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Obesity is one of the most common diseases caused by an imbalance in the intake and expenditure of energy, and it is associated with various metabolic complications. This study aimed at investigating the anti-obesity effects and mechanisms of porcine collagen peptide (PCP) using 3T3-L1 preadipocytes and high-fat diet (HFD)-fed mice. The PCP treatment significantly inhibited the adipocyte differentiation and attenuated the mRNA expression of transcription factors (CCAAT/enhancer-binding protein alpha [C/EBP

Silymarin is found in

For this research article, we investigated the protective effects of enzyme-treated caviar powder extract (CV) in ultraviolet B (UVB)-irradiated hairless mice and keratinocytes by confirming moisturizing-related factors and elasticity-related factors. UVB irradiation induced wrinkle formation, dehydration, oxidative stress, and inflammation in the dorsal skin of mice; however, these were suppressed in the CV-supplemented groups in UVB-irradiated hairless mice. Furthermore, in UVB-irradiated keratinocytes, CV treatment increased the antioxidant enzyme activities and the levels of sphingomyelin and hyaluronic acid and decreased the production of pro-inflammatory cytokines and the expression of IkB-α and p65 phosphorylation. These findings indicate that CV can directly protect keratinocytes against UVB irradiation-induced oxidative stress and inflammation. Therefore, we suggest that CV can protect against UVB-induced skin photoaging. Therefore, we suggest that caviar is effective for skin health by preventing UVB-induced skin photoaging.

To determine the correlation between obesity and insulin resistance in skeletal muscle and liver tissues, this study isolates exosomes from adipose tissue under obese conditions and investigates the effect of adipose tissue-derived exosomes (Ad-exosomes) in mouse muscle (C2C12 cells) and liver cell lines (AML12 cells).The study isolates exosomes from the adipose tissue of normal diet-fed mice or high-fat diet (HFD)-fed obese mice and confirms the uptake into differentiated C2C12 and AML12 cells. Ad-exosomes from HFD-fed mice induce insulin resistance, triglyceride (TG) accumulation, endoplasmic reticulum stress, and inflammation in both C2C12 and AML12 cells. Interestingly, the study finds that the TG accumulation induces by Ad-exosomes from HFD-fed obese mice is dramatically increased in AML12 cells compared with that in the differentiated C2C12 cells, and glucose uptake following the same treatment is decreased in C2C12 cells and increased in AML12 cells. In addition, Ad-exosomes from HFD-fed obese mice cause not only TG accumulation but also lipogenesis in AML12 cells.The results suggest that Ad-exosomes from HFD-fed obese mice cause insulin resistance in both the muscles and liver, but their effects on metabolism during the development of insulin resistance vary between tissues.

With aging, men inevitably encounter irreversible changes, including progressive loss of testosterone and physical strength, and increased fat mass. To assess the alleviatory effects of EUAJ on andropause symptoms, including in vivo testosterone deficiency, we administered EUAJ for 6 weeks in 22-week-old Sprague-Dawley rats. Before EUAJ (3:1) (

We examined the efficacy of fermented

Cranberry powder (CR) is reported to be effective against lower urinary tract symptoms (LUTS) and recurrent urinary tract infections. Benign prostatic hyperplasia (BPH) in men older than 50 years is a common cause of LUTS. Here, we attempted to evaluate if CR is also effective for treating BPH using a BPH-induced rat model, which was orally administered CR. Male Sprague-Dawley rats weighing 200-250 g were randomly divided into the following six groups (

Cancer stem-like cells (CSCs) can generate solid tumors through the properties of stem cells such as self-renewal and differentiation and they cause drug resistance, metastasis and recurrence. Therefore, establishing CSC lines is necessary to conduct various studies such as on the identification of CSC origin and specific targeted therapies. In this study, we stimulated NIH3T3 fibroblasts to exhibit the characteristics of CSCs using the whole protein lysates of B16F10 melanoma cells. As a result, we induced colony formation that displayed self-renewal and differentiation capacities through anchorage-independent culture and re-attached culture. Moreover, colonies showed drug resistance by being maintained in the G0/G1 state. Colonies expressed various CSC markers and displayed high-level drug efflux capacity. Additionally, colonies clearly demonstrated tumorigenic ability by forming a solid tumor in vivo. These results show that proteins of cancer cells could transform normal cells into CSCs by increasing expression of CSC markers. This study argues the tremendous importance of the extracellular microenvironmental effect on the generation of CSCs. It also provides a simple experimental method for deriving CSCs that could be based on the development of targeted therapy techniques.

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg−1∙d−1 had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg−1∙d−1. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.

The aim of this study was to evaluate the effects of ethanol extracts of

This study investigated the immunomodulatory effect of Salvia plebeia R. aqueous extract (FIE-SP, SPW) in forced swimming exercise-induced mice and the immunostimulatory effects on Raw264.7 cells. Mice were randomly assigned to four groups: the control group (CON), the forced swimming test group (FST), and two FIE-SP groups (low and high dose of FIE-SP). Compared with the control group, the FIE-SP groups showed significantly increased ratios of T lymphocyte surface markers CD4+/CD8+ and major histocompatibility complex (MHC)I/MHCII, as well as increased concentrations of immunoglobulin (Ig)A and IgG. FIE-SP groups significantly increased Th1 cytokines and decreased Th2 cytokines compared with negative control exercise-induced mice. Conversely, the immunostimulatory effects of FIE-SP significantly increased phagocytic activities, nitric oxide (NO) production, and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-&alpha, ) and interleukin (IL)-1&beta, in Raw264.7 cells. Furthermore, FIE-SP increased natural killer (NK) cell activities and cytokines (IL-12) in splenocytes compared with the CON group. These results indicated that FIE-SP supplementation could prevent imbalanced immune states and produce immunostimulatory effects to support innate immunity.

Obesity is the most common metabolic disease in developed countries and has become a global epidemic in recent years. Obesity is associated with various metabolic abnormalities, including glucose intolerance, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Leaves from the plant Dendropanax morbiferus are beneficial to health as they contain high levels of vitamin C and tannin. There have been seminal studies on the anticancer, antimicrobial, antidiabetes, and antihyperglycemic effects of treatments with D. morbiferus trees. Herein, we investigated the toxicity of D. morbiferus water (DLW) extracts in vitro, and demonstrated no toxicity at 5-500 μg/mL in 24-72-h experiments with 3T3-L1 cells. The DLW increased cell viability at 48 h and inhibited adipogenesis in 3T3-L1 cells by reducing intracellular triglyceride levels and glucose uptake. In addition, mRNA and protein expression levels of adipogenesis-related genes were lowered by DLW, suggesting antiobesity effects in mouse 3T3-L1 cells. Because few studies have demonstrated cholesterol-lowering effects of D. morbiferus, we investigated the activities of adipogenic transcriptional factors following treatments of 3T3-L1 cells with D. morbiferus and observed increased CEBPα, CEBPβ, PPARγ, and SREBP1 activities in the cells, indicating that DLW extracts inhibit adipogenesis.

The hepatoprotective effect of 10% ethanolic extract of Curdrania tricuspidata (CTE) was investigated in HepG2/2E1 cells and C57BL/6 J mice. When compared ethanol-only treated HepG2/2E1 cells, pretreatment of CTE prevented increased intra-cellular reactive oxygen species levels and decreased antioxidant activities by ethanol-induced oxidative stress. In C57BL/6 J mice, CTE at a dose of 250 mg/kg/day was administered for 10 days, with ethanol (5 g/kg/day) administered for the final 3 days. Pretreatment with CTE prevented the elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase caused by ethanol-induced hepatic damage. CTE-treated mice displayed a reduced level of malondialdehyde and increased antioxidant activities of catalase, glutathione S-transferase, glutathione peroxidase, and superoxide dismutase, as well as a reduced level of glutathione as compared with ethanol-only-treated mice. CTE-treated mice exhibited significant inhibition of CYP2E1 activities and expression. These results suggest that CTE could be a useful agent for the prevention of ethanol-induced oxidative damage in the liver, elevating antioxidative potentials and alleviating oxidative stress by suppressing CYP2El.

Our aim was to investigate whether hot water extract (CLW) of Curcuma longa L. could prevent non-alcoholic fatty liver disease (NAFLD). HepG2 cells were treated with free fatty acid (FFA) mixture (oleic acid: palmitic acid, 2:1) for 24 h to stimulate in vitro fatty liver. In addition, C57BL/6 mice were fed 60 kcal% high-fat (HF) diet for eight weeks to induce fatty liver in vivo. Intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) productions were increased by FFA and HF-diet, but supplementation with CLW significantly decreased these levels. CLW treatment ameliorated antioxidant activities that were suppressed by exposure to the FFA and HF-diet. Cluster of differentiation 36 (CD36) and fatty acid transport proteins (FATP2 and FATP5) were increased in HF-diet groups, while CLW suppressed their expression levels. Moreover, sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) expression levels were down-regulated in the CLW groups compared to HF-diet groups. On the other hand, 5&prime, adenosine monophosphate-activated protein kinase (AMPK), Peroxisome proliferator-activated receptor alpha (PPAR-&alpha, ), and carnitine palmitoyltransferase 1 (CPT-1) expressions were up-regulated in the CLW groups. HF-diet fed mice showed high hepatic triglycerides (TG) content compared to the normal diet mice. However, the administration of CLW restored the hepatic TG level, indicating an inhibitory effect against lipid accumulation by CLW. These results suggest that CLW could be a potentially useful agent for the prevention of NAFLD through modulating fatty acid uptake.

Alzheimer's disease accounts for the majority of dementia and shows hallmarks such as sequential cognitive dysfunction and abnormal behavior.

Folk medicine has long employed leaves from Eriobotrya japonica Lindl. (Rosaceae) (LEJ) as relieving many diseases including chronic bronchitis and high fever. In this study, we investigated the immunomodulatory effects of leaves from LEJ water extracts (LEJE) in LP-BM5 murine leukemia viruses (MuLV)-induced immune-deficient animal model. Dietary supplementation of LEJE (100, 300, 500 mg/kg) began on the day of LP-BM5 MuLV infection and continued for 12 weeks. Dietary supplementation of LEJE inhibited LP-BM5 MuLV-induced splenomegaly and lymphadenopathy. Moreover, LEJE attenuated reductions of T- and B-cell proliferation and Th1/Th2 cytokine imbalance in LP-BM5. We found that dietary supplements of LEJE suppressed the hypergammaglobulinemia by ameliorating LP-BM5 MuLV infection-induced B-cell dysfunction and production of pro-inflammatory cytokines. We suggest that Eriobotrya japonica may have beneficial immunomodulatory effects, improving the balance of Th1/Th2 cytokines and anti-inflammatory effects.

The protective activity of a mixture of aqueous and ethanolic extracts from Houttuynia cordata Thunb, Nelumbo nucifera G. leaves, and Camellia sinensis seed (HNC) was evaluated in C57BL/6 mice. Pretreatment with HNC prevented the elevation of serum aspartate aminotransferase and alanine aminotransferase caused by ethanol-induced hepatic damage. The HNC-treated mice showed significantly lower triglyceride levels, reduced CYP2E1 activity, and increased antioxidant enzyme activities and lipogenic mRNA levels. These results suggest that HNC might be a candidate agent for liver protection against ethanol-induced oxidative damage, through enhancement of antioxidant and antilipogenic activity.

Low-grade chronic inflammation (metaflammation) is a major contributing factor for the onset and development of metabolic diseases, such as type 2 diabetes, obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present in milk and beer, is a functional vitamin B3 having advantageous effects on metabolic regulation. However, the anti-inflammatory capacity of NR is unknown. This study evaluated whether NR modulates hepatic nucleotide binding and oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Male, 8-week-old KK/HlJ mice were allocated to the control or NR group. NR (100 mg/kg/day) or vehicle (phosphate-buffered saline) was administrated by an osmotic pump for 7 days. Glucose control, lipid profiles, NLRP3 inflammasome, and inflammation markers were analyzed, and structural and histological analyses were conducted. NR treatment did not affect body weight gain, food intake, and liver function. Glucose control based on the oral glucose tolerance test and levels of serum insulin and adiponectin was improved by NR treatment. Among tested lipid profiles, NR lowered the total cholesterol concentration in the liver. Histological and structural analysis by hematoxylin and eosin staining and transmission electron microscopy, respectively, showed that NR rescued the disrupted cellular integrity of the mitochondria and nucleus in the livers of obese and diabetic KK mice. In addition, NR treatment significantly improved hepatic proinflammatory markers, including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1. These ameliorations were accompanied by significant shifts of NLRP3 inflammasome components (NLRP3, ASC, and caspase1). These results demonstrate that NR attenuates hepatic metaflammation by modulating the NLRP3 inflammasome.

The immunomodulatory effects of a dietary supplement of purple sweet potato extract (PSPE) in LP-BM5 murine leukemia virus (MuLV)-induced immune-deficient mice were investigated. Mice were divided into six groups: normal control, infected control (LP-BM5 MuLV infection), positive control (LP-BM5 MuLV infection+dietary supplement of red ginseng 300 mg/kg), purple sweet potato water extract (PSPWE) (LP-BM5 MuLV infection+dietary supplement of PSPE 300 mg/kg), PSP10EE (LP-BM5 MuLV infection+dietary supplement of 10% ethanol PSPE 300 mg/kg), and PSP80EE (LP-BM5 MuLV infection+dietary supplement of 80% ethanol PSPE 300 mg/kg). Dietary supplementation began on the day of LP-BM5 MuLV infection and continued for 12 weeks. Dietary supplementation of PSPE inhibited LP-BM5 MuLV-induced splenomegaly and lymphadenopathy and attenuated the suppression of T- and B-cell proliferation and T helper 1/T helper 2 cytokine imbalance in LP-BM5 MuLV-infected mice. Dietary supplement of PSPE increased the activity of the antioxidant enzymes, superoxide dismutase and glutathione peroxidase. The data suggest that PSPE may ameliorate immune dysfunction due to LP-BM5 MuLV infection by modulating antioxidant defense systems.

Gecko proteins have long been used as anti-tumor agents in oriental medicine, without any scientific background. Although anti-tumor effects of Gecko proteins on several cancers were recently reported, their effect on bladder cancer has not been investigated. Thus, we explored the anti-tumor effect of Gecko proteins and its cellular mechanisms in human bladder cancer 5637 cells. Gecko proteins significantly reduced the viability of 5637 cells without any cytotoxic effect on normal cells. These proteins increased the Annexin-V staining and the amount of condensed chromatin, demonstrating that the Gecko proteinsinduced cell death was caused by apoptosis. Gecko proteins suppressed Akt activation, and the overexpression of constitutively active form of myristoylated Akt prevented Gecko proteins-induced death of 5637 cells. Furthermore, Gecko proteins activated caspase 9 and caspase 3/7. Taken together, our data demonstrated that Gecko proteins suppressed the Akt pathway and activated the intrinsic caspase pathway, leading to the apoptosis of bladder cancer cells. [BMB Reports 2015; 48(9): 531-536].

Porphyra tenera, also known as nori, is a red algal species of seaweed. It is cultivated in Asia for culinary purposes. We report that P. tenera extract (PTE) enhances the immune response in mouse macrophages. We found that P. tenera extract regulates the NF-κB IκB kinase (IKK) signaling pathway, and we assessed the expression and translocation of p65, a subunit of NF-κB, in RAW264.7 mouse macrophage cells after treatment with PTE. We also investigated the effects of 10% ethanol PTE (PTE10) in RAW264.7 cells. The production of IL-10, IL-6, TNF-α, and IFN-γ was induced by PTE treatment of the macrophages, and PTE also enhanced p-IκB and p-AKT. PTE10 showed no cytotoxicity at 10-20 μg/mL in RAW264.7 cells. PTE10, in fact, increased cell viability at 24 h, stimulated macrophage cells, and induced the phosphorylation of Akt. Akt stimulates IKK activity through the phosphorylation of IKKα and enhances immune activity through the activation of NF-κB. In this study, NF-κB activation was induced by increasing p-NF-κB and p-IKK. A subunit of NF-κB, p65, was located in the nucleus and increased the expression of various cytokines. PTE thus enhanced the immune response through IκB-α immunostimulation signaling in RAW264.7 cells. PTE10 has potential therefore for development of future treatments requiring immune system stimulation.

We investigated the potential effects of Costaria costata (CC) on atopic dermatitis (AD) development in chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. CC is a brown alga distributed across the seas of Korea, China, and Japan. A total of 40 mice were randomly assigned to 5 groups with 8 mice per group: untreated Balb/c mice, AD control (0.1% w/v DNCB-treated NC/Nga mice), positive control (i.e., DNCB-treated NC/Nga mice fed a dietary supplement of 66.6 mg/kg of body weight [b.w.] of CJLP133), DNCB-treated NC/Nga mice fed a dietary supplement of 100 mg/kg b.w. of CCE10 (CCE10 100), and DNCB-treated mice fed a dietary supplement of 300 mg/kg b.w. of CCE10 (CCE10 300) groups. The CCE10 100 and CCE10 300 treatment groups suppressed AD development including clinical and histopathological changes and a reduction in skin hydration induced by DNCB. In addition, Th2 cytokine production in primary splenocytes, serum IgE and histamine production, and mast cell infiltration into the skin were suppressed in the CCE10 300 mice compared to the CCE10 100 mice. Our finding demonstrated an inhibitory effect of CCE10 in AD development by means of improving the Th1/Th2 cytokine balance and anti-inflammatory effect in an in vivo model.

In this study, we performed two-dimensional electrophoresis with protein extracts from lizard tails, and analyzed the protein expression profiles during the tissue regeneration to identify the dedifferentiation factor. As a result, we identified 18 protein spots among total of 292 spots, of which proteins were specifically expressed during blastema formation. We selected lactoferrin as a candidate because it is the mammalian homolog of leech-derived tryptase inhibitor, which showed the highest frequency among the 18 proteins. Lactoferrin was specifically expressed in various stem cell lines, and enhanced the efficiency of iPSC generation upto approximately 7-fold relative to the control. Furthermore, lactoferrin increased the efficiency by 2-fold without enforced expression of Klf4. These results suggest that lactoferrin may induce dedifferentiation, at least partly by increasing the expression of Klf4.

This study was performed to investigate the effect of water extract from Rosa rugosa (RRW) on endurance exercise-induced stress in mice. The mice were orally administered with distilled water or RRW, respectively. The endurance capacity was evaluated by exhaustive swimming using an adjustable-current water pool. Mice administered RRW swam longer before becoming exhausted. Also, RRW administration resulted in less lipid peroxidation, lower muscular antioxidant enzyme activities, and lower cortisol level. The results suggest that RRW can prevent exercise-induced stress by decreasing oxidative stress levels.

Recent studies have emphasized the functional role of the P300/CBP-associated factor (PCAF) enzyme in resistance to β-amyloid (Aβ)-mediated neurotoxicity; however, the underlying mechanisms through which PCAF regulates inflammation and neurotoxicity have not yet been elucidated. In this study, we used computer-based molecular docking simulations to perform structure-based artificial screening for PCAF-specific inhibitors. Our results revealed that one of the compounds from the screened library, compound C-11, selectively inhibited PCAF, but not p300 or GCN5, with a half-maximal inhibitory concentration (IC50) of approximately 0.25 µM. Furthermore, C-11 had no effects on the activities of other epigenetic enzymes. Western blot analysis using an antibody against acetyl-nuclear factor-κB (NF-κB) demonstrated that PCAF mediated the Aβ-induced activation of NF-κB by acetylation at Lys-122. We also found that the knockdown of PCAF completely inhibited Aβ-induced cytokine production in BV-2 cells in a similar manner to C-11 treatment. Finally, PCAF inhibition suppressed both Aβ-induced cytokine production and Aβ-mediated neuronal cell death. Therefore, our results suggest that in neuronal cells, PCAF is a promising therapeutic target for alleviating the inflammatory progression of Alzheimer's disease.

This study was conducted to determine the effects of 50% ethanolic extract from Sasa borealis leaves (SBE) on swimming capacity and oxidative metabolism in mice. The mice were divided into 2 groups with similar swimming times and body weights; Ex-Control and Ex-SBE were orally administered with distilled water and 250 mg/kg body weight/d of SBE. Exhaustive swimming times were prolonged by 1.5-fold in the Ex-SBE group compared to the Ex-Control. The Ex-SBE group displayed lower lactate and higher non-esterified fatty acid levels 15 min after swimming and the hepatic and muscle glycogen levels were significantly higher than that in the Ex-Control. SBE potentially enhanced mRNA expression of citrate synthase (CS), carnitine palmitoyltransferase (CPT-1), and β-hydroxyacyl coenzyme A dehydrogenase (β-HAD) in skeletal muscle. The activities and mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were elevated in the Ex-SBE compared with the Ex-Control after exhaustive swimming. These results suggest that SBE might be used as an effective agent to enhance swimming capacity by utilization of energy substrates and might ameliorate physical exhaustion by facilitating energy-generating metabolic genes and enhancing endogenous antioxidants.

Maesil (the fruit of Prunus mume SieboldZucc.) has long been used as an alternative medicine and functional food in Korea and Japan for preventive and therapeutic purposes. We examined the laxative effect of unripe Maesil (UM) and ripe Maesil (RM) in a rat model on constipation induced by a low-fibre diet and the possible mechanisms of Maesil in the rat colon. In vivo studies were conducted on the low-fibre diet-induced constipation rat model, and isolated rat colon was used in in vitro experiments to measure the changes in spontaneous colon contraction generated by Maesil and organic acids as standard and effectual ingredients, respectively. The aqueous extract of both UM and RM applied orally (100 and 300 mg/kg) produced significant increase of faeces frequency (p 0.05) and moisture (p 0.001). Moreover, the number faecal pellets number was reduced (p 0.05) in the distal colons of the Maesil-treated rats. Gastrointestinal (GI) motility, measured by charcoal meal, was activated more fully by UM than in the low-fibre diet group. Both UM and RM and its organic acids produced a dose-dependent stimulation of the spontaneous contractile amplitude (p 0.001) and frequency (p 0.01) of the isolated rat colon. Although both UM and RM were an effective laxative, the RM was significantly more effective than the UM in the in vivo and in vitro constipation experiments because of the changes in the composition of organic acids during the ripening of the fruit. Our results demonstrated that Maesil was effective in promoting the frequency of defaecation and contraction of the rat colon, which provided scientific basis to support the use of Maesil as potential therapeutics in treating constipation.

Cardiac involvement has been reported in as many as 45–55% of patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), and significant cardiac morbidity is reported in 6–7% of HIV patients. We investigated the inhibitory effects of isothiocyanates (ITCs) on heart dysfunction and mortality by regulating apoptosis in the left ventricle of the heart in a murine AIDS model. Mice were divided into six groups: an uninfected group, an untreated LP-BM5 retrovirus-infected group, and four LP-BM5 retrovirus-infected groups treated with one of four ITCs (sulforaphane [SUL], indolo[3,2-b]carbazole, benzyl isothiocyanate [BITC], or phenethyl isothiocyanate [PEITC]). After 16 weeks, the median survival time of the LP-BM5 retrovirus-infected mice was 87 days, whereas that of the uninfected control group and all ITC treatment groups was over 112 days. SUL, PEITC, and BITC significantly inhibited apoptosis in the left ventricle by increasing the Bcl-2/Bax ratio compared with LP-BM5-infected mice. In addition, SUL and PEITC suppressed inducible nitric oxide synthase (iNOS) expression at both the mRNA and protein levels in the left ventricle of heart tissue infected with the LP-BM5 retrovirus by inactivating cytoplasmic nuclear factor κB (NF-κB). In conclusion, LP-BM5 retrovirus infection was related to survival of murine AIDS mice, and NF-κB-mediated iNOS expression may be an important mediator of left ventricle dysfunction of the heart. Furthermore, certain ITCs may have the potential to improve AIDS-related heart dysfunction due to their inhibition of apoptosis by decreasing iNOS and Bax expression through suppression of NF-κB.

The purpose of this study was to determine the effect of isothiocyanates (ITCs) in delaying the progression of the murine immunodeficiency virus to murine AIDS, resulting in increased life span. Furthermore, we investigated the role of ITCs in modulating immune dysfunction caused by LP-BM5 retrovirus infection. Among the tested ITCs, oral administration of sulforaphane (SUL), benzyl isothiocyante (BITC), and phenethyl isothiocyanate (PEITC) showed the inhibition of premature death caused by LP-BM5 retrovirus infection, while indolo[3,2-b] carbazole (ICZ) and indole-3-carbinol (I3C) did not delay the progress of the LP-BM5 retrovirus to murine AIDS. Inhibition of premature death by BITC, PEITC, and SUL could be explained by restoration of the immune system and down regulation of free radicals. Dysfunction of T and B cell mitogenesis caused by retrovirus infection in primary cultured splenocytes has been partially recovered with administration of BITC, PEITC, and SUL. There was a shift from imbalanced cytokine production (increased Th2 and decreased Th1 cell cytokine production) into balanced Th1/Th2 cell secretion of cytokines under administration of these ITCs during the development of murine AIDS. Hepatic vitamin E level was significantly restored by administration of these ITCs, in accordance with reduced hepatic lipid peroxidation levels. This study suggests that certain types of ITCs have beneficial effects in preventing premature death during progression to murine AIDS by restoration of immune dysfunction and removal of excessive free radicals, implying that selective usage of ITCs would be helpful in retarding the progression from HIV infection to AIDS.

This study investigated the effects of epichlorohydrin (ECH) on spermatogenesis and antioxidant system in rats. An increase in the incidence of clinical signs, gross pathology and histopathology findings in the epididymidis, and sperm abnormalities and a decrease in the testicular spermatid counts, epididymal sperm counts, and sperm motility were observed at 30 mg/kg/day. Oxidative stress in the epididymal tissue was detected ator =3.3 mg/kg/day. The results show that graded doses of ECH elicit depletion of antioxidant defense system and that the adverse effects on male reproductive function in ECH-treated rats may be due to the induction of oxidative stress.

Oxidative damage is implicated in the pathogenesis of various liver injuries. In the present study the ability of Pycnogenol (PYC) as an antioxidant to protect against CCl4-induced oxidative stress and hepatotoxicity in rats was investigated. Four experimental groups of six rats each were constructed: a vehicle control group received the respective vehicles (distilled water and corn oil) only; a CCl4 group received a 14-day repeated intraperitoneal (i.p.) dose of distilled water and then a single oral dose of CCl4 at 1.25 ml/kg; and the CCl4&PYC 10 and CCl4&PYC 20 groups received a 14-day repeated i.p. dose of PYC 10 and 20 mg/kg, respectively, and then a single oral dose of CCl4 at 1.25 ml/kg. Hepatotoxicity was assessed 24 h after the CCl4 treatment by measurement of serum aminotransferase (AST) and alanine aminotransferase (ALT) activities, hepatic malondialdehyde (MDA) and glutathione (GSH) concentrations, and catalase, superoxide dismutase (SOD), and glutathione-S-transferase (GST) activities. The results were confirmed histopathologically. The single oral dose of CCl4 produced significantly elevated levels of serum AST and ALT activities. Histopathological examinations showed extensive liver injuries, characterized by extensive hepatocellular degeneration/necrosis, fatty changes, inflammatory cell infiltration, congestion, and sinusoidal dilatation. In addition, an increased MDA concentration and decreased GSH, catalase, SOD, and GST were observed in the hepatic tissues. On the contrary, PYC treatment prior to the administration of CCl4 significantly prevented the CCl4-induced hepatotoxicity, including the elevation of serum AST and ALT activities and histopathological hepatic lesions, in a dose-dependent manner. Moreover, MDA and GSH levels and catalase, SOD, and GST activities in hepatic tissues were not affected by administration of CCl4, indicating that the pretreatment of PYC efficiently protects against CCl4-induced oxidative damage in rats. The results indicate that PYC has a protective effect against acute hepatotoxicity induced by the administration of CCl4 in rats, and that the hepatoprotective effects of PYC may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.

Canavalia gladiata has been used as a Chinese traditional folk medicine for its anti-inflammatory properties. However, the use of C. gladiata is limited because it contains antinutritional and allergy-causing proteins. We fermented C. gladiata with Aspergillus oryzae and investigated the effects of fermented C. gladiata (FCG) on the development of atopic dermatitis (AD) in mice. The mice were divided into five groups: untreated Balb/c mice; AD control (NC/Nga mice); FCGH (NC/Nga mice fed a dietary supplement of 300 mg/kg fermented C. gladiata water extract); FCG30 (NC/Nga mice fed a dietary supplement of 300 mg/kg of fermented C. gladiata 30% ethanol extract), and FCG80 (NC/Nga mice fed a dietary supplement of 300 mg/kg of fermented C. gladiata 80% ethanol extract). We found increases in the nonessential amino acids and essential amino acid in the FCG compared with the non-FCG. FCG attenuated macroscopic and histopathological changes in dorsal skin of mice when compared with the AD control group. The FCG30 and FCG80 groups, in particular, showed significant decreases in scratching episodes when compared with the AD control group. FCG improved immune responses, including increases in IgE and histamine for AD, through attenuation of Th1/Th2 cytokine imbalance and the production of proinflammatory cytokines and chemokines. We suggest that FCG may have benefits for improvement of AD function by improving the balance of Th1/Th2 cytokines and by producing anti-inflammatory effects.

This study investigated the PKA-dependent inhibitory effect of pycnogenol (Pyc) on lipolysis using ob/ob mice and primary mouse adipocytes. Supplementation of Pyc at 30 mg/kg significantly reduced body weight gain and visceral fat mass. The serum and hepatic triglyceride (TG) and total cholesterol (TC) levels were reduced by Pyc supplementation, and high density lipoprotein (HDL)-cholesterol level significantly increased. In addition, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) mRNA levels increased with Pyc supplementation in adipose tissue of ob/ob mice. The treatment of primary cultured adipocytes with Pyc at 100 μg/mL significantly increased glycerol release, cAMP level by reduction of phosphodiestersae-3B (PDE3B), and HSL levels, but decreased protein levels of perilipin A and fatty acid synthetase (FAS). The PKA inhibitor (H89) clearly blocked the cellular levels of perilipin A and HSL, suggesting that Pyc promotes lipolysis of adipocytes through activation of cAMP-dependent PKA, resulting in induction of HSL and reduction of perilipin A. Therefore, this study may elucidate the possible mechanism of Pyc, which is a candidate for weight loss through stimulation of lipolysis.

The performance-enhancing effects of Pseudosasa japonica were investigated in mice using an adjustable-current water pool. Compared to the control group, a 1.5-fold increase in swimming time was observed in the mouse group administered an 80% ethanol extract (PJE) of the leaves of P. japonica. The blood lactate level, an important indicator of fatigue, was significantly lower (28%, P

The ripe fruit of Terminalia chebula RETZIUS (T. chebula RETZ) (Combretsceae), which is a native plant in India and Southeast Asia, has traditionally been used as a popular folk medicine for homeostatic, antitussive, laxative, diuretic, and cardiotonic treatments. The objective of this study was to evaluate the protective effects of an aqueous extract of fruit of T. chebula on the tert-butyl hydroperoxide (t-BHP)-induced oxidative injury observed in cultured rat primary hepatocytes and rat liver. Both treatment and pretreatment of the hepatocytes with the T. chebula extract (TCE) significantly reversed the t-BHP-induced cell cytotoxicity and lactate dehydrogenase leakage. In addition, TCE exhibited in vitro ferric-reducing antioxidant activity and 2,2-diphenyl-1-picryhydrazyl free radical-scavenging activities. The in vivo study showed that pretreatment with TCE (500 or 1000 mg/kg) by gavage for 5 d before a single dose of t-BHP (0.1 mmol/kg i.p.) significantly lowered the serum levels of the hepatic enzyme markers aspartate aminotransferase and alanine aminotransferase and reduced the indicators of oxidative stress in the liver, such as the glutathine disulfide content and lipid peroxidation, in a dose-dependent manner. Histopathologic examination of the rat livers showed that TCE reduced the incidence of liver lesions, including hepatocyte swelling and neutrophilic infiltration, and repaired necrosis induced by t-BHP. Based on the results described above, we speculate that TCE has the potential to play a role in the hepatic prevention of oxidative damage in living systems.

The administration of an ethanolic extract (RCE) from Rubus coreanus significantly reduced the body weight and epididymal fat tissue of mice under conditions of a high-fat diet (HFD) and exercise. The mice also displayed enhanced muscular carnitine palmitoyltransferase 1 (CPT1) expression and increased superoxide dismutase and glutathione levels. These results suggest that RCE exerted an anti-obesity effect by up-regulating CPT1 and elevating the level of antioxidants.

The hepatoprotective effect of fermented Curcuma longa L. (FC) was investigated in rats under CCl4-induced oxidative stress. FC at a dose of 30 or 300 mg/kg body weight (b.w.) was orally administered for 14 days followed by a single dose of CCl4 (1.25 mL/kg b.w. in 20% corn oil) on day 14. Pretreatment with FC drastically prevented the elevated activities of serum AST, ALT, LDH, and ALP caused by CCl4-induced hepatotoxicity. Histopathologically evident hepatic necrosis was significantly ameliorated by FC pretreatment. When compared to the CCl4-alone treated group, rats pretreated with FC displayed the reduced level of malondialdehyde. Furthermore, FC enhanced antioxidant capacities with higher activities of catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase, and level of reduced glutathione. These results suggest that FC could be a candidate used for the prevention against various liver diseases induced by oxidative stress via elevating antioxidative potentials and decreasing lipid peroxidation.

Alzheimer's disease (AD) is the most common neurodegenerative disease to cause dementia in the elderly. Amyloid β (Aβ)-peptide induced oxidative stress causes the initiation and progression of AD. Recently, new chalcone derivatives termed the Chana series were synthesized. Among them, Chana 1 showed high free radical scavenging activity (72.5%), as measured by a DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. In this study, we investigated the effect of Chana 1 against Aβ-induced cytotoxicity and cognitive deficits. Additionally, we sought to estimate the lethal dose, 50% (LD50) of Chana 1 in mice using an acute oral toxicity test. We found that Chana 1 significantly protected against Aβ-induced neuronal cell death in PC12 cells. Oral administration of Chana 1 at a dose of 50 mg/kg body weight/day significantly improved Aβ-induced learning and memory impairment in mice, as measured in Y-maze and passive avoidance tests. In acute toxicity tests, the LD50 in mice was determined to be 520.44 mg/kg body weight. The data are valuable for future studies and suggest that Chana 1 has therapeutic potential for the management of neurodegenerative disease.

The fatigue-alleviating effects on mice of Rubus coreanus were investigated by using an adjustable-current water pool. The mice were exhaustively exercised for 2 consecutive days, and those administered with the 80% ethanol extract (RCE) of R. coreanus displayed a lower reduction (20%) in swimming time on day 2 than the control group (41% reduction). RCE significantly prevented the depletion of hepatic antioxidants during exercise-induced fatigue. These results suggest that RCE alleviated fatigue by elevating the antioxidative potential.

We examined the anti-obesity effect of fermented Curcuma longa L. (turmeric) standardised ethanol extract (FTE) in the C57BL/6J ob/ob mouse model. Mice were fed a chow diet containing FTE (0, 200, or 500 mg kg⁻¹ body weight) for 9 weeks.Supplementation with FTE significantly reduced body weight gain and retroperitoneal and epididymal adipose tissue weights compared to the ob/ob control group. Additionally, total cholesterol and triglyceride levels in serum and liver were significantly decreased in FTE-200 and FTE-500 groups when compared to those of the ob/ob control group, whereas the high-density lipoprotein-cholesterol level was significantly increased. The levels of serum adiponectin as well as mRNA expression of lipases, such as hormone sensitive lipase and adipose triglyceride lipase, were clearly increased. In primary adipocytes of C57BL/6J mice, FTE treatment caused a significant increase glycerol release and hormone sensitive lipase levels and decreased perilipin A levels.These results suggest that supplementation of FTE has potent anti-obesity effects by controlling body weight, fat mass, serum lipids, and hepatic lipids. Moreover, FTE could be considered a potential resource for the treatment of obesity through its promotion of lipolysis via the protein kinase A pathway.

Ferulic acid derived from Pseudosasa japonica leaves, which possessed antioxidative potentials with DPPH- (54%) and ABTs- (65%) radical scavenging activities, and lipid-peroxidation inhibitory activity (71%), was orally administered to mice for 12 days in order to investigate its effects on exercise endurance capacity and alterations of antioxidant defense systems. Exhaustive swimming time was increased in the ferulic acid-supplemented group compared with the control group on days 6 and 12 (1.7- and 1.8-fold, respectively). When the mice were exhaustively exercised for 2 consecutive days, a high decrease (53%) was shown in the control group, but no change was found in the ferulic acid-treated group. The administration of ferulic acid significantly protected the depletion of enzymatic- and non enzymatic-antioxidants due to exhaustive exercise. Also, lipid-peroxidation levels decreased in the ferulic acid-treated group compared with the non exercised- and control-groups. These results suggest that ferulic acid from Pseudosasa japonica leaves has a chronic effect on endurance exercise capacity, which is attributed to its ability to ameliorate oxidative stress by improving antioxidant potentials.

The fruit of Terminalia chebula Retz. (T. chebula), which is a member of the Combfreetaceae family, is used widely in Asian countries as a traditional folk medicine, and its extract has been reported to be an anticancer, antidiabetic and anticaries agent. In our previous study, chebulic acid isolated from T. chebula extract was confirmed to show antioxidant activity and protective action against endothelial cell dysfunction. In order to support the safety-in-use of the ethyl acetate (EtOAc)-soluble portion of a T. chebula ethanol extract containing 29.4% chebulic acid content, the prepared portion was tested in an in vitro mutagenicity assay, and a single- and 14-day repeated dose oral toxicity study. In the bacterial mutation assay, up to 5000 µg/mL concentration of the EtOAc-soluble portion, the numbers of colonies did not increase whether with or without metabolic activation. In the oral toxicity study, the single oral dose of the extract at 2000 mg/kg did not produce mortality or abnormal lesions in the internal organs of rats. The results of a 14-day orally repeated dose showed that the EtOAc-soluble portion of T. chebula ethanol extracts gave no adverse effects at dosages of 2000 mg/kg in rats in the study.

The effects of the turmeric ethyl acetate fraction (TEF) from the methanolic extract from Curcuma longa L. on lipid metabolism and underlying mechanisms of lipolysis were investigated in 3T3-L1 adipocytes. The intracellular lipid droplets were stained with Oil red O dye and quantified. Compared to the control, lipid accumulation was significantly decreased by 46.6% with treatment by TEF at the concentration of 20 microg/mL. The intracellular triglyceride (TG) level was also reduced by 37.9% at the concentration of 20 microg/mL. To determine the mechanism for TG content reduction, levels of glucose uptake and glycerol release were measured. Incubation of the 3T3-L1 adipocytes with TEF for 4 hours significantly lowered the cellular level of glucose in a dose-dependent manner. Furthermore, cellular expression of insulin-responsive glucose transporter (GLUT)-4 was decreased by 46%, indicating that reduced glucose uptake was due to a decrease in cellular GLUT-4 expression. In addition, the level of free glycerol released into the cultured medium was increased by 36.4% with the treatment by TEF. In subsequent measurements using quantitative real-time polymerase chain reaction, mRNA levels of hormone-sensitive lipase (HSL) and adipose TG lipase (ATGL) were elevated by 34.8% and 16.9%, respectively, at the concentration of 20 microg/mL. These results suggest that TEF partially inhibits lipogenesis by the suppression of glucose uptake via the decreased expression of cellular GLUT-4 and stimulates lipolysis through the induction of HSL and/or ATGL gene expression, resulting in the increased glycerol release.

The protective effects of Taraxacum officinale (dandelion) root against alcoholic liver damage were investigated in HepG2/2E1 cells and ICR mice. When an increase in the production of reactive oxygen species was induced by 300 mM ethanol in vitro, cell viability was drastically decreased by 39%. However, in the presence of hot water extract (TOH) from T. officinale root, no hepatocytic damage was observed in the cells treated with ethanol, while ethanol-extract (TOE) did not show potent hepatoprotective activity. Mice, which received TOH (1 g/kg bw/day) with ethanol revealed complete prevention of alcohol-induced hepatotoxicity as evidenced by the significant reductions of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities compared to ethanol-alone administered mice. When compared to the ethanol-alone treated group, the mice receiving ethanol plus TOH exhibited significant increases in hepatic antioxidant activities, including catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and glutathione. Furthermore, the amelioration of malondialdehyde levels indicated TOH's protective effects against liver damage mediated by alcohol in vivo. These results suggest that the aqueous extract of T. officinale root has protective action against alcohol-induced toxicity in the liver by elevating antioxidative potentials and decreasing lipid peroxidation.

Ferulic acid was orally administered to mice in order to investigate its effects on exercise endurance capacity. When a single administration of ferulic acid was given to the mice in an adjustable-current water pool, the duration of exhaustive swimming was longer than that exhibited by the mice in the control group. Also, when the mice were exhaustively exercised for 3 consecutive days, no change in swimming time was found in the ferulic acid-administered group on the final day, and a large decrease in the untreated mice. Administration of ferulic acid efficiently activated the hepatic antioxidative defense system during exercise. The mice that received ferulic acid showed significant increases in the activity of hepatic antioxidant enzymes such as superoxide dismutase, catalase, and glutathione-S-transferase. Furthermore, an increased glutathione level was observed, while the malondialdehyde content was reduced. These results suggest that ferulic acid possesses stimulatory effects that can enhance exercise endurance capacity and reduce fatigue by elevating antioxidative potentials.

This study evaluated the putative antioxidant activity of Pycnogenol (PYC) against CCl4-induced hepatic oxidative damage in Sprague-Dawley rats. A single oral dose of CCl4 (1.25 mL/kg) produced significantly increased levels of serum aminotransferase (AST) and alanine aminotransferase (ALT) activities. In addition, increased malondialdehyde (MDA) concentration, reduced glutathione (GSH) content, and decreased catalase, superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were observed in the hepatic tissues. However, concomitant administration with PYC (10 or 20 mg/kg) significantly improved CCl4-induced hepatic injury, as evidenced by the decline of serum AST and ALT activities in a dose dependent manner. Moreover, PYC reduced MDA concentration and increased GSH levels and catalase, SOD and GST activities in hepatic tissues, indicating that concomitant administration with PYC efficiently prevent the CCl4-induced oxidative damage in rats. The free radical scavenging assay showed that PYC has a dose-dependent scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals. These results indicate that PYC has an antioxidant effect against CCl4-induced hepatic oxidative damage and is useful as a hepatoprotective agent against various liver diseases induced by oxidative stress.