The Protective Effects of Ramelteon Against Isoflurane-Induced Insults and Inflammatory Response in Brain Microvascular Endothelial Cells

Wang, Tao; Li, Zhen; Xia, Shuyun; Xu, Zhixin; Chen, Xiaofang; Sun, Hu

doi:10.1007/s12640-020-00309-7

Cited by 12 publications

(12 citation statements)

References 32 publications

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“…As a synthetic melatonin receptor agonist with an affinity for melatonin type 1 and 2 receptors, ramelteon has been reported to possess anti-inflammatory and antioxidant properties [ 8 , 12 ]. Additionally, ramelteon exerts an ameliorative effect on ventilator-induced lung injury in a mouse model [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…HPMECs were obtained from ScienCell Research Laboratories, Inc. and maintained in DMEM (Gibco; Thermo Fisher Scientific, Inc.) supplemented with 10% fetal bovine serum (FBS; Gibco; Thermo Fisher Scientific, Inc.) at 37 ° C in a 5% CO 2 atmosphere. HPMECs were treated with ramelteon at 10, 25, 50 and 100 nM concentrations for 12 h or 24 h [ 8 ]. For LPS stimulation, cells were induced with 100 ng/ml LPS (Sigma-Aldrich; Merck KGaA) for 24 h. HPMECs were then treated with ramelteon at 10, 25 and 50 nM concentrations for 24 h to perform the subsequent experiments.…”

Section: Methodsmentioning

confidence: 99%

“…Ramelteon is a synthetic melatonin receptor agonist with an affinity for melatonin type 1 and 2 receptors [ 8 ]. These receptors are considered to be involved in the maintenance of circadian rhythms that regulate the normal sleep-wake cycle [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…In terms of antioxidant effects, ramelteon has been found to improve liver injury caused by ischemic shock through the inhibition of oxidative stress [ 13 ]. Through antioxidant effects, ramelteon improves cardiovascular damage and reduces angiotensin II–induced vascular endothelial cell injury [ 8 , 14 , 15 ]. With regard to anti-inflammatory effects, ramelteon improves brain microvascular endothelial cell injury by inhibiting inflammation, reducing the LPS-induced increase in endothelial cell dysfunction within the blood-brain barrier [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Ramelteon protects against human pulmonary microvascular endothelial cell injury induced by lipopolysaccharide (LPS) via activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway

Yang

Zhang

et al. 2022

Bioengineered

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Acute lung injury (ALI) is classified as a moderate or mild acute respiratory distress syndrome and is a prominent cause of morbidity and mortality among the critically ill population. Ramelteon is a melatonin receptor agonist with anti-inflammatory and antioxidant effects. The current study investigated the role of ramelteon in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMECs) and its potential regulatory mechanisms. A CCK-8 assay was used to examine the effect of ramelteon on the viability of LPS-induced HPMECs, HPMECs treated with ML385 [a Nrf2 inhibitor] and HPMECs treated with SnPP [a HO-1 inhibitor]. The Nrf2/HO-1 signaling pathway was additionally assessed by performing Western blotting. The levels of oxidative stress and inflammatory cytokines in HPMECs were detected using kits and reverse transcription-quantitative PCR. Cell apoptosis was evaluated via TUNEL staining. Furthermore, cell permeability was assessed using a FITC-dextran fluorescent probe, ZO-1 and occludin expression was determined via Western blotting. The results demonstrated that ramelteon elevated HPMEC viability after LPS stimulation. Additionally, ramelteon markedly reduced LPS-induced oxidative stress, inflammation and apoptosis. Moreover, cell permeability was notably decreased in ramelteon-treated groups and was accompanied by upregulated ZO-1 and occludin expression. Ramelteon treatment also activated the Nrf2/HO-1 signaling pathway in LPS-induced HPMECs. Furthermore, the addition of ML385 or SnPP reversed the protective effects of ramelteon on LPS-induced oxidative stress, inflammation, apoptosis and cell dysfunction in HPMECs. Collectively, the results suggested that ramelteon alleviated LPS-induced HPMEC damage by activating the Nrf2/HO-1 signaling pathway, making it an effective treatment for ALI.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ramelteon protects against human pulmonary microvascular endothelial cell injury induced by lipopolysaccharide (LPS) via activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway

Yang

Zhang

et al. 2022

Bioengineered

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“…As the first agonist of melatonin receptor, Ramelteon showed promising therapeutic effects against acute insomnia and chronic insomnia during clinical treatments [13,14]. Recently, protective effects of Ramelteon against damage induced by oxidative stress have been reported [15,16]. However, whether Ramelteon exerts any protective benefits in PD is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Ramelteon ameliorated 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in neuronal cells in a mitochondrial-dependent pathway

Zhang

Liu

et al. 2021

Bioengineered

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Parkinson's disease (PD) is a common neurodegenerative disease with global health and economic impact. 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and oxidative stress are reported to participate in the pathological mechanism of PD. Ramelteon is a novel oral hypnotic agent that has recently been reported to display neuronal protective effects. However, it is unknown whether Ramelteon possesses a beneficial effect in PD. In this study, we aimed to examine the potential function of Ramelteon in MPP+-challenged neurons. We found that Ramelteon rescued the cell viability reduced by MPP+-stimulation. Further, oxidative stress in MPP+-challenged SH-SY5Y cells was mitigated by Ramelteon as verified by the upregulated levels of mitochondrial reactive oxygen species (ROS) and protein carboxyl, and the upregulation of NADPH oxidase 4 (NOX-4). Furthermore, the declined mitochondrial membrane potential ( Δ Ψ m ) caused by MPP+ was reversed by Ramelteon. Importantly, Ramelteon attenuated MPP+-induced apoptosis, accompanied by a decreased ratio of Bax/Bcl-2, inhibition of cytochrome C release, and downregulation of cleaved caspase-3. For the first time, we conclude that Ramelteon might ameliorate MPP+-induced neurotoxicity in neuronal cells in a mitochondrial-dependent pathway.

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Ameliorative effects of topical ramelteon on imiquimod-induced psoriasiform inflammation in mice

Khafaji,

Al-Zubaidy,

Farhood

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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The Protective Effects of Ramelteon Against Isoflurane-Induced Insults and Inflammatory Response in Brain Microvascular Endothelial Cells

Cited by 12 publications

References 32 publications

Ramelteon protects against human pulmonary microvascular endothelial cell injury induced by lipopolysaccharide (LPS) via activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway

Ramelteon protects against human pulmonary microvascular endothelial cell injury induced by lipopolysaccharide (LPS) via activating nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway

Ramelteon ameliorated 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in neuronal cells in a mitochondrial-dependent pathway

Ameliorative effects of topical ramelteon on imiquimod-induced psoriasiform inflammation in mice

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