6-Gingerol inhibits ROS and iNOS through the suppression of PKC-α and NF-κB pathways in lipopolysaccharide-stimulated mouse macrophages

Lee, Tzung-Yan; Lee, Ko-Chen; Chen, Shih‐Yuan; Chang, Hen-Hong

doi:10.1016/j.bbrc.2009.02.160

Cited by 141 publications

(97 citation statements)

References 31 publications

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“…Based on the widespread therapeutic use of ginger in Asia for the treatment of inflammatory diseases, several studies have been dedicated to the elucidation of potential anti-inflammatory mechanisms (4)(5)(6)(7). At relatively high mM concentrations, ginger constituents such as gingerols, shogaols, and diarylheptanoids have been reported to weakly inhibit components of proinflammatory signal transduction pathways in vitro, such as NF-kB, protein kinase C, and MAPKs (8,9). Moreover, ginger constituents have been shown to inhibit inducible NO synthase, cyclooxygenase (COX)-1/-2, and lipoxygenase in vitro (9)(10)(11)(12).…”

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confidence: 99%

“…At relatively high mM concentrations, ginger constituents such as gingerols, shogaols, and diarylheptanoids have been reported to weakly inhibit components of proinflammatory signal transduction pathways in vitro, such as NF-kB, protein kinase C, and MAPKs (8,9). Moreover, ginger constituents have been shown to inhibit inducible NO synthase, cyclooxygenase (COX)-1/-2, and lipoxygenase in vitro (9)(10)(11)(12). A significant inhibition of PGE 2 formation by ginger constituents has already been shown in vivo (13).…”

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confidence: 99%

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Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Nievergelt

Marazzi

Schoop³

et al. 2011

The Journal of Immunology

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The rhizome of ginger (Zingiber officinale) is employed in Asian traditional medicine to treat mild forms of rheumatoid arthritis and fever. We have profiled ginger constituents for robust effects on proinflammatory signaling and cytokine expression in a validated assay using human whole blood. Independent of the stimulus used (LPS, PMA, anti-CD28 Ab, anti-CD3 Ab, and thapsigargin), ginger constituents potently and specifically inhibited IL-1β expression in monocytes/macrophages. Both the calcium-independent phospholipase A2 (iPLA2)-triggered maturation and the cytosolic phospholipase A2 (cPLA2)-dependent secretion of IL-1β from isolated human monocytes were inhibited. In a fluorescence-coupled PLA2 assay, most major ginger phenylpropanoids directly inhibited i/cPLA2 from U937 macrophages, but not hog pancreas secretory phospholipase A2. The effects of the ginger constituents were additive and the potency comparable to the mechanism-based inhibitor bromoenol lactone for iPLA2 and methyl arachidonyl fluorophosphonate for cPLA2, with 10-gingerol/-shogaol being most effective. Furthermore, a ginger extract (2 μg/ml) and 10-shogaol (2 μM) potently inhibited the release of PGE2 and thromboxane B2 (>50%) and partially also leukotriene B4 in LPS-stimulated macrophages. Intriguingly, the total cellular arachidonic acid was increased 2- to 3-fold in U937 cells under all experimental conditions. Our data show that the concurrent inhibition of iPLA2 and prostanoid production causes an accumulation of free intracellular arachidonic acid by disrupting the phospholipid deacylation-reacylation cycle. The inhibition of i/cPLA2, the resulting attenuation of IL-1β secretion, and the simultaneous inhibition of prostanoid production by common ginger phenylpropanoids uncover a new anti-inflammatory molecular mechanism of dietary ginger that may be exploited therapeutically.

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confidence: 99%

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confidence: 99%

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Nievergelt

Marazzi

Schoop³

et al. 2011

The Journal of Immunology

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“…In our experiment, the increase of intracellular ROS formation, induced by hydrogen peroxide treatment, was prevented by 6-gingerol, suggesting that ROS are involved in the inhibitory effect of 6-gingerol on hydrogen peroxide -induced DNA damage. As a potent antioxidant, treatment of cells with 6-gingerol significantly affected the ROS production in many experiments (Lee et al, 2009). The present result suggested that the mechanisms of the preventive effects of 6-gingerol may underlie ROS scavenging.…”

Section: Discussionmentioning

confidence: 99%

6-Gingerol Attenuates Hydrogen Peroxide-induced DNA Damage in Human Umbilical Vein Endothelia Cells

Wang

Yang

Jiang

et al. 2014

FSTR

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An imbalance of oxidation and antioxidation is one of the primary causes of atherosclerosis. The use of naturalplant compounds with effects has been proven to have clinical relevance. 6-Gingerol, one of the major components of ginger, has diverse pharmacologic effects. In this study, the chemoprotective effect of 6-gingerol against hydrogen peroxide-induced DNA damage in human umbilical vein endothelia cells (HUVECs) was investigated. The comet assay was used to monitor DNA strand breaks. To further elucidate the underlying mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH). Our data revealed that 6-gingerol significantly reduced the DNA strand breaks caused by hydrogen peroxide. 6-Gingerol effectively suppressed hydrogen peroxide-induced intracellular ROS formation. The GSH depletion in HUVECs was also attenuated by 6-gingerol pretreatment. Moreover, lysosomal membrane stability was destroyed and mitochondrial membrane potential decreased after treated by hydrogen peroxide. Those effects can be protected by 6-gingerol. These firmly indicate 6-gingerol has a strong protective ability against the DNA damage caused by hydrogen peroxide in HUVECs, and the mechanism may relate to the antioxidant activity. Our data suggest 6-gingerol may be beneficial in the prevention of atherosclerosis.

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“…43) It was reported that intracellular ROS can modulates the expression of proin- flammatory genes via activation of diverse downstream signaling molecules including NF-κB, MAPK and protein kinase C. 23,44,45) In the present study, we also demonstrated that ROS inhibitor suppressed activation of NF-kB and ERK and subsequent NO production in activated microglia cells, suggesting that inhibition of ROS/NF-κB and ROS/ERK pathways are, at least in partly involved in anti-inflammatory mechanisms of OGA.…”

Section: )mentioning

confidence: 99%

Antiinflammatory Effects of Orientin-2″-<i>O</i>-Galactopyranoside on Lipopolysaccharide-Stimulated Microglia

Zhou

Gan

Hao

et al. 2014

Biological & Pharmaceutical Bulletin

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6-Gingerol inhibits ROS and iNOS through the suppression of PKC-α and NF-κB pathways in lipopolysaccharide-stimulated mouse macrophages

Cited by 141 publications

References 31 publications

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2

6-Gingerol Attenuates Hydrogen Peroxide-induced DNA Damage in Human Umbilical Vein Endothelia Cells

Antiinflammatory Effects of Orientin-2″-<i>O</i>-Galactopyranoside on Lipopolysaccharide-Stimulated Microglia

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