Exogenous Vitamins K Exert Anti-Inflammatory Effects Dissociated from Their Role as Substrates for Synthesis of Endogenous MK-4 in Murine Macrophages Cell Line

Abstract

Vitamins K exert a range of activities that extend far beyond coagulation and include anti-inflammatory effects, but the mechanisms involved in anti-inflammatory action remain unclear. In the present study, we showed that various forms of exogenous vitamins—K1, K3, K2 (MK-4, MK-5, MK-6 and MK-7)—regulated a wide scope of inflammatory pathways in murine macrophages in vitro, including NOS-2, COX-2, cytokines and MMPs. Moreover, we demonstrated for the first time that macrophages are able to synthesise endogenous MK-4 on their own. Vitamins with shorter isoprenoid chains—K1, K3 and MK-5—exhibited stronger anti-inflammatory potential than vitamins with longer isoprenoid chains (MK-6 and MK-7) and simultaneously were preferably used as a substrate for MK-4 endogenous production. Most interesting, atorvastatin pretreatment inhibited endogenous MK-4 production but had no impact on the anti-inflammatory activity of vitamin K. In summary, our results demonstrate that macrophages are able to synthesise endogenous MK-4 using exogenous vitamin K, and statin inhibits this process. However, the anti-inflammatory effect of exogenous vitamin K was independent of endogenous MK-4 synthesis.

Effect of phylloquinone on indomethacin‐induced gastric ulceration in rats: Role of SIRT‐1

“…The decreased level of COX‐2 indicates good prognosis as COX‐2 triggers inflammation and apoptosis by secreting prostaglandins and thromboxanes and is activated by NFK‐B which is the master regulator of the inflammatory process. This effect correlates with previous studies on vitamin k reporting its role in decreasing COX‐2 expression however, the exact mechanism for this effect remains unclear 49 …”

“…Moreover, a significant increase in NF‐κB was detected. These results were reversed by phylloquinone treatment in agreement with previous studies 39,49 . We assume that the ability of phylloquinone to increase NAD+ resulted in increased SIRT‐1 activity by acting as a substrate for NADH: quinone oxidoreductase 1 (NQO1), which is a catalyst that reduces quinone compounds by NADH oxidation 17 .…”

Antioxidants, minerals and vitamins in relation to Crohn's disease and ulcerative colitis: A Mendelian randomization study

“…Studies suggested that vitamin D may affect intestinal epithelium integrity and innate immune barrier function in the involvement of IBD 60 . Emerging studies support that vitamin K1 is involved in immune response and anti‐inflammation 61 and is associated with the protective and promoting role in the intestine 62 . It has been proved that folate plays a role in regulating reactive oxygen species production and reducing oxidative stress by acting directly as an antioxidant 63 .…”

“…60 Emerging studies support that vitamin K1 is involved in immune response and anti-inflammation 61 and is associated with the protective and promoting role in the intestine. 62 It has been proved that folate plays a role in regulating reactive oxygen species production and reducing oxidative stress by acting directly as an antioxidant. 63 Vitamin E reduces lipid peroxidation and thus has a significant role in membrane stabilization 64 The main strength of this study is the MR design that incorporated data from large consortia to provide solid genetic evidence for the reported associations.…”

Vitamin K Contribution to DNA Damage—Advantage or Disadvantage? A Human Health Response

“…There is evidence that vitamin K antagonists (VKA) contribute to cardiovascular damage [ 20 , 21 ] In turn, dietary supplementation with vitamin K is a safe and feasible option for slowing down vascular disease [ 22 ]. Recent evidence points to the protective effect of vitamin K on blood vessels, by reducing inflammation and stress ER [ 23 , 24 ]. Similarly, vitamin K has been observed to play an important role in the protection of immature oligodendrocytes or neurons, which are highly sensitive to oxidative damage.…”