Menaquinone 7

Menaquinone-7 is involved in bone metabolism and can be used to prevent and treat osteoporosis. However, as a fat-soluble vitamin, menaquinone-7 has poor water solubility. As a surfactant, hydrophobins can change the affinity/hydrophobicity of the covered interface. In this study, menaquinone-7 was modified by hydrophobins, and the different addition ratios were explored. Moreover, Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and water contact angle (WCA) measurements indicated that hydrophobins effectively bind to menaquinone-7 and greatly increase the hydrophilicity of the surface of menaquinone-7. Studies on the metabolism of MC3T3-E1 cells showed that compared with native menaquinone-7, HGFI-modified menaquinone-7 can significantly promote osteoblast differentiation but inhibit osteoclast differentiation. Besides, the Mito-Tracker Green experiments show that HGFI-modified menaquinone-7 can significantly promote the activity of mitochondria in cells. These findings indicate that hydrophobins can be used as an effective biomaterial to modify menaquinone-7, promote the formation of osteoblasts, and better to bone balance.

Objective: Astrocytes play a key role in hypoxic brain injury. The aim of our research was to determine the effects of menaquinone-7 (MK-7), a subtype of vitamin K2 (VK2), on astrocytes during hypoxia and its potential mechanisms. Materials and methods: Astrocytes from the palliums of newborn Sprague Dawley rats were cultured. An astrocyte-hypoxia model was established using a hypoxia workstation. Cell Counting Kit-8 (CCK-8) and BrdU assays were used to determine the effects of MK-7 on hypoxic astrocytes. 2',7'-Dichlorodihydrofluorescein diacetate (DCFDA) or dihydroethidium (DHE) assays were conducted to detect the levels of reactive oxygen species (ROS). An ATP assay was used to measure intracellular ATP production. The levels of proinflammatory cytokines and chemokines containing interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), CC-chemokine ligand 2 (CCL2), and CXC-chemokine ligand 10 (CXCL10), as well as vitamin K-dependent protein growth arrest-specific 6 (Gas6), were determined in hypoxia-induced astrocytes, in the presence or absence of MK-7 pretreatment. Small interfering RNA (siRNA) was used to knockdown Gas6 expression to determine its role in hypoxic astrocytes pretreated with MK-7. Results: Hypoxia reduced astrocyte viability and proliferation significantly; however, when pretreated with MK-7, these conditions remarkably increased. MK-7 also inhibited hypoxia-induced ROS production and enhanced ATP generation of hypoxic astrocytes. Pretreatment with MK-7 effectively reduced the expression of IL-6, TNF-α, CCL2, and CXCL10 but enhanced the expression of Gas6 in hypoxic astrocytes. Gas6 inhibition markedly attenuated the decline in MK-7-induced ROS generation and IL-6 expression, and weakened MK-7-induced cell viability and ATP production in hypoxic astrocytes. Conclusions: Our study is the first to confirm that MK-7 can protect astrocytes from hypoxia-induced cytotoxicity, possibly by inhibiting mitochondrial dysfunction and the expression of proinflammatory cytokines. Gas6 may also participate in these protective effects.

Menaquinone (MK)-7 is a vitamin K2 analog that functions as a cofactor of γ-glutamyl carboxylase involved in the activation of vitamin K (VK)-dependent proteins. The present study aimed to evaluate the effect of MK-7 on memory and cognitive function in aged C57BL/6 mice. Eighteen-month-old mice were raised for a further 4 months, fed on a standard or calcium-rich diet (3 % [w/w]), and were orally given MK-7 (40 and 400 μg/day/mouse) five times per week during the same period. The Morris water maze (MWM) test was performed at 19 and 22 months. The aged mice showed noticeable memory declines in the MWM test at all time points compared with 6-week-old mice, and this memory loss was significantly restored by the daily administration of high-dose MK-7 for 4 months. MK-7 administration also improved micro-computed tomography-based cerebrovascular calcification and aging-associated declines in growth arrest-specific 6, total and carboxylated matrix Gla proteins, and ganglioside levels in the brain of aged mice. It serologically reduced phosphorous levels in the blood, but not the urea, cholesterol, and calcium. Taken together, the long-term administration of MK-7 significantly improved age-related memory and cognitive impairments, possibly through inhibition of cerebrovascular calcification in aged mice, indicating that it can be used to develop new drugs for improving memory and cognitive function in older adults.