Vitamin E isoform γ-tocotrienol protects against emphysema in cigarette smoke-induced COPD

Peh, Hong Yong; Tan, W.S. Daniel; Chan, Taizan; Pow, Chen Wei; Foster, Paul S.; Wong, W.S. Fred

doi:10.1016/j.freeradbiomed.2017.06.023

Cited by 38 publications

(40 citation statements)

References 63 publications

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“…Mice were randomly divided into six groups of eight mice per group (Figure 4b). The sample size was determined based on our previous study (Peh et al, 2017). Mice were placed in a ventilated chamber filled with 4% CS delivered using peristaltic pumps (Masterflex, Cole‐Parmer Instrument Co., Niles, IL) at a constant rate of 1 L˙min −1 as described (Guan et al, 2013).…”

Section: Methodsmentioning

confidence: 99%

“…Mice were placed in a ventilated chamber filled with 4% CS delivered using peristaltic pumps (Masterflex, Cole‐Parmer Instrument Co., Niles, IL) at a constant rate of 1 L˙min −1 as described (Guan et al, 2013). Mice were exposed to three sticks of 3R4F research cigarettes thrice per day for 2 weeks (five consecutive days per week) to induce lung injury (Peh et al, 2017). Mice in the sham air group were simultaneously placed in another ventilated chamber but exposed to fresh air.…”

Section: Methodsmentioning

confidence: 99%

“…Ice‐cold PBS (0.5 ml × 3) was instilled into the lungs, and BAL fluid was collected. BAL fluid total and differential cell counts (Figure 4b) were determined as described in a blinded manner (Bao et al, 2009; Peh et al, 2017). BAL fluid supernatants were analysed for cytokines including TNF‐α (BD Biosciences), IL‐1β (BD Biosciences), IL‐17A (R&D Systems, Inc., Minneapolis, MN), IL‐27 p28 (R&D Systems, Inc.), KC (R&D Systems, Inc.) and IL‐36γ (MyBioSource, Inc., San Diego, CA), and oxidative damage markers 8‐isoprostane and 8‐OHdG (Cayman Chemical, Ann Arbor, MI), using sandwich elisa .…”

Section: Methodsmentioning

confidence: 99%

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Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease

Liao

Lim

Tan

et al. 2020

British J Pharmacology

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Background and Purpose Corticosteroid resistance poses a major barrier to an effective anti‐inflammatory therapy for chronic obstructive pulmonary disease (COPD). The present study aimed to investigate potential corticosteroid re‐sensitization actions of andrographolide, a bioactive molecule from the herb Andrographis paniculata, in COPD models, particularly in peripheral blood mononuclear cells (PBMCs) from COPD patients. Experimental Approach Corticosteroid sensitivity in PBMCs collected from COPD patients, or in human monocytic U937 cells exposed to cigarette smoke extract (CSE), was determined by measuring LPS‐induced IL‐8 production, in the presence and absence of andrographolide. The mechanisms of corticosteroid re‐sensitization action of andrographolide were evaluated in a mouse cigarette smoke (CS)‐induced acute lung injury model. Key Results Impaired inhibition of IL‐8 production by dexamethasone was detected in PBMCs from COPD patients and in CSE‐exposed U937 cells, together with reduced levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and histone deacetylase‐2 (HDAC2). In both PBMCs and CSE‐exposed U937 cells, andrographolide restored dexamethasone inhibition of IL‐8 production, accompanied by the up‐regulation of Nrf2 and HDAC2 levels. In the U937 cells, andrographolide was able to block CSE‐induced Akt and reduce the level of c‐Jun. Besides, andrographolide also augmented dexamethasone actions on lowering total and neutrophil counts, cytokine levels, and oxidative damage markers in bronchoalveolar lavage fluid from CS‐exposed mice. Conclusion and Implications We report here for the first time a novel corticosteroid re‐sensitization property of andrographolide in human PBMCs and provide mechanistic evidence to support clinical evaluation of andrographolide in reversing steroid resistance in COPD.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease

Liao

Lim

Tan

et al. 2020

British J Pharmacology

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“…(C) A 2-week CS-induced acute lung injury mouse model based on our previous report. 41 Mice were given six consecutive daily intratracheal doses of RPS3 siRNA to silence the RPS3 gene in the lungs. (D) Gene silencing effects of RPS3 siRNA (5 nmol) in CS-exposed mouse lungs (n = 6 mice per group).…”

Section: Resultsmentioning

confidence: 99%

“…Quantitative analyses of epithelium thickness were performed blinded as described. 41 To visualize the lung distribution of RPS3-siRNA, mice were exposed to CS for 5 consecutive days, followed by intratracheal administration of 5 nmol Cy5-labeled RPS3 siRNA (red) (Thermo Scientific) on day 6. Mice were sacrificed 1 hr and 12 hr later, and lung sections were probed with anti-CD68 primary antibody followed by Alexa Fluor 488 fluorescent dye-conjugated secondary antibody (green) (Abcam).…”

Section: Methodsmentioning

confidence: 99%

Ribosomal Protein S3 Gene Silencing Protects Against Cigarette Smoke-Induced Acute Lung Injury

Dong

Liao

Peh

et al. 2018

Molecular Therapy - Nucleic Acids

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Chronic obstructive pulmonary disease (COPD) is estimated to be the third leading cause of death by 2030. Transcription factor NF-κB may play a critical role in COPD pathogenesis. Ribosomal protein S3 (RPS3), a 40S ribosomal protein essential for executing protein translation, has recently been found to interact with the NF-κB p65 subunit and promote p65 DNA-binding activity. We sought to study whether RPS3 gene silencing could protect against cigarette-smoke (CS)-induced acute lung injury in a mouse model. Effects of an intratracheal RPS3 siRNA in CS-induced lung injury were determined by measuring bronchoalveolar lavage (BAL) fluid cell counts, levels of inflammatory and oxidative damage markers, and NF-κB translocation. Lung RPS3 level was found to be upregulated for the first time with CS exposure, and RPS3 siRNA blocked CS-induced neutrophil counts in BAL fluid. RPS3 siRNA suppressed CS-induced lung inflammatory mediator and oxidative damage marker levels, as well as nuclear p65 accumulation and transcriptional activation. RPS3 siRNA was able to disrupt CS extract (CSE)-induced NF-κB activation in an NF-κB reporter gene assay. We report for the first time that RPS3 gene silencing ameliorated CS-induced acute lung injury, probably via interruption of the NF-κB activity, postulating that RPS3 is a novel therapeutic target for COPD.

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Revisiting the therapeutic potential of tocotrienol

2022

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The therapeutic potential of the tocotrienol group stems from its nutraceutical properties as a dietary supplement. It is largely considered to be safe when consumed at low doses for attenuating pathophysiology as shown by animal models, in vitro assays, and ongoing human trials. Medical researchers and the allied sciences have experimented with tocotrienols for many decades, but its therapeutic potential was limited to adjuvant or concurrent treatment regimens. Recent studies have focused on targeted drug delivery by enhancing the bioavailability through carriers, self‐sustained emulsions, nanoparticles, and ethosomes. Epigenetic modulation and computer remodeling are other means that will help increase chemosensitivity. This review will focus on the systemic intracellular anti‐cancer, antioxidant, and anti‐inflammatory mechanisms that are stimulated and/or regulated by tocotrienols while highlighting its potent therapeutic properties in a diverse group of clinical diseases.

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Vitamin E isoform γ-tocotrienol protects against emphysema in cigarette smoke-induced COPD

Cited by 38 publications

References 63 publications

Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease

Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease

Ribosomal Protein S3 Gene Silencing Protects Against Cigarette Smoke-Induced Acute Lung Injury

Revisiting the therapeutic potential of tocotrienol

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