Menaquinone-4 (Vitamin K2) is a vitamin K2 containing four isoprene units and belongs to the naphthoquinone family [1]. Menaquinone-4 is mainly formed through the conversion of intracellular vitamin K1 and accumulates in various tissues, playing an important role in protecting the heart and brain and building strong bones [2]. Menaquinone-4 can be used as a hemostatic agent and is used to treat osteoporosis [3].
In vitro, Menaquinone-4 (0, 1.0, 5.0 and 10.0μM; 0, 3, 7 and 11 days) increased the ALP activity in Caco-2 cells in a time-dependent manner, and the expression of TNSALP mRNA also increased [4]. In LPS-induced MG6 cells, Menaquinone-4 (0-10μM; 24h) dose-dependently inhibited the upregulation of inflammatory cytokines at the mRNA level, significantly reduced the phosphorylation of p65, but did not affect TAK1 and IKKα/β. Menaquinone-4 could inhibit the nuclear translocation of NF-κB in LPS-induced MG6 cells [5].
In vivo, Menaquinone-4 (200mg/kg diet; 12 weeks) increased the serum osteocalcin level in obese mice induced by a high-fat diet and increased the bone density of mice [6]. Menaquinone-4 (40mg/kg/day; i.p.; single injection) significantly reduced the content of iron metabolism genes in mice with acute liver injury induced by CCl4, and the mRNA expression levels of FPN and HJV significantly increased, while the mRNA expression level of TFR1 significantly decreased [7].
References:
[1] Sogabe N, Maruyama R, Hosoi T, et al. Enhancement effects of vitamin K1 (phylloquinone) or vitamin K2 (menaquinone-4) on intestinal alkaline phosphatase activity in rats[J]. Journal of nutritional science and vitaminology, 2007, 53(3): 219-224.
[2] Okano T, Shimomura Y, Yamane M, et al. Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice[J]. Journal of Biological Chemistry, 2008, 283(17): 11270-11279.
[3] Okamoto H, Shidara K, Hoshi D, et al. Anti‐arthritis effects of vitamin K2 (menaquinone‐4)− a new potential therapeutic strategy for rheumatoid arthritis[J]. The FEBS journal, 2007, 274(17): 4588-4594. [4] Noda S, et al. Menaquinone-4 (vitamin K2) up-regulates expression of human intestinal alkaline phosphatase in Caco-2 cells. Nutr Res. 2016 Nov;36(11):1269-1276.
[5] Saputra W D, Aoyama N, Komai M, et al. Menaquinone-4 suppresses lipopolysaccharide-induced inflammation in MG6 mouse microglia-derived cells by inhibiting the NF-κB signaling pathway[J]. International journal of molecular sciences, 2019, 20(9): 2317.
[6] Kim M, et al. Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice. J Clin Biochem Nutr. 2013 Sep;53(2):108-13.
[7] YE L, ZHAO F, HUANG Q, et al. Menaquinone-4 exerts a protective effect against carbon tetrachloride-induced acute liver injury in mice by alleviating ferroptosis[J]. Journal of Clinical Hepatology, 2024: 121-128.
Menaquinone-4 (Vitamin K2)是一种含有四个异戊二烯单元的维生素K2，属于萘醌家族 [1]。 Menaquinone-4主要通过体内维生素K1的转化形成，并在各种组织中积累，在保护心脏和大脑、构建强壮的骨骼过程中发挥重要作用 [2]。Menaquinone-4可用作一种止血剂并且可以治疗骨质疏松 [3]。
在体外，Menaquinone-4（0, 1.0, 5.0和10.0μM; 0, 3, 7和11 days）以时间依赖性增加了Caco-2细胞中的ALP活性，同时TNSALP mRNA表达增加 [4]。在LPS诱导的 MG 6细胞中，Menaquinone-4（0-10µM; 24h）在mRNA水平上剂量依赖性地抑制炎性细胞因子的上调，显著降低p65的磷酸化，但不影响TAK 1和IKKα/β。Menaquinone-4可抑制LPS诱导的MG 6细胞NF-κB核转位 [5]。
在体内，Menaquinone-4（200mg/kg饮食; 12周）提高了高脂饮食诱导的肥胖小鼠的血清骨钙素水平，同时增加了小鼠的骨密度 [6]。Menaquinone-4（40mg/kg/day; i.p.; 单次注射）显著降低CCl4诱导的急性肝损伤小鼠的铁代谢基因含量，FPN和HJV的mRNA表达水平显著增加，TFR 1 mRNA表达水平显著降低 [7]。