Erratum to: Oxya chinensis sinuosa (OC) Extracts Protects ARPE-19 Cells against Oxidative Stress via Activation of the Mitogen-Activated Protein Kinases (MAPKs)/Nuclear Factor-κB (NF-κB) Pathway.

[This corrects the article DOI: 10.5851/kosfa.2024.e15.].

Oxya chinensis sinuosa (OC) Extracts Protects ARPE-19 Cells against Oxidative Stress via Activation of the Mitogen-Activated Protein Kinases (MAPKs)/ Nuclear Factor-κB (NF-κB) Pathway.

Oxya chinensis sinuosa (OC) is a well-known edible insect. Several researches on the health benefits of OC consumption have been performed to date; however, their effect on eye health remains largely unknown. This study aimed to assess the protective effects of OC extracts on the oxidative stress on the retinal pigment epithelium (RPE) cells. Oxidative damage has been identified as one of the key regulatory factors in age-related macular degeneration. H2O2-induced reactive oxygen species (ROS) production, a well-known oxidative stress factor, can cause cell death in retinal pigment epithelia cells. In this study, we found that three OC extracts effectively prevented H2O2-induced ROS production and subsequent death of ARPE-19 cells in a dose-dependent manner. In addition, the OC extracts inhibited the phosphorylation of mitogen-activated protein kinases including p38, JNK, and ERK. The OC extracts restored IκBα degradation induced by H2O2, indicating that OC extracts suppressed the activation of nuclear factor-κB. Furthermore, the three OC extracts were shown to have antioxidant effects by up-regulating the intracellular expression of key antioxidant proteins such as SOD, NQO, and HO-1. Here we demonstrated the antioxidant and anti-apoptotic effects of the OC extracts on ARPE-19, indicating their potential role in improving eye health. These results suggest that three OC extracts plays a critical role in oxidative stress-induced cell death protects in ARPE-19 cells.

Effects of Mealworm Fermentation Extract and Soy Protein Mix Ratio on Hepatic Glucose and Lipid Metabolism in Obese-Induced Mice.

Previous studies found that mealworm fermentation extract (TMP) reduced alcoholic hepatic steatogenesis. This study examined how the ratio of TMP and soy protein (SP) mix affected glucose and lipid metabolism in obese mice given a high-fat diet (HFD). Mice were given HFD supplemented with 100% SP or the following three ratios of TMP and SP mix for 12 weeks: 20% (S4T1), 40% (S3T2), and 60% (S2T3) TMP. When compared to the SP group, the S2T3 group had considerably lower body weight gain and food consumption. When compared to the SP group, the S2T3 group had slightly lower blood insulin and leptin levels, as well as a lower homeostasis model assessment of insulin resistance score. The use of TMP instead of SP reduced the size of epididymal adipose tissue cells. An increase in the extent of substitution of SP with TMP inhibited the gene expression of hepatic fructolysis/gluconeogenesis (KHK, ALDOB, DLD, and FBP1), lipogenesis (FAS, SCD1, CD36, and DGAT2), and its transcriptional factors (PPARγ and ChREBP). Furthermore, the S2T3 group dramatically reduced the expression of hepatic genes implicated in endoplasmic reticulum stress (PDI) and antioxidant defense (SOD1). The 60% TMP mix, in particular, reduced the expression of hepatic glucose and lipid metabolismrelated genes in HFD-fed mice. The manufacturing of functional processed goods may be accomplished by combining SP and TMP in a 2:3 ratio.

Protaetia brevitarsis seulensis larvae ethanol extract inhibits RANKL-stimulated osteoclastogenesis and ameliorates bone loss in ovariectomized mice.

Modulation of osteoclast formation could be a therapeutic target for inhibiting pathological bone destruction. The receptor activator of nuclear factor (NF)-κB ligand (RANKL) is known to be an essential factor in osteoclast differentiation and activation inducers. However, whether Protaetia brevitarsis seulensis (P. brevitarsis) larvae-a traditional animal-derived medicine used in many Asian countries-can inhibit RANKL-induced osteoclast formation and prevent ovariectomy (OVX)-induced bone loss has not been evaluated. Here, we aimed to investigate the anti-osteoporotic effects of P. brevitarsis larvae ethanol extract (PBE) in RANKL-stimulated RAW264.7 cells and OVX mice. In vitro, PBE (0.1, 0.5, 1, and 2 mg/mL) decreased RANKL­induced tartrate-resistant acid phosphatase (TRAP) activity and expression of osteoclastogenesis-associated genes and proteins. Furthermore, PBE (0.1, 0.5, 1, and 2 mg/mL) significantly inhibited the phosphorylation of p38 and NF-κB. Female C3H/HeN mice were divided into five groups (n = 5 per group), namely, sham-operated, OVX, OVX+PBEL (100 mg/kg, oral gavage), OVX+PBEH (200 mg/kg, oral gavage), and OVX+estradiol (0.03 µg/day, subcutaneous injection). High doses of PBE significantly increased femoral bone mineral density (BMD) and bone volume/tissue volume (BV/TV), whereas femoral bone surface/bone volume (BS/BV) and osteoclastogenesis-associated protein expression decreased compared to those in the OVX group. Moreover, PBE (200 mg/kg) significantly increased estradiol and procollagen type I N-terminal propeptide and decreased N-terminal telopeptide of type I collagen and C-terminal telopeptide of type I collagen compared to those in the OVX group. Our results suggest that PBE can be an effective therapeutic candidate for preventing or treating postmenopausal osteoporosis.

The Preparation and Physiochemical Characterization of Tenebrio molitor Chitin Using Alcalase.

Chitin is mostly produced from crustaceans, but it is difficult to supply raw materials due to marine pollution, and the commonly used chemical chitin extraction method is not environmentally friendly. Therefore, this study aims to establish a chitin extraction process using enzymes and to develop edible insect-derived chitin as an eco-friendly new material. The response surface methodology (RSM) was used to determine the optimal conditions for enzymatic hydrolysis. The optimal conditions for enzymatic hydrolysis by RSM were determined to be the substrate concentration (7.5%), enzyme concentration (80 µL/g), and reaction time (24 h). The solubility and DDA of the mealworm chitosan were 45% and 37%, respectively, and those of the commercial chitosan were 61% and 57%, respectively. In regard to the thermodynamic properties, the exothermic peak of mealworm chitin was similar to that of commercial chitin. In the FT-IR spectrum, a band was observed in mealworm chitin corresponding to the C=O of the NHCOCH3 group at 1645 cm-1, but this band showed low-intensity C=O in the mealworm chitosan due to deacetylation. Collectively, mealworm chitosan shows almost similar physical and chemical properties to commercial chitosan. Therefore, it is shown that an eco-friendly process can be introduced into chitosan production by using enzyme-extracted mealworms for chitin/chitosan production.

Mealworm Ethanol Extract Enhances Myogenic Differentiation and Alleviates Dexamethasone-Induced Muscle Atrophy in C2C12 Cells.

Aging, and other disease-related muscle disorders are serious health problems. Dexamethasone (DEX), a synthetic glucocorticoid, can trigger skeletal muscle atrophy. This study examined the effects of mealworm (Tenebrio molitor larva) ethanol extract (TME) on C2C12 myoblast differentiation and DEX-induced myotube atrophy. TME induced myotube formation compared to the differentiation medium (DM) group. TME also significantly increased the mRNA expression of muscle creatine kinase (CKm) and myogenic regulatory factors (MRFs), such as myogenin (MyoG), myogenic factor (Myf)5, and MRF4 (Myf6). TME dramatically increased the muscle-specific protein, MyoG, compared to the control, whereas the expression of myogenic differentiation 1 (MyoD) remained unchanged. It also activated the mammalian target of rapamycin (mTOR) signaling pathway. In the DEX-induced muscle atrophy C2C12 model, TME reduced the gene expression of atrogin-1, muscle RING finger protein-1 (MuRF-1), and myostatin, which are involved in protein degradation in skeletal muscles. Furthermore, TME elevated the phosphorylation of forkhead box O3 (FoxO3α) and protein kinase B (Akt). These findings suggest that TME can enhance myotube hypertrophy by regulating the mTOR signaling pathway, and can rescue DEX-induced muscle atrophy by alleviating atrophic muscle markers mediated by Akt activation. Thus, TME can be a potential therapeutic agent for treating muscle weakness and atrophy.

Polygonum multiflorum Thunb. Hot Water Extract Reverses High-Fat Diet-Induced Lipid Metabolism of White and Brown Adipose Tissues in Obese Mice.

The purpose of the present study was to determine whether an anti-obesity effect of a Polygonum multiflorum Thunb. hot water extract (PW) was involved in the lipid metabolism of white adipose tissue (WAT) and brown adipose tissue (BAT) in high-fat diet (HFD)-induced C57BL/6N obese mice. Mice freely received a normal diet (NCD) or an HFD for 12 weeks; HFD-fed mice were orally given PW (100 or 300 mg/kg) or garcinia cambogia (GC, 200 mg/kg) once a day. After 12 weeks, PW (300 mg/kg) or GC significantly alleviated adiposity by reducing body weight, WAT weights, and food efficiency ratio. PW (300 mg/kg) improved hyperinsulinemia and enhanced insulin sensitivity. In addition, PW (300 mg/kg) significantly down-regulated expression of carbohydrate-responsive element-binding protein (ChREBP) and diacylglycerol O-acyltransferase 2 (DGAT2) genes in WAT compared with the untreated HFD group. HFD increased BAT gene levels such as adrenoceptor beta 3 (ADRB3), peroxisome proliferator-activated receptor γ (PPARγ), hormone-sensitive lipase (HSL), cluster of differentiation 36 (CD36), fatty acid-binding protein 4 (FABP4), PPARγ coactivator 1-α (PGC-1α), PPARα, and carnitine palmitoyltransferase 1B (CPT1B) compared with the NCD group; however, PW or GC effectively reversed those levels. These findings suggest that the anti-obesity activity of PW was mediated via suppression of lipogenesis in WAT, leading to the normalization of lipid metabolism in BAT.

Anticancer Activity of Periplanetasin-5, an Antimicrobial Peptide from the Cockroach Periplaneta americana.

Cockroaches live in places where various pathogens exist and thus are more likely to use antimicrobial compounds to defend against pathogen intrusions. We previously performed an in silico analysis of the Periplaneta americana transcriptome and detected periplanetasin-5 using an in silico antimicrobial peptide prediction method. In this study, we investigated whether periplanetasin-5 has anticancer activity against the human leukemia cell line K562. Cell growth and survival of K562 cells treated with periplanetasin-5 were decreased in a dose-dependent manner. By using flow cytometric analysis, acridine orange/ethidium bromide (AO/EB) staining and DNA fragmentation, we found that periplanetasin-5 induced apoptotic and necrotic cell death in leukemia cells. In addition, these events were associated with increased levels of the pro-apoptotic proteins Fas and cytochrome c and reduced levels of the anti-apoptotic protein Bcl-2. Periplanetasin-5 induces the cleavage of pro-caspase-9, pro-caspase-8, pro-caspase-3, and poly (ADP-ribose) polymerase (PARP). The above data suggest that periplanetasin-5 induces apoptosis via both the intrinsic and extrinsic pathways. Moreover, caspase-related apoptosis was further confirmed by using the caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (Z-VAD-FMK), which reversed the periplanetasin-5-induced reduction in cell viability. In conclusion, periplanetasin-5 caused apoptosis in leukemia cells, suggesting its potential utility as an anticancer therapeutic agent.

Antiseptic effect of antimicrobial peptide psacotheasin 2 derived from the yellow-spotted longicorn beetle (Psacothea hilaris).

Given the challenges posed by antibiotic resistant microbes and the high mortality rate associated with sepsis, there is an urgent need to develop novel peptide antibiotics that exhibit both antimicrobial and anti-inflammatory activities. Herein, we evaluated antimicrobial activity and anti-inflammatory activity of psacotheasin 2, one of the antimicrobial peptide candidates identified previously using an in silico analysis on the transcriptome of Psacothea hilaris. In addition to exhibiting antimicrobial activities against microorganisms without inducing hemolysis, psacotheasin 2 also decreased the nitric oxide production in lipopolysaccharide (LPS)-induced Raw264.7 cells. Moreover, ELISA and western blot analysis revealed that psacotheasin 2 reduced the expression levels of pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Further, we found that psacotheasin 2 markedly reduced the expression levels of pro-inflammatory cytokines (IL-6 and IL-1ß) by regulating mitogen-activated protein kinases (MAPKs) and nuclear factor-kB (NF-kB) signaling in LPS-induced Raw264.7 cells. We also confirmed that the binding of psacotheasin 2 to bacterial cell membranes occurs via a specific interaction with LPS. In mouse models of LPS-induced shock, psacotheasin 2 significantly enhanced the survival rate and recovered weight by attenuating pro-inflammatory cytokines. Thus, psacotheasin 2 could be a promising candidate as a peptide antiseptic agent.

Effects of Edible Insect Tenebrio molitor Larva Fermentation Extract as a Substitute Protein on Hepatosteatogenesis and Proteomic Changes in Obese Mice Induced by High-Fat Diet.

Mealworms (Tenebrio molitor larva) are an edible insect and a protein-rich food; however, research on mealworms as a substitute protein is insufficient. In this study, mealworm fermentation extract (TMP) was assessed as a replacement for soy protein (SP) in a control diet (CON) or a high-fat diet (HFD) of mice for 12 weeks. TMP substitution reduced body weight, body weight gain, body fat mass (perirenal and mesenteric), fat size, glucose intolerance, and insulin resistance compared to the HFD-SP group. TMP alleviated hepatic steatosis (lipid contents and lipid droplets) in high-fat-fed mice and down-regulated the PPARγ, CD36, and DGAT2 gene levels. Proteomic analysis showed that a HFD for 12 weeks up-regulated 20 proteins and down-regulated 17 proteins in mice fed SP. On the other hand, TMP reversed the protein profiles. TMP significantly down-regulated KHK, GLO1, ATP5H, SOD, and DDAH1 and up-regulated DLD, Mup1, CPS1, Ces3b, PDI, and HYOU1 compared to the HFD-SP group. These proteins are involved in the glucose, lipid, and amino acid metabolism, as well as in oxidative stress and endoplasmic reticulum stress. Thus, substituting SP for TMP helped improve HFD-induced obesity, steatosis, and insulin resistance in mice. These results suggest that TMP is a potential substitute for commonly used protein sources.

Metabolomics Study of Serum from a Chronic Alcohol-Fed Rat Model Following Administration of Defatted Tenebrio molitor Larva Fermentation Extract.

We have previously showed that defatted mealworm fermentation extract (MWF) attenuates alcoholic liver injury by regulating lipid, inflammatory, and antioxidant metabolism in chronic alcohol-fed rats. The current metabolomics study was performed to monitor biochemical events following the administration of MWF (daily for eight weeks) to a rat model of alcoholic liver injury by gas chromatography-tandem mass spectrometry (GC-MS/MS). The levels of 15 amino acids (AAs), 17 organic acids (OAs), and 19 free fatty acids (FFAs) were measured in serum. Analysis of variance (ANOVA), principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) were used to compare the levels of 51 metabolites in serum. In particular, 3-hydroxybutyric acid (3-HB), pyroglutamic acid (PG), octadecanoic acid, and docosahexaenoic acid (DHA) were evaluated as high variable importance point (VIP) scores and PCA loading scores as determined by PLS-DA and PCA, and these were significantly higher in the MWF and silymarin groups than in the EtOH group. MWF showed a protective effect from alcohol-induced liver damage by elevating hepatic ß-oxidation activity, and serum 3-HB levels were significantly higher in the MWF group than in the EtOH control group. Glycine levels were higher in the MWF group than in the EtOH group, and PG levels (related to glutathione production) were also elevated, indicating a reduction in alcohol-related oxidative stress. In addition, MWF is protected from alcohol-induced inflammation and steatosis by increasing serum DHA, palmitic, and octadecanoic acid levels as compared with the EtOH group. These results suggest that MWF might attenuate alcoholic liver disease, due to its anti-inflammatory and antioxidant effects by up-regulating hepatic ß-oxidation activity and down-regulating liver FFA uptake.

Defatted Tenebrio molitor Larva Fermentation Extract Modifies Steatosis, Inflammation and Intestinal Microflora in Chronic Alcohol-Fed Rats.

This study examined the effects of defatted mealworm fermentation extract (MWF) on alcoholic liver injury in rats. The rats were fed either a Lieber-DeCarli control (Con) or alcohol liquid diet (EtOH). The alcohol-fed rats were administered MWF (50, 100, or 200 mg/kg/day) and silymarin (200 mg/kg/day) orally for eight weeks. MWF prevented alcohol-induced hepatocellular damage by decreasing their serum aspartate transaminase, alanine transaminase, and gamma-glutamyl transpeptidase levels significantly compared to the EtOH group. MWF effectively reduced the relative hepatic weight, lipid contents, and fat deposition, along with the down-regulation of transcriptional factors and genes involved in lipogenesis compared to the EtOH group. It also enhanced the antioxidant defense system by elevating the glutathione level and glutathione reductase activity. MWF attenuated the alcohol-induced inflammatory response by down-regulating hepatic inflammation-associated proteins expression, such as phosphorylated-inhibitor of nuclear factor-kappa B-alpha and tumor necrosis factor-alpha, in chronic alcohol-fed rats. Furthermore, sequencing analysis in the colonic microbiota showed that MWF tended to increase Lactobacillus johnsonii reduced by chronic alcohol consumption. These findings suggest that MWF can attenuate alcoholic liver injury by regulating the lipogenic and inflammatory pathway and antioxidant defense system, as well as by partially altering the microbial composition.

Protective Effects of Methoxsalen Supplementation on Chronic Alcohol-Induced Osteopenia and Steatosis in Rats.

Osteopenia or osteoporosis occurs frequently in alcoholics and patients with alcoholic fatty liver disease. Methoxsalen (MTS), 8-methoxypsoralen, improved osteoporosis in ovariectomized and diabetic mouse models; however, its effects on alcohol-induced osteopenia and steatosis have not been reported. This study examined the effects of MTS on alcohol-induced bone loss and steatosis. Rats in the alcohol groups were fed a Liber-DeCarli liquid diet containing 36% of its calories as alcohol. MTS was at 0.005% in their diet, while alendronate (positive control; 500 µg/kg BW/day) was administered orally for eight weeks. The pair-fed group received the same volume of isocaloric liquid diet containing dextrin-maltose instead of alcohol as the alcohol control group consumed the previous day. In the alcohol-fed rats, the MTS and alendronate increased the bone volume density, bone surface density and trabecular number, while the bone specific surface, trabecular separation and structure model index were decreased in the tibia. MTS down-regulated tibial tartrate-resistant acid phosphatase 5 (TRAP) expression compared to the alcohol control group. MTS or alendronate prevented chronic alcohol-induced hepatic lipid accumulation and the triglyceride level in the alcohol-fed rats by decreasing the lipogenic enzyme activities and increasing the fatty acid oxidation enzyme activities. MTS reduced significantly the serum levels of alcohol, TRAP and tumor necrosis factor-α compared to the alcohol control group. Overall, these results suggest that MTS is likely to be an alternative agent for alcoholic osteopenia and hepatosteatosis.

Heshouwu (Polygonum multiflorum Thunb.) Extract Attenuates Bone Loss in Diabetic Mice.

This study investigated the effects and mechanism of Heshouwu (Polygonum multiflorum Thunb.) water extract (HSW) on diabetes-related bone loss in mice. HSW was orally administered (300 mg/kg body weight) to high-fat diet and streptozotocin-induced diabetic mice for 10 weeks. HSW significantly alleviated mouse body weight loss and hyperglycemia compared with the control group, and elevated serum levels of insulin, osteocalcin, and bone-alkaline phosphatase. HSW supplementation also significantly increased the bone volume/tissue volume ratio and trabecular thickness and number, and decreased the bone surface/bone volume ratio and trabecular structure model index in the femur and tibia. Moreover, HSW significantly increased femoral bone mineral density. In addition, HSW down-regulated osteoclastogenic genes, such as nuclear factor of activated T-cells, cytoplasmic 1 and tartrate-resistant acid phosphatase 5 (TRAP), in both the femur and tibia tissue, and reduced serum TRAP level compare to those of control mice. These results indicate that HSW might relieve diabetes-related bone disorders through regulating osteoclast-related genes, suggesting HSW may be used as a preventive agent for diabetes-induced bone loss.

Gentiopicroside isolated from Gentiana scabra Bge. inhibits adipogenesis in 3T3-L1 cells and reduces body weight in diet-induced obese mice.

Gentiopicroside is a major active component of the Gentiana scabra Bge., which is commonly used as herbal medicine for the treatment of inflammation in Asia. Gentiopicroside significantly down-regulated expression of key adipogenic transcription factors (PPARγ, C/EBPα, SREBP-1c) and dose-dependently inhibited the lipid uptake-related gene (LPL), fatty acid transport-related gene (FABP4) and triglyceride (TG) synthesis-related gene (DGAT2), as well as fatty acid synthesis-related genes (FAS, SCD1), which resulted in reduced intracellular lipid droplet accumulation and TG content in 3T3-L1 cells. Gentiopicroside also down-regulated expression of inflammatory cytokine genes (NFκB1, TNFα, IL6) compared with vehicle. Oral administration of gentiopicroside (50 mg/kg) in mice fed with high-fat diet for 12 weeks resulted in reduced body weight and visceral fat mass compared with the control group. Overall, the results of this study showed that gentiopicroside had positive anti-obesity effects by regulating the expression of adipogenesis/lipogenesis-related genes and inflammatory genes in 3T3-L1, and that it effectively reduced body weight and visceral fat mass in vivo.

Methoxsalen and Bergapten Prevent Diabetes-Induced Osteoporosis by the Suppression of Osteoclastogenic Gene Expression in Mice.

This study evaluated whether bergapten and methoxsalen could prevent diabetes-induced osteoporosis and its underlying mechanism. For 10 weeks, bergapten or methoxsalen (0.02%, w/w) was applied to diabetic mice that were provided with a high-fat diet and streptozotocin. Bone mineral density (BMD) and microarchitecture quality were significantly reduced in the diabetic control group; however, both bergapten and methoxsalen reversed serum osteocalcin, bone-alkaline phosphatase and femur BMD. These coumarin derivatives significantly increased bone volume density and trabecular number, whereas they decreased the structure model index of femur tissue in diabetic mice. Conversely, tartrate-resistant acid phosphatase 5 (TRAP) staining revealed that these derivatives reduced osteoclast numbers and formation in diabetic bone tissue. Additionally, both bergapten and methoxsalen tended to downregulate the expression of osteoclast-related genes such as receptor activator of nuclear factor kappa-B ligand (RANKL), nuclear of activated T-cells, cytoplasmic 1 (NFATc1) and TRAP in diabetic femurs, with NFATc1 and TRAP expression showing significant reductions. Our data suggest that both bergapten and methoxsalen prevent diabetic osteoporosis by suppressing bone resorption.

Heshouwu (Polygonum multiflorum Thunb.) ethanol extract suppresses pre-adipocytes differentiation in 3T3-L1 cells and adiposity in obese mice.

This study investigated whether Heshouwu (Polygonum multiflorum Thunb.) root ethanol extract (PME) has anti-obesity activity using 3T3-L1 cells and high-fat diet (HFD)-induced obese mice. Treatment with PME (5 and 10 µg/mL) dose-dependently suppressed 3T3-L1 pre-adipocyte differentiation to adipocytes and cellular triglyceride contents. In addition, PME inhibited mRNA and protein expression of adipogenic transcription factors such as CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which led to down-regulation of fatty acid synthase gene expression. After feeding mice PME (0.05%) with HFD for 12 weeks, their visceral fat mass, size and body weight were significantly reduced compared with the HFD group. Furthermore, PME supplementation significantly up-regulated the PPARα, CPT1, CPT2, UCP1 and HSL mRNA levels compared with the HFD group, whereas it down-regulated expression of the PPARγ and DGAT2 genes. Finally, HFD increased serum leptin, insulin, glucose and insulin and glucose levels; however, PME reversed these changes. These results demonstrated that PME might relieve obesity that occurs via inhibition of adipogenesis and lipogenesis as well as through lipolysis and fatty acid oxidation in 3T3-L1 cells and HFD-induced obese mice.

Methoxsalen supplementation attenuates bone loss and inflammatory response in ovariectomized mice.

Methoxsalen (MTS) is a natural bioactive compound found in a variety of plants that has many known biofunctions; however, its effects on osteoporosis and related mechanisms are not clear. This study examined whether MTS exhibited preventive effects against postmenopausal osteoporosis. Female C3H/HeN mice were divided into four groups: Sham, ovariectomy (OVX), OVX with MTS (0.02% in diet), and OVX with estradiol (0.03 µg/day, s.c). After 6 weeks, MTS supplementation significantly increased femur bone mineral density and bone surface along with bone surface/total volume. MTS significantly elevated the levels of serum formation markers (estradiol, osteocalcin and bone-alkaline phosphatase) such as estradiol in OVX mice. Tartrate resistant acid phosphatase staining revealed that MTS suppressed osteoclast numbers and formation in femur tissues compared with the OVX group. Supplementation of MTS slightly up-regulated osteoblastogenesis-related genes (Runx-2, osterix, osteocalcin, and Alp) expression, whereas it significantly down-regulated inflammatory genes (Nfκb and Il6) expression in femur tissue compared with the OVX group. These results indicate that MTS supplementation effectively prevented OVX-induced osteoporosis via enhancement of bone formation and suppression of inflammatory response in OVX mice. Our study provides valid scientific information regarding the development and application of MTS as a food ingredient, a food supplement or an alternative agent for preventing postmenopausal osteoporosis.

Scopoletin Supplementation Ameliorates Steatosis and Inflammation in Diabetic Mice.

Scopoletin is a bioactive component in many edible plants and fruits. This study investigated the effects of scopoletin on hepatic steatosis and inflammation in a high-fat diet fed type 1 diabetic mice by comparison with metformin. Scopoletin (0.01%, w/w) or metformin (0.5%, w/w) was provided with a high-fat diet to streptozotocin-induced diabetic mice for 11 weeks. Both scopoletin and metformin lowered blood glucose and HbA1c , serum ALT, TNF-α and IL-6 levels, glucose intolerance, and hepatic lipid accumulation compared with the diabetic control group. Scopoletin or metformin down-regulated hepatic gene expression of triglyceride (Pparg, Plpp2, and Dgat2) and cholesterol (Hmgcr) synthesis as well as inflammation (Tlr4, Myd88, Nfkb1, Tnfa, and Il6), while it up-regulated Cyp7a1 gene. Hepatic PPARγ and DGAT2 protein levels were also down-regulated in scopoletin or metformin group compared with the control group. Scopoletin or metformin also inhibited hepatic fatty acid synthase and phosphatidate phosphohydrolase activities. These results suggest that scopoletin protects against diabetes-induced steatosis and inflammation by inhibiting lipid biosynthesis and TLR4-MyD88 pathways. Copyright © 2017 John Wiley & Sons, Ltd.

Anti-steatotic and anti-inflammatory effects of Hovenia dulcis Thunb. extracts in chronic alcohol-fed rats.

The anti-steatotic and anti-inflammatory effects of fruit water extract (FW) and seed ethanol extract (SE) of Hovenia dulcis Thunb. in chronic alcohol-fed rats were investigated. Rats were fed a liquid diet containing 36% calories from alcohol and orally administered FW or SE (300 and 500mg/kg/day). Both FW and SE reduced hepatic lipid contents and droplets, serum lipid concentration and inflammatory markers (hs-CRP, TNF-α and IL-6) levels compared with the alcohol control group. Alcohol led to significant decreases in the hepatic fatty acid oxidative gene (Ppargc1a, Cpt1a and Acsl1) levels, while it significantly increased the Myd88 and Tnfa gene levels. However, FW or SE supplementation significantly up-regulated gene expression of Ppargc1a, Ppara, Cpt1a and Acsl1, and down-regulated gene expression of Myd88, Tnfa and Crp compared with the alcohol control group. FW or SE supplementation also significantly decreased hepatic activities of fatty acid synthase and phosphatidate phosphohydrolase in chronic alcohol-fed rats. Plasma alcohol and acetaldehyde levels, hepatic enzyme activity and protein expression of CYP2E1 were lowered by FW or SE supplementation. These results indicate that both FW and SE play an important role in improvement of alcoholic hepatic steatosis and inflammation via regulation of lipid and inflammation metabolism.