PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A

LU, YU; Miyamoto, Tsutomu; Takeuchi, Hiroyasu; Tsunoda, Fumiyoshi; Tanaka, Naoki; Shiozawa, Tanri

doi:10.32604/or.2023.026067

Cited by 3 publications

(1 citation statement)

References 70 publications

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“…Compared with other angiotensin receptor antagonist drugs, Irbesartan has the highest bioavailability with a plasma half-life of one hour, second only to telmisartan, which is a long-acting antihypertensive drug that can be taken daily [ 12 ]. Recently, several studies have revealed the anti-OS effects of Irbesartan in acute liver injury [ 13 ], renal tissues of type 2 diabetic rats [ 14 ], and angiotensin II treated endothelial cells [ 15 ]. However, the effects of Irbesartan on cognitive functions are less reported.…”

Section: Introductionmentioning

confidence: 99%

The protective effects of Irbesartan in cognitive impairment in hypertension

Hao,

He,

Yuan

et al. 2024

Aging

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Vascular cognitive impairment (VCI) is claimed as the second most common type of dementia after Alzheimer’s disease (AD), in which hypertension is a critical inducer. Currently, hypertension-induced cognitive impairment lacks clinical treatments. Irbesartan is a long-acting angiotensin receptor antagonist with promising antihypertensive properties. Our research will focus on the potential function of Irbesartan on hypertension-induced cognitive impairment. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were orally dosed with normal saline or 20 mg/kg/day Irbesartan for 14 consecutive days, with 4 groups divided shown as below: WKY, Irbesartan, SHR, SHR+ Irbesartan. Firstly, the markedly increased systolic blood pressure observed in SHR rats was signally repressed by Irbesartan on Day 7 and 14 post-dosing. Moreover, notably decreased time of exploring the novel object in the object recognition task (ORT) test, elevated escape latency, and reduced time in the target quadrant in the Morris water maze (MWM) test were observed in SHR rats, which were prominently reversed by Irbesartan. Furthermore, the declined superoxide dismutase (SOD) activity, elevated malondialdehyde (MDA) level, increased cyclin-dependent kinase-5 (CDK5) activity, and enhanced protein level of p35/p25, p-Tau (pSer 214 )/Tau46, and brain-derived neurotrophic factor (BDNF) were memorably rescued by Irbesartan. Lastly, the activity of cAMP/cAMP response element binding protein (CREB) signaling in the hippocampus of SHR rats was markedly repressed, accompanied by an upregulation of phosphodiesterase 4B (PDE4B), which was observably rescued by Irbesartan. Collectively, Irbesartan protected against the hypertension-induced cognitive impairment in SHR rats by regulating the cAMP/CREB signaling.

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Section: Introductionmentioning

confidence: 99%

The protective effects of Irbesartan in cognitive impairment in hypertension

Hao,

He,

Yuan

et al. 2024

Aging

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Emerging methods and techniques for cancer biomarker discovery

Dakal,

Dhakar,

Beura

et al. 2024

Pathology - Research and Practice

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Interaction of telmisartan and related sartans with the programmed cell death-ligand 1 (PD-L1) protein dimer: a molecular docking analysis

Vergoten,

Bailly

2023

Futur J Pharm Sci

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BackgroundTelmisartan (TLT) is a prototypic angiotensin receptor blocker largely used to treat hypertension worldwide. In addition to its cardioprotective effects, TLT presents pleiotropic activities and notably displays noticeable anti-inflammatory and antitumor effects. The repression of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint may be implicated antitumor action of TLT, as it is the case with many other compounds equipped with a biphenyl moiety. We have used molecular modeling to compare the interaction of TLT and derivatives with the PD-L1 dimer protein.ResultsTwo molecules, TLT-dimer and TLT-acylglucuronide, were found to form more stable complexes with PD-L1 than TLT itself. In parallel, the docking analysis performed with a series of 12 sartans led to the identification of Olmesartan as a potential PD-L1 binder. The stacked biphenyl unit of Olmesartan positions the molecule along the groove delimited by the two protein monomers. The flanking tetrazole and imidazole moieties, on each side of the biphenyl unit of Olmesartan, contribute favorably to the protein interaction via specific hydrogen bonding interactions.ConclusionsThe computational analysis suggests a possible binding of Olmesartan to PD-L1 dimer and thus offers novel perspectives for the design of small molecules capable of interrupting the PD-1/PD-L1 immune checkpoint. Experimental studies are warranted to validate the hypothesis.Graphical abstract

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PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A

Cited by 3 publications

References 70 publications

The protective effects of Irbesartan in cognitive impairment in hypertension

The protective effects of Irbesartan in cognitive impairment in hypertension

Emerging methods and techniques for cancer biomarker discovery

Interaction of telmisartan and related sartans with the programmed cell death-ligand 1 (PD-L1) protein dimer: a molecular docking analysis

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