Telmisartan mediates anti-inflammatory and not cognitive function through PPAR-γ agonism via SARM and MyD88 signaling

Balaji, S. Prathab; Chand, C. Vijay; Justin, Antony; Ramanathan, Meena

doi:10.1016/j.pbb.2015.08.007

Cited by 28 publications

(15 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the coadministration of MTX and Azil was not evaluated clinically or in animal models of RA. Apart from the cardiovascular modulatory effects, certain ARBs, like losartan and telmisartan, have well-characterized anti-inflammatory activities [ 21 , 22 ]. Based on data that suggested the anti-inflammatory activity of azilsartan [ 15 ], we assessed the influence of adjunct use of azilsartan with MTX on the clinical and biochemical markers in RA patients.…”

Section: Discussionmentioning

confidence: 99%

Azilsartan as “Add-On” Treatment with Methotrexate Improves the Disease Activity of Rheumatoid Arthritis

Mahmood

Hussain

Khan

2018

BioMed Research International

View full text Add to dashboard Cite

Objective The present study aimed to evaluate the efficacy and safety of azilsartan (Azil) as “add-on” treatment with methotrexate (MTX) in patients with active rheumatoid arthritis (RA). MethodsThis single center, randomized, placebo-controlled, double-blind, pilot study included 64 patients with active RA. Patients received either placebo or Azil in addition to their currently used MTX doses for 90 days. The primary outcomes were DAS-28, SDAI, HAQ-DI, CDAI, EGA, and swollen and tender joints count. The secondary outcomes were the changes in the pain visual analogue scale (VAS-100), serum levels of TNF-α, IL-1β, IL-6, and anti-CCP, the lipid profile, and the markers of kidney and liver functions in the two groups at baseline and after 90 days. ResultsAfter 90 days, most clinical scores were significantly better in the Azil-treated group than in the placebo group. All inflammatory biomarkers were significantly improved after treatment with MTX + Azil compared to baseline and placebo group. No safety concerns were reported during the study period. Conclusions Azilsartan improved the effects of methotrexate on the clinical scores and certain inflammatory biomarkers of patients with active RA. Trial Registration The protocol was registered under the number 507/SA/1024 at the local clinical studies database, College of Medicine, Sulaimani University.

show abstract

Section: Discussionmentioning

confidence: 99%

Azilsartan as “Add-On” Treatment with Methotrexate Improves the Disease Activity of Rheumatoid Arthritis

Mahmood

Hussain

Khan

2018

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…PPAR-γ belongs to nuclear receptor superfamily which is primarily expressed in adipose tissues ( 16 ). Previous studies have also indicated that PPAR-γ agonists reduce inflammation and myocardial injury caused by MI/R ( 17 , 18 ). Therefore, PPAR-γ is a novel treatment target used to prevent heart disease complications including heart failure ( 19 ).…”

Section: Introductionmentioning

confidence: 91%

Rosuvastatin relieves myocardial ischemia/reperfusion injury by upregulating PPAR‑γ and UCP2

2018

View full text Add to dashboard Cite

The present study aimed to investigate whether pretreatment with rosuvastatin (RS) can provide cardioprotection in a myocardial ischemia/reperfusion (MI/R) model. The protective effect of RS on myocardial oxygen-glucose deprivation/reperfusion (OGD/R) injury was also evaluated by upregulating peroxisome proliferator-activated receptor-γ (PPAR-γ). In the present study, MI/R model was established and activities of superoxide dismutase (SOD), lactate dehydrogenase (LDH), creatine kinase-muscle/brain (CK-MB), malondialdehyde (MDA), and troponin I/T were measured. The infarct size was measured using Evans blue staining and cell viability was measured by MTT assay. Reactive oxygen species (ROS) levels were assessed by flow cytometry. Caspase-9, cytochrome c (cyt c), mitochondrial uncoupling protein 2 (UCP2) and PPAR-γ expression levels were detected by reverse transcription-quantitative polymerase chain reaction and western blotting. The results indicated that RS increased SOD activity, and decreased LDH, CK-MB, MDA and troponin I/T activities. The effect of RS was reversed by atractyloside (ATR). RS inhibited myocardial infarct size, downregulated expression of caspase-9 and cyt c and upregulated expression of UCP2 and PPAR-γ by inhibiting ATR. Furthermore, the results indicated that RS promoted cardiomyocyte viability, inhibited LDH release, reduced ROS production, decreased expression of caspase-9 and cyt c, and increased expression of UCP2 and PPAR-γ following OGD/R damage. Therefore, the present study demonstrated that RS protects primary myocardial cells against OGD/R injury by regulating PPAR-γ and UCP2. RS may be a promising therapeutic agent for treatment of MI/R injury.

show abstract

“…For example, the AT1R blocker, telmisartan, improved memory impairment in a model of repeated cerebral ischemia [ 81 ], in a model of chronic cerebral hypoperfusion [ 82 ], in a model of acute and chronic stress [ 83 ], in LPS-induced neuroinflammation [ 84 ], and in uremic mice with chronic kidney disease [ 85 ]. Also, treatment of stroke prone spontaneously hypertensive rats (SP-SHR) with telmisartan improved spatial learning and reference memory [ 86 ].…”

Section: Cognitive Benefits Of Ras Modulators In Preclinical Animamentioning

confidence: 99%

Within the Brain: The Renin Angiotensin System

Jackson

Eldahshan

Fagan

et al. 2018

IJMS

255

209

View full text Add to dashboard Cite

For many years, modulators of the renin angiotensin system (RAS) have been trusted by clinicians for the control of essential hypertension. It was recently demonstrated that these modulators have other pleiotropic properties independent of their hypotensive effects, such as enhancement of cognition. Within the brain, different components of the RAS have been extensively studied in the context of neuroprotection and cognition. Interestingly, a crosstalk between the RAS and other systems such as cholinergic, dopaminergic and adrenergic systems have been demonstrated. In this review, the preclinical and clinical evidence for the impact of RAS modulators on cognitive impairment of multiple etiologies will be discussed. In addition, the expression and function of different receptor subtypes within the RAS such as: Angiotensin II type I receptor (AT1R), Angiotensin II type II receptor (AT2R), Angiotensin IV receptor (AT4R), Mas receptor (MasR), and Mas-related-G protein-coupled receptor (MrgD), on different cell types within the brain will be presented. We aim to direct the attention of the scientific community to the plethora of evidence on the importance of the RAS on cognition and to the different disease conditions in which these agents can be beneficial.

show abstract

Telmisartan mediates anti-inflammatory and not cognitive function through PPAR-γ agonism via SARM and MyD88 signaling

Cited by 28 publications

References 34 publications

Azilsartan as “Add-On” Treatment with Methotrexate Improves the Disease Activity of Rheumatoid Arthritis

Azilsartan as “Add-On” Treatment with Methotrexate Improves the Disease Activity of Rheumatoid Arthritis

Rosuvastatin relieves myocardial ischemia/reperfusion injury by upregulating PPAR‑γ and UCP2

Within the Brain: The Renin Angiotensin System

Contact Info

Product

Resources

About