Search

Shikonin is a naturally occurring naphthoquinone pigment and a major constituent present in Lithospermum erythrorhizon . Since microRNAs (miRNAs) are one of the key post-transcriptional regulators of adipogenesis, their manipulation represents a potential new strategy to inhibit adipogenesis. Our aim was to investigate shikonin-dependent inhibition of adipogenesis with an emphasis on miRNA-related processes. Mir-34a increased during induced adipogenesis, and this was suppressed in the presence of shikonin. mRNA expression of FKBP1B, a suggested target of mir-34a according to bioinformatics studies, decreased during adipogenesis, but was recovered by shikonin treatment, which reversely correlated with mir-34a expression. A mir-34a inhibitor suppressed MDI-induced adipogenesis by blocking PPARγ and C/EBPα expression, while suppression of mir-34a recovered MDI-induced down-regulation of FKBP1B expression. A mir-34a mimic decreased FKBP1B mRNA expression in 3T3-L1 preadipocytes. We also observed that mir-34a bound directly to the 3′-untranslated region of FKBP1B. Finally, FKBP1B overexpression attenuated MDI-induced adipogenesis, PPARγ, and C/EBPα expression. These results suggest that mir-34a regulates adipogenesis by targeting FKBP1B expression. Our findings reveal that shikonin prevents adipogenesis by blocking the mir-34a-FKBP1B pathway which represents a promising potential target for preventing obesity. [ABSTRACT FROM AUTHOR]

Summary mTORC1 plays a key role in autophagy as a negative regulator. The currently known targets of mTORC1 in the autophagy pathway mainly function at early stages of autophagosome formation. Here, we identify that mTORC1 inhibits later stages of autophagy by phosphorylating UVRAG. Under nutrient-enriched conditions, mTORC1 binds and phosphorylates UVRAG. The phosphorylation positively regulates the association of UVRAG with RUBICON, thereby enhancing the antagonizing effect of RUBICON on UVRAG-mediated autophagosome maturation. Upon dephosphorylation, UVRAG is released from RUBICON to interact with the HOPS complex, a component for the late endosome and lysosome fusion machinery, and enhances autophagosome and endosome maturation. Consequently, the dephosphorylation of UVRAG facilitates the lysosomal degradation of epidermal growth factor receptor (EGFR), reduces EGFR signaling, and suppresses cancer cell proliferation and tumor growth. These results demonstrate that mTORC1 engages in late stages of autophagy and endosome maturation, defining a broader range of mTORC1 functions in the membrane-associated processes. [ABSTRACT FROM AUTHOR]

Abstract: Fisetin, a flavonol present in vegetables and fruits, possesses antioxidative and anti-inflammatory properties. In this study, we have demonstrated that fisetin prevents diet-induced obesity through regulation of the signaling of mammalian target of rapamycin complex 1 (mTORC1), a central mediator of cellular growth, cellular proliferation and lipid biosynthesis. To evaluate whether fisetin regulates mTORC1 signaling, we investigated the phosphorylation and kinase activity of the 70-kDa ribosomal protein S6 kinase 1 (S6K1) and mTORC1 in 3T3-L1 preadipocytes. Fisetin treatment of preadipocytes reduced the phosphorylation of S6K1 and mTORC1 in a time- and concentration-dependent manner. To further our understanding of how fisetin negatively regulates mTORC1 signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells. The results suggested that fisetin treatment inhibits mTORC1 activity in an Akt-dependent manner. Recent studies have shown that adipocyte differentiation is dependent on mTORC1 activity. Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of fisetin on mTOR. The inhibitory effect of fisetin on adipogenesis is dependent of mTOR activity, suggesting that fisetin inhibits adipogenesis and the accumulation of intracellular triglycerides during adipocyte differentiation by targeting mTORC1 signaling. Fisetin supplementation in mice fed a high-fat diet (HFD) significantly attenuated HFD-induced increases in body weight and white adipose tissue. We also observed that fisetin efficiently suppressed the phosphorylation of Akt, S6K1 and mTORC1 in adipose tissue. Collectively, these results suggest that inhibition of mTORC1 signaling by fisetin prevents adipocyte differentiation of 3T3-L1 preadipocytes and obesity in HFD-fed mice. Therefore, fisetin may be a useful phytochemical agent for attenuating diet-induced obesity. [Copyright &y& Elsevier]

Abstract: Fruits of Schisandra have been traditionally used in East Asia for the treatment of dyspnea, cough, dysentery, insomnia, tonic-clonic seizures, and amnesia. Schisandrin B, a dibenzocyclooctadiene derivative isolated from Fructus Schisandrae, has been shown to produce antioxidant effect on rodent liver and heart. In the present study, we investigated the neuroprotective effects of Schisandrin B, a constituent drug of the fruit of Schisandra, against focal cerebral ischemia in rats. Schisandrin B (10, 30mg/kg, i.p.) was twice administered 30min before the onset of ischemia and 2h after reperfusion. Schisandrin B 10 and 30mg/kg treated groups showed infarct volumes reduced by 25.7% and 53.4%, respectively, 2h after occlusion. Also, Schisandrin B treated animal treatment abrogated protein expression of TNF-α and IL-1β and degradation of MMP-2 and MMP-9 in ischemic hemispheres. These results suggest that Schisandrin B treatment provides a neuroprotective effect to rats after transient focal cerebral ischemia by inhibiting inflammation and by protecting against metalloproteinase degradation. [Copyright &y& Elsevier]

Context: Botulinum neurotoxins (BoNTs) are popularly used to treat various diseases and for cosmetic purposes. They act by blocking neurotransmission through specific cleavage of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, several polyphenols were shown to interfere with SNARE complex formation by wedging into the hydrophobic core interface, thereby leading to reduced neuroexocytosis. Objective: In order to find industrially-viable plant extract that functions like BoNT, 71 methanol extracts of flowers were screened and BoNT-like activity of selected extract was evaluated. Materials and methods: After evaluating the inhibitory effect of 71 flower methanol extracts on SNARE complex formation, seven candidates were selected and they were subjected to SNARE-driven membrane fusion assay. Neurotransmitter release from neuronal PC12 cells and SNARE complex formation inside the cell was also evaluated. Finally, the effect of one selected extract on muscle contraction and digit abduction score was determined. Results: The extract of Potentilla chinensis Ser. (Rosaceae)(Chinese cinquefoil) flower inhibited neurotransmitter release from neuronal PC12 cells by approximately 90% at a concentration of 10 μg/mL. The extract inhibited neuroexocytosis by interfering with SNARE complex formation inside cells. It reduced muscle contraction of phrenic nerve-hemidiaphragm by approximately 70% in 60 min, which is comparable to the action of the Ca2+-channel blocker verapamil and BoNT type A. Discussion and conclusion: While BoNT blocks neuroexocytosis by cleaving SNARE proteins, the Potentilla chinensis extract exhibited the same activity by inhibiting SNARE complex formation. The extract paralyzed muscle as efficiently as BoNT, suggesting the potential versatility in cosmetics and therapeutics. [ABSTRACT FROM AUTHOR]

Undoped and Nb-doped Ba0.7Sr0.3TiO3 (BST) thin films were fabricated by RF magnetron sputtering. The bipolar resistance switching behaviors of both thin films were observed with the stable endurance by DC voltage sweep. Nb doping in BST influenced the defect distribution and improved the uniformity of resistance switching random access memory (ReRAM) properties. The defect distribution was strongly related to the resistance switching properties and the decrease in the grain size caused by Nb doping made the oxygen migration more efficient. The oxygen migration in BST was assisted by Nb dopants which increased the concentration of the non-lattice oxygen in BST layer during ReRAM operation. [ABSTRACT FROM AUTHOR]

Objectives Rhus verniciflua Stokes (RVS), which has valuable medicinal properties, has for many years been prescribed for inflammation in east Asian medicine. Recent studies suggest that RVS has potent antioxidative, antitumor and anti-inflammatory properties. Methods In this study, the anti-inflammatory effects of RVS in vitro and in vivo were investigated. The ethanol extract from RVS was partitioned with different solvents in order of increasing polarity. Key findings Among the various extracts, the n-butanol extract displayed the most potent activity against nitric oxide and reactive oxygen species. The n-butanol extract also significantly regulates expression of nitric oxide synthase, which inhibits nitric oxide production at the transcriptional level in activated macrophages. Immunoblot analysis also showed that n-butanol extract suppresses the phosphorylation of extracellular signal-regulated kinase and Akt, suggesting that nitric oxide synthase suppression might be mediated via the extracellular signal-regulated kinase and Akt signaling pathways. This study also investigated whether n-butanol exerts an anti-inflammatory effect in an animal model. n-butanol extract significantly reduces carrageenan-induced mouse paw edema at 5 h. Conclusions These results suggest that RVS could be a promising candidate agent for inflammation prevention and combination therapy with anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Abstract: BaTiO3 (BTO) thin film was fabricated to investigate its non-volatile and reversible resistance switching phenomena by RF-sputtering method. The reversible resistance switching phenomenon was observed by DC voltage sweep and Pt/BTO/Pt metal–insulator–metal structure devices showed the bipolar resistance switching such as Pr0.7Ca0.3MnO3 and Cr-doped SrTiO3. The typical leakage current–voltage characteristic measurements were performed. High resistance state (HRS) and low resistance state (LRS) were maintained without power supply. The margin of the resistance between HRS and LRS is considerable during 120th cycles. The current emission mechanisms were suggested by double logarithm plot of leakage current vs. voltage. The comparison of the spreading current mapping images for two different resistance states showed that local conduction path was formed at LRS and was destroyed at HRS. [Copyright &y& Elsevier]

Abstract: Nutrient starvation induces autophagy in eukaryotic cells through inhibition of TOR (target of rapamycin), an evolutionarily-conserved protein kinase. TOR, as a central regulator of cell growth, plays a key role at the interface of the pathways that coordinately regulate the balance between cell growth and autophagy in response to nutritional status, growth factor and stress signals. Although TOR has been known as a key regulator of autophagy for more than a decade, the underlying regulatory mechanisms have not been clearly understood. This review discusses the recent advances in understanding of the mechanism by which TOR regulates autophagy with focus on mammalian TOR (mTOR) and its regulation of the autophagy machinery. [Copyright &y& Elsevier]

Herbal medicines including Agrimonia pilosa Ledeb. (APL) have been traditionally used to treat inflammations including allergic disease as valuable medicinal properties. To investigate the attenuating ability of APL on inflammation, the NO release and ROS production, which play a key role in inflammatory and immune responses, was first tested using in vitro assay. The 80% ethanol extract of APL showed a significant activity to inhibit NO release and ROS production. In additional extracts from 80% ethanol extract of APL, n-butanol (BuOH) extract displayed the most potent anti-inflammatory effects based on in vitro assay. The extract also significantly reduced nitric oxide in lipopolysaccharide-activated RAW 264.7 macrophage cells (p < 0.05), and suppressed the nitric oxide synthase (iNOS) expression, whereas the extract showed no inhibitory effect on cyclooxygenase-2 (COX-2) expression, suggesting that the BuOH extract of APL could reduce the NO production through suppression of iNOS, but not COX-2. The BuOH extract also showed a significant effect in a carrageenan-induced rat paw edema in vivo model, consistent with our in vitro results. Our findings suggest that the BuOH extract of APL shows a potential anti-inflammatory activity, substantiating its traditional use in medicine. [ABSTRACT FROM AUTHOR]

Rhus verniciflua Stokes (RVS) is a plant with a long history of medicinal use in Eastern Asia. RVS has been widely used to treat gastritis, stomach cancer and atherosclerosis. The cytotoxic effects of different solvent fractions from an RVS ethanol extract were measured in 11 human cancer cell lines. The study showed that the ethyl-acetate (EtOAC) fraction was the most cytotoxic. This fraction contains a number of phenolic compounds, and this phenolic-rich EtOAC fraction was particularly effective against gastric and breast cancer cells. A purified phenolic-rich EtOAC fraction (PPEF) had a stronger apoptotic effect on these cells. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that the PPEF contained gallic acid, protocatechuic acid, fisetin, sulfuretin, butein and 8 unknown compounds. There were only small amounts of flavonoids: fisetin, sulfuretin and butein. The results showed that PPEF induces apoptosis only in gastric and breast cancer cell lines, but not in lung, colon or liver cancer cell lines. Therefore, PPEF may have a significant potential as an organ-specific anti-cancer agent. [ABSTRACT FROM AUTHOR]

Abstract: Eleutherococcus senticosus (Araliaceae) is immunological modulator which has been successfully used for anti-inflammatory effectors on anti-rheumatic diseases in oriental medicine. Mitogen-activated protein kinases (MAPKs) and Akt modulate the transcription of many genes involved in the inflammatory process. In this study, we investigated the inhibitory effects of Eleutherococcus senticosus on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharides (LPS)-activated macrophages. Finally, we studied the involvement of MAPKs and Akt signaling in the protective effect of Eleutherococcus senticosus in LPS-activated macrophages. Eleutherococcus senticosus significantly attenuated LPS-induced iNOS expression but not COX-2 expression. In using the standard inhibitors (MAPKs and Akt), our results show that Eleutherococcus senticosus downregulates inflammatory iNOS expression by blocking JNK and Akt activation. [Copyright &y& Elsevier]

Abstract: The effects of phenolic-rich fraction (PRF) from Rhus verniciflua Stokes (Anacardiaceae) on the activities of cellular signaling molecules that mediate inflammatory responses in LPS-induced RAW 264.7 macrophages were investigated. At various concentrations of PRF significantly inhibited NO, PGE2 and TNF-α production in LPS-induced RAW 264.7 macrophage cells. The PRF also significantly inhibited iNOS and COX-2 protein expression in LPS-induced RAW 264.7 macrophage in a concentration-dependent manner. Transcription factor NF-κB plays a key role for the inducible expression of genes mediating proinflammatory effects and here, we show that PRF can inhibit the induction of NF-κB activity. The PRF effectively inhibited the iNOS and COX-2 protein expression through suppression of phospho-JNK1/2 activation. Study using PDA HPLC has found that the PRF contains several low molecular compounds (i.e. p-coumaric acid, fustin, kaempferol-3-O-glucoside, sulfuretin, butein, kaempferol). Our results indicate that the anti-inflammatory properties of PRF might result from the inhibition of pro-inflammatory mediators (e.g., NO, PGE2 and TNF-α) by suppression of such signaling pathways as NF-κB and JNK1/2. [Copyright &y& Elsevier]

Abstract: Water, methanol and ethanol extracts of freeze-dried leaves of wild ginseng were examined for their antioxidant properties. All leaf extracts were capable of free radicals scavenging activity. Among solvent extracts of wild ginseng leaves, ethanol extract showed the highest DPPH, hydroxyl radical scavenging and ferrous ion chelating activity. Otherwise, the highest superoxide radical scavenging activity was found in water extract followed by ethanol and methanol extracts of wild ginseng leaves. Ethanol extracts contained more phenolics (2333.2mg/100g) and flavonoids (1199.1mg/100g) than other extracts. These differences in concentrations of key antioxidants among various solvent extracts seemed to be responsible for their differences in antioxidant activities. When various solvent extracts were hydrolysed by acid, two aglycons of flavonoid, quercetin and kaempferol, were detected. According to the results obtained from this study, wild ginseng leaves showed marked antioxidant activities due to their abundant antioxidants. [Copyright &y& Elsevier]

Abstract: Cultivated and wild ginseng leaves were examined for their various antioxidant activities. Both ginseng leaves were extracted with methanol and sequentially partitioned with solvents in an order of increasing polarity. Among various solvent extracts in cultivated and wild ginseng leaves, EtOAC extracts in both ginseng leaves showed the most powerful scavenging activities against DPPH radicals. Data on other antioxidant activities, measured by inhibition rates against lipid peroxidation and linoleate oxidation, revealed similar results, showing the highest activities in EtOAC extracts, followed by butanol, water, chloroform and hexane extracts, in both cultivated and wild ginseng leaves. EtOAC extracts of wild ginseng leaves contained more phenolics (9.71 g:4.87 g/100 g, dry basis) and flavonoids (3.03 g:2.34 g/100 g, dry basis) than cultivated ginseng leaves. When EtOAC extracts were acid-hydrolyzed, two aglycones of flavonoids, quercetin (0.43 and 0.66 g/100 g, dry basis) and kaempferol (1.23 and 1.50 g/100 g, dry basis) were detected in cultivated and wild ginseng leaves. These differences in concentrations of key antioxidants between two different ginseng leaves seemed to be responsible for their differences in antioxidant activities. [Copyright &y& Elsevier]

Abstract: The aim of this study was to examine the possible antioxidant activities of wild Panax ginseng leaf extract intake in streptozotocin (STZ)-induced diabetic rats (WGLE). Initial blood glucose levels increased abruptly after streptozotocin injection. After 4 weeks of WGLE supplementation, blood glucose levels were lower in animals fed 40mg/kg (266mg/dL) and 200mg/kg (239mg/dL) than those in no-WGLE fed diabetic rats (464mg/dL). The concentration of blood TBARS, which are considered the main products of glucose oxidation in blood, was also lowered by WGLE supplementation. These results indicate that WGLE supplementation is involved in suppressing a sudden increase in blood glucose levels and a consequent decrease in TBARS levels in diabetic rats. TBARS levels in the liver, kidney and spleen of WGLE-fed diabetic groups were also significantly lower than in the control diabetic group indicating that oral administration of WGLE effectively suppresses lipid peroxidation that occurs in the organs of diabetic rats. Antioxidant activities of WGLE supplementation further extend in suppressing activities of antioxidant related enzymes, such as glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), in organs of diabetic rats. These results confirm the effectiveness of WGLE supplementation in detoxifying free radicals that are produced excessively in diabetic-induced complications. [Copyright &y& Elsevier]

Gracilaria chorda (GC) is a red algal species that is primarily consumed in Asia. Here, we investigated the effect of GC on obesity‐related skeletal muscle wasting. Furthermore, elucidating its impact on the activation of sirtuin 1 (SIRT1)/peroxisome proliferator‐activated receptor gamma coactivator 1α (PGC1α) constituted a critical aspect in understanding the underlying mechanism of action. In this study, 6‐week‐old male C57BL/6 mice were fed a high‐fat diet (HFD) for 8 weeks to induce obesity, then continued on the HFD for another 8 weeks while orally administered GC. GC decreased ectopic fat accumulation in skeletal muscle and increased muscle weight, size, and function in obese mice. Furthermore, GC reduced skeletal muscle atrophy and increased hypertrophy in mice. We hypothesized that the activation of SIRT1/PGC1α by GC regulates skeletal muscle atrophy and hypertrophy. We observed that GC increased the expression of SIRT1 and PGC1α in skeletal muscle of mice and in C2C12 cells, which increased mitochondrial function and biogenesis. In addition, when C2C12 cells were treated with the SIRT1‐specific inhibitor EX‐527, no changes were observed in the protein levels of SIRT1 and PGC1α in the GC‐treated C2C12 cells. Therefore, GC attenuated obesity‐related muscle wasting by improving mitochondrial function and biogenesis through the activation of SIRT1/PGC1α in the skeletal muscle of mice. [ABSTRACT FROM AUTHOR]

Background: Muscle atrophy is characterized by decreased muscle mass, function, and strength. Synthetic glucocorticoids, including dexamethasone (Dexa), are commonly used to treat autoimmune diseases. However, prolonged exposure of Dexa with high dose exerts severe side effects, including muscle atrophy. The purpose of this study was to investigate whether Gromwell root extract (GW) can prevent Dexa-induced muscle atrophy in C2C12 cells and mice and to characterize the composition of GW to identify bioactive compounds. Methods: For in vitro experiments, GW (0.5 and 1 µg/mL) or lithospermic acid (LA, 5 and 10 µM) was added to C2C12 myotubes on day 4 of differentiation and incubated for 24 h, along with 50 µM Dexa. For in vivo experiment, four-week-old male C57BL/6 mice were randomly divided into the four following groups (n = 7/group): Con group, Dexa group, GW0.1 group, and GW0.2 group. Mice were fed experimental diets of AIN-93 M with or without 0.1 or 0.2% GW for 4 weeks. Subsequently, muscle atrophy was induced by administering an intraperitoneal injection of Dexa at a dose of 15 mg/kg/day for 38 days, in conjunction with dietary intake. Results: In Dexa-induced myotube atrophy, treatment with GW increased myotube diameter, reduced the expression of muscle atrophy markers, and enhanced the expression of myosin heavy chain (MHC) isoforms in C2C12 cells. Supplementation with the GW improved muscle function and performance in mice with Dexa-induced muscle atrophy, evidenced in the grip strength and running tests. The GW group showed increased lean body mass, skeletal muscle mass, size, and myosin heavy chain isoform expression, along with reduced skeletal muscle atrophy markers in Dexa-injected mice. Supplementation with GW increased protein synthesis and decreased protein degradation through the Akt/mammalian target of rapamycin and glucocorticoid receptor/forkhead box O3 signaling pathways, respectively. We identified LA as a potential bioactive component of the GW. LA treatment increased myotube diameter and decreased the expression of muscle atrophy markers in Dexa-induced C2C12 cells. Conclusions: These findings underscore the potential of the GW in preventing Dexa-induced skeletal muscle atrophy and highlight the contribution of LA to its effects. [ABSTRACT FROM AUTHOR]

Significance: Hydrogen sulfide (H2S) is a recently recognized gasotransmitter involved in physiological and pathological conditions in mammals. It protects organs from oxidative stress, inflammation, hypertension, and cell death. With abundant expression of H2S-production enzymes, the liver is closely linked to H2S signaling. Recent Advances: Hepatic H2S comes from various sources, including gut microbiota, exogenous sulfur salts, and endogenous production. Recent studies highlight the importance of hepatic H2S in liver diseases such as nonalcoholic fatty liver disease (NAFLD), liver injury, and cancer, particularly at advanced stages. Endogenous H2S production deficiency is associated with severe liver disease, while exogenous H2S donors protect against liver dysfunction. Critical Issues: However, the roles of H2S in NAFLD, liver injury, and liver cancer are still debated, and its effects depend on donor type, dosage, treatment duration, and cell type, suggesting a multifaceted role. This review aimed to critically evaluate H2S production, metabolism, mode of action, and roles in liver function and disease. Future Direction: Understanding H2S's precise roles and mechanisms in liver health will advance potential therapeutic applications in preclinical and clinical research. Targeting H2S-producing enzymes and exogenous H2S sources, alone or in combination with other drugs, could be explored. Quantifying endogenous H2S levels may aid in diagnosing and managing liver diseases. Antioxid. Redox Signal. 40, 122–144. [ABSTRACT FROM AUTHOR]

The beneficial effects of Akkermansia muciniphila (Akk) on gut health and inflammation reduction have been demonstrated; however, scientific evidence of hair growth enhancement by Akk has not been reported. Therefore, this study was undertaken to investigate the effect of Akk on improving testosterone‐mediated hair growth inhibition. Hair growth inhibition was induced through subcutaneous injection of testosterone into the shaved dorsal skin of C57BL/6 male mice. Live and pasteurized Akk were orally administered at a concentration of 1 × 108 colony‐forming unit. After 5 weeks, hair length and skin tissues were analyzed. The live and pasteurized Akk significantly stimulated hair growth, countering the inhibitory effect of testosterone compared to the testosterone‐alone group. Hematoxylin and eosin staining revealed a significant increase in hair follicle size in the Akk‐treated group. An increase in β‐catenin levels, which are associated with hair growth and cell cycle progression, was also observed. Moreover, the Akk‐treated group exhibited increased levels of fibroblast growth factors, including Fgf7, Igf1, Fgf7, Fgf10, and Fgf21. However, no significant difference was observed between the live and pasteurized Akk groups. These results underscore the potential of live and pasteurized Akk in improving testosterone‐mediated hair growth inhibition. [ABSTRACT FROM AUTHOR]

The human life span has been markedly extended since the 1900s, but it has not brought healthy aging to everyone. This increase in life expectancy without an increase in healthspan is a major global concern that imposes considerable health care budgets and degrades the quality of life of older adults. Dietary interventions are a promising strategy to increase healthspan. In this study, we evaluated whether a Gardenia jasminoides Ellis fruit ethanol extract (GFE) increases the life span of Caenorhabditis elegans (C. elegans). Treatment with 10 mg/mL GFE increased the life span by 27.1% when compared to the vehicle group. GFE (10 mg/mL) treatment improved healthspan-related markers (pharyngeal pumping, muscle quality, age–pigment, and reactive oxygen species accumulation) and exerted a protective effect against amyloid β 1–42 toxicity. These effects of GFE are related to the inhibition of insulin/IGF-1 signaling and activation of SKN-1/Nrf, thereby promoting the expression of stress resistance-related genes. In addition, treatment with 10 mM geniposide, the most abundant component of GFE, improved healthspan-related markers and increased life span by 18.55% when compared to the vehicle group. Collectively, these findings demonstrate that GFE and its component geniposide increase the life span along with healthspan in C. elegans. [ABSTRACT FROM AUTHOR]

High pathogenicity avian influenza (HPAI) viruses of clade 2.3.4.4 H5Nx have been circulating in poultry and wild birds worldwide since 2014. In South Korea, after the first clade 2.3.4.4b H5N1 HPAI viruses were isolated from wild birds in October 2021, additional HPAIV outbreaks occurred in poultry farms until April 2022. In this study, we genetically characterized clade 2.3.4.4b H5N1 HPAIV isolates in 2021–2022 and examined the pathogenicity and transmissibility of A/mandarin duck/Korea/WA585/2021 (H5N1) (WA585/21) in chickens and ducks. Clade 2.3.4.4b H5N1 HPAI viruses caused 47 outbreaks in poultry farms and were also detected in multiple wild birds. Phylogenetic analysis of HA and NA genes indicated that Korean H5N1 HPAI isolates were closely related to Eurasian viruses isolated in 2021–2022. Four distinct genotypes of H5N1 HPAI viruses were identified in poultry, and the majority were also found in wild birds. WA585/21 inoculated chickens showed virulent pathogenicity with high mortality and transmission. Meanwhile, ducks infected with the virus showed no mortality but exhibited high rates of transmission and longer viral shedding than chickens, suggesting that they may play an important role as silent carriers. In conclusion, consideration of both genetic and pathogenic traits of H5N1 HPAI viruses is required for effective viral control. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is associated with insulin resistance. Although chicoric acid (CA) is known to have beneficial effects on insulin sensitivity, the involvement of mitochondrial function has not been elucidated yet. Here, we investigated the effect of CA on insulin resistance and mitochondrial dysfunction. In palmitate-induced insulin-resistant C2C12 myotubes, CA improved impaired glucose uptake and insulin signaling pathways, along with enhanced mitochondrial membrane potential and oxygen consumption. CA treatment in diet-induced obese mice ameliorated glucose tolerance and increased insulin sensitivity. CA treatment also recovered the dysregulated expression of glucose metabolism-related genes in the high-fat-fed mice. CA significantly increased the mitochondrial DNA content, citrate synthase, and ATP content, as well as the expression of genes related to mitochondrial biogenesis and oxidative phosphorylation in the liver and skeletal muscle in high-fat- fed obese mice. These findings suggested that CA attenuates insulin resistance and promotes insulin sensitivity by enhancing mitochondrial function. [ABSTRACT FROM AUTHOR]

Codium fragile (C. fragile) is a marine alga with high functional food potential. Recent studies have proven C. fragile extract (CFE) effective against obesity. However, the exact underlying mechanism of CFE's anti‐obesity effects remains unclear. Herein, CFE was orally administered to male C57BL/6 mice for 7 weeks, along with a high‐fat diet. CFE (100 mg/kg) effectively induced weight loss, lowered serum cholesterol levels, and suppressed adipocyte differentiation in white adipose tissue (WAT). Furthermore, CFE effectively reduced hepatic total triglyceride, cholesterol, and lipid levels, while significantly improving liver size and color. mRNA expression analysis in WAT and liver tissue revealed that CFE significantly suppressed the expression of PPARγ and aP‐2 in adipocyte differentiation, and SREBP‐1c and FAS in de novo lipogenesis, suggesting that CFE's anti‐obesity effect is exerted by gene inhibition. Practical applications: Research on marine plants with anti‐obesity effects has been increasing recently. This study demonstrated that C. fragile extract (CFE) is effective in reducing body weight and suppressing adipocyte differentiation, along with the improvement of fatty liver in mice fed with a high‐fat diet (HFD). The anti‐obesity effect of CFE was exhibited by the down‐regulation of adipogenesis and lipogenesis, respectively. Based on these results, C. fragile could be useful, not only to effectively combat obesity but also in improving obesity‐induced liver dysfunction. [ABSTRACT FROM AUTHOR]

Dysfunction of pancreatic β-cell is a major determinant for the development of type 2 diabetes. Because of the stimulated insulin secretion in metabolic syndrome, endoplasmic reticulum (ER) stress plays a central mediator for β-cell failure. In this study, we investigated whether an antioxidant phenolic compound, tyrosol protects against β-cell dysfunction associated with ER stress. To address this issue, we exposed pancreatic β cells, NIT-1 to tunicamycin with tyrosol. We found tyrosol diminished tunicamycin-induced cell death in a dose-dependent manner. We also detected tyrosol decreased the expressions of apoptosis-related markers. Exposure to tunicamycin evoked UPR response and co-treatment of tyrosol led to reduction of ER stress. These effects of tyrosol were mediated by the phosphorylation of JNK. Moreover, we confirmed supplement of tyrosol ameliorated β-cell loss induced by high fat feeding. Taken together, our study provides a molecular basis for signaling transduction of protective effect of tyrosol against ER stress-induced β-cell death. Therefore, we suggest tyrosol could be a potential therapeutic candidate for amelioration of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. [ABSTRACT FROM AUTHOR]

Fuzhuan brick tea (FBT) is a post-fermented tea fermented by the fungus Eurotium cristatum and is mainly produced in Hunan Province, China. Our previous study revealed that FBT extract prevents obesity by increasing energy expenditure and mitochondrial content in mice. Therefore, in this study, we hypothesized that FBT extract could be effective in alleviating obesity-induced muscle atrophy by addressing mitochondrial dysfunction, and aimed to explore the underlying molecular mechanism of FBT extract in high-fat diet-induced obese mice. FBT extract increased skeletal muscle weight and size, myosin heavy chain isoforms, and muscle performance in obese mice. Additionally, FBT extract reduced obesity-induced intramuscular lipids, skeletal muscle inflammation, and the expression of skeletal muscle atrophy markers, and increased the expression of fibronectin type III domain-containing protein 5 in skeletal muscles. Obesity-induced skeletal muscle mitochondrial dysfunction was improved by FBT extract as analyzed through mitochondrial morphology, fatty acid oxidation, respiratory chain complexes, and mitochondrial dynamics and biogenesis. Epigallocatechin, a major bioactive compound in FBT extract, attenuated palmitic acid-induced muscle atrophy by regulating mitochondrial functions in C2C12 cells. In conclusion, FBT extract may prevent obesity-induced muscle atrophy by alleviating mitochondrial dysfunction in mice. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: We investigated the molecular basis of the ability of wogonin to control the intracellular signaling cascades of AMP-activated protein kinase (AMPK). This activity induces antitumor activities in glioblastoma multiforme (GBM) cells. Recently, the evolutionarily conserved serine/threonine kinase AMPK has emerged as a possible target for tumor control. We investigated the effects of wogonin on apoptosis regulation and the activation of AMPK. Wogonin treatment resulted in a series of antitumor effects such as cell death and apoptotic appearance. Activation of AMPK suppressed downstream substrates, such as the mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), and resulted in a general decrease in translation. Moreover, wogonin-activated AMPK decreased the activity and/or expression of lipogenic enzymes such as acetyl-CoA carboxylase. Furthermore, in GBM cells, wogonin blocked cell cycle progression at the G1 phase and induced apoptosis by inducing p53 expression and further upregulating p21 expression. Taken together, our findings demonstrated that wogonin has the potential to be a chemopreventive and therapeutic agent against human GBM. [Copyright &y& Elsevier]

The plant Justicia procumbens is traditionally used in Asia to treat fever, cough, and pain. Previous studies have reported its anticancer and anti-asthmatic properties. However, its potential for preventing androgenic alopecia (AGA) has not yet been reported. AGA is a widespread hair loss condition primarily caused by male hormones. In this study, we examined the hair loss-preventing effects of an aqueous extract of J. procumbens (JPAE) using human hair follicle dermal papilla cell (HFDPC) and a mouse model of testosterone-induced AGA. JPAE treatment increased HFDPC proliferation by activating the Wnt/β-catenin signaling pathway. Additionally, JPAE increased the expression of Wnt targets, such as cyclin D1 and VEGF, by promoting the translocation of β-catenin to the nucleus. Administration of JPAE reduced hair loss, increased hair thickness, and enhanced hair shine in an AGA mouse model. Furthermore, it increased the expression of p-GSK-3β and β-catenin in the dorsal skin of the mice. These findings imply that JPAE promotes the proliferation of HFDPC and prevents hair loss in an AGA mouse model. JPAE can therefore be used as a functional food and natural treatment option for AGA to prevent hair loss. [Display omitted] [ABSTRACT FROM AUTHOR]

The effects of a mixture of Hippophae rhamnoides (HR) and Zingiber mioga (ZM) extract (ZH) on intracellular lipid accumulation were investigated in vitro and the anti-obesity effects of ZH evaluated in mice with high-fat diet-induced obesity. The results revealed that ZH inhibited lipid accumulation in 3T3-L1 adipocytes and Huh-7 cells by suppressing adipogenic and lipogenic gene and protein expression. To evaluate the anti-obesity effects of ZH, mice fed a high-fat diet were orally administered low and high doses of ZH (low, ZM 400 mg/kg + HR 100 mg/kg; high, ZM 800 mg/kg + HR 200 mg/kg) for 9 weeks. ZH significantly reduced body weight gain and adipose tissue accumulation with no reduction in food intake when compared to control treatment. Furthermore, ZH reduced hepatic triglyceride and total cholesterol levels, as well as adipose cell size, in the liver and epididymal fat pads, respectively, through inhibition of adipogenesis and lipogenesis-related gene expression. These results suggested that ZH inhibits lipid accumulation, thereby indicating its potential for use as a new therapeutic strategy for obesity. [ABSTRACT FROM AUTHOR]

Patrinia scabiosaefolia (PS) and Hippophae rhamnoides (HR) are traditionally used functional foods. Extracts from the root of PS are known for their anti‐inflammatory effects, whereas those from the leaf of HR are effective at both preventing and treating obesity. This study investigated whether the extract combination of PS and HR (PHE) affected weight loss in obese mice. In vitro experiments demonstrated that PHE showed a synergistic effect on inhibiting adipocyte differentiation as compared with treatment with the single extracts. Additionally, PHE suppressed adipogenic‐related genes in a concentration‐dependent manner. In vivo PHE supplementation suppressed body weight gain, inhibited hepatic lipid accumulation, decreased adipose size, serum triglycerides, and improved insulin resistance in obese mice. These results suggest that a treatment strategy using a combination of plant‐derived extracts might be effective at ameliorating obesity. Practical applications: Currently, common methods for reducing obesity are diet and exercise. These can stimulate oxidative phosphorylation and metabolic activation so have significantly effects. However, these are largely due to individual compliance; there is no significant effect of reducing the worldwide obesity rate. Recently, herbal extracts has been reported as alternative medicine about inflammatory and obesity because diet with the herbal extracts can improve obesity with minimal side effects. Of particular, a mixture of herbal products was investigated for the treatment of obesity. Our reports demonstrated the synergistic effects of natural products and emphasizes the need for studies investigating other combinations of herbal extracts in the treatment of obesity. The results of our studies highlight the synergistic effects of combination phytochemical extracts and their role in ameliorating obesity. [ABSTRACT FROM AUTHOR]

Dietary habits can alter the skeletal muscle performance and mass, and Undaria pinnatifida extracts are considered a potent candidate for improving the muscle mass and function. Therefore, in this study, we aimed to assess the effect of U pinnatifida extracts on exercise endurance and skeletal muscle mass. C57BL/6 mice were fed a 0.25% U pinnatifida extract‐containing diet for 8 weeks. U pinnatifida extract‐fed mice showed increased running distance, total running time, and extensor digitorum longus and gastrocnemius muscle weights. U pinnatifida extract supplementation upregulated the expression of myocyte enhancer factor 2C, oxidative muscle fiber markers such as myosin heavy chain 1 (MHC1), and oxidative biomarkers in the gastrocnemius muscles. Compared to the controls, U pinnatifida extract‐fed mice showed larger mitochondria and increased gene and protein expression of molecules involved in mitochondrial biogenesis and oxidative phosphorylation, including nuclear respiratory factor 2 and mitochondrial transcription factor A. U pinnatifida extract supplementation also increased the mRNA expression of angiogenesis markers, including VEGFa, VEGFb, FGF1, angiopoietin 1, and angiopoietin 2, in the gastrocnemius muscles. Importantly, U pinnatifida extracts upregulated the estrogen‐related receptor γ and peroxisome proliferator‐activated receptor gamma co‐activator 1‐alpha (PGC‐1α)/AMP‐activated protein kinase (AMPK)/sirtuin 1 (SIRT1) networks, which are partially increased by fucoxanthin, hesperetin, and caffeic acid treatments. Collectively, U pinnatifida extracts enhance mitochondrial biogenesis, increase oxidative muscle fiber, and promote angiogenesis in skeletal muscles, resulting in improved exercise capacity and skeletal muscle mass. These effects are attributable to fucoxanthin, hesperetin, and caffeic acid, bioactive components of U pinnatifida extracts. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress and autophagy are regulated by shared signaling pathways, and their dysfunction is directly related to pathological conditions. This study investigated the function of the unc-51 like autophagy activating kinase 1 (ULK1)-autophagy related 13 (ATG13) complex in ER stress conditions through a knockout (KO) approach. Unlike other autophagy genes, KO of ULK1 or ATG13 attenuated ER stress and promoted mammalian target of rapamycin complex 1 (mTORC1) activation. Compared with wild type (WT) cells, ULK1 and ATG13 KO cells displayed increased viability, while beclin 1, ATG14 , and ULK1/2 KO cells did not. Tunicamycin treatment upregulated the expression of ER stress markers (DNA damage inducible transcript 3, heat shock protein family A (Hsp70) member 5, and phosphorylated eukaryotic translation initiation factor 2 alpha kinase 3, eukaryotic translation initiation factor 2 subunit alpha, and endoplasmic reticulum to nucleus signaling 1); however, these were decreased in ULK1 and ATG1 3 KO cells. Insulin treatment upregulates the phosphorylation of ribosomal protein S6 kinase B1 (RPS6KB1) and AKT serine/threonine kinase 1 (AKT1), which was suppressed by tunicamycin. Notably, ATG13 and ULK1 deficiency ameliorated tunicamycin-induced insulin resistance, with enhanced RPS6KB1 and AKT1 phosphorylation in KO cells compared to WT cells. Although ULK1 and ATG13 are necessary for autophagy induction after tunicamycin-induced ER stress, autophagy does not seem to directly affect tunicamycin-induced cell death, ER stress, or insulin resistance. Our results indicate that loss of the ULK1-ATG13 complex attenuates ER stress and cell death and increases mTORC1 signaling. • Tunicamycin-induced apoptosis is enhanced by autophagy inhibition. • Loss of the autophagy genes ULK1 and ATG13 reduced tunicamycin-induced apoptosis. • ULK1 and ATG13 loss reduced tunicamycin-induced endoplasmic reticulum (ER) stress. • ULK1 and ATG13 loss alleviated insulin resistance caused by ER stress. [ABSTRACT FROM AUTHOR]

Senile osteoporosis increases the risk of skeletal fractures with age. Cheonggukjang (CGJ), a traditional Korean dry fermented soybean product, has numerous therapeutic effects; however, its effects on bone mineral density (BMD) and bone metabolism in senile osteoporosis are unclear. In this study, we treated the senescence-accelerated mouse prone 6 (SAMP6) model of senile osteoporosis with CGJ to determine its potential for ameliorating and preventing osteoporosis progression. High-performance liquid chromatography analysis for isoflavone profiles revealed that short-term fermentation significantly increased the isoflavone aglycone content in soybeans. Thereafter, we fed 6-week-old SAMP6 mice with experimental diets containing 5% or 10% CGJ for 15 weeks. Microcomputed tomography revealed that CGJ supplementation effectively increased the BMD and relative bone length. In vitro, CGJ increased the osteopontin reactivity and upregulated the expression of Alp, Col1a1, Fak, Bmp2/4, Smad1/5/8, and Runx2 in osteoblasts, and decreased Cathepsin K reactivity and downregulated Rankl and Nfatc1 expression in osteoclasts. In addition, CGJ increased the osteoprotegerin/Rankl ratio. Collectively, these results demonstrate that CGJ can ameliorate the detrimental effects of senile osteoporosis by improving osteogenesis and decreasing osteoclast activity. [ABSTRACT FROM AUTHOR]

Recent studies suggest an alternative pathway of lipid breakdown called lipophagy, which delivers lipid droplets (LDs) to lysosomes for degradation of LDs. However, molecular mechanisms regulating lipophagy are still largely unknown. In this study, we evaluated the effect of oleic acid (OA) on lipophagy in cells. We found that OA treatment results in accumulation of p62 and LC3-II proteins and reduces red fluorescence in cells stably expressing mCherry-GFP-LC3. In addition, OA inhibits the co-localization of LC3 with LAMP1 under serum-deprived condition, suggesting that OA blocks autophagosome-lysosome fusion. In the cells with ATG5 or ULK1 gene deletion, LDs did not increase upon OA treatment more than in wild type cells. However, cell starvation following OA removal resulted in reduced lipid accumulation by lipophagy and recovery of autophagy flux, suggesting that the specific condition of OA treatment and cell starvation are important for lipophagy flux activity. • Autolysosome is inhibited in oleic acid-treated cells under serum starvation. • ATG5 or ULK1 deficiency did not show further increase in the lipid accumulation than the wild types. • OA inhibits autophagy flux by blocking autophagosome-lysosome fusion. • Defective autolysosome by OA results in impaired lipid degradation. [ABSTRACT FROM AUTHOR]

Osteopenia is a preclinical phase of osteoporosis, it occurs naturally with aging and increases the risk of bone fractures in elderly males. Previous studies have revealed the beneficial effects of soybean on preventing bone loss due to its isoflavone contents. Fermentation alters the soybean isoflavone contents, that is, isoflavone glucosides is hydrolyzed into aglycones. However, it is not clear how these alterations influences the preventive effect of soybean on bone loss. In this study, we fed senescence‐accelerated mouse prone 6 (SAMP6), a model of senile osteopenia, with an equal dosage of nonfermented soybean (NS) or fermented soybean, Doenjang (DJ) for 18 weeks. Mice supplemented with DJ showed 1.13‐fold higher bone densities and 1.06‐fold longer relative bone lengths than those of osteopenic SAMP6 mice old control (OC), while NS‐supplemented mice showed no significant improvement. Supplementation with DJ effectively prevented bone loss in the osteopenia model by the improvement of bone formation and reduction of osteoclastogenesis. In addition, we discovered that DJ increased osteogenesis in SAMP6 mice via BMP2‐Smad‐Runx2 signaling. These results suggest that the fermentation process could enhance bone loss prevention by soybean and dietary supplementation with fermented soybeans may be beneficial for bone health. Practical Application: Soybean fermentation improved the preventive effects of soybean on bone loss. Therefore, the consumption of fermented soybean, Doenjang, is a potential alternative for aging‐related bone loss therapy. [ABSTRACT FROM AUTHOR]

Introduction: Apigenin (AP) has been reported to elicit anti-inflammatory effects. In this study, we investigated the effect of AP on sciatic nerve denervation-induced muscle atrophy.Methods: Sciatic nerve-denervated mice were fed a 0.1% AP-containing diet for 2 weeks. Muscle weight and cross-sectional area (CSA), and the expression of atrophic genes and inflammatory cytokines in the gastrocnemius were analyzed.Results: Denervation significantly induced muscle atrophy. However, values for muscle weight and CSA were greater in the denervated muscle of the AP mice than the controls. AP suppressed the expression of MuRF1, but upregulated both myosin heavy chain (MHC) and MHC type IIb. AP also significantly suppressed expression of tumor necrosis-alpha in the gastrocnemius and soleus muscles, and interleukin-6 expression in the soleus muscle.Discussion: AP appears to inhibit denervation-induced muscle atrophy, which may be due in part to its inhibitory effect on inflammatory processes within muscle. Muscle Nerve 58: 314-318, 2018. [ABSTRACT FROM AUTHOR]

Abstract: Doenjang (DJ), a fermented soybean product used in soups, stews, and sauces, contains high quality proteins, fats, vitamins, minerals, and other functional ingredients, including isoflavones and saponins. This study investigated whether DJ improves the bioavailability of isoflavones compared to boiled soybean (BS) in sham‐operated or ovariectomized (OVX) rats. We also examined the effects of ovariectomy on the differences in bioavailability of isoflavones. BS and DJ were administered in sham‐operated and OVX rats, and blood samples were collected. Twenty‐six isoflavone‐derived metabolites were identified. Pharmacokinetic analysis revealed that T1/2 values of the individual isoflavone metabolites were most different in sham and OVX rats, even after the same sample treatment; however, Tmax values were significant different in a few metabolites such as daidzein 4′‐glucuronide, daidzein 4′‐sulfate, 2‐(4‐hydroxyphenyl)propionic acid, and benzoic acid. For most of the individual metabolites, Cmax was higher in both sham and OVX rats administered BS than those administered DJ. The AUC was generally lower in OVX rats than in sham rats. The AUC of daidzein and genistein in BS‐fed sham rats was approximately 1.7‐fold higher than those administered DJ, whereas glycitein was detected only in the DJ group. No significant differences in AUC of daidzein and genistein were observed between BS and DJ administration in OVX rats, although the total isoflavone content of DJ was lower; thus, DJ‐mediated isoflavone bioavailability was more effective in OVX rats. Similar tendencies were observed for phase II and gut‐mediated metabolites. These results suggested that DJ enhanced isoflavone bioavailability under estrogen deficiency, even when the total isoflavone content was decreased by fermentation. [ABSTRACT FROM AUTHOR]

Although classification of an individual’s Sasang constitution is a key step in the prescription of traditional Korean medicine, the classifying process is complex and not objective. Identification of metabolic-based biomarkers could allow the development of a reliable and sensitive classification technique and even therapeutic management. Our pilot study investigated whether metabolites in plasma are characteristic of Sasang constitutions. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolic analysis was conducted against 15 Soyangin (SY), 15 Taeeumin (TE), and 18 Soeumin (SE) individuals, as classified according to the Questionnaire for Sasang Constitution Classification II (QSCC II) and specialist diagnosis. Metabolomics data showed that the TE group was significantly separated from the SY and SE groups. Nine canonical pathways related to constitution; phenylalanine metabolism, aminoacyl-tRNA, tyrosine, and tryptophan biosynthesis were activated in the TE group as compared with the other groups. Similar to the results of the metabolomics analysis, the TE group was also significantly separated from the other two groups by lipidomic analysis. On the other hand, the intensity of lipid metabolites was higher in the SY group than in the other groups. Our findings suggest that the combined analysis of metabolomics and lipidomics can provide useful information for characteristics of Sasang constitutions. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the effect of ovariectomy on nutrikinetics of genistein metabolites. To characterize the time-dependent changes in genistein metabolite concentrations, we identified 13 genistein metabolites using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The nutrikinetics of the individual metabolites at different time points were analyzed. Nutrikinetic analysis showed that genistein, genistein 4′-glucuronide, genistein 7-glucuronide, 3-hydroxygenistein, and hippuric acid showed relatively high bioavailability in the sham group compared to that in the ovariectomy group, suggesting that ovariectomy likely results in lower genistein bioavailability. These results may be related to alteration of gut microbiota by ovariectomy. The relative abundance of species of the Parabacteroides, Dorea, and Butyricimonas genera, and Desulfovibrionaceae_unclassified, Lachnospiraceae_unclassified, and Rikenellaceae_unclassified families increased in the ovariectomy group while the relative abundance of 523_7_unclassified and Y52_unclassified_unclassified increased in the sham group. These results suggest that gut microbiota alteration by ovariectomy may affect genistein bioavailability. [ABSTRACT FROM AUTHOR]

There has been great interest in the browning of fat for the treatment of obesity. Although β-lapachone (BLC) has potential therapeutic effects on obesity, the fat-browning effect and thermogenic capacity of BLC on obesity have never been demonstrated. Here, we showed that BLC stimulated the browning of white adipose tissue (WAT), increased the expression of brown adipocyte-specific genes (e.g., uncoupling protein 1 [UCP1]), decreased body weight gain, and ameliorated metabolic parameters in mice fed a high-fat diet. Consistently, BLC-treated mice showed significantly higher energy expenditure compared with control mice. In vitro, BLC increased the expression of brown adipocyte-specific genes in stromal vascular fraction-differentiated adipocytes. BLC also controlled the expression of miR-382, which led to the upregulation of its direct target, Dio2. Upregulation of miR-382 markedly inhibited the differentiation of adipocytes into beige adipocytes, whereas BLC recovered beige adipocyte differentiation and increased the expression of Dio2 and UCP1. Our findings suggest that the BLC-mediated increase in the browning of WAT and the thermogenic capacity of BAT significantly results in increases in energy expenditure. Browning of WAT by BLC was partially controlled via the regulation of miR-382 targeting Dio2 and may lead to the prevention of diet-induced obesity. [ABSTRACT FROM AUTHOR]

Allyl-isothiocyanate (AITC) is an organosulfur phytochemical found in abundance in common cruciferous vegetables such as mustard, wasabi, and cabbage. Although AITC is metabolized primarily through the mercapturic acid pathway, its exact pharmacokinetics remains undefined and the biological function of AITC metabolites is still largely unknown. In this study, we evaluated the inhibitory effects of AITC metabolites on lipid accumulation in vitro and elucidated the pharmacokinetics and tissue distribution of AITC metabolites in rats. We found that AITC metabolites generally conjugate with glutathione (GSH) or N-acetylcysteine (NAC) and are distributed in most organs and tissues. Pharmacokinetic analysis showed a rapid uptake and complete metabolism of AITC following oral administration to rats. Although AITC has been reported to exhibit anti-tumor activity in bladder cancer, the potential bioactivity of its metabolites has not been explored. We found that GSH-AITC and NAC-AITC effectively inhibit adipogenic differentiation of 3T3-L1 preadipocytes and suppress expression of PPAR-γ, C/EBPα, and FAS, which are up-regulated during adipogenesis. GSH-AITC and NAC-AITC also suppressed oleic acid-induced lipid accumulation and lipogenesis in hepatocytes. Our findings suggest that AITC is almost completely metabolized in the liver and rapidly excreted in urine through the mercapturic acid pathway following administration in rats. AITC metabolites may exert anti-obesity effects through suppression of adipogenesis or lipogenesis. [ABSTRACT FROM AUTHOR]

[Display omitted] • OM increased skeletal muscle weight and improved muscle function in obese mice. • OM upregulated AKT/mTOR pathway and downregulated Smad-FOXO signaling. • Schizandrin B, a major bioactive compoenet of OM, downregulated Smad-FOXO signaling in palmitic acid-treated C2C12 cells. • These results suggest the OM ameliorated obesity-induced skeletal muscle atrophy in mice. Schisandra chinensis fruit (Omiza in Korean), used for the production tea or liquor, and is known to enhance skeletal muscle function. However, the effect of Omiza extract (OM) on obesity-induced skeletal muscle atrophy remains unclear. This study investigated the effect of OM on skeletal muscle mass and performance in obese mice. OM increased skeletal muscle weight, size and improved skeletal muscle performance. Further, it also suppressed obesity-induced increases in proinflammatory cytokines, MuRF1, and Atrogin1 in mouse skeletal muscle and enhanced the expression of MHC and the phosphorylation of AKT/mTOR signaling molecules, thereby suppressing myostatin expression and regulating Smad-FOXO signaling. Schizandrin B, a major component of OM inhibited palmitic acid induced atrophy in C2C12 cells via Smad-FOXO regulation, suggesting that it partially contributed to the effects of OM against obesity-induced muscle atrophy. Taken together, OM may have the potential to prevent and treat obesity-induced muscle atrophy. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) stress induces hepatic steatosis and inflammation in the liver. Although melatonin ameliorates ER stress-target genes, it remains unknown whether melatonin protects against hepatic steatosis as well as inflammation through regulation of miRNA. MicroRNAs have been identified as pivotal regulators in the field of gene regulation and their dysfunctions are a common feature in a variety of metabolic diseases. Especially, among miRNAs, miR-23a has been shown to regulate ER stress. Herein, we investigated the crucial roles of melatonin in hepatic steatosis and inflammation in vivo . Tunicamycin challenge caused increase of hepatic triglyceride and intracellular calcium levels through activation of ER stress, whereas these phenomena were partially disrupted by melatonin. We also demonstrated that expression of miR-23a stimulated with tunicamycin was rescued by melatonin treatment, resulting in reduced ER stress in primary hepatocytes. Overall, these results suggest a new function of melatonin that is involved in ameliorating ER stress-induced hepatic steatosis and inflammation by attenuating miR-23a. Melatonin may be useful as a pharmacological agent to protect against hepatic metabolic diseases due to its ability to regulate expression of miR-23a. [ABSTRACT FROM AUTHOR]

Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet–induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is associated with the pathophysiology of insulin resistance. Allylisothiocyanate (AITC) is found in many cruciferous vegetables and has been reported to possess anticancer activity. However, the effect of AITC on insulin resistance and mitochondrial function has not yet been investigated. Here, we show that AITC increased glucose uptake in insulin-resistant C2C12 myotubes and augmented glucose transporter 4 (GLUT4) translocation in L6-GLUT4 myc cells. AITC recovered the impaired insulin signaling evoked by free fatty acid exposure and increased mitochondrial membrane potential and mitochondrial DNA content. AITC also elevated the rate of oxygen consumption in C2C12 cells. Furthermore, mice that were fed a high-fat diet with AITC for 10 weeks had reduced diet-induced obesity and hepatic steatosis. AITC also inhibited the hyperglycemia and hyperinsulinemia induced by the consumption of a high-fat diet. Glucose and insulin tolerance tests indicated that AITC improved both glucose tolerance and insulin sensitivity. In addition, AITC inhibited hepatic gluconeogenesis and ameliorated high fat diet-induced mitochondrial dysfunction. Collectively, these data suggest that the protective effect of AITC on insulin resistance is partly mediated through the modulation of mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Although rice has been shown to have beneficial health effects, little is known about the effect of rice on hepatic lipid accumulation as a carbohydrate source. This study investigated the effects and mechanism of action of cooked rice on high-fat diet (HF)-induced fat accumulation. The C57BL/6 mice were divided into three groups and fed a normal diet (NOR), HF, or HF with cooked rice (HF-CR) for 12 weeks. The HF-CR-fed mice had significantly lower body weight gains and abdominal fat mass compared with the HF-fed mice. Consuming cooked rice resulted in significantly lower serum total cholesterol, low-density lipoprotein cholesterol, hepatic lipid content, and lipid droplet number and size. Cooked rice consumption also suppressed the HF-induced increase in expression of lipogenic genes, such as sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS), stearoyl CoA desaturase 1 (SCD-1), peroxisome proliferator-activated receptor gamma (PPAR γ), and CD36. The expression of cholesterol metabolism-related genes, such as acyl-CoA:cholesterol acyltransferase 1 (ACAT1), were also downregulated in the HF-CR-fed mice. Cooked rice may prevent HF-induced fat accumulation by regulating lipid metabolism-related gene expression, and it may be a useful carbohydrate source for preventing nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]