease Treatments

Aliskiren, tadalafil, and cinnamaldehyde alleviate joint destruction biomarkers; MMP-3 and RANKL; in complete Freund's adjuvant arthritis model: Downregulation of IL-6/JAK2/STAT3 signaling pathway

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