RESUMEN
Innate immune response is critical for the control of Listeria monocytogenes infection. Here, we identified developmentally regulated GTP-binding protein 2 (DRG2) in macrophages as a major regulator of the innate immune response against L. monocytogenes infection. Both whole-body DRG2 knockout (KO) mice and macrophage-specific DRG2 KO mice had low levels of IL-6 during early infection and increased susceptibility to L. monocytogenes infection. Following an initial impaired inflammatory response of macrophages upon i.p. L. monocytogenes infection, DRG2-/- mice showed delayed recruitment of neutrophils and monocytes into the peritoneal cavity, which led to elevated bacterial burden, inflammatory cytokine production at a late infection time point, and liver micro-abscesses. DRG2 deficiency decreased the transcriptional activity of NF-κB and impaired the inflammatory response of both bone marrow-derived and peritoneal macrophages upon L. monocytogenes stimulation. Our findings reveal that DRG2 in macrophages is critical for the initial inflammatory response and protection against L. monocytogenes infection.
Asunto(s)
Proteínas de Unión al GTP , Listeria monocytogenes , Listeriosis , Macrófagos , Animales , Ratones , Inmunidad Innata , Listeriosis/inmunología , Macrófagos/inmunología , Ratones Noqueados , Monocitos , Proteínas de Unión al GTP/metabolismoRESUMEN
Obesity is a major global public health concern associated with an increased risk of many health problems, including type 2 diabetes, heart disease, stroke, and some types of cancer. Obesity is also a critical factor in the development of insulin resistance and type 2 diabetes. Insulin resistance is associated with metabolic inflexibility, which interferes with the body's ability to switch from free fatty acids to carbohydrate substrates, as well as with the ectopic accumulation of triglycerides in non-adipose tissue, such as that of skeletal muscle, the liver, heart, and pancreas. Recent studies have demonstrated that MondoA (MLX-interacting protein or MLXIP) and the carbohydrate response element-binding protein (ChREBP, also known as MLXIPL and MondoB) play crucial roles in the regulation of nutrient metabolism and energy homeostasis in the body. This review summarizes recent advances in elucidating the function of MondoA and ChREBP in insulin resistance and related pathological conditions. This review provides an overview of the mechanisms by which MondoA and ChREBP transcription factors regulate glucose and lipid metabolism in metabolically active organs. Understanding the underlying mechanism of MondoA and ChREBP in insulin resistance and obesity can foster the development of new therapeutic strategies for treating metabolic diseases.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Resistencia a la Insulina/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción/metabolismo , Glucosa/metabolismo , Hígado/metabolismo , Obesidad/metabolismoRESUMEN
The mRNA destabilizing factor tristetraprolin (TTP) functions as a tumor suppressor by down-regulating cancer-associated genes. TTP expression is significantly reduced in various cancers, which contributes to cancer processes. Enforced expression of TTP impairs tumorigenesis and abolishes maintenance of the malignant state, emphasizing the need to identify a TTP inducer in cancer cells. To search for novel candidate agents for inducing TTP in cancer cells, we screened a library containing 1019 natural compounds using MCF-7 breast cancer cells transfected with a reporter vector containing the TTP promoter upstream of the luciferase gene. We identified one molecule, of which the enantiomers are betamethasone 21-phosphate (BTM-21-P) and dexamethasone 21-phosphate (BTM-21-P), as a potent inducer of TTP in cancer cells. We confirmed that BTM-21-P, DXM-21-P, and dexamethasone (DXM) induced the expression of TTP in MDA-MB-231 cells in a glucocorticoid receptor (GR)-dependent manner. To identify potential pathways linking BTM-21-P and DXM-21-P to TTP induction, we performed an RNA sequencing-based transcriptome analysis of MDA-MB-231 cells at 3 h after treatment with these compounds. A heat map analysis of FPKM expression showed a similar expression pattern between cells treated with the two compounds. The KEGG pathway analysis results revealed that the upregulated DEGs were strongly associated with several pathways, including the Hippo signaling pathway, PI3K-Akt signaling pathway, FOXO signaling pathway, NF-κB signaling pathway, and p53 signaling pathway. Inhibition of the FOXO pathway using a FOXO1 inhibitor blocked the effects of BTM-21-P and DXM-21-P on the induction of TTP in MDA-MB-231 cells. We found that DXM enhanced the binding of FOXO1 to the TTP promoter in a GR-dependent manner. In conclusion, we identified a natural compound of which the enantiomers are DXM-21-P and BTM-21-P as a potent inducer of TTP in breast cancer cells. We also present new insights into the role of FOXO1 in the DXM-21-P- and BTM-21-P-induced expression of TTP in cancer cells.
Asunto(s)
Neoplasias , Tristetraprolina , Tristetraprolina/genética , Glucocorticoides/farmacología , Fosfatidilinositol 3-Quinasas , Receptores de Glucocorticoides/genéticaRESUMEN
Although KRASG12C inhibitors have shown promising activity in lung adenocarcinomas harbouring KRASG12C, acquired resistance to these therapies eventually occurs in most patients. Re-expression of KRAS is thought to be one of the main causes of acquired resistance. However, the mechanism through which cancer cells re-express KRAS is not fully understood. Here, we report that the Hedgehog signal is induced by KRASG12C inhibitors and mediates KRAS re-expression in cancer cells treated with a KRASG12C inhibitor. Further, KRASG12C inhibitors induced the formation of primary cilia and activated the Hedgehog-GLI-1 pathway. GLI-1 binds to the KRAS promoter region, enhancing KRAS promoter activity and KRAS expression. Inhibition of GLI using siRNA or the smoothened (Smo) inhibitor suppressed re-expression of KRAS in cells treated with a KRASG12C inhibitor. In addition, we demonstrate that KRASG12C inhibitors decreased Aurora kinase A (AURKA) levels in cancer cells, and inhibition of AURKA using siRNA or inhibitors led to increased expression levels of GLI-1 and KRAS even in the absence of KRAS inhibitor. Ectopic expression of AURKA attenuated the effect of KRASG12C inhibitors on the expression of GLI-1 and re-expression of KRAS. Together, these findings demonstrate the important role of AURKA, primary cilia, and Hedgehog signals in the re-expression of KRAS and therefore the induction of acquired resistance to KRASG12C inhibitors, and provide a rationale for targeting Hedgehog signalling to overcome acquired resistance to KRASG12C inhibitors.
Asunto(s)
Proteínas Hedgehog , Neoplasias Pulmonares , Humanos , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Aurora Quinasa A/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Mutación/genética , ARN Interferente Pequeño/metabolismoRESUMEN
More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet to be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response of PD-L1-expressing tumors to anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling and increased the PD-L1 level in melanoma cells. However, it inhibited recycling of endosomal PD-L1 and reduced surface PD-L1 levels, which led to defects in interaction with PD-1. Anti-PD-1 did not expand effector-like T cells within DRG2-depleted tumors and failed to improve the survival of DRG2-depleted tumor-bearing mice. Cohort analysis revealed that patients bearing melanoma with low DRG2 protein levels were resistant to anti-PD-1 therapy. These findings identify DRG2 as a key regulator of recycling of endosomal PD-L1 and response to anti-PD-1 therapy and provide insights into how to increase the correlation between PD-L1 expression and response to anti-PD-1 therapy.
RESUMEN
The molecular mechanisms underlying the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD), and Huntington's disease remain enigmatic, resulting in an unmet need for therapeutics development. Here, we suggest that filbertone, a key flavor compound found in the fruits of hazel trees of the genus Corylus, can ameliorate PD via lowering the abundance of aggregated α-synuclein. We previously reported that inhibition of hypothalamic inflammation by filbertone is mediated by suppression of nuclear factor kappa-B. Here, we report that filbertone activates PERK through mitochondrial reactive oxygen species production, resulting in the increased nuclear translocation of transcription factor-EB in SH-SY5Y human neuroblastoma cells. TFEB activation by filbertone promotes the autophagy-lysosomal pathway, which in turn alleviates the accumulation of α-synuclein. We also demonstrate that filbertone prevented the loss of dopaminergic neurons in the substantia nigra and striatum of mice on high-fat diet. Filbertone treatment also reduced high-fat diet-induced α-synuclein accumulation through upregulation of the autophagy-lysosomal pathway. In addition, filbertone improved behavioral abnormalities (i.e., latency time to fall and decrease of running distance) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD murine model. In conclusion, filbertone may show promise as a potential therapeutic for neurodegenerative disease.
Asunto(s)
Neuroblastoma , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Ratones , Animales , alfa-Sinucleína/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neuroblastoma/patología , Enfermedad de Parkinson/tratamiento farmacológico , Autofagia/fisiología , Neuronas Dopaminérgicas/metabolismo , Lisosomas/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismoRESUMEN
The effect of menaquinone-7 isolated from cheonggukjang was comparatively investigated with vitamin K1 and menaquinone-4 on cell differentiation and mineralization of the osteoblastic cell line MC3T3-E1. Results indicated that all vitamin K species significantly increased MC3T3-E1 cell proliferation, cellular alkaline phosphatase activity, osteocalcin synthesis, and calcium deposition in a dose-dependent manner. Menaquinone-4 and menaquinone-7 had more potent effects on calcium deposition than vitamin K1, and their effects were only partly reduced by warfarin (γ-carboxylation inhibitor) treatment, while warfarin abolished the induction activity of vitamin K1 on calcification. This suggests that vitamin K1 and K2 (menaquinone-4 & menaquinone-7) may have different mechanisms in stimulating osteoblast mineralization. In addition, the mRNA expression ratio of osteoprotegerin and the receptor activator of nuclear factor-kB ligand was also dramatically increased by treatment with vitamin K1 (62%), menaquinone-4 (247%), and menaquinone-7 (329%), suggesting that vitamin K may suppress the formation of osteoclast by up-regulating the ratio of osteoprotegerin/receptor activator of nuclear factor-kB ligand in osteoblasts. These results provide compelling evidence that vitamin K1, menaquinone-4, and menaquinone-7 all can promote bone health, which might be associated with elevations in the osteoprotegerin/receptor activator of nuclear factor-kB ligand ratio.
Asunto(s)
Biomineralización/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Alimentos de Soja , Vitamina K 1/farmacología , Vitamina K 2/análogos & derivados , Fosfatasa Alcalina/metabolismo , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Ratones , Osteoblastos , Osteocalcina/metabolismo , Osteoprotegerina/genética , Ligando RANK/genética , Vitamina K 2/aislamiento & purificación , Vitamina K 2/farmacologíaRESUMEN
Obesity-related insulin resistance is associated with intramyocellular lipid accumulation in skeletal muscle. We hypothesized that in contrast to current dogma, this linkage is related to an upstream mechanism that coordinately regulates both processes. We demonstrate that the muscle-enriched transcription factor MondoA is glucose/fructose responsive in human skeletal myotubes and directs the transcription of genes in cellular metabolic pathways involved in diversion of energy substrate from a catabolic fate into nutrient storage pathways including fatty acid desaturation and elongation, triacylglyeride (TAG) biosynthesis, glycogen storage, and hexosamine biosynthesis. MondoA also reduces myocyte glucose uptake by suppressing insulin signaling. Mice with muscle-specific MondoA deficiency were partially protected from insulin resistance and muscle TAG accumulation in the context of diet-induced obesity. These results identify MondoA as a nutrient-regulated transcription factor that under normal physiological conditions serves a dynamic checkpoint function to prevent excess energy substrate flux into muscle catabolic pathways when myocyte nutrient balance is positive. However, in conditions of chronic caloric excess, this mechanism becomes persistently activated leading to progressive myocyte lipid storage and insulin resistance.
Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Resistencia a la Insulina/fisiología , Metabolismo de los Lípidos , Músculo Esquelético/metabolismo , Obesidad/metabolismo , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Línea Celular , Modelos Animales de Enfermedad , Femenino , Fructosa/metabolismo , Glucosa/metabolismo , Glucógeno/metabolismo , Humanos , Insulina/metabolismo , Resistencia a la Insulina/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Lípidos , Masculino , Redes y Vías Metabólicas/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fibras Musculares Esqueléticas/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo , Transcriptoma , Triglicéridos/biosíntesisRESUMEN
Optimization of the culture medium to maximize menaquinone-7 (MK-7) production by Bacillus subtilis strain KCTC 12392BP in static culture was carried out using statistical experimental methods, including one factor at a time, fractional factorial design, and response surface methodology (RSM). Maltose (carbon source), tryptone (nitrogen source), and glycerol (activator) were identified as the key medium components for MK-7 synthesis by the fractional factorial design, and were selected for statistical optimization by RSM. The statistical analysis indicated that, in the range that was studied, maltose, tryptone, and glycerol were all critical factors having profound effects on the production of MK-7, with their coefficients for linear and quadratic all significant at the p < 0.05 level. The established model was efficient and feasible, with a determination coefficient (R²) of 0.9419. The predicted concentrations of maltose, tryptone, and glycerol in the optimal medium were determined as 36.78, 62.76, and 58.90 g/l, respectively. In this optimized medium, the maximum yield of MK-7 reached a remarkably high level of 71.95 ± 1.00 µg/ml after 9 days of static fermentation, which further verified the practicability of this optimized strategy.
Asunto(s)
Bacillus subtilis/crecimiento & desarrollo , Bacillus subtilis/metabolismo , Medios de Cultivo/química , Vitamina K 2/análogos & derivados , Vitaminas/metabolismo , Biotecnología/métodos , Modelos Estadísticos , Vitamina K 2/metabolismoRESUMEN
The number of diabetic patients worldwide is increasing, and complications such as stroke and cardiovascular disease are becoming a serious cause of death. Diabetes mellitus is classified into two types according to the etiopathogenic mechanism and insulin dependence. Type 1 diabetes (T1D), an insulin-dependent diabetes mellitus, is caused by damage and destruction of pancreatic ß cells that produce insulin. It is a disease that is characterized by hyperglycemia and hypoinsulinemia. Aronia berry has been used as a medicinal food in Europe. Aronia contains a variety of ingredients such as polyphenols, anthocyanins, flavonoids, and tannins. Especially, anthocyanin content in aronia berry is known to be much higher than in other plants and berries. It is known for exerting antioxidant, anti-inflammation, and anti-aging effects. Therefore, this study was conducted to investigate the effects of aronia berry extract intake in multiple low-dose streptozotocin (STZ)-induced T1D and to confirm the functional properties of aronia berry. ICR mice (6-week male) were divided into four groups: control (normal control group), STZ (100 mg/kg of STZ-induced T1D group), AR 10 (STZ with oral administration of aronia 10 mg/kg), and AR 100 (STZ with oral administration of aronia 100 mg/kg). Afterward, STZ was injected in a single dose to induce T1D, and the extract was orally administered daily. Dietary intake and body weight were measured twice a week. We confirmed that aronia berry has the effect of decreasing the increase of blood glucose level and also has the protection effect of pancreas ß cell (RINm5F cell). This study confirms the anti-diabetic activity of aronia berry, and it can be expected to increase the utilization according to the results.
Asunto(s)
Diabetes Mellitus Tipo 1/dietoterapia , Suplementos Dietéticos , Frutas/química , Hiperglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Photinia/química , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/metabolismo , Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/administración & dosificación , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular , Ciclooxigenasa 2/química , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patología , Alimentos Funcionales , Regulación Enzimológica de la Expresión Génica , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/metabolismo , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Células Secretoras de Insulina/inmunología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos ICR , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/metabolismoRESUMEN
Intramuscular lipid accumulation is a common manifestation of chronic caloric excess and obesity that is strongly associated with insulin resistance. The mechanistic links between lipid accumulation in myocytes and insulin resistance are not completely understood. In this work, we used a high-throughput chemical biology screen to identify a small-molecule probe, SBI-477, that coordinately inhibited triacylglyceride (TAG) synthesis and enhanced basal glucose uptake in human skeletal myocytes. We then determined that SBI-477 stimulated insulin signaling by deactivating the transcription factor MondoA, leading to reduced expression of the insulin pathway suppressors thioredoxin-interacting protein (TXNIP) and arrestin domain-containing 4 (ARRDC4). Depleting MondoA in myocytes reproduced the effects of SBI-477 on glucose uptake and myocyte lipid accumulation. Furthermore, an analog of SBI-477 suppressed TXNIP expression, reduced muscle and liver TAG levels, enhanced insulin signaling, and improved glucose tolerance in mice fed a high-fat diet. These results identify a key role for MondoA-directed programs in the coordinated control of myocyte lipid balance and insulin signaling and suggest that this pathway may have potential as a therapeutic target for insulin resistance and lipotoxicity.
Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/fisiología , Insulina/metabolismo , Metabolismo de los Lípidos , Células Musculares/metabolismo , Músculo Esquelético/citología , Animales , Arrestinas/metabolismo , Biopsia , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular , Dieta Alta en Grasa , Glucosa/metabolismo , Homeostasis , Resistencia a la Insulina/fisiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Fibras Musculares Esqueléticas/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Transducción de Señal , Tiorredoxinas/metabolismo , Transfección , Triglicéridos/metabolismoRESUMEN
To further understand the correlation between vitamin K and bone metabolism, the effects of vitamins K1, menaquinone-4 (MK-4), and menaquinone-7 (MK-7) on RANKL-induced osteoclast differentiation and bone resorption were comparatively investigated. Vitamin K2 groups (MK-4 and MK-7) were found to significantly inhibit RANKL-medicated osteoclast cell formation of bone marrow macrophages (BMMs) in a dose-dependent manner, without any evidence of cytotoxicity. The mRNA expression of specific osteoclast differentiation markers, such as c-Fos, NFATc1, OSCAR, and TRAP, as well as NFATc1 protein expression and TRAP activity in RANKL-treated BMMs were inhibited by vitamin K2, although MK-4 exhibited a significantly greater efficiency compared to MK-7. In contrast, the same dose of vitamin K1 had no inhibitory effect on RANKL-induced osteoclast cell formation, but increased the expression of major osteoclastogenic genes. Interestingly, vitamins K1, MK-4 and MK-7 all strongly inhibited osteoclastic bone resorption (p < 0.01) in a dose dependent manner. These results suggest that vitamins K1, MK-4 and MK-7 have anti-osteoporotic properties, while their regulation effects on osteoclastogenesis are somewhat different.
Asunto(s)
Resorción Ósea/tratamiento farmacológico , Diferenciación Celular/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Ligando RANK/metabolismo , Vitamina K/farmacología , Fosfatasa Ácida/genética , Fosfatasa Ácida/metabolismo , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ligando RANK/genética , ARN Mensajero , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Transducción de Señal , Fosfatasa Ácida Tartratorresistente , Vitamina K/análogos & derivados , Vitamina K 1/farmacología , Vitamina K 2/análogos & derivados , Vitamina K 2/farmacologíaRESUMEN
Response surface methodology (RSM) was used to determine the optimum vitamin D2 synthesis conditions in oyster mushrooms (Pleurotus ostreatus). Ultraviolet B (UV-B) was selected as the most efficient irradiation source for the preliminary experiment, in addition to the levels of three independent variables, which included ambient temperature (25-45°C), exposure time (40-120 min), and irradiation intensity (0.6-1.2 W/m2). The statistical analysis indicated that, for the range which was studied, irradiation intensity was the most critical factor that affected vitamin D2 synthesis in oyster mushrooms. Under optimal conditions (ambient temperature of 28.16°C, UV-B intensity of 1.14 W/m2, and exposure time of 94.28 min), the experimental vitamin D2 content of 239.67 µg/g (dry weight) was in very good agreement with the predicted value of 245.49 µg/g, which verified the practicability of this strategy. Compared to fresh mushrooms, the lyophilized mushroom powder can synthesize remarkably higher level of vitamin D2 (498.10 µg/g) within much shorter UV-B exposure time (10 min), and thus should receive attention from the food processing industry.
Asunto(s)
Ergocalciferoles/metabolismo , Pleurotus/metabolismo , Pleurotus/efectos de la radiación , Estadística como Asunto/métodos , Rayos Ultravioleta , Temperatura , Factores de TiempoRESUMEN
The effect of dietary vitamin K2 (menaquinone-7, MK-7) and cheonggukjang (CGJ) on the prevention of ovariectomy (OVX)-induced bone loss was studied in rats. Female Sprague-Dawley rats were divided into eight groups: sham-operated; OVX control; OVX treated with MK-7 at doses of 2, 4, and 8 µg/day; and OVX treated with CGJ at doses of 0.063, 0.125, and 0.250 g/day referenced to MK-7 levels at 2, 4, and 8 µg/day, respectively. After 8 weeks of treatment, the preventive effects of MK-7 and CGJ were evaluated by measuring body weights, serum levels of bone turnover markers, bone mineral content (BMC), bone mineral density (BMD), trabecular microarchitectural properties, and bone histological characteristics. Our results showed that rats treated with a high dose of MK-7 (8 µg/day) exhibited a minor inhibitory effect on OVX-induced bone loss, as indicated by a significant increase in trabecular number, as well as BMC and BMD (P<.01). Moreover, the preventive effects of MK-7 were augmented by administration of CGJ at the same MK-7 dose. In addition, the preventive effects of CGJ were shown to be dose dependent, with the highest dose (0.250 g/day) significantly (P<.01) increasing BMC and BMD by 31.8% and 47.6%, respectively. In summary, these results suggest that administration of CGJ containing abundant levels of MK-7 may be a promising approach for the treatment and prevention of osteoporosis.