Aster glehni Extract, Including Caffeoylquinic Acids as the Main Constituents, Induces PPAR ß/δ-Dependent Muscle-Type Change and Myogenesis in Apolipoprotein E Knockout Mice.

To probe the functions of Aster glehni (AG) extract containing various caffeoylquinic acids on dyslipidemia, obesity, and skeletal muscle-related diseases focused on the roles of skeletal muscle, we measured the levels of biomarkers involved in oxidative phosphorylation and type change of skeletal muscle in C2C12 cells and skeletal muscle tissues from apolipoprotein E knockout (ApoE KO) mice. After AG extract treatment in cell and animal experiments, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to estimate the levels of proteins that participated in skeletal muscle type change and oxidative phosphorylation. AG extract elevated protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), phosphorylated 5'-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor beta/delta (PPARß/δ), myoblast determination protein 1 (MyoD), and myoglobin in skeletal muscle tissues. Furthermore, it elevated the ATP concentration. However, protein expression of myostatin was decreased by AG treatment. In C2C12 cells, increments of MyoD, myoglobin, myosin, ATP-producing pathway, and differentiation degree by AG were dependent on PPARß/δ and caffeoylquinic acids. AG extract can contribute to the amelioration of skeletal muscle inactivity and sarcopenia through myogenesis in skeletal muscle tissues from ApoE KO mice, and function of AG extract may be dependent on PPARß/δ, and the main functional constituents of AG are trans-5-O-caffeoylquinic acid and 3,5-O-dicaffeoylquinic acid. In addition, in skeletal muscle, AG has potent efficacies against dyslipidemia and obesity through the increase of the type 1 muscle fiber content to produce more ATP by oxidative phosphorylation in skeletal muscle tissues from ApoE KO mice.

Actinidia polygama Water Extract (APWE) Protects Against UVB-Induced Photoaging via MAPK/AP-1 and TGFß-Smad Pathway.

BACKGROUND: Actinidia polygama (silver vine) has been used in oriental medicine to treat gout, rheumatoid arthritis, and inflammation. Actinidia polygama water extract (APWE) is named PB203. OBJECTIVE: To investigate whether PB203 has anti-photoaging effects and to understand the molecular mechanism underlying such effects. METHODS: The antioxidant effect was assessed by 1,1-diphenyl-2-picrylhydrazyl assay and 2',7'-dichlorodihydrofluorescein diacetate staining in ultraviolet B (UVB)-irradiated HaCaT cells with or without PB203 treatment. Type I collagen, matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase (TIMP-1), hyaluronic acid (HA), hyaluronan synthase 1 (HAS1) and HAS2 levels were measuring by enzyme-linked immunosorbent assay or reverse transcription quantitative polymerase chain reaction. Also, we investigate the effects of PB203 on wrinkle formation, and the potential mechanisms underlying such effects were investigated in UVB-induced wrinkle mouse model mice. RESULTS: PB203 alleviated the UVB-induced reactive oxygen species production, phosphorylation of JNK, ERK, and p38, and formation of AP-1. In addition, PB203 inhibited the decreases in type I collagen and TIMP-1 levels, and the increase in MMP-1 levels in UVB-exposed HaCaT cells. In UVB-induced wrinkle mouse model, PB203 inhibited the decreases in elastin and type I collagen levels as well as the increases in MMP-1 expression, wrinkle formation, and skin dehydration. Furthermore, PB203 increased the expression of filaggrin, HAS1, and HAS2, improving the skin barrier function. CONCLUSION: Taken together, we found that PB203 is as a potent candidate to serve as a functional ingredient or therapeutic agent to improve UVB-mediated skin aging.

Buspirone Induces Weight Loss and Normalization of Blood Pressure via the Stimulation of PPARδ Dependent Energy Producing Pathway in Spontaneously Hypertensive Rats.

Introduction: Buspirone, as a partial agonist for a 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A), has been prescribed as an anxiolytic drug for patients. In addition, the lowering effect of serotonin on blood pressure was reported in hypertensive animal model. We investigated the therapeutic mechanism of buspirone against lipid metabolism disturbed by hypertension of early stage via hypertensive and obese animal model. Methods: The levels of various biomarkers related to lipid metabolism and hypertension were estimated through the measurement of body weight and fat weight, blood analysis, western blotting, immunohistochemistry, and staining methods. Results: The lipid accumulation was lowered in differentiated 3T3-L1 cells by buspirone treatments of 50 and 100 µM compared with untreated differentiated control. Body weight and abdominal fat weight were lowered in spontaneously hypertensive rats (SHRs) administered with buspirone of 10 mg/kg/day for 4 weeks than 8-week untreated group. Triglyceride (TG) level was decreased in SHRs administered with buspirone of 5 and 10 mg/kg/day compared to 8-week untreated group. High-density lipoprotein (HDL)-cholesterol concentration was elevated by buspirone 10 mg/kg/day treatment compared to 8-week untreated group. Blood pressures in SHRs were lowered by buspirone treatments of 5 and 10 mg/kg/day compared with 8-week untreated group. Protein levels for peroxisome proliferator-activated receptor δ (PPARδ), 5' adenosine monophosphate-activated protein kinase (AMPK), and PPARγ coactivator-1 alpha (PGC-1α) were increased both in C2C12 cells treated by buspirone of 100 µM and in SHRs administered by buspirone of 1, 5, and 10 mg/kg/day compared to untreated control cells and 8-week untreated group. Fat cell numbers decreased in 8-week untreated group were increased in SHRs administered by buspirone treats of 1, 5, and 10 mg/kg/day. Protein expression levels for angiotensin II type 1 receptor (AT1R) and vascular cell adhesion molecule 1 (VCAM1) were increased in 8-week untreated group compared to 4-week group, however, they were decreased by buspirone treatments of 1, 5, and 10 mg/kg/day. Conclusion: Buspirone may induce the losses of body weight and abdominal fat weight through the activation of PPARδ dependent catabolic metabolism producing energy, and eventually, the ameliorated lipid metabolism could normalize high blood pressure.

Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells.

PURPOSE: Since diabetes and hypertension frequently occur together, it is thought that these conditions may have a common pathogenesis. This study was designed to evaluate the anti-diabetic function of the anti-hypertensive drug fimasartan on C2C12 mouse skeletal muscle and HepG2 human liver cells in a high glucose state. MATERIALS AND METHODS: The anti-diabetic effects and mechanism of fimasartan were identified using Western blot, glucose uptake tests, oxygen consumption rate (OCR) analysis, adenosine 5'-triphosphate (ATP) enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining for diabetic biomarkers in C2C12 cells. Protein biomarkers for glycogenolysis and glycogenesis were evaluated by Western blotting and ELISA in HepG2 cells. RESULTS: The protein levels of phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), p-AKT, insulin receptor substrate-1 (IRS-1), and glucose transporter type 4 (Glut4) were elevated in C2C12 cells treated with fimasartan. These increases were reversed by peroxisome proliferator-activated receptor delta (PPARδ) antagonist. ATP, OCR, and glucose uptake were increased in cells treated with 200 µM fimasartan. Protein levels of glycogen phosphorylase, glucose synthase, phosphorylated glycogen synthase, and glycogen synthase kinase-3 (GSK-3) were decreased in HepG2 cells treated with fimasartan. However, these effects were reversed following the addition of the PPARδ antagonist GSK0660. CONCLUSION: In conclusion, fimasartan ameliorates deteriorations in glucose metabolism as a result of a high glucose state by regulating PPARδ in skeletal muscle and liver cells.

Stimulation of Alpha-1-Adrenergic Receptor Ameliorates Obesity-Induced Cataracts by Activating Glycolysis and Inhibiting Cataract-Inducing Factors.

BACKGROUND: Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts. METHODS: To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity. RESULTS: Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5'-adenosine monophosphate-activated protein kinase-alpha, adenosine 5´-triphosphate, peroxisome proliferator-activated receptordelta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase. CONCLUSION: The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

Aspirin Improves Nonalcoholic Fatty Liver Disease and Atherosclerosis through Regulation of the PPARδ-AMPK-PGC-1α Pathway in Dyslipidemic Conditions.

This study is aimed at elucidating how aspirin could systemically and simultaneously normalize nonalcoholic fatty liver disease (NAFLD) and atherosclerosis through both in vitro and in vivo studies in hyperlipidemic conditions. We evaluated the effects and mechanism of aspirin on the levels of various biomarkers related to NAFLD, atherosclerosis, and oxidative phosphorylation in cells and animals of hyperlipidemic conditions. The protein levels of biomarkers (PPARδ, AMPK, and PGC-1α) involved in oxidative phosphorylation in both the vascular endothelial and liver cells were elevated by the aspirin in hyperlipidemic condition. Also in the stimulation pathway of oxidative phosphorylation by aspirin, PPARδ was a superior regulator than AMPK and PGC-1α in HepG2 cells. In the vascular endothelial cells, the phosphorylated endothelial nitric oxide synthase level was increased by the treatment. The protein levels of biomarkers related to lipid synthesis were decreased by the treatment in the liver cells. In rabbits administered with cholesterol diet, the levels of triglyceride, HDL-cholesterol, and alanine amino transferase in serums were ameliorated by the aspirin treatment, the levels of ATP and TNFα were increased or decreased, respectively, by the aspirin in liver and aorta tissues, and mannose receptor and C-C chemokine receptor type 2 levels were increased or decreased by the aspirin in spleen, respectively. The elevated levels of macrophage antigen, angiotensin II type1 receptor, and lipid accumulation were decreased in both the liver and aorta tissues in the aspirin-treated group. In conclusion, aspirin can systemically and simultaneously ameliorate NAFLD and atherosclerosis by inhibiting lipid biosynthesis and inflammation and by elevating catabolic metabolism through the activation of the PPARδ-AMPK-PGC-1α pathway. Furthermore, aspirin may normalize atherosclerosis and NAFLD by modulating the mannose receptor and CCR2 in macrophages.

Comparative Evaluation of the Effectiveness of Novel Hyaluronic Acid-Polynucleotide Complex Dermal Filler.

HA (Hyaluronic acid) filler, the most commonly used dermal filler, causes several side effects. HA-PN (Hyaluronic acid-Polynucleotide), a new composite filler, has excellent biocompatibility and induces tissue regeneration. In this study, we compare the efficacies and safety profiles of these fillers. The characteristics of HA and HA-PN fillers were compared using scanning electron microscopy and rheometry. No morphological difference was noted between the fillers. However, the latter had higher viscosity and elasticity values. The HA-PN filler induced higher cell migration than the HA filler in a wound healing assay. It was also found to stimulate better collagen synthesis in human and mouse fibroblasts. The HA and HA-PN fillers were injected into SKH1 hairless mice to determine changes in their volume for up to 24 weeks. Increased cell migration and collagen synthesis were observed in mice injected with the HA-PN complex filler. Although the safety and durability of the HA and HA-PN fillers were similar, the latter induced a lower transient receptor potential vanilloid 4 expression and caused less stimulation upon injection. In conclusion, HA-PN complex fillers can stimulate fibroblast growth and facilitate volume growth and skin regeneration.

The Effects of Nurses' Knowledge of Withdrawal of Life-Sustaining Treatment, Death Anxiety, Perceptions of Hospice on Their Attitudes toward Withdrawal of Life-Sustaining Treatment.

PURPOSE: This descriptive study investigated the effects of nurses' knowledge of withdrawal of life-sustaining treatment, death anxiety, and perceptions of hospice care on their attitudes toward withdrawal of life-sustaining treatment. METHODS: Data were collected from 262 nurses at tertiary hospitals, general hospitals, or primary hospitals in Busan, Korea, and statistically analyzed using the t-test, analysis of variance, the Scheffé test, Pearson correlation coefficients, and hierarchical regression analysis. RESULTS: The participants' scores were 3.68±0.45 (out of 5) for attitudes toward withdrawal of life-sustaining treatment, 0.65±0.15 (out of 1) for knowledge of withdrawal of life-sustaining treatment, 2.61±0.26 (out of 4) for death anxiety, and 4.06±0.43 (out of 5) for perceptions of hospice care. Furthermore, knowledge of withdrawal of life-sustaining treatment and perceptions of hospice care showed positive correlations with attitudes toward withdrawal of life-sustaining treatment, while death anxiety showed a negative correlation. The most significant factors influencing attitudes toward withdrawal of life-sustaining treatment were perceptions of hospice care, followed by having experienced caring for patients who withdrew life-sustaining treatment, death anxiety, having a spouse, and ethical values, and the overall explanatory power was 43.0%. CONCLUSION: This study showed that perceptions of hospice were an important factor influencing nurses' attitudes toward withdrawal of life-sustaining treatment. Therefore, it is necessary to develop and validate educational intervention programs that can improve perceptions of hospice care.

Corrigendum to "Caffeoylquinic Acid-Rich Extract of Aster glehni F. Schmidt Ameliorates Nonalcoholic Fatty Liver through the Regulation of PPARδ and Adiponectin in ApoE KO Mice".

[This corrects the article DOI: 10.1155/2017/3912567.].

Aster glehni Extract Containing Caffeoylquinic Compounds Protects Human Keratinocytes through the TRPV4-PPARδ-AMPK Pathway.

Aster glehni (AG) has been used in cooking and as a medicine to treat various diseases for over hundreds of years in Korea. To speculate the protective effects of AG on skin barrier, we estimated the protein levels of biomarkers related to skin barrier protection in human keratinocytes, HaCaT cells treated with sodium dodecyl sulfate (SDS), or 2,4-dinitrochlorobenzene (DNCB). The protein levels for keratin, involucrin, defensin, tumor necrosis factor alpha (TNFα), peroxisome proliferator-activated receptor delta (PPARδ), 5' adenosine monophosphate-activated protein kinase (AMPK), serine palmitoyltransferase long chain base subunit 2 (SPTLC2), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were evaluated using western blotting or immunocytochemistry in HaCaT cells. AG extract increased the protein levels of PPARδ, phosphorylated AMPK, SPTLC2, keratin, involucrin, and defensin compared to the SDS or DNCB control group. However, TNFα expression increased by SDS or DNCB was decreased with AG extract. The order of action of each regulatory biomarker in AG pathway was identified TRPV4→PPARδ→AMPK from antagonist and siRNA treatment studies. AG can ameliorate the injury of keratinocytes caused by SDS or DNCB through the sequential regulation of TRPV4→PPARδ→AMPK pathway.

6-Gingerol Normalizes the Expression of Biomarkers Related to Hypertension via PPARδ in HUVECs, HEK293, and Differentiated 3T3-L1 Cells.

Hypertension is a disease with a high prevalence and high mortality rates worldwide. In addition, various factors, such as genetic predisposition, lifestyle factors, and the abnormality of organs related to blood pressure, are involved in the development of hypertension. However, at present, there are few available drugs for hypertension that do not induce side effects. Although the therapeutic effects of ginger on hypertension are well established, the precise mechanism has not been elucidated. Therefore, this study was designed to evaluate the antihypertensive mechanism of 6-gingerol, one of the main ingredients of ginger, and to assist in the development of new drugs for hypertension without side effects. The antihypertensive effects and mechanism of 6-gingerol were identified through reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunocytochemical staining for biomarkers involved in hypertension in human umbilical vein endothelial cells (HUVECs), human embryonal kidney cells (HEK293 cells), and mouse preadipocytes (3T3-L1 cells). The lipid accumulation in differentiated 3T3-L1 cells was evaluated by using Oil Red O staining. 6- Gingerol increased the level of phosphorylated endothelial nitric oxide synthase (eNOS) protein but decreased that of vascular cell adhesion protein 1 (VCAM1) and tumor necrosis factor alpha (TNFα) in HUVECs. In HEK293 cells, the expression of the epithelial sodium channel (ENaC) protein was reduced by 6-gingerol. Lipid accumulation was attenuated by 6-gingerol treatment in differentiated 3T3-L1 cells. These effects were regulated via peroxisome proliferator-activated receptor delta (PPARδ). 6-Gingerol ameliorated the expression of biomarkers involved in the development of hypertension through PPARδ in HUVECs, HEK293, and differentiated 3T3-L1 cells.

Caffeoylquinic Acid-Rich Extract of Aster glehni F. Schmidt Ameliorates Nonalcoholic Fatty Liver through the Regulation of PPARδ and Adiponectin in ApoE KO Mice.

Aster glehni is well known for its therapeutic properties. This study was performed to investigate the effects of A. glehni on nonalcoholic fatty liver disease (NAFLD) in atherosclerotic condition, by determining the levels of biomarkers related to lipid metabolism and inflammation in serum, liver, and adipose tissue. Body and abdominal adipose tissue weights and serum triglyceride level decreased in all groups treated with A. glehni. Serum adiponectin concentration and protein levels of peroxisome proliferator-activated receptor δ, 5' adenosine monophosphate-activated protein kinase, acetyl-CoA carboxylase, superoxide dismutase, and PPARγ coactivator 1-alpha in liver tissues increased in the groups treated with A. glehni. Conversely, protein levels of ATP citrate lyase, fatty acid synthase, tumor necrosis factor α, and 3-hydroxy-3-methylglutaryl-CoA reductase and the concentrations of interleukin 6 and reactive oxygen species decreased upon A. glehni. Triglyceride concentration in the liver was lower in mice treated with A. glehni than in control mice. Lipid accumulation in HepG2 and 3T3-L1 cells decreased upon A. glehni treatment; this effect was suppressed in the presence of the PPARδ antagonist, GSK0660. Our findings suggest that A. glehni extracts may ameliorate NAFLD through regulation of PPARδ, adiponectin, and the related subgenes.

Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPARδ Regulation in Hyperlipidemic and Hypertensive Conditions.

To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs) given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ), phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase (p-ACC), malonyl-CoA decarboxylase (MCD), medium chain acyl-CoA dehydrogenase (MCAD), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11ß-HSDH1), fatty acid synthase (FAS), and tumor necrosis factor-alpha (TNF-α). Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδ antagonist (GSK0660). Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1α pathway.