The unc-51 like autophagy activating kinase 1-autophagy related 13 complex has distinct functions in tunicamycin-treated cells.

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 ATG13 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.

Surgical Outcomes of Endoscopic Conjunctivodacryocystorhinostomy Using a Castroviejo Double-Ended Lacrimal Dilator.

PURPOSE: The aim of this study was to describe the surgical method of endoscopic conjunctivodacryocystorhinostomy with Jones tube insertion using a Castroviejo double-ended lacrimal dilator and to elucidate the surgical outcomes. METHODS: Under general anesthesia and preoperative epinephrine soaking, a monopolar needle cautery instrument was used to remove the nasal mucosa over the lacrimal and maxillary bone junction. After the lacrimal and maxillary bone junction was exposed, an oval osteotomy was formed. A Castroviejo double-ended lacrimal dilator was then inserted to create a direct fistula from the conjunctiva to the nasal cavity through the bony ostium. The dilator was grasped and withdrawn using smooth forceps to determine the tube length. The selected tube was then inserted into the fistula with a guide probe. Following removal of the probe, the inserted tube was fixed with 7-0 Ethilon suturing. RESULTS: Among 39 patients, a total of 49 cases were examined. The success rate was 73.4% (36/49 eyes). The average surgical time was 29.1 minutes for single-eye operations and 47.3 minutes for double-eye operations. Lateral migration (6/13; 46.2%), medial migration (3/13; 23.1%), granulation tissue obstruction (2/13; 15.4%), inflammation (1/13; 7.7%), and malpositioning (1/13; 7.7%) were the noted complications that led to reoperation. CONCLUSIONS: In conclusion, surgical management of endoscopic conjunctivodacryocystorhinostomy using a Castroviejo double-ended lacrimal dilator has several advantages. Using this device, easier surgical procedure, shorter surgical time, and more favorable success rate can be achieved without serious complications.

Magma Seawater Inhibits Hepatic Lipid Accumulation through Suppression of Lipogenic Enzymes Regulated by SREBPs in Thioacetamide-Injected Rats.

Thioacetamide (TAA) is known to induce lipid accumulation in the liver. In the present study, we investigated the effects of magma seawater (MS) rich in minerals on hepatic lipid metabolism by evaluating lipogenic enzymes regulated by sterol regulatory element-binding proteins (SREBPs). Rats (n = 10 per group) were intraperitoneally injected with TAA (200 mg/kg bw) thrice a week for seven weeks in combination with a respective experimental diet. Rats in the TAA-treated group received either a chow diet (Control group) or a chow diet containing MS (TMS group, 2.05%) or silymarin (TSM group, 0.05%). Rats in the normal group were injected with PBS as a vehicle and received a chow diet. Rats in the TMS group showed significantly lower hepatic lipid concentrations than rats in the control group (p < 0.05). Hepatic protein expression levels of fatty acid synthase, SREBP-1, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and SREBP-2 were significantly downregulated in the TMS group, whereas carnitine palmitoyltransferase 1 levels were upregulated (p < 0.05). Hepatic thiobarbituric acid reactive substances levels were lower in the TMS group, whereas protein levels of glutathione peroxidase and catalase were elevated (p < 0.05). The effects of MS were comparable to those of silymarin. Our results evidently showed that MS inhibits hepatic lipid accumulation by suppressing lipid synthesis, accompanied by lipid oxidation and elevation of antioxidative status.

Anti-Obesity Effects of Collagen Peptide Derived from Skate (Raja kenojei) Skin Through Regulation of Lipid Metabolism.

This study investigated the anti-obesity effects of collagen peptide derived from skate skin on lipid metabolism in high-fat diet (HFD)-fed mice. All C57BL6/J male mice were fed a HFD with 60% kcal fat except for mice in the normal group which were fed a chow diet. The collagen-fed groups received collagen peptide (1050 Da) orally (100, 200, or 300 mg/kg body weight per day) by gavage, whereas the normal and control groups were given water (n = 9 per group). The body weight gain and visceral adipose tissue weight were lower in the collagen-fed groups than in the control group (p < 0.05). Plasma and hepatic lipid levels were significantly reduced by downregulating the hepatic protein expression levels for fatty acid synthesis (sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)) and cholesterol synthesis (SREBP-2 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)) and upregulating those for ß-oxidation (peroxisome proliferator-activated receptor alpha (PPAR-α) and carnitine palmitoyltransferase 1 (CPT1)) and synthesis of bile acid (cytochrome P450 family 7 subfamily A member 1 (CYP7A1)) (p < 0.05). In the collagen-fed groups, the hepatic protein expression level of phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK) and plasma adiponectin levels were higher, and the leptin level was lower (p < 0.05). Histological analysis revealed that collagen treatment suppressed hepatic lipid accumulation and reduced the lipid droplet size in the adipose tissue. These effects were increased in a dose-dependent manner. The findings indicated that skate collagen peptide has anti-obesity effects through suppression of fat accumulation and regulation of lipid metabolism.

Chondroitin Sulfate-Rich Extract of Skate Cartilage Attenuates Lipopolysaccharide-Induced Liver Damage in Mice.

The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling.

Clinical Outcomes of Intrascleral Fixation of Intraocular Lens Compared to Ciliary Sulcus Implantation and Transscleral Fixation.

PURPOSE: To compare the clinical outcomes of intrascleral fixation of the three-piece intraocular lenses (IOLs) 2.5 mm posterior to the limbus with ciliary sulcus implantation and transscleral fixation 2.5 mm posterior to the limbus. METHODS: Sixty-five eyes of 65 patients who underwent ciliary sulcus implantation or transscleral or intrascleral fixation of the AMO Sensar AR40e IOL were retrospectively reviewed. The postoperative refractive prediction error, back-calculated effective lens position (ELP), corrected distance visual acuity (CDVA), and postoperative residual cylinder were compared. RESULTS: There were significant differences in the median (interquartile range) postoperative refractive prediction error (diopters [D]) among the three groups (p < 0.001): for ciliary sulcus implantation (33 eyes), -0.89 D (-1.21 to -0.56 D); for transscleral fixation (10 eyes), -0.40 D (-0.78 to -0.22 D); and for intrascleral fixation (22 eyes), 0.01 D (-0.28 to 0.34 D). Significant differences (p < 0.001) were observed in the median back-calculated ELP: for ciliary sulcus implantation, 4.35 mm (3.95 to 4.55 mm); for transscleral fixation, 4.51 mm (4.34 to 4.76 mm); and for intrascleral fixation, 4.90 mm (4.56 to 5.35 mm). There were no differences in the median postoperative CDVA (0, 0.10, and 0 logarithm of the minimum angle of resolution, respectively; p = 0.083) and the residual cylinder (-0.75, -1.50, and -0.63 D, respectively; p = 0.074) among three groups. CONCLUSIONS: Intrascleral fixation showed no myopic shift and the most posterior lens position, while ciliary sulcus implantation induced the greatest myopic shift and the most anterior lens position. However, there was no significant difference in the postoperative CDVA or astigmatism among the eyes with different IOL insertion methods, demonstrating good IOL stability and vision outcomes.

The Status of Enteral Nutrition Formula Use by Dietitians in Hospitals Within Busan and Gyeongnam Area.

This study was conducted to analyze the status of medical food selection process in hospitals within Busan and Gyeongnam area. The survey was distributed to 396 hospitals (general, tertiary and long-term care hospitals) and finally 68 surveys were used for analysis. The questionnaire consisted of 9 general items and 10 items related to enteral nutrition (EN). From the survey we found out that general hospitals and tertiary hospitals normally hire clinical dietitian, while long-term care hospitals hire dietitians with no further qualifications (χ2 = 27.918, p < 0.001). A significant relationship was found between hospital size and the priority for choosing medical foods for patients (χ2 = 11.852, p < 0.05). In general and tertiary hospitals, medical foods were provided exactly according to the doctor's prescription, whereas in long-term care hospitals, only half followed the doctor's direction and half of them provided the products that has been conventionally used. There was also a significant relationship between hospital size and the method for determination of nutrition requirements (χ2 = 20.496, p < 0.001). Finally, the priority of considerations when developing a 'medical food guidelines' was shown in the following order; 1) the type of medical food that can be selected according to the disease state, 2) the nutrient content and comparison table for commercial products, and 3) how to manage complications that may occur when supplying medical food for patients. Developing an EN practice guideline for making a sensible selection of medical foods will provide a valuable information for better patient care.

Regulatory Effects of Skate Skin-Derived Collagen Peptides with Different Molecular Weights on Lipid Metabolism in the Liver and Adipose Tissue.

This study investigated the effects of skate skin collagen peptide (SSCP) with different molecular weights (MWs) on the lipid metabolism in the liver and adipose tissue. Male db/db mice were orally administered with water (control group) or low SSCP (LCP group) or high SSCP (HCP group) MW for 8 weeks whereas male m/m mice were used for comparison (normal group) (n = 10 each group). Compared to the control group, the LCP and HCP groups had lower adipose tissue mass, plasma and hepatic lipid concentrations, and plasma leptin levels (p < 0.05). Protein expression levels of lipogenesis-related protein were reduced in both liver and adipose tissues of SSCP-fed groups whereas those for lipolysis were elevated (p < 0.05). In particular, the LCP had the higher effects relative to the HCP. The above results were supported by histological analysis, revealing that SSCP administration decreased the size of adipose droplets and suppressed hepatic lipid accumulation. Our results showed that SSCP has potential antiobesity properties through the improvement of lipid metabolism in the liver and adipose tissue; in particular, the lower MW of collagen peptide had the greater effects.

Effect of propolis phenolic compounds on free fatty acid receptor 4 activation.

Propolis is known to have multiple biological and pharmacological properties including the regulation of energy homeostasis. Although phenolic compounds are considered to be the major active components in propolis, there is little information available about their mechanisms underlying the regulation of energy homeostasis. In this study, the effects of five phenolic compounds in propolis, chrysin, pinocembrin, galangin, pinobanksin, and caffeic acid phenethyl ester (CAPE) were evaluated on the activation of free fatty acid receptor 4 (FFA4), which are involved in the control of energy homeostasis by enhancing insulin signaling, increasing glucose uptake, and regulating adipogenesis. The results showed that three phenolic compounds exhibited the activation of FFA4, which were ranked in the order of pinocembrin, CAPE and pinobanksin in FFA4-expressing cells. These results suggest that some phenolic compounds in propolis, particularly pinocembrin, may affect the control of energy homeostasis via the activation of FFA4.

Effects of collagen peptides from skate (Raja kenojei) skin on improvements of the insulin signaling pathway via attenuation of oxidative stress and inflammation.

It has been well established that hepatic insulin signaling is significantly affected by the antioxidative status of the liver. In this study, we first confirmed that skate skin collagen peptide (SSCP) administration has dose-dependent positive effects on the change in the glucose level as evidenced by oral glucose tolerance tests. Therefore, the beneficial effects of SSCP-showing antioxidative and anti-inflammatory activities-on insulin resistance were examined in high-fat diet (HFD)-fed mice. C57BL/6J mice orally received SSCP at doses of 100, 200, and 300 mg per kg bw per day along with a HFD for 8 weeks (n = 9 per group). Water was given to the HFD- or chow diet-only group as a vehicle. Compared with the HFD group, the final body weight was reduced in all the SSCP-treated groups in a dose-dependent manner. The hepatic protein expression levels of the phosphorylated insulin receptor substrate, phosphorylated phosphatidylinositol 3-kinase, and phosphorylated protein kinase B were increased in the SSCP-treated groups, which led to reduced plasma insulin and HOMA-IR levels (P < 0.05). The hepatic protein expression levels of nuclear factor erythroid 2-related factor 2-mediated antioxidant enzymes were increased in the SSCP-treated groups, whereas those of nuclear factor kappa B-regulated inflammatory enzymes and mediators were decreased (P < 0.05). These effects were dose-dependent. It is apparent that SSCP might enhance insulin sensitivity by increasing the antioxidative status and suppressing the inflammatory response in the liver.

Skate cartilage extracts containing chondroitin sulfate ameliorates hyperlipidemia-induced inflammation and oxidative stress in high cholesterol diet-fed LDL receptor knockout mice in comparison with shark chondroitin sulfate.

BACKGROUND/OBJECTIVES: In this study, we investigated the beneficial effects of skate cartilage extracts containing chondroitin sulfate (SCS) on hyperlipidemia-induced inflammation and oxidative stress in high cholesterol diet (HCD)-fed mice in comparison with the effects of shark cartilage-derived chondroitin sulfate (CS). MATERIALS/METHODS: Low-density lipoprotein receptor knockout (LDLR-KO) mice were fed HCD with an oral administration of CS (50 and 100 mg/kg BW/day), SCS (100 and 200 mg/kg BW/day), or water, respectively, for ten weeks. RESULTS: The administration of CS or SCS reduced the levels of serum triglyceride (TG), total cholesterol (TC), and LDL cholesterol and elevated the levels of high-density lipoprotein cholesterol, compared with those of the control group (P < 0.05). Furthermore, CS or SCS significantly attenuated inflammation by reducing the serum levels of interleukin (IL)-1ß and hepatic protein expression levels of nuclear factor kappa B, inducible nitric oxide synthase, cyclooxygenase-2, and IL-1beta (P < 0.05). In particular, the serum level of tumor necrosis factor-alpha was reduced only in the 100 mg/kg BW/day of SCS-fed group, whereas the IL-6 level was reduced in the 100 and 200 mg/kg BW/day of SCS-fed groups (P < 0.05). In addition, lipid peroxidation and nitric oxide production were attenuated in the livers of the CS and SCS groups mediated by the upregulation of hepatic proteins of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase (P < 0.05). CONCLUSIONS: These results suggest that the biological effects of SCS, similar to those of CS, are attributed to improved lipid profiles as well as suppressed inflammation and oxidative stress induced by the intake of HCD.

Effect of fermented oyster extract on growth promotion in Sprague-Dawley rats.

BACKGROUND: Oysters (Crassostrea gigas) are a popular marine product worldwide and have the advantage of nutritional benefits. This study aimed to investigate the effect of fermented oyster extract (FO) on growth promotion, including analysis of body size, bone microarchitecture, hematology and biochemistry in vivo. METHODS: The amount of nutrients and gamma aminobutyric acid (GABA) were determined. Sprague-Dawley rats were randomly divided into four groups: the control group, FO 50 group (FO 50 mg/kg), and FO 100 group (FO 100 mg/kg) were administered orally once daily and the recombinant human growth hormone (rhGH) group (200 µg/kg) was intraperitoneally injected once daily for 14 days. RESULTS: Oral administration of FO 100 significantly increased body length and had no effect on organ damage or hematological profiles. However, administration of rhGH significantly induced hypertrophy of the liver, kidney and spleen along with a marked increase in body length. Tibia length and the growth plate were increased, and bone morphometric parameters were slightly improved by FO and rhGH administration. Serum analysis showed that the levels of GH and insulin like growth factor-1 (IGF-1) were slightly upregulated by FO administration. Nevertheless, the protein expression of hepatic IGF-1 was markedly increased by FO 100 and rhGH administration. CONCLUSIONS: FO have high content of GABA, and induced positive effects on body length, tibial length, growth-plate length and hepatic IGF-1 synthesis in SD rats with no toxicity or alterations of hematological profile. Therefore, these results suggest that GABA-enriched FO could be considered a potential alternative treatment for growth stimulation.

Sesame Oil Attenuates Renal Oxidative Stress Induced by a High Fat Diet.

The antioxidative effects of the bioactive compounds enriched sesame oil (e.g. lignans and tocopherols) are well established. This study aims to elucidate whether sesame oil could reduce renal oxidative stress induced by a high fat diet (HFD). Mice received HFD for 12 weeks (n=7 per group), which was prepared by adding 20% (w/w) lard (lard group) or sesame oil (sesame group) to the chow diet, respectively. Compared with mice in the lard group, renal lipid levels of those in the sesame group were reduced, shown by decreases in protein expression of transcription factors and enzymes involved in fatty acid synthesis (sterol regulatory element-binding protein-1 and acetyl coenzyme A carboxylase α) and an increase in ß-oxidation (peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase I) (P<0.05). In the sesame group, levels of peroxynitrite and thiobarbituric acid reactive substances were also reduced, whereas the level of glutathione was increased. In addition, there was elevated protein expression levels of antioxidant enzymes regulated by nuclear factor-like 2, such as superoxide dismutase, glutathione peroxidase, and glutathione S-transferase (P<0.05), and decreased expression for nuclear factor kappa B and cyclooxygenase 2 (P<0.05). These results suggest that sesame oil could ameliorate HFD-induced renal damage by suppressing oxidative stress and inflammation.

Bioactive Compounds in Kimchi Improve the Cognitive and Memory Functions Impaired by Amyloid Beta.

This study investigated the abilities of kimchi and its bioactive compounds to ameliorate amyloid beta (Aß)-induced memory and cognitive impairments. Mice were given a single intracerebroventricular injection of Aß25-35, followed by a daily oral administration of capsaicin (10 mg·kg-bw⁻1), 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (50 mg/kg bw), quercetin (50 mg/kg bw), ascorbic acid (50 mg/kg bw), or kimchi methanol extract (KME; 200 mg/kg bw) for 2 weeks (n = 7 per group). Carboxymethylcellulose was used as a vehicle for the normal and control groups. Behavioral task tests showed that the learning and memory abilities were significantly waned by the injected Aß25-35, but these cognitive deficits were recovered by the administrated KME and kimchi bioactive compounds (p < 0.05). The reactive oxygen species, peroxynitrite, and thiobarbituric acid reactive substances levels were lower, and the glutathione level was higher, in the KME and bioactive compound groups than in the control group (p < 0.05). In the KME and bioactive compound groups, the protein expression levels of antioxidant enzymes (nuclear factor (erythroid-derived 2)-like 2-regulated superoxide dismutase-1 and glutathione peroxidase) were increased, whereas those of inflammation-related enzymes (nuclear factor-kappaB -regulated inducible nitric oxide synthase and cyclooxygenase-2) were decreased (p < 0.05). Thus, the antioxidative and anti-inflammatory properties of bioactive compounds-rich kimchi might help to attenuate the symptoms of Alzheimer's disease.

Preventative activity of kimchi on high cholesterol diet-induced hepatic damage through regulation of lipid metabolism in LDL receptor knockout mice.

This study investigated the effect of kimchi on hepatic lipid metabolism and inflammatory response. Low-density lipoprotein receptor knockout mice fed high cholesterol diet (HCD) with an oral administration of kimchi methanol extracts (KME, 200 mg kg bw-1 day-1) or distilled water for 8 weeks (n = 10 per group). Compared with the control group, plasma and hepatic lipid concentrations were lower in the kimchi group (p < 0.05), which was confirmed with hepatic histological examination by Oil Red O staining. Hepatic expressions for fatty acid synthesis were downregulated whereas those for beta-oxidation were upregulated in the kimchi group (p < 0.05). Hepatic expressions for cholesterol synthesis were decreased but those for cholesterol export was increased in the kimchi group (p < 0.05). Moreover, kimchi intake reduced expression for inflammatory cytokines (p < 0.05). Kimchi exerted beneficial effects on HCD-induced hepatic damage by suppressing lipid synthesis and inflammation, and facilitating fatty acid oxidation and cholesterol excretion.

Hypolipidemic and Antidiabetic Effects of Functional Rice Cookies in High-Fat Diet-Fed ICR Mice and db/db Mice.

We have previously reported the lipid-lowering effects of a Korean rice cookie called dasik (RCD) in comparison with a western style cookie. In this study, Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) fruit-supplemented RCD (SRCD) was added to a diet, and the hypolipidemic and antidiabetic effects of different diets were examined by using the ICR and db/db mouse models, respectively. ICR mice were fed the AIN-76 diet, or high-fat diet (HFD), or the RCD- or SRCD-supplemented HFD (10%, w/w) for 9 weeks (n = 7 per group). Compared with the RCD group, plasma and hepatic triglyceride and cholesterol concentrations were decreased in the SRCD group. Hepatic expressions for fatty acid and cholesterol synthesis were downregulated, whereas those for beta-oxidation and cholesterol export were upregulated (P < .05). The antidiabetic effects of SRCD were tested in db/db mice for 10 weeks (n = 7 per group). Glucose tolerance was improved in the SRCD group through the regulation of gluconeogenic enzymes and biomarkers related to the insulin signaling pathway (P < .05). In addition, SRCD increased the expression levels of antioxidative enzymes, and decreased those of inflammatory cytokines (P < .05). Moreover, oxidative stress, leptin, and insulin levels were lower in the SRCD group than in the other groups (P < .05). In conclusion, the lipid-lowering and antidiabetic effects of SRCD were greater than those of RCD with respect to the suppression of lipid synthesis, oxidative stress, and inflammation and the improvement of glucose metabolism.

Neuroprotective Effects of the Methanol Extract of Kimchi, a Korean Fermented Vegetable Food, Mediated Via Suppression of Endoplasmic Reticulum Stress and Caspase Cascade Pathways in High-Cholesterol Diet-Fed Mice.

Endoplasmic reticulum (ER) stress-related unfolded peptide accumulation is closely associated with the development of neurodegenerative diseases known as protein misfolding disorders. The antioxidative properties of kimchi, a traditional Korean fermented vegetable dish, have been well established. In this study, the neuroprotective effects of the kimchi methanol extract (KME) were examined in high-cholesterol diet (HCD)-fed mice. The animals were fed a HCD, with oral administration of either KME (KME group, 200 mg·kg bw-1·day-1, n = 10) or distilled water (Control group, n = 10) for 8 weeks. Compared with the levels in the control group, the reactive oxygen species, peroxynitrite, and lipid peroxidation levels in the brain were significantly decreased in the KME group (P < .05), whereas the glutathione level was increased (P < .05). In addition, the ER stress biomarkers, phospho-eukaryotic initiation factor 2 subunit α, glucose-regulated protein 78, X-box binding protein 1, inositol-requiring enzyme 1, and C/EBP homologous protein and the nuclear factor-kappaB-mediated inflammation were significantly reduced in the KME group (P < .05). In contrast, the expression levels of antioxidative enzymes regulated by nuclear factor erythroid 2-related factor-2 were elevated (P < .05). The amyloid-beta expression levels of the KME group were lower than that of the control group (P < .05). Moreover, the expression levels of Bcl-2-associated X, and caspases-3 and -9 were downregulated, with a concomitant upregulation of B cell lymphoma 2 (P < .05). Accordingly, KME provide neuronal cell protection via suppressing ER stress and caspase cascade signaling.

Antioxidative and Cholesterol-Lowering Effects of Lemon Essential Oil in Hypercholesterolemia-Induced Rabbits.

The cholesterol-lowering and anti-atherogenic effects of lemon essential oil (LEO) were investigated and compared with the effects of limonene. Owing to their volatility, both LEO and limonene were microencapsulated before preparation of the diet (20%, w/w). Hypercholesterolemia-induced rabbits were divided into 3 groups based on plasma total cholesterol (TC) levels and fed coating matrix (control group), LEO (LEO group), or limonene (Limonene group) for 8 weeks. LEO dose-dependently inhibited low-density lipoprotein oxidation in vitro. Plasma TC levels were the lowest in the LEO group (P<0.05). Erythrocytes in the LEO group had a normal disc shape, whereas the erythrocytes in the limonene and control groups were aggregated and star-shaped, respectively. The aortic intima thickness was thinnest in the LEO group followed by the control and limonene groups. Plasma TC lowering and anti-atherogenic effects of LEO were greater than limonene, suggesting that other bioactive compounds besides limonene in LEO might contribute to these effects. The bioactive compounds in LEO were limonene (67.57%), ß-pinene (10.00%), and γ-terpinene (9.95%). In addition, sabinene, α-pinene, myrcene, and geranial were also present but the amount was in the range of 1~2%. Several bioactive compounds were also detected. In conclusion, LEO had beneficial effects on hypercholesterolemia due to its antioxidative and cholesterol lowering effects.

Bioactive Compounds of Kimchi Inhibit Apoptosis by Attenuating Endoplasmic Reticulum Stress in the Brain of Amyloid ß-Injected Mice.

This study investigated the inhibitory effects of kimchi bioactive compounds against endoplasmic reticulum (ER) stress-induced apoptosis in amyloid beta (Aß)-injected mice. Mice received a single intracerebroventricular injection of Aß25-35, except for the normal group. Mice were subjected to oral administration of 10 mg of capsaicin, 50 mg of 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA), 50 mg of quercetin, 50 mg of ascorbic acid, or 200 mg of kimchi methanol extract (KME) per kilogram of body weight for 2 weeks ( n = 7 per group). In the in vitro blood-brain barrier (BBB) permeability test, all bioactive compounds penetrated the BBB except ascorbic acid. The protein expression level of APP, BACE, and p-Tau elevated by Aß injection was decreased by kimchi bioactive compounds ( P < 0.05). Quercetin, HDMPPA, and KME decreased oxidative stress, as indicated by ROS and TBARS levels ( P < 0.05). The protein expression level of ER stress markers GRP78, p-PERK, p-eIF2α, XBP1, and CHOP and the proapoptotic molecules Bax, p-JNK, and cleaved caspases-3 and -9 decreased ( P < 0.05). In contrast, the protein expression level of antiapoptotic molecules Bcl2 and cIAP increased ( P < 0.05). These results were supported by histological analysis.