Sarcopenia, characterized by progressive age-related declines in skeletal muscle mass and function, is exacerbated by inadequate protein intake in elderly populations. This study aimed to evaluate the effects of fermented Tenebrio molitor with Lactobacillus plantarum as a sustainable protein supplement against dexamethasone-induced myotube atrophy in C2C12 myoblasts and muscle atrophy in a C57BL/6 mouse model. We evaluated the effect of Tenebrio molitor with Lactobacillus plantarum using various methods, including immunofluorescence staining, Western blot, quantitative polymerase chain reaction, exercise performance measurement, and muscle tissue analysis. The results showed that Tenebrio molitor with Lactobacillus plantarum treatment significantly improved myotube area, myotube diameter, expression of myogenin and myosin heavy chain in dexamethasone-induced C2C12 myotubes. In addition, Tenebrio molitor with Lactobacillus plantarum enhanced the expression of myogenic regulatory factors, such as myogenic factor 5 and myogenin and reduced the expression of protein degradation marker, including atrogin-1, muscle really interesting new gene finger protein-1, and myostatin in the myotubes. In dexamethasone-treated mice, Tenebrio molitor with Lactobacillus plantarum increased exercise capacity and muscle weight, while inhibiting myosin heavy chain and muscle atrophy markers’ expression. These findings highlight the potential of Tenebrio molitor with Lactobacillus plantarum as a sustainable protein source for managing sarcopenia by preserving muscle mass and improving physical function, suggesting it as a potential therapeutic agent for treating muscle weakness and atrophy in aging populations.

Vascular remodeling is a key process involved in arterial dysfunction. Ferroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, is emerging as a central mechanism in vascular injury. Chrysanthemum coronarium (CC), a traditional edible plant, is known for its potent antioxidant and anti-inflammatory properties. This study evaluated the vascular protective effects of CC against ferroptosis and inflammation in a carotid artery ligation (CAL) mouse model, focusing on sex-specific responses. CC administration significantly attenuated neointimal hyperplasia by inhibiting cell proliferation in ligated carotid arteries, with more pronounced effects observed in male mice. Additionally, CC markedly suppressed the increase in lipid peroxidation and reversed the decrease in ferroptosis-related markers, including xCT, GPX4, and the transferrin receptor, with stronger ferroptotic signatures evident in male mice. Furthermore, CC supplementation downregulated Ptgs2 and 4-HNE expression, suppressed inflammatory responses, and prevented abnormal vascular smooth muscle cell phenotype switching observed in males. Importantly, CC reduced fibrotic markers, with a significant reduction observed in females. These findings suggest that CC provides vascular protection by targeting ferroptosis, inflammation, and fibrosis in a sex-dependent manner and could be developed as a functional food or nutraceutical for preventing vascular dysfunction.

Fermentation is widely used to enhance the nutritional and functional properties of food substrates; however, the biological effects of insect-derived materials fermented with riboflavin-producing lactic acid bacteria remain largely unexplored. This study investigated the anti-inflammatory potential of Hermetia illucens hot-water extract fermented with Leuconostoc mesenteroides KCCM13067P (HeHi_Lm) using LPS-stimulated RAW 264.7 macrophages and a dextran sulfate sodium (DSS)-induced chronic colitis mouse model. Fermentation significantly increased vitamin B2 derivatives, with riboflavin, flavin adenine dinucleotide (FAD), and flavin mononucleotide (FMN) increasing from 7.82, 10.58, and 2.60 μg/g to 18.53, 29.84, and 9.29 μg/g, respectively, representing an approximately 2.7-fold increase in total vitamin B2 content. Fermentation also enriched free amino acids and bioactive amines, including glycine, alanine, cystathionine, γ-aminobutyric acid, and ethanolamine. In vitro, HeHi_Lm significantly suppressed LPS-induced nitric oxide production and reduced IL-6 secretion, whereas TNF-α reduction was not statistically significant. In vivo, HeHi_Lm administration alleviated DSS-induced colitis symptoms, as demonstrated by improved body weight recovery, reduced disease activity index scores, and attenuation of colon shortening. Histopathological damage and spleen and liver weight/body weight ratios were also improved. Furthermore, HeHi_Lm significantly reduced colonic expression of inflammatory mediators, including iNOS, COX-2, IL-6, and IL-1β. Gut microbiota analysis revealed compositional shifts characterized by increased Firmicutes and Bacteroidetes and reduced Verrucomicrobia, with enrichment of Lactobacillaceae and Oscillospiraceae. These findings indicate that fermentation of H. illucens with L. mesenteroides enhances functional metabolite profiles and is associated with reduced inflammatory responses and microbiota restructuring in experimental colitis, supporting its potential as a sustainable functional food ingredient.

This study was conducted to assess the protective effects of the aqueous green tea extract (GTE) against particulate matter (PM)2.5-induced cardiac dysfunction in BALB/c mice. The GTE treatment ameliorated PM2.5-induced ferroptosis and vascular smooth muscle cells (VSMC) switching in cardiovascular A7r5 cells. The administration of GTE regulated the body weight change, heart index, serum biomarkers, and cardiac antioxidant system. GTE downregulated the inflammatory reaction by inhibiting the protein expression levels of TLR2, TLR4, NOX4, p-Akt, p-JNK, p-IκB-α, Cas-1, iNOS, Ptgs2, HO-1, TNF-α, and IL-1β. In addition, the supplement of GTE ameliorated cardiac damage by regulating the ferroptotic biomarkers such as p53, xCT, GPX4, TFR, and FtH, and mitochondrial apoptosis indicators such as Cas-3, BCl-2, and BAX. It also protected VSMC phenotype levels of SM22α, αSMA, and calponin. This study suggests that GTE might be a potential material to protect PM2.5-induced cardiac damage via ferroptosis and inflammation pathway.

BACKGROUND:Hair serves both physiological functions such as thermoregulation and protection, and psychosocial roles related to self-esteem. Age-related hair loss is a complex, multifactorial process involving follicular miniaturization, inflammation, stem cell exhaustion, and vascular deterioration. Although Justicia procumbens has been shown to prevent androgenic alopecia through modulation of β-catenin signaling, its broader potential in promoting general hair growth and preventing age-related hair degeneration remains to be fully elucidated. PURPOSE:This study investigated the effects of Justicia procumbens aqueous extract (JPAE) cultivated under plant factory (PF) and smart farm (SF) systems on hair growth and aging-induced hair damage in mice. STUDY DESIGN AND METHOD:The proliferative effect of JPAE was evaluated in vitro using human hair follicle dermal papilla cells (HFDPCs) through MTT assay and gene expression analysis. In vivo efficacy was assessed using two mouse models: thioglycolic acid-induced depilation and natural aging. A comprehensive set of analyses was conducted, including histological analyses, western blotting, qPCR, ELISA, and scanning electron microscopy (SEM), and LC-MS/MS-based phytochemical profiling. RESULTS:JPAE promoted HFDPC proliferation and enhanced hair regrowth in depilation-induced mice by upregulating β-catenin and downstream hair growth-associated genes, showing consistent efficacy regardless of cultivation method (PF or SF). In aged mice, JPAE treatment alleviated aging-induced epidermal thinning, hair follicle miniaturization, and cuticle damage. Additionally, JPAE normalized the Ang-1, Ang-2, Vcam1, Icam1 expression, suppressed pro-inflammatory cytokines such as TNF-α and IL-6, and improved vascular health by reducing aortic wall thickening and restoring nitric oxide (NO) levels. CONCLUSION:JPAE promotes hair regeneration in chemically depilated models and mitigates age-related hair and vascular deterioration. These findings suggest that JPAE may have potential benefits in maintaining hair health during aging, although further studies are needed to confirm its efficacy and safety in humans.

Steroid hormones and nutrient-sensitive signaling pathways play critical roles in the regulation of stem cell activity, maintenance of tissue homeostasis, and the coordination of metabolic functions. In Drosophila, the steroid hormone ecdysone and the nutrient-responsive posttranslational modification O-linked N-acetylglucosaminylation (O-GlcNAcylation) are emerging as key regulators of intestinal stem cell (ISC) behavior. This study aimed to investigate how the interplay between ecdysone signaling and O-GlcNAcylation controls ISC proliferation and gut homeostasis, particularly in the context of aging. We showed that ecdysone receptor (EcR) expression increases during aging and upon increased O-GlcNAcylation and that both genetic overexpression of EcR and exogenous 20-hydroxyecdysone treatment promote ISC proliferation and increase O-GlcNAc levels. Conversely, the knockdown of EcR or O-GlcNAc transferase suppressed ISC proliferation and reduced DNA damage accumulation. Our results show that EcR signaling induces DNA damage response and cooperates with O-GlcNAcylation to regulate ISC activity, suggesting a positive feedback loop involving hormones and nutrients. These results highlight the interaction between EcR and O-GlcNAc as a metabolic gatekeeper that balances regenerative activity and genomic integrity in the aging gut. These findings provide a potential mechanistic link for therapeutic strategies for age-related and metabolic diseases involving abnormal stem cell proliferation.

This study examined the antioxidant and neuroprotective effects of extracts derived from different parts of Citrus junos, such as seed (YS), pulp (YP), and flavedo (YF), using stress-induced neuronal cells. The total phenolic and flavonoid content were analyzed, and the antioxidant activities were assessed using DPPH, ABTS radical scavenging, and FRAP assays. The YF showed the highest levels of TPC and TFC, followed by YS and YP. Consistently, the YF exhibited the lowest IC50 values in the antioxidant activities. High-performance liquid chromatography analysis showed that YF contains considerably higher vitamin C, hesperidin, and naringin contents than YS and YP. The neuroprotective effects were assessed by treating HT22 hippocampal neuronal cells with H2O2 and corticosterone to induce oxidative stress. Treatment with YF, YS, and YP significantly improved the cell viability and reduced intracellular ROS levels in response to H2O2 and corticosterone-induced oxidative stresses by regulating the expression of antioxidant (SOD1) and anti-stress (BDNF) proteins. These findings show that the YF is rich in bioactive compounds with potent antioxidant and neuroprotective potential. Accordingly, the flavedo of C. junos can be considered a high-value natural source for use in health-enhancing dietary supplements or pharmaceutical preparations.

Intestinal inflammation is closely linked to aging, metabolic disorders, and immune dysregulation. Maintaining epithelial homeostasis and regulating immune responses in the gut are critical for systemic health. Natural bioactive compounds are currently garnering attention as potential agents for controlling intestinal inflammation. Among them, Chrysanthemum coronarium has emerged as a promising candidate owing to its antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of C. coronarium on intestinal homeostasis under inflammatory conditions using a Drosophila model. Intestinal inflammation was induced by feeding Drosophila dextran sodium sulfate (DSS), and C. coronarium's efficacy was assessed across parallel treatment groups. We quantitatively analyzed stem cell proliferation, gut length, intestinal barrier integrity (using the Smurf assay), Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation, and cell death. DSS treatment resulted in increased intestinal stem cell (ISC) proliferation, shortened gut length, impaired barrier function, and elevated STAT signaling, all of which were significantly mitigated by cotreatment with C. coronarium. Notably, C. coronarium also restored the compromised gut barrier in DSS-treated Drosophila and suppressed STAT activation, indicating modulation of inflammatory signaling. These findings show that C. coronarium supports intestinal tissue homeostasis by suppressing DSS-induced ISC hyperproliferation, restoring barrier integrity, inhibiting STAT pathway activation, reducing cell death, and improving lifespan under inflammatory conditions. Our results offer experimental evidence supporting C. coronarium as a promising functional food ingredient for preventing inflammatory bowel disease and management of metabolic disorders.

Magnolia kobus DC. (MO) is a medicinal plant that reportedly possesses various bioactive properties, including anti-hyperplastic, anti-inflammatory, and anti-cancer effects. Chronic kidney disease (CKD) is a progressive disorder characterized by inflammation, fibrosis, and oxidative stress, which leads to renal dysfunction. This study aimed to evaluate the renoprotective effects of MO against adenine-induced CKD in C57BL/6 mice. MO significantly attenuated renal injury by reducing blood urea nitrogen level and morphological change. Additionally, MO effectively reduced inflammation by inhibiting the expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, F4/80, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. MO also considerably ameliorated adenine-induced renal fibrosis by regulating the suppressor of mothers against decapentaplegic/matrix metalloproteinase signaling. Furthermore, MO significantly protected against renal senescence by reducing the protein expression of p53, p16, and p21 induced by CKD. Additionally, MO supplementation suppressed CKD-induced ferroptosis and ferritinophagy by regulating the protein expression of SLC7A11 glutathione peroxidase 4, prostaglandin-endoperoxide synthase 2, human palmitoyl-CoA ligase, NADPH oxidase 4, 4-hydroxynonenal, transferrin receptor, heme oxygenase-1, nuclear receptor coactivator 4, beclin-1, microtubule-associated proteins 1A/1B light chain 3B, and kallikrein-related peptidase 4. In conclusion, this study suggests that MO may be a potential functional food, pharmaceutical, or medicinal plant that can help regulate mechanisms associated with renal health.

Vascular aging involves structural remodeling, oxidative stress, lipid peroxidation, and phenotypic switching of vascular smooth muscle cells (VSMCs), all contributing to age-related cardiovascular diseases. Ferroptosis, a regulated iron-dependent cell death, is a key mechanism of vascular aging. Justicia procumbens (JP), a medicinal plant rich in lignans and flavonoids, exhibits antioxidant properties; however, its effects on vascular aging are unclear. This study investigated the vascular protective effects of JP using senescent mice and Erastin-induced A7r5 smooth muscle cells. In aged mice, JP suppressed aortic thickening, reduced serum iron levels, and normalized transferrin receptor and apoptosis-inducing factor mitochondria-associated 2 expression. JP attenuated ferroptosis by decreasing the levels of 4-hydroxynonenal, prostaglandin-endoperoxide synthase 2, and acyl-CoA synthetase long-chain family member 1, and restoring the levels of solute carrier family 7 member 11 and glutathione peroxidase 4. Furthermore, JP preserved the expression of the VSMC contractile markers (alpha-smooth muscle actin, smooth muscle 22 alpha, and calponin), reduced the level of the synthetic marker osteopontin, and enhanced the activity of antioxidant enzymes (superoxide dismutase, catalase, and NADPH oxidase 1). In vitro, JP protected A7r5 cells from ferroptosis-induced cytotoxicity, promoted proliferation and migration, and restored ferroptosis and antioxidant markers. These results suggest that JP mitigates vascular aging by modulating ferroptosis, iron homeostasis, oxidative stress, and VSMC phenotype. JP may serve as a promising natural therapeutic agent for preventing age-related vascular degeneration and promoting vascular health.

Chronic exposure to particulate matter (PM)2.5 causes brain damage through intestinal imbalance. This study was estimated to confirm the regulatory activity of green tea against chronic PM2.5 exposure-induced abnormal gut-brain axis (GBA) in BALB/c mice. The green tea, as an aqueous extract of matcha (EM), ameliorated the colon length, short chain fatty acid contents, antioxidant biomarkers, myeloperoxidase (MPO) activity, and serum inflammatory cytokines. EM regulated the gut microbiota related to tryptophan intake and hormone metabolism. EM showed regulatory effect of intestinal tight junction (TJ) protein, inflammatory response, and apoptotic biomarkers. In addition, EM improved PM2.5-induced tryptophan-related hormonal metabolic dysfunction in intestinal tissue and serum. Through the ameliorating effect on GBA function, the consumption of EM presented the protective effect against inflammatory effect, apoptosis, synaptic damage, and hormonal activity in cerebral tissue, and suppressed abnormal change of brain lipid metabolites. In particular, EM intake showed relatively excellent improvement effects on indicators including Bacteroides, Ruminococcus, Murinobaculaceae, Allopreyotella, cyclooxygenase-2 (COX-2), acetylcholinesterase (AChE), 11,12-dihydroxyeicosatrienoic acid (DHET), and intestinal acetate from the PM group. These findings indicate that the dietary intake of EM might provide a regulatory effect against PM2.5-exposed GBA dysfunction via the intestinal microbiota and hormonal changes.

Vascular smooth muscle cells (VSMCs) undergo metabolic pathway transitions, including aerobic glycolysis, fatty acid oxidation, and amino acid metabolism, which are important for their function. Metabolic dysfunction in VSMCs can lead to age-related vascular diseases. O-GlcNAcylation, a nutrient-dependent posttranslational modification linked specifically to glucose metabolism, plays an important role in this context. Magnolia kobus DC. (MK), derived from the flower buds of Magnolia biondii, is known for its anticancer, anti-allergy, and anti-inflammatory properties. However, the role of O-GlcNAcylation in VSMCs under aging and the association between MK and O-GlcNAc remain unclear. Therefore, the present study aimed to determine the effects of O-GlcNAc on VSMC proliferation, along with the expression of MOF (males absent on the first, KAT8) and its correlation with the efficacy of MK. The results showed that aging and O-GlcNAc induction increased the expression levels of O-GlcNAc, O-GlcNAc transferase (OGT), ataxia telangiectasia mutated (ATM) protein, and MOF in mouse vascular smooth muscle cells (MOVAS) and aorta tissue. Transfection with OGT siRNA reduced the expression of MOF and OGT, indicating that OGT regulates MOF and influences cell proliferation. MK treatment reduced the expression of OGT, ATM, and MOF, which was correlated with O-GlcNAc levels. These findings suggest that O-GlcNAcylation is important for VSMC homeostasis and may be a novel target for vascular diseases. Thus, MK exhibits potential as a new drug candidate for treating vascular diseases by modulating O-GlcNAcylation and MOF interactions.

Renal diseases, including cancer, are rapidly increasing worldwide, driven by rising temperatures and changing diets, especially among younger people. Renal stones, a major risk for chronic renal disease, are increasingly common due to various health issues. Research on the underlying mechanisms, drug discovery, and the effects of aging and stress is limited. We used Drosophila, due to its similarity to the human renal system and ease of use, to identify cancer hallmarks and renal stone formation related to aging and oxidative stress. Our results indicate that centrosome amplification and stone formation increase with age and oxidative stress, and high sucrose feeding also heightens stone formation in the renal system. Our results show a close relationship between these diseases and aging, reactive oxygen species (ROS) stress, and chronic diseases. We suggest that the Drosophila renal model could be a powerful tool to study the relationship between age and age-related diseases and to discovering new agents for nephropathy.

Introduction Ginseng berry (GB) has previously been demonstrated to improve systemic insulin resistance and regulate hepatic glucose metabolism and steatosis in mice with diet-induced obesity (DIO). Objectives In this study, the role of GB in metabolism was assessed using metabolomics analysis on the total liver metabolites of DIO mice. Methods Metabolomic profiling was performed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF/MS) of liver tissue from mice on a 12-wk normal chow diet (NC), high-fat diet (HFD), and HFD supplemented with 5% GB (HFD + GB). The detected metabolites, their pathways, and functions were analyzed through partial least square discriminant analysis (PLS-DA), the small molecular pathway database (SMPDB), and MetaboAnalyst 5.0. Results The liver metabolite profiles of the NC, HFD, and GB-fed mice (HFD + GB) were highly compartmentalized. The metabolites involved in major liver functions, such as mitochondrial function, gluconeogenesis/glycolysis, fatty acid metabolism, and primary bile acid biosynthesis, showed differences after GB intake. The metabolites that showed significant correlations with fasting blood glucose (FBG), insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were highly related to mitochondrial membrane function, energy homeostasis, and glucose metabolism. Ginseng berry intake increased the levels of metabolites involved in mitochondrial membrane function, decreased those involved in glucose metabolism, and was highly correlated with metabolic phenotypes. Conclusion This study demonstrated that long-term intake of GB changed the metabolite of hepatosteatotic livers in DIO mice, normalizing global liver metabolites involved in mitochondrial function and glucose metabolism and indicating the potential mechanism of GB in improving hyperglycemia in DIO mice.

Hyperhomocysteinemia is a main risk factor for phenotypic modulation of vascular smooth muscle cells (VSMCs) and atherosclerosis. Phenotypic switching and proliferation of VSMCs are related to the progression of vascular inflammation. Chrysanthemum coronarium L. is a leafy vegetable with various biological functions, such as antioxidative, anti-inflammatory, and antiproliferative effects. In this study, we aimed to identify the mechanisms underlying the therapeutic and preventive effects of C. coronarium L. extract (CC) in regulating homocysteine (Hcy)-induced vascular inflammation in human aortic VSMCs. CC did not exhibit cytotoxicity and inhibited Hcy-stimulated VSMC proliferation and migration. In addition, CC promoted Hcy-induced expression of VSMC contractile phenotype proteins, including alpha-smooth muscle actin, calponin, and smooth muscle 22α. CC also decreased Hcy-induced accumulation of reactive oxygen species and expression of inflammatory markers nicotinamide adenine dinucleotide phosphate oxidase-4 and soluble epoxide hydrolase. These results showed that CC attenuates Hcy-induced inflammatory responses, highlighting its potential as a therapeutic or preventive target for Hcy-induced vascular inflammation.

Chronic kidney disease (CKD) gradually leads to loss of renal function and is associated with inflammation and fibrosis. Chrysanthemum coronarium L., a leafy vegetable, possesses various beneficial properties, including anti-oxidative, anti-inflammatory, and antiproliferative effects. In this study, we investigated the renoprotective effect of Chrysanthemum coronarium L. extract (CC) on adenine (AD)-induced CKD in mice. CKD was induced by feeding mice with an AD diet (0.25% w/w) for 4 weeks. Changes in renal function, histopathology, inflammation, and renal interstitial fibrosis were analyzed. The adenine-fed mice were characterized by increased blood urea nitrogen, serum creatinine, and histological changes, including inflammation and fibrosis; however, these changes were significantly restored by treatment with CC. Additionally, CC inhibited the expression of the inflammatory markers, monocyte chemoattractant protein-1, interleukins-6 and -1β, intercellular adhesion molecule-1, and cyclooxygenase 2. Moreover, CC suppressed the expression of the fibrotic markers, type IV collagen, and fibronectin. Furthermore, CC attenuated the expression of profibrotic genes (tumor growth factor-β and α-smooth muscle actin) in AD-induced renal injury mice. Thus, our results suggest that CC has the potential to attenuate AD-induced renal injury and might offer a new option as a renoprotective agent or functional food supplement to manage CKD.

Inflammatory bowel disease (IBD) can severely affect humans and animals and is difficult to treat. Black soldier fly (Hermetia illucens; Hi) larvae (BSFL) are a sustainable source of protein. However, no studies exist on the antioxidant and anti-inflammatory functions of BSFL or fermented BSFL with respect to IBD. In this study, riboflavin-producing Lactobacillus plantarum KCCM12757P was isolated from a fish farm tank, and in conjunction with hot water-extracted Hi (HeHi) (termed HeHi_Lp), was used to determine optimal fermentation conditions to increase vitamin B2 concentration. This in vivo study investigated the therapeutic effects and mechanistic role of HeHi_Lp in chronic colitis-induced murine models. Histological changes, inflammatory cytokine levels, and intestinal barrier function were explored. Gut microbial communities and gene expression in the nuclear factor (NF)-κB signaling pathway were also studied. HeHi_Lp remarkably reduced the disease activity index, inflammatory cytokine (inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor α, interleukin (IL-6 and IL-1β) levels, and increased body weight and colon length. HeHi_Lp administration significantly raised zonula occludens 1, occludin and claudin 1 and improved the composition of the gut microbiota and beneficial intestinal bacteria. These results suggest that HeHi_Lp can be used as a dietary supplement in pet food to alleviate colitis.

Osteoporosis is a progressive metabolic disease characterized by decreased bone mineral density and increased fracture risk. Previous studies have shown that higher intake of vitamin K (VK) correlates with a reduced risk of osteoporosis. However, the effect of menaquinone-4 (MK-4), a specific form of VK, still remains obscure. Therefore, in this study, we investigated the effects of MK-4 on osteoclast differentiation by differentiating RAW 264.7 cells into osteoclasts with the help of receptor activator of nuclear factor-kappa B ligand (RANKL), assessed the mRNA expression of osteoclast-specific genes, and studied the effects of MK-4 in vivo in ovariectomized mice, a postmenopausal osteoporosis murine model. MK-4 inhibited osteoclast differentiation, decreased the mRNA expression of nuclear factor of activated T cells c1 (NFATc1), osteoclast-associated receptor (OSCAR), and cathepsin K (CTSK), and inhibited bone loss in ovariectomized mice. The findings strongly suggest that MK-4 is a therapeutic alternative for postmenopausal osteoporosis.

Atherosclerosis manifests as a chronic inflammation resulting from multiple interactions between circulating factors and various cell types in blood vessel walls. Growing evidence shows that phenotypic switching and proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the progression of atherosclerosis. Soluble epoxide hydrolase (sEH)/epoxyeicosatrienoic acids are mediated by vascular inflammation. N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl]-urea (TPPU) is an sEH inhibitor. This study investigated the therapeutic effect of TPPU on atherosclerosis in vivo and homocysteine-induced vascular inflammation in vitro and explored their molecular mechanisms. We found that TPPU decreased WD-induced atherosclerotic plaque lesions, inflammation, expression of sEH, and nicotinamide adenine dinucleotide phosphate oxidase-4 (Nox4), and increased the expression of contractile phenotype marker of aortas in ApoE (-/-) mice. TPPU also inhibited homocysteine-stimulated VSMC proliferation, migration, and phenotypic switching, and reduced Nox4 in human-aorta-VSMC regulation. We conclude that TPPU has anti-atherosclerotic effects, potentially because of the suppression of VSMC phenotype switching. Thus, TPPU could be a potential therapeutic target for phenotypic switching attenuation in atherosclerosis.

Spinach (Spinacia oleracea L.), a green leafy vegetable, is widely regarded as a functional food due to its biological activities; however, to the best of our knowledge, there are no previous studies that have investigated the protective effects of fermented spinach against endothelial dysfunction and its underlying mechanisms. Therefore, this study investigated the effects and possible mechanisms of action of fresh spinach juice (S.juice) and fermented S.juice on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs). The HUVECs were treated with S.juice and fermented S.juice for 18 h before LPS exposure, and the levels of cytokines and chemokines, such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), were detected using enzyme-linked immunosorbent assays (ELISA). Furthermore, to examine the changes in inflammatory responses to the two treatments, immunofluorescence analysis was used to visualize the nuclear translocation of nuclear factor-κB (NF-κB). Western blot analysis was also performed to detect the differences in the expression of endothelial cell adhesion molecules, specifically vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Both S.juice and fermented S.juice inhibited the LPS-induced expression of MCP-1 and IL-6, and suppressed VCAM-1 and ICAM-1. Additionally, fermented S.juice inhibited the LPS-induced activation of NF-κB and degradation of the inhibitor of NF-κB (IκBα) in an LPS dose-dependent manner. These results suggest that the anti-inflammatory effect of vitamin K2-enriched fermented S.juice is mediated by the suppression of the NF-κB pathway, suggesting its potential as a novel therapeutic candidate for inflammatory cardiovascular disease.