Protective effects of resveratrol and SR1001 on hypoxia-induced pulmonary hypertension in rats

Li, Cheng; Peng, Ganlin; Jiang, Long; Xiao, Pan; Zeng, Xiaoyuan; Yang, Hongzhong

doi:10.1080/10641963.2020.1714643

Cited by 10 publications

(7 citation statements)

References 36 publications

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“…Further, RORα inhibitor: SR1001, presented a therapeutic effect in hypoxia-induced pulmonary hypertension (45), and the expression of RORα was up-regulated after CS exposure as well as in COPD/emphysema patients compared to healthy control (46).…”

Section: Discussionmentioning

confidence: 97%

“…Further, RORα inhibitor, SR1001, presented a therapeutic effect in hypoxia-induced pulmonary hypertension ( 45 ), and the expression of RORα was upregulated after CS exposure as well as in patients with COPD/emphysema compared with healthy controls ( 46 ). The casein kinases (CKs) are required in the phosphorylation of PERs, which are also important in circadian rhythm regulation ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular clock REV-ERBα regulates cigarette smoke–induced pulmonary inflammation and epithelial-mesenchymal transition

Wang¹,

Sundar²,

Lucas³

et al. 2021

JCI Insight

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Cigarette smoke (CS) is the main etiological factor in the pathogenesis of emphysema/Chronic Obstructive Pulmonary Disease (COPD), which is associated with abnormal epithelial-mesenchymal-transition (EMT). Previously, we have shown an association between circadian rhythms and CS-induced lung inflammation, and nuclearheme-receptor α (REV-ERBα) acting as an anti-inflammatory target in both pulmonary epithelial cells and fibroblasts. We hypothesized that molecular clock REV-ERBα plays an important role in CS-induced circadian dysfunction and EMT alteration. C57BL/6J wild type (WT) and REV-ERBα heterozygous (Het) and knockout (KO) mice were exposed to CS for 30 days (sub-chronic) and 4 months (chronic), and WT mice were exposed to CS for 10 days with or without REV-ERBα agonist (SR9009) administration.Sub-chronic/chronic CS exposure caused circadian disruption and dysregulated EMT in the lungs of WT and REV-ERBα KO mice, both circadian and EMT dysregulation were exaggerated in REV-ERBα KO condition. REV-ERBα agonist, SR9009 treatment reduced acute CS-induced inflammatory response and abnormal EMT in the lungs.Further, REV-ERBα agonist (GSK4112) inhibited TGFβ/CS-induced fibroblast differentiation in human fetal lung fibroblast 1 (HFL-1).Thus, CS-induced circadian gene alterations and EMT activation are mediated through a Rev-erbα-dependent mechanism, which suggests activation of REV-ERBα as a novel therapeutic approach for smoking-induced chronic inflammatory lung diseases.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Molecular clock REV-ERBα regulates cigarette smoke–induced pulmonary inflammation and epithelial-mesenchymal transition

Wang¹,

Sundar²,

Lucas³

et al. 2021

JCI Insight

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“…Importantly, the multiple actions attributed to resveratrol on the systemic and cardiac vasculature may also target the mediators of PAH ( Chicoine et al, 2009 ). In recent studies, the remarkable efficacy of resveratrol in preventing and treating the PAH has been demonstrated in experimental animal models of PAH induced by hypoxia and MCT ( Csiszar et al, 2009 ; Yang et al, 2010 ; Paffett et al, 2012 ; Chen et al, 2014 ; Wilson et al, 2016 ; Xu et al, 2016 ; Guan et al, 2017 ; Yu et al, 2017 ; Li C. et al, 2020 ; Chen et al, 2020d ; Liu YY. et al, 2020 ; Vazquez-Garza et al, 2020 ).…”

Section: Preclinical Studies Of Traditional Herbal Medicine For Pulmonary Arterial Hypertension Treatmentmentioning

confidence: 99%

“…et al, 2020 ; Vazquez-Garza et al, 2020 ). In the hypoxia-induced PAH model, resveratrol has protective effects mainly through preventing PASMC arginase II induction and proliferation that is mediated by the PI3K-Akt signaling pathway ( Chen et al, 2014 ; Guan et al, 2017 ), enhancing the activation of SIRT1 ( Yu et al, 2017 ), inhibiting the differentiation of Th17 cells ( Li C. et al, 2020 ), suppressing HIF1α expression, and upregulating the Nrf-2/Trx-1 signaling pathway ( Xu et al, 2016 ). In MCT-induced PAH, resveratrol also significantly alleviated the proliferation in PASMCs and vascular remodeling of PAH by improving swollen mitochondrial and cardiomyocyte apoptosis in RV ( Yang et al, 2010 ), inhibiting inflammation and oxidative stress ( Csiszar et al, 2009 ), promoting decreased atrogin-1 levels induced by MCT ( Paffett et al, 2012 ), and targeting NR4A3/cyclin D1 pathway regulated by miR-638 ( Liu YY.…”

Section: Preclinical Studies Of Traditional Herbal Medicine For Pulmonary Arterial Hypertension Treatmentmentioning

confidence: 99%

Traditional Herbal Medicine Discovery for the Treatment and Prevention of Pulmonary Arterial Hypertension

Xue

Zhou

et al. 2021

Front. Pharmacol.

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Pulmonary arterial hypertension (PAH) is characterized by pulmonary artery remodeling that may subsequently culminate in right heart failure and premature death. Although there are currently both non-pharmacological (lung transplantation, etc.) and pharmacological (Sildenafil, Bosentan, and new oral drugs on trial) therapies available, PAH remains a serious and fatal pulmonary disease. As a unique medical treatment, traditional herbal medicine (THM) treatment has gradually exerted its advantages in treating PAH worldwide through a multi-level and multi-target approach. Additionally, the potential mechanisms of THM were deciphered, including suppression of proliferation and apoptosis of pulmonary artery smooth muscle cells, controlling the processes of inflammation and oxidative stress, and regulating vasoconstriction and ion channels. In this review, the effects and mechanisms of the frequently studied compound THM, single herbal preparations, and multiple active components from THM are comprehensively summarized, as well as their related mechanisms on several classical preclinical PAH models. It is worth mentioning that sodium tanshinone IIA sulfonate sodium and tetramethylpyrazine are under clinical trials and are considered the most promoting medicines for PAH treatment. Last, reverse pharmacology, a strategy to discover THM or THM-derived components, has also been proposed here for PAH. This review discusses the current state of THM, their working mechanisms against PAH, and prospects of reverse pharmacology, which are expected to facilitate the natural anti-PAH medicine discovery and development and its bench-to-bedside transformation.

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“… 13 In terms of effects on inflammation, Resveratrol is also reported to inhibit PE-induced MCP-1 expression and MAPK pathway and reduced mean pulmonary artery pressure (mPAP) in rats with PE. 14 Moreover, Resveratrol inhibits the RhoA-ROCK signaling pathway, suppresses Th17 cell differentiation, and improves PH 15 .…”

Section: Introductionmentioning

confidence: 99%

Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy

Liu

Zhou

2022

Clinics

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Protective effects of resveratrol and SR1001 on hypoxia-induced pulmonary hypertension in rats

Cited by 10 publications

References 36 publications

Molecular clock REV-ERBα regulates cigarette smoke–induced pulmonary inflammation and epithelial-mesenchymal transition

Molecular clock REV-ERBα regulates cigarette smoke–induced pulmonary inflammation and epithelial-mesenchymal transition

Traditional Herbal Medicine Discovery for the Treatment and Prevention of Pulmonary Arterial Hypertension

Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy

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