Schisandra chinensis α-iso-cubebenol induces heme oxygenase-1 expression through PI3K/Akt and Nrf2 signaling and has anti-inflammatory activity in Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages

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

doi:10.1016/j.intimp.2011.07.023

Cited by 46 publications

(23 citation statements)

References 30 publications

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“…Anti-inflammatory effect of ASE involved in HO-1 expression P. gingivalis LPS induces excessive and uncontrolled release of pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) in macrophages, and thereby affects the development of periodontitis (Park et al, 2011). According to our earlier results, ASE can reduce the production of pro-inflammatory cytokines and activation of TFs in P. gingivalis LPS-stimulated RAW 264.7 cells.…”

Section: Ase Mediates Ho-1 Expression Via Pi3k/akt and Mapkmentioning

confidence: 55%

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Acanthopanax senticosus has a heme oxygenase-1 signaling-dependent effect on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages

Kim¹,

Park²,

Kim

et al. 2012

Journal of Ethnopharmacology

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Section: Ase Mediates Ho-1 Expression Via Pi3k/akt and Mapkmentioning

confidence: 55%

“…In particular, the PI3K/Akt and MAPK pathways play a central role (Park et al, 2011). We first investigated whether PI3K/Akt and MAPK (p38, extracellular signal-regulated kinase [ERK], and Janus kinase [JNK]) are phosphorylated following treatment with ASE.…”

Section: Ase Mediates Ho-1 Expression Via Pi3k/akt and Mapkmentioning

confidence: 99%

Acanthopanax senticosus has a heme oxygenase-1 signaling-dependent effect on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages

Kim¹,

Park²,

Kim

et al. 2012

Journal of Ethnopharmacology

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“…Recent studies have indicated that NQO1 possesses the capacity to enzymatically reduce NAPQI to amelioriate APAP toxicity (Moffit et al, 2007). Several studies revealed that some lignans isolated from fruits of Schisandra chinensis, including Schisandrin B, a-iso-cubebenol, and Tigloylgomisin H, exhibited anti-inflammatory activities and potential liver cancer prevention effects through activating NRF2 pathway (Lee et al, 2009;Park et al, 2011;Checker et al, 2012). However, the content of the above lignans is low in WZ tablets.…”

Section: Discussionmentioning

confidence: 99%

Wuzhi Tablet (Schisandra SphenantheraExtract) Protects against Acetaminophen-Induced Hepatotoxicity by Inhibition of CYP-Mediated Bioactivation and Regulation of NRF2-ARE and p53/p21 Pathways

et al. 2014

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Schisandra sphenanthera is widely used as a tonic and restorative in many countries to enhance the function of liver and other organs. Wuzhi tablet (WZ) is a preparation of an ethanol extract of Schisandra sphenanthera. Our previous study demonstrated that WZ exerted a protective effect toward acetaminophen (APAP)-induced hepatotoxicity. However, the molecular mechanisms of this protection remain unclear. This study aimed to determine what molecular pathways contributed to the hepatoprotective effects of WZ against APAP toxicity. Administration of WZ 3 days before APAP treatment significantly attenuated APAP hepatotoxicity in a dose-dependent manner and reduced APAP-induced JNK activation. Treatment with WZ resulted in potent inhibition of CYP2E1, CYP3A11, and CYP1A2 activities and then caused significant inhibition of the formation of the oxidized APAP metabolite N-acetyl-p-benzoquinone imine-reduced glutathione. The expression of NRF2 was increased after APAP and/or WZ treatment, whereas KEAP1 levels were decreased. The protein expression of NRF2 target genes including Gclc, Gclm, Ho-1, and Nqo1 was significantly increased by WZ treatment. Furthermore, APAP increased the levels of p53 and its downstream gene p21 to trigger cell cycle arrest and apoptosis, whereas WZ pretreatment could inhibit p53/p21 signaling to induce cell proliferation-associated proteins including cyclin D1, CDK4, PCNA, and ALR to promote hepatocyte proliferation. This study demonstrated that WZ prevented APAP-induced liver injury by inhibition of cytochrome P450-mediated APAP bioactivation, activation of the NRF2-antioxidant response element pathway to induce detoxification and antioxidation, and regulation of the p53, p21, cyclin D1, CDK4, PCNA, and ALR to facilitate liver regeneration after APAP-induced liver injury.

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“…P. gingivalis activates the PI3K/Akt signaling pathway, which is linked to cell survival (30,31) and immune responses (32). Among several known virulence factors of P. gingivalis, both LPS and fimbriae regulate immune responses through PI3K/Akt activation in monocytes/macrophages (5,(33)(34)(35) and human gingival fibroblasts (36). Gingipains have the potential to control both cell survival and apoptosis via the PI3K/Akt pathway (37).…”

mentioning

confidence: 99%

Attenuation of the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway by Porphyromonas gingivalis Gingipains RgpA, RgpB, and Kgp

Nakayama

Inoue

Naito

et al. 2015

Journal of Biological Chemistry

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Background:The significance of gingipains on the PI3K/Akt signaling pathway is poorly understood. Results: The inactivation of PI3K and Akt was induced by P. gingivalis, which was associated with gingipains. Conclusion: Gingipains are critical for suppressing the PI3K/Akt signaling pathway via extracellular proteolysis independent of P. gingivalis invasion. Significance: This study shows the first evidence that the gingipains negatively regulate the PI3K/Akt signaling pathway.

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Schisandra chinensis α-iso-cubebenol induces heme oxygenase-1 expression through PI3K/Akt and Nrf2 signaling and has anti-inflammatory activity in Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages

Cited by 46 publications

References 30 publications

Acanthopanax senticosus has a heme oxygenase-1 signaling-dependent effect on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages

Acanthopanax senticosus has a heme oxygenase-1 signaling-dependent effect on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages

Wuzhi Tablet (Schisandra SphenantheraExtract) Protects against Acetaminophen-Induced Hepatotoxicity by Inhibition of CYP-Mediated Bioactivation and Regulation of NRF2-ARE and p53/p21 Pathways

Attenuation of the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway by Porphyromonas gingivalis Gingipains RgpA, RgpB, and Kgp

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