Vitamin K Suppresses Lipopolysaccharide-Induced Inflammation in the Rat

Ohsaki, Yusuke; Shirakawa, Hitoshi; Hiwatashi, Koichi; Furukawa, Yuji; Mizutani, Takeo; Komai, Michio

doi:10.1271/bbb.70.926

Cited by 166 publications

(144 citation statements)

References 21 publications

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“…In the vitamin K supplemented animal experiments, there was a suppression of the hepatic mRNA levels of the inflammation response protein macrophage migration inhibitory factor (MIF), compared to animals fed a vitamin K-deficient diet. This study also found that supplementation with vitamin K1 also caused a rise in hepatic tissue menaquinone-4 levels [57]. Extension of these in vivo findings in the two cell lines, THP-1 and RAW264.7, demonstrated that the suppression of LPS-stimulated IL-6 mRNA by vitamin K2 was consistent with inhibition of NF-κB activity via the restricted phosphorylation of IKK kinases [58].…”

Section: Nf-κb and Vitamin Ksupporting

confidence: 65%

“…These include studies using germ-free rats, THP-1 human monocyte-like cells and murine RAW264.7 macrophage-like cells [57,58] and have noted a significant reduction in the LPS-stimulated cellular IL-6 mRNA levels. In the vitamin K supplemented animal experiments, there was a suppression of the hepatic mRNA levels of the inflammation response protein macrophage migration inhibitory factor (MIF), compared to animals fed a vitamin K-deficient diet.…”

Section: Nf-κb and Vitamin Kmentioning

confidence: 99%

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Anti-Inflammatory Actions of Vitamin K

Hodges¹,

Pitsillides²,

Ytrebø³

et al. 2017

Vitamin K2 - Vital for Health and Wellbeing

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Naphthoquinone compounds have received attention for their ability to regulate diseases from bacterial and parasite infections through to chronic human diseases. Inflammation is widely considered to be at the root of many chronic diseases. The reports of anti-inflammatory activity of naphthoquinones, including vitamin K1 (phylloquinone) and vitamin K2s (menaquinones), are of interest due to their very low toxicity. Most of the evidence for the anti-inflammatory mechanisms of vitamin K suggests a role in the inhibition of the cell signalling complex nuclear factor kappa-B (NF-κB).

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Section: Nf-κb and Vitamin Ksupporting

confidence: 65%

Section: Nf-κb and Vitamin Kmentioning

confidence: 99%

Anti-Inflammatory Actions of Vitamin K

Hodges¹,

Pitsillides²,

Ytrebø³

et al. 2017

Vitamin K2 - Vital for Health and Wellbeing

View full text Add to dashboard Cite

show abstract

“…These results suggest that vitamin K is involved in steroid production in the testis. To link these results with the antiinflammatory properties of vitamin K observed in the lipopolysaccharide (LPS)-induced models [5,6], we examined the effects of dietary vitamin K on steroidogenesis in LPSinduced rats [27]. We found that dietary vitamin K intake affected testicular vitamin K concentration and offset the LPS-induced lowering of testosterone synthesis in the testis.…”

Section: Mk-4 Enhances Steroidogenesis By Activating Pkamentioning

confidence: 99%

“…Vitamin K is a well-known nutrient required for blood coagulation and bone metabolism. In recent years, novel functions of vitamin K against inflammation [5,6], tumors [7][8][9], and ligand of the nuclear receptor PXR (also known as SXR) [10,11] have been reported. These findings suggest the beneficial role of vitamin K, including MK-4, in several biological processes.…”

Section: Introductionmentioning

confidence: 99%

Menaquinone‐4 Enhances Steroidogenesis in Testis Derived Tumor Cells Via the Elevation of cAMP Level

Ho¹,

Shirakawa²,

Komai³

2017

Vitamin K2 - Vital for Health and Wellbeing

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Naturally existing vitamin K consists of vitamins K1 and K2. Menaquinone-4 (MK-4), an analog of vitamin K2 and a product of vitamin K1 metabolism, can be detected in several organs, including the testis; however, the function of MK-4 in these tissues has not been well characterized. Recent studies have suggested that vitamin K is involved in enhancing protein kinase A (PKA) activity in several cell types, thus regulating numerous PKA-dependent biological processes. To highlight the effect of vitamin K, we focused on its role in the steroidogenic pathway. Experiments on vitamin K-deficient rats revealed a reduced expression of genes involved in the biosynthesis of cholesterol and steroid hormones in the testis. Moreover, compared with control animals, rats fed on MK-4 diet presented significantly higher testosterone levels in the plasma and testis. These results suggest that vitamin K is involved in the steroidogenic pathway in the testis. Testosterone levels were found to increase in a dose-dependent manner also in cell-based experiments upon addition of MK-4, but such an effect was not observed in vitamin K1 levels. Furthermore, the effect of MK-4 on testosterone production was abolished by the specific PKA inhibitor H89, thus confirming the regulatory role of MK-4 on PKA activation. Here, we describe how MK-4 modulates PKA activation by enhancing intracellular 3′,5′-cyclic adenosine monophosphate (cAMP) levels in testisderived I-10 cells. The presented evidence supports the role of MK-4 in cAMP/PKA signaling and steroidogenesis.

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“…Recently, DNA microarray was used to identify the effect of VK status on gene expression in rat liver. The expression of genes involved in the acute inflammation response was enhanced in rats fed a VK-deficient diet relative to the control and VK-supplemented diet groups (4). VK comprises a family of structurally similar, fat-soluble 2-methyl-1,4-naphthoquinones, including phylloquinone (VK 1 ), menaquinone (VK 2 ) and menadione (VK3).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity

Mizushina

Nishiumi

Nishida

et al. 2013

International Journal of Oncology

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Abstract. Vitamin Ks (VKs) are fat-soluble quinone compounds known to have various bioactivities. This review describes the inflammatory effects of VKs and their related quinone derivatives based on DNA polymerase (pol) inhibition. VK 3 , but not VK 1 or VK 2 (=MK-4), inhibited the activity of human pol γ, which is the DNA replicative pol in mitochondria. Of the intermediate compounds between VK 2 and VK 3 (namely MK-3, MK-2 and MK-1), MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B-, Y-and X-families of pols, respectively. Among the VK 3 based quinone derivatives, such as 1,4-naphthoquinone (NQ), 2-dimethyl-1,4-naphthoquinone (1,2-dimethyl-NQ), 1,4-benzoquinone (BQ), 9,10-anthraquinone (AQ) and 5,12-naphthacenequinone (NCQ), NQ was the strongest inhibitor of mammalian pols α and λ, in particular, DNA repair-related pol λ. Among the all compounds tested, NQ displayed the strongest suppression of tumor necrosis factor (TNF)-α production induced by lipopolysaccharide (LPS) in a cell culture system using RAW264.7 mouse macrophages. NQ also suppressed the expression of pol λ protein in these cells, after LPS-treated RAW264.7 cells were stimulated to induce pol λ expression. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of NQ into mice suppressed TNF-α production in peritoneal macrophages and serum. In an in vivo colitis mouse model induced using dextran sulfate sodium (DSS), NQ markedly suppressed DSS-evoked colitis. The promising anti-inflammatory candidates based on the inhibition of DNA repair-related pols, such as pol λ, by VKs quinone derivatives, such as NQ, are discussed.

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Vitamin K Suppresses Lipopolysaccharide-Induced Inflammation in the Rat

Cited by 166 publications

References 21 publications

Anti-Inflammatory Actions of Vitamin K

Anti-Inflammatory Actions of Vitamin K

Menaquinone‐4 Enhances Steroidogenesis in Testis Derived Tumor Cells Via the Elevation of cAMP Level

Inhibition of repair-related DNA polymerases by vitamin Ks, their related quinone derivatives and associated inflammatory activity

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