Upregulation of heme oxygenase-1 via PI3K/Akt and Nrf-2 signaling pathways mediates the anti-inflammatory activity of Schisandrin in Porphyromonas gingivalis LPS-stimulated macrophages

Park, Sun Young; Park, Da Jung; Kim, Young Hun; Kim, Young‐Hee; Kim, Sun Gun; Shon, Kwang Jae; Choi, Yang-Ho; Lee, Sang-Joon

doi:10.1016/j.imlet.2011.05.007

Cited by 68 publications

(32 citation statements)

References 30 publications

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“…However, these alternations were completely reversed after supplement with high dose of triterpenoid from Schisandra chinensis. Our findings were consistent with a previous report in which the authors claimed that a novel a-iso-cubebenol isolated from dried fruits of Schisandra chinensis up-regulated the expression of HO-1 at both mRNA and protein levels [41]. Therefore, the induction of HO-1 by triterpenoid administration may contribute to its beneficial effects on alcohol-induced liver injury.…”

Section: Discussionsupporting

confidence: 93%

Effects of Triterpenoid From Schisandra chinensis on Oxidative Stress in Alcohol-Induced Liver Injury in Rats

Zhu

et al. 2014

Cell Biochem Biophys

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Alcohol-induced oxidative stress plays a crucial role in the pathological development of alcoholic liver disease. The aim of this study was to investigate the effects of triterpenoid from Schisandra chinensis on oxidative stress in alcohol-induced liver injury in rats. We found that the administration of triterpenoid attenuated alcohol-induced oxidative stress in multiple organs including liver. Moreover, the impaired liver function and histological changes resulted from alcohol consumption was improved by triterpenoid treatment. Finally, we found that pretreatment with triterpenoid from Schisandra chinensis to alcohol-fed rats increased the expression level of haem oxygenase-1 (HO-1) while inhibited the induction of cytochrome P-450 2E1 (CYP2E1) in liver microsomes. Further assays revealed that the microsomal activity of HO-1 was accordingly induced whereas CYP2E1 was suppressed in rats received triterpenoid intervention. Our findings suggest that triterpenoid from Schisandra chinensis may protect against alcohol-induced liver injury through ameliorating oxidative stress in rats.

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Section: Discussionsupporting

confidence: 93%

Effects of Triterpenoid From Schisandra chinensis on Oxidative Stress in Alcohol-Induced Liver Injury in Rats

Zhu

et al. 2014

Cell Biochem Biophys

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“…An et al 29 reported the beneficial effect of HO-1 to ventilator-induced lung injury. Park et al 30 found that the overexpression of HO-1 mediated the antiinflammatory response through Nrf-2, PI3K/Akt, and ERK activation. During those downstream products of HO-1, CO has been demonstrated to modulate the inflammatory pathway in a variety of experimental models, reducing the production of inflammatory cytokines, while increasing the production of antiinflammatory cytokines through interaction with the MAPK pathways.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice

Xiong¹,

Lin²,

Wang³

2013

IJN

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Background: Mechanical ventilation has been documented to paradoxically cause lung injury. As a commonly used volatile anesthetic, sevoflurane has been proven to possess antiinflammatory and antioxidative properties. This study aims to investigate the protective effects of sevoflurane on inflammation and ventilator-induced lung injury during mechanical ventilation in healthy mice. Methods: The adult healthy mice were divided into four groups, each consisting of ten subjects: mice in group Con-L VT and group Sev-L VT were ventilated with tidal volumes of 8 mL/kg for 4 hours, while those in group Con-H VT and group Sev-H VT were ventilated with tidal volumes of 16 mL/kg instead. Control mice (group Con-L VT and Con-H VT ) were subjected to fresh air, while sevoflurane-treated mice (groups Sev-L VT and Sev-H VT ) were subjected to air mixed with 1 vol% sevoflurane. After 4 hours of ventilation, the bronchoalveolar lavage (BAL) fluid was collected and analyzed for the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10. Lung homogenates were harvested to detect the expression of nuclear factorkappa B (NF-κB) and heme oxygenase (HO)-1 mRNA by reverse transcription-polymerase chain reaction method. Lung damage was evaluated using the modified Ventilator-Induced Lung Injury histological scoring system. Results: Compared to group Con-L VT , the levels of TNF-α, IL-1β, IL-6, and IL-10 in BAL fluid, mRNA expressions of NF-κB and HO-1 in lung tissue, and lung injury scores were significantly increased in group Con-H VT ; compared to group Con-H VT , group Sev-H VT BAL samples showed decreased levels of TNF-α, IL-1β, and IL-6; they also showed increased levels of IL-10, the downregulation of NF-κB mRNA, and HO-1 mRNA upregulation; the lung injury scores were significantly lower in group Sev-H VT than group Con-H VT . Conclusion: Mechanical ventilation with high tidal volume might lead to lung injury, which could be significantly, but not completely, attenuated by sevoflurane inhalation by inhibiting the NF-κB-mediated proinflammatory cytokine generation and upregulating HO-1 expression.

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“…In the inflamed state, NF-jB and Nrf2 activation is required for HO-1 gene or protein expression and is regulated by kinases of the MAPK and PI3K/Akt signaling pathways. 31,32 SCF4 induced the nuclear translocation of p65 (a subunit of the NF-jB transcription complex) and Nrf2 in the presence of inflammatory stimuli. Taken together, these results indicate that signaling mechanisms related to NF-jB and Nrf2 phosphorylation via p38 MAPK and Akt activation are responsible for SCF4-induced HO-1 up-regulation.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory effects of Saururus chinensis aerial parts in murine macrophages via induction of heme oxygenase-1

Xue

Kim

Jeong

et al. 2015

Exp Biol Med (Maywood)

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Saururus chinensis (Lour.) Baill. is a perennial plant distributed throughout Northeast Asia and its roots have been widely used as a traditional medicine for hepatitis, asthma, pneumonia, and gonorrhea. This study was designed to investigate the anti-inflammatory activity of an extract of S. chinensis of the aerial parts (rather than the root), and the signaling pathway responsible for this effect in lipopolysaccharide-stimulated murine macrophages. The subfraction 4 (SCF4) from the n-hexane layer of the ethanol extract of the aerial parts of S. chinensis exhibited the highest nitrite-inhibitory activity. SCF4 significantly inhibited the production of nitrite and the expression of pro-inflammatory mediators via heme oxygenase-1 upregulation. SCF4 caused significant phosphorylation of p38 MAPK and Akt, which subsequently induced the nuclear translocation of p-p65 nuclear factor-jB and Nrf2. SCF4 also suppressed the phosphorylation of signal transducers and activators of transcription 1 (p-STAT1). The heme oxygenase-1 inhibitor zinc protoporphyrin attenuated the inhibitory effect of SCF4 on lipopolysaccharide-stimulated nitrite production and expression of inflammatory mediators, tumor necrosis factor alpha, and p-STAT1. We identified sauchinone as the active compound in S. chinensis extract and SCF4. Sauchinone was shown to significantly inhibit nitrite production and inflammatory mediators expression via heme oxygenase-1 upregulation. These results suggest that S. chinensis extract, SCF4, and its active compound, sauchinone, could be used as an anti-inflammatory agent.

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Upregulation of heme oxygenase-1 via PI3K/Akt and Nrf-2 signaling pathways mediates the anti-inflammatory activity of Schisandrin in Porphyromonas gingivalis LPS-stimulated macrophages

Cited by 68 publications

References 30 publications

Effects of Triterpenoid From Schisandra chinensis on Oxidative Stress in Alcohol-Induced Liver Injury in Rats

Effects of Triterpenoid From Schisandra chinensis on Oxidative Stress in Alcohol-Induced Liver Injury in Rats

Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in mice

Anti-inflammatory effects of Saururus chinensis aerial parts in murine macrophages via induction of heme oxygenase-1

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