Effects of Quercetin Nanoemulsion on Cholesterol Efflux and MicroRNA-33/34a Expression in the Liver of Mice Fed with a High-Cholesterol Diet.

Quercetin is a flavonoid widely present in plants; despite its beneficial physiological activity, it exhibits considerably low bioavailability. Nanoemulsion technology is used for improving the bioavailability of lipophilic phenolic compounds. This study aimed to investigate the potential effects of quercetin nanoemulsion (QN) on regulating the microRNA (miR)-33/34a pathway involved in cholesterol efflux in the liver of mice fed with a high-cholesterol (HC) diet. Subsequently, C57BL/6J mice were divided into four groups and fed a normal chow diet, HC diet supplemented with 1% cholesterol and 0.5% cholic acid, or HC diet supplemented with 0.05% QN or 0.1% QN for 6 weeks. Serum and hepatic lipid profiles were assayed using commercial enzymatic kits. Gene expression and miR levels were quantified using real-time quantitative reverse transcription polymerase chain reaction, and adenosine monophosphate-activated protein kinase (AMPK) activity was measured using an AMPK Kinase Assay kit. QN supplementation improved serum and liver lipid profiles. QN upregulated the mRNA levels of adenosine triphosphate (ATP)-binding cassette subfamily A1, ATP-binding cassette subfamily G1, and scavenger receptor class B type 1, which are related to cholesterol efflux. In the QN group, the hepatic AMPK activity increased, whereas miR-33, and miR-34a expression levels decreased. These results suggest that QN may enhance cholesterol efflux, at least partly through modulating AMPK activity and miR-33/34a expression in the liver.

Green Tea and Java Pepper Mixture Prevents Obesity by Increasing Energy Expenditure and Modulating Hepatic AMPK/MicroRNA-34a/370 Pathway in High-Fat Diet-Fed Rats.

This study was performed to evaluate the anti-obesity effects of green tea and java pepper mixture (GJ) on energy expenditure and understand the regulatory mechanisms of AMP-activated protein kinase (AMPK), microRNA (miR)-34a, and miR-370 pathways in the liver. Sprague-Dawley rats were divided into four groups depending on the following diets given for 14 weeks: normal chow diet (NR), 45% high-fat diet (HF), HF + 0.1% GJ (GJL), and HF + 0.2% GJ (GJH). The results revealed that GJ supplementation reduced body weight and hepatic fat accumulation, improved serum lipids, and increased energy expenditure. In the GJ-supplemented groups, the mRNA levels of genes related to fatty acid syntheses, such as a cluster of differentiation 36 (CD36), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1) were downregulated, and mRNA levels of peroxisome proliferator-activated receptor alpha (PPARα), carnitine/palmitoyl-transferase 1 (CPT1), and uncoupling protein 2 (UCP2), which participate in fatty acid oxidation, were upregulated in the liver. GJ increased the AMPK activity and decreased the miR-34a and miR-370 expression. Therefore, GJ prevented obesity by increasing energy expenditure and regulating hepatic fatty acid synthesis and oxidation, suggesting that GJ is partially regulated through AMPK, miR-34a, and miR-370 pathways in the liver.

Portulaca oleracea L. Extract Regulates Hepatic Cholesterol Metabolism via the AMPK/MicroRNA-33/34a Pathway in Rats Fed a High-Cholesterol Diet.

This study examined the effect of extruded Portulaca oleracea L. extract (PE) in rats fed a high-cholesterol diet through the AMP-activated protein kinase (AMPK) and microRNA (miR)-33/34a pathway. Sprague-Dawley rats were randomized into three groups and fed either a standard diet (SD), a high-cholesterol diet containing 1% cholesterol and 0.5% cholic acid (HC), or an HC diet containing 0.8% PE for 4 weeks. PE supplementation improved serum, liver, and fecal lipid profiles. PE upregulated the expression of genes involved in cholesterol efflux and bile acids' synthesis such as liver X receptor alpha (LXRα), ATP-binding cassette subfamily G5/G8 (ABCG5/8), and cholesterol 7 alpha-hydroxylase (CYP7A1), and downregulated farnesoid X receptor (FXR) in the liver. In addition, hepatic gene expression levels of apolipoprotein A-l (apoA-1), paraoxonase 1 (PON1), ATP-binding cassette subfamily A1/G1 (ABCA1/G1), lecithin-cholesterol acyltransferase (LCAT), and scavenger receptor class B type 1 (SR-B1), which are related to serum high-density lipoprotein cholesterol metabolism, were upregulated by PE. Furthermore, hepatic AMPK activity in the PE group was higher than in the HC group, and miR-33/34a expression levels were suppressed. These results suggest that PE improves the cholesterol metabolism by modulating AMPK activation and miR-33/34a expression in the liver.

Green Tea Extract Containing Piper retrofractum Fruit Ameliorates DSS-Induced Colitis via Modulating MicroRNA-21 Expression and NF-κB Activity.

The aim of the present study was to examine the effect of green tea extract containing Piper retrofractum fruit (GTP) on dextran-sulfate-sodium (DSS)-induced colitis, the regulatory mechanisms of microRNA (miR)-21, and the nuclear factor-κB (NF-κB) pathway. Different doses of GTP (50, 100, and 200 mg/kg) were administered orally once daily for 14 days, followed by GTP with 3% DSS for 7 days. Compared with the DSS-treated control, GTP administration alleviated clinical symptoms, including the disease activity index (DAI), colon shortening, and the degree of histological damage. Moreover, GTP suppressed miR-21 expression and NF-κB activity in colon tissue of DSS-induced colitis mice. The mRNA levels of inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were downregulated by GTP. Colonic nitric oxide (NO) and prostaglandin E2 (PGE2) production, and myeloperoxidase (MPO) activity were also lowered by GTP. Taken together, our results revealed that GTP inhibits DSS-induced colonic inflammation by suppressing miR-21 expression and NF-κB activity, suggesting that it may be used as a potential functional material for improving colitis.

High Hydrostatic Pressure Extract of Mulberry Leaf Attenuated Obesity-Induced Inflammation in Rats.

Low-grade inflammation might be a link between obesity and obesity-associated metabolic dysfunction, including diabetes, hepatic steatosis, and other health complications. This study investigated whether the supplementation of high hydrostatic pressure extract of mulberry (Morus alba L.) leaves (HML) to obese rats could counteract obesity-related inflammation. Three-week-old male Sprague-Dawley rats were separated into three groups as follows: (a) a normal diet, (b) 45% high-fat (HF) diet, and HF diet containing 0.4% HML (c) or 0.8% HML (d) (IACUC No. 17-033). After 14 weeks of HML supplementation, adipose tissue mass, mRNA expression of adipogenic genes, such as aP2, peroxisome proliferator-activated receptor γ (PPARγ), and sterol regulatory element binding protein 1c (SREBP1c), and macrophage recruitment were significantly decreased in HF-fed obese rats. Serum concentrations of nitric oxide and mRNA levels of arginase1 (Arg1), CD11c, and inducible nitric oxide synthase (iNOS) involved in adipose tissue macrophage M1 polarization were also significantly reduced by HML. Moreover, HML alleviated the serum and hepatic lipid profiles and reduced hepatic lipogenic gene expression of acetyl-CoA carboxylase (ACC), cluster of differentiation 36 (CD36), CPT1, fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD1), and SREBP1c, and inflammation-associated genes, including IL1ß, interleukin 6 (IL6), and tumor necrosis factor α (TNFα). Serum IL6 and TNFα levels were remarkedly suppressed in the 0.8% HML group. These results suggested that the favorable effect of HML on obesity-associated inflammation might be related in part to the decrease in adipose tissue and hepatic fat deposition and inflammation.

Chrysanthemum morifolium Flower Extract Ameliorates Obesity-Induced Inflammation and Increases the Muscle Mitochondria Content and AMPK/SIRT1 Activities in Obese Rats.

Decreased energy expenditure and chronically positive energy balance contribute to the prevalence of obesity and associated metabolic dysfunctions, such as dyslipidemia, hepatic fat accumulation, inflammation, and muscle mitochondrial defects. We investigated the effects of Chrysanthemum morifolium Ramat flower extract (CE) on obesity-induced inflammation and muscle mitochondria changes. Sprague-Dawley rats were randomly divided into four groups and fed either a normal diet, 45% high-fat diet (HF), HF containing 0.2% CE, or 0.4% CE for 13 weeks. CE alleviated HF-increased adipose tissue mass and size, dyslipidemia, hepatic fat deposition, and systematic inflammation, and increased energy expenditure. CE significantly decreased gene expression involved in adipogenesis, pro-inflammation, and the M1 macrophage phenotype, as well as glycerol-3-phosphate dehydrogenase (GPDH) and nuclear factor-kappa B (NF-kB) activities in epididymal adipose tissue. Moreover, CE supplementation improved hepatic fat accumulation and modulated gene expression related to fat synthesis and oxidation with an increase in adenosine monophosphate-activated protein kinase (AMPK) activity in the liver. Furthermore, CE increased muscle mitochondrial size, mitochondrial DNA (mtDNA) content, and gene expression related to mitochondrial biogenesis and function, including sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and PGC-1α-target genes, along with AMPK-SIRT1 activities in the skeletal muscle. These results suggest that CE attenuates obesity-associated inflammation by modulating the muscle AMPK-SIRT1 pathway.

Mulberry (Morus alba L.) Fruit Extract Ameliorates Inflammation via Regulating MicroRNA-21/132/143 Expression and Increases the Skeletal Muscle Mitochondrial Content and AMPK/SIRT Activities.

The Mulberry (Morus alba L.) fruit is a rich source of polyphenolic compounds; most of these are anthocyanins. Obesity is intimately related to low-grade inflammation, with increased pro-inflammatory cytokine secretion and macrophage infiltration in white adipose tissue (WAT). This study investigated whether mulberry fruit extract (ME) has beneficial effects on obesity-induced inflammation and skeletal muscle mitochondrial dysfunction. Sprague-Dawley rats were divided into four groups and fed either a low-fat diet (LFD), high-fat diet (HFD), HFD + 5 g/kg of ME (ME-L), or HFD + 10 g/kg of ME (ME-H) for 14 weeks. ME alleviated dyslipidemia and lipid accumulation, as well as pro-inflammatory cytokine production such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and monocyte chemoattractant protein 1 (MCP1) in the WAT. ME mitigated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation and macrophage infiltration in WAT. Notably, microRNA (miR)-21, miR-132, and miR-43 expressions were downregulated in the WAT of the ME groups compared to the HFD group. Moreover, ME increased the mitochondrial size and mitochondrial DNA (mtDNA) content, as well as key genes' expression related to mitochondrial function, including sirtuin (SIRT)1, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), carnitine palmitoyltransferase 1ß (CPT-1ß), and uncoupling protein 3 (UCP3), and adenosine monophosphate-activated protein kinase (AMPK)/SIRT activities in skeletal muscle. These results suggested that ME might alleviate obesity-induced inflammation and mitochondrial dysfunction by regulating miR-21, miR-132, and miR-43 expression in WAT, and by activating the PGC-1α/SIRT1 pathway in muscle.

High hydrostatic pressure extract of mulberry leaves ameliorates hypercholesterolemia via modulating hepatic microRNA-33 expression and AMPK activity in high cholesterol diet fed rats.

BACKGROUND: Mulberry leaf (Morus alba L.) contains multiple bioactive ingredients and has been used in the treatment of obesity, diabetes, inflammation, and atherosclerosis. High hydrostatic pressure (HHP) processing has been developed for the extraction of bioactive compounds from plants. However, the hypocholesterolemic effect of the HHP extract from mulberry leaves and its underlying mechanism have never been investigated. OBJECTIVE: The specific aim of the present study was to investigate the hypocholesterolemic property of a novel extract obtained from mulberry leaves under HHP in rats. DESIGN: Sprague-Dawley rats were divided into four groups and fed either a normal diet (NOR), a high cholesterol diet containing 1% cholesterol and 0.5% cholic acid (HC), an HC diet containing 0.5% mulberry leaf extract (ML), or a 1% mulberry leaf extract (MH) for 4 weeks. RESULTS: High hydrostatic pressure extract of mulberry leaves significantly reduced the HC-increased serum levels of triglyceride (TG), cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and hepatic contents of TG and TC. The HHP extraction from mulberry leaves also increased the HC-decreased fecal TC and bile acid levels without changing body weight, food intake, liver weight, and serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) (P < 0.05). The mulberry leaf extract significantly enhanced the expression of hepatic genes such as cholesterol 7 alpha-hydroxylase (CYP7A1), liver X receptor alpha (LXRα), and ATP-binding cassette transporters, ABCG5/ABCG8, involved in hepatic bile acid synthesis and cholesterol efflux (P < 0.05). In addition, the HHP extraction of mulberry leaves significantly suppressed hepatic microRNA(miR)-33 expression and increased adenosine monophosphate-activated protein kinase (AMPK) activity. CONCLUSION: These results suggest that the HHP extract of mulberry leaves lowers serum cholesterol levels by partially increasing hepatic bile acid synthesis and fecal cholesterol excretion through the modulation of miR-33 expression and AMPK activation in the liver.

Chrysanthemum morifolium Flower Extract Inhibits Adipogenesis of 3T3-L1 Cells via AMPK/SIRT1 Pathway Activation.

Chrysanthemum (Chrysanthemum morifolium Ramat) flowers (CF) are widely consumed as herbal tea in many countries, including China. The aim of the present study was to examine the anti-adipogenic effect of hot water extraction of CF (HCF) on 3T3-L1 cells and their underlying cellular mechanisms. HCF treatment inhibited lipid accumulation under conditions that did not show the toxicity of 3T3-L1 adipocytes. The activity of glycerol-3-phosphate dehydrogenase (GPDH), which plays an important role in glycerol lipid metabolism, was also reduced by HCF. Adipogenesis/lipogenesis-related mRNA expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (CEBP-α), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid-binding protein 4 (FABP4), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS) were suppressed by HCF in a dose-dependent manner. Moreover, HCF increased activities of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1), involved in lipid metabolism. These findings suggest that HCF inhibits adipocyte lipid accumulation through suppression of adipogenesis/lipogenesis-related gene expression and activation of the AMPK/SIRT1 pathway. Therefore, it suggests that HCF may be used as a potentially beneficial plant material for preventing obesity.

Mulberry Fruit Extract Promotes Serum HDL-Cholesterol Levels and Suppresses Hepatic microRNA-33 Expression in Rats Fed High Cholesterol/Cholic Acid Diet.

Serum high-density lipoprotein cholesterol (HDL-C) levels and cholesterol excretion are closely associated with the risk of cardiovascular complications. The specific aim of the present study was to investigate the cholesterol lowering effect of mulberry fruit in rats fed a high cholesterol/cholic acid diet. Four-week supplementation with mulberry fruit extract significantly decreased serum and hepatic cholesterol (TC), serum low-density lipoprotein cholesterol (LDL-C), and fecal bile acid levels without changes in body weight and food intake (p < 0.05). Mulberry fruit extract significantly inhibited hepatic sterol-regulatory element binding protein (Srebp) 2 gene expression and upregulated hepatic mRNA levels of liver X receptor alpha (Lxr-α), ATP-binding cassette transporter 5 (Abcg5), and cholesterol 7 alpha-hydroxylase (Cyp7a1), which are involved in hepatic bile acid synthesis and cholesterol metabolism (p < 0.05). In addition, hepatic microRNA-33 expression was significantly inhibited by supplementation of mulberry fruit extract (p < 0.05). These results suggest the involvement of miR-33, its associated hepatic bile acid synthesis, HDL formation, and cholesterol metabolism in mulberry fruit-mediated beneficial effects on serum and hepatic lipid abnormalities.

Mulberry Fruit Extract Ameliorates Adipogenesis via Increasing AMPK Activity and Downregulating MicroRNA-21/143 in 3T3-L1 Adipocytes.

Mulberry (Morus alba L.) fruits have long been used in traditional medicine and as edible berries in many countries. This study investigated the antiadipogenic effect of high hydrostatic pressure mulberry fruit extract (MFE) during 3T3-L1 adipocyte differentiation. MFE decreased lipid and triglyceride accumulation and glycerol-3-phosphate dehydrogenase activity. The mRNA expression levels of genes related to adipogenesis, such as the adipocyte protein 2, proliferator-activated receptor-γ, and CCAAT/enhancer binding protein-α, were suppressed by MFE. They also reduced microRNA (miR)-21 and miR-143 expression, which are involved in adipogenesis. In contrast, adenosine monophosphate-activated protein kinase (AMPK) activity was increased by MFE. These results suggested that MFE may suppress adipogenesis through modulating miR-21/143 expression and AMPK activity in 3T3-L1 adipocytes, which may be useful as antiobesity food agents.

Anti-Inflammatory Effects of High Hydrostatic Pressure Extract of Mulberry (Morus alba) Fruit on LPS-Stimulated RAW264.7 Cells.

Mulberry fruit (Morus alba L.) contains abundant bioactive compounds, including anthocyanins and flavonols, and has been reported to possess potent beneficial properties including anticancer, antidiabetic, and anti-oxidant effects. High hydrostatic pressure (HHP) processing, a nonthermal food processing technology, is suitable for the extraction of bioactive compounds from plants. Nevertheless, the anti-inflammatory effects of HHP extract of mulberry fruit (HM) in RAW264.7 cells remain unclear. The present study aimed to investigate the anti-inflammatory effects of HM on lipopolysaccharide (LPS)-induced inflammation in vitro. RAW264.7 cells were treated with various concentrations (0.1-1 µg/mL) of HM in the presence or absence of LPS. HM inhibited the inflammatory mediator, nitric oxide (NO) release, and mRNA expression of nitric oxide synthase 2 (NOS2) in LPS-induced RAW264.7 cells. In addition, HM suppressed both mRNA and protein expressions of prostaglandin-endoperoxide synthase 2 (PTGS2). Moreover, it reduced the LPS-induced secretion of proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α. These results revealed that HM exerts anti-inflammatory effects by inhibiting several mediators and cytokines involved in the inflammatory process.

Tartary Buckwheat Extract Attenuated the Obesity-Induced Inflammation and Increased Muscle PGC-1a/SIRT1 Expression in High Fat Diet-Induced Obese Rats.

Obesity is intimately related to a chronic inflammatory state, with augmentation of macrophage infiltration and pro-inflammatory cytokine secretion in white adipose tissue (WAT) and mitochondrial dysfunction in skeletal muscle. The specific aim of this study is to evaluate effects of tartary buckwheat extract (TB) on obesity-induced adipose tissue inflammation and muscle peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α/sirtulin 1 (SIRT1) pathway in rats fed a high-fat diet. Sprague-Dawley rats were divided into four groups and fed either a normal diet (NOR), 45% high-fat diet (HF), HF + low dose of TB (TB-L; 5 g/kg diet), or HF + high dose of TB (TB-H; 10 g/kg diet) for 13 weeks. TB significantly reduced adipose tissue mass with decreased adipogenic gene expression of PPAR-γ and aP2. Serum nitric oxide levels and adipose tissue macrophage M1 polarization gene markers, such as iNOS, CD11c, and Arg1, and pro-inflammatory gene expression, including TNF-α, IL-6, and MCP-1, were remarkably downregulated in the TB-L and TB-H groups. Moreover, TB supplementation increased gene expression of PGC-1α and SIRT1, involved in muscle biogenesis and function. These results suggested that TB might attenuate obesity-induced inflammation and mitochondrial dysfunction by modulating adipose tissue inflammation and the muscle PGC-1α/SIRT1 pathway.

Formulation and Characterization of Quercetin-loaded Oil in Water Nanoemulsion and Evaluation of Hypocholesterolemic Activity in Rats.

Due to poor water solubility and high susceptibility to chemical degradation, the applications of quercetin have been limited. This study investigated the effects of pH on the formation of quercetin-loaded nanoemulsion (NQ) and compared the hypocholesterolemic activity between quercetin and NQ to utilize the quercetin as functional food ingredient. NQ particle size exhibited a range of 207⁻289 nm with polydispersity index range (<0.47). The encapsulation efficiency increased stepwise from 56 to 92% as the pH increased from 4.0 to 9.0. Good stability of NQ was achieved in the pH range of 6.5⁻9.0 during 3-month storage at 21 and 37 °C. NQ displayed higher efficacy in reducing serum and hepatic cholesterol levels and increasing the release of bile acid into feces in rats fed high-cholesterol diet, compared to quercetin alone. NQ upregulated hepatic gene expression involved in bile acid synthesis and cholesterol efflux, such as cholesterol 7 alpha-hydroxylase (CYP7A1), liver X receptor alpha (LXRα), ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette sub-family G member 1 (ABCG1). These results suggest at least partial involvement of hepatic bile acid synthesis and fecal cholesterol excretion in nanoemulsion quercetin-mediated beneficial effect on lipid abnormalities.

Ginger Extract Ameliorates Obesity and Inflammation via Regulating MicroRNA-21/132 Expression and AMPK Activation in White Adipose Tissue.

Ginger is a plant whose rhizome is used as a spice or folk medicine. We aimed to investigate the effect of ginger root extract on obesity and inflammation in rats fed a high-fat diet. Sprague-Dawley rats were divided into three groups and fed either a 45% high-fat diet (HF), HF + hot-water extract of ginger (WEG; 8 g/kg diet), or HF + high-hydrostatic pressure extract of ginger (HPG; 8 g/kg diet) for 10 weeks. The HPG group had lower body weight and white adipose tissue (WAT) mass compared to the HF group. Serum and hepatic lipid levels of HPG group were lower, while fecal lipid excretion of the HPG group was higher than that of the HF group. In the WAT of the WEG and HPG groups, mRNA levels of adipogenic genes were lower than those of the HF group. Moreover, HPG group had lower mRNA levels of pro-inflammatory cytokines than did the HF group. MicroRNA (miR)-21 expression was down-regulated by both WEG and HPG. Additionally, miR-132 expression was down-regulated by HPG. The adenosine monophosphate-activated protein kinase (AMPK) activity of HPG group was greater than that of the HF group. HPG may have beneficial effects on obesity and inflammation, partially mediated by regulation of miR-21/132 expression and AMPK activation in WAT.

Effects of Isorhamnetin on Adipocyte Mitochondrial Biogenesis and AMPK Activation.

Isorhamnetin (ISOR), 3-O-methylquercetin, is a naturally occurring flavonoid in many plants. It is a metabolite derived from quercetin and is known to exert beneficial effects on the prevention of obesity. However, the molecular mechanism of action involved in ISOR-mediated mitochondrial biogenesis, and AMP-activated protein kinase (AMPK) activation in 3T3-L1 cells remains unclear. The aim of this study was to determine whether ISOR affected mitochondrial biogenesis and AMPK activation, during 3T3-L1 adipocyte differentiation. Intracellular lipid and triglyceride accumulation, and glycerol-3-phosphate dehydrogenase (GPDH) activity decreased in ISOR-treated cells. The mRNA levels of adipogenic genes, such as the proliferator-activated receptor-γ (PPAR-γ), and adipocyte protein 2 (aP2), were inhibited by ISOR. In contrast, mRNA levels of mitochondrial genes, such as peroxisome proliferator-activated reporter gamma coactivator-1α (PGC-1α), nuclear respiratory factor (NRF)-1, transcription factor A (Tfam), and carnitine palmitoyl transferase-1α (CPT-1α), were all stimulated by ISOR treatment. Mitochondria DNA (mtDNA) copy number and AMPK activity were also stimulated by ISOR. The results suggested that the mitochondrial biogenic effect of ISOR in adipocytes might have been associated with stimulation of mitochondrial gene expression, mtDNA replication, and AMPK activation.

Echinacea purpurea Protects Against Restraint Stress-Induced Immunosuppression in BALB/c Mice.

Echinacea purpurea has been widely used for the prevention and treatment of upper respiratory tract infections and the common cold. The restraint stress has been reported to suppress a broad spectrum of immune functions. The aim of this study was to investigate the protective effects of the pressed juice of E. purpurea (L.) Moench (EFLA®894; Echinacea) against restraint stress-induced immunosuppression in BALB/c mice. Echinacea significantly normalized the restraint stress-induced reduction in splenocyte proliferation and splenic natural killer (NK) cell activity (P < .05). Echinacea treatment significantly increased the percentages of CD4+ and CD8+ T lymphocytes in the blood (P < .05). In addition, Echinacea restored serum cytokine levels, including interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-17 (IL-17), as well as the mRNA expressions of these cytokines in spleen (P < .05). Our findings suggest that Echinacea might have beneficial effects on restraint stress-induced immunosuppression by increasing splenocyte proliferation and NK cell activity, while modulating T lymphocyte subsets and cytokine levels in the blood.

Lipolytic efficacy of alginate double-layer nanoemulsion containing oleoresin capsicum in differentiated 3T3-L1 adipocytes.

Background: Oleoresin capsicum (OC) is an organic extract from fruits of the genus Capsicum, and has been reported to have an anti-obesity effect. Objective: This study comparatively investigated lipolytic effects of single-layer nanoemulsion (SN) and alginate double-layer nanoemulsion (AN) containing OC in 3T3-L1 adipocytes. Methods: SN and AN were compared by analyzing the intracellular lipid accumulation, triglyceride (TG) content, release of free fatty acids (FFAs) and glycerol, and mRNA expression of genes related to adipogenesis and lipolysis were analyzed in fully differentiated 3T3-L1 adipocytes. Results: Compared with SN, AN exhibited higher efficiency in inhibiting the intracellular lipid accumulation and TG content, and enhanced the release of FFAs and glycerol into the medium. In AN-treated cells, mRNA levels of peroxisome proliferator-activated receptor-γ and the fatty acid-binding protein adipocyte protein-2, which are involved in adipogenesis, were down-regulated, whereas those of genes related to lipolysis, including hormone-sensitive lipase and carnitine palmitoyl transferase-1α, were up-regulated compared with SN-treated cells. Conclusion: The lipolytic effect of AN was greater than that of SN; this was partly associated with the increased TG hydrolysis via induction of lipolytic gene expression and suppression of adipogenic gene expression in 3T3-L1 adipocytes.​​​​.

High Hydrostatic Pressure Extract of Ginger Exerts Antistress Effects in Immobilization-Stressed Rats.

Stress contributes to physiological changes such as weight loss and hormonal imbalances. The aim of the present study was to investigate antistress effects of high hydrostatic pressure extract of ginger (HPG) in immobilization-stressed rats. Male Sprague-Dawley rats (n = 24) were divided into three groups as follows: control (C), immobilization stress (2 h daily, for 2 weeks) (S), and immobilization stress (2 h daily, for 2 weeks) plus oral administration of HPG (150 mg/kg body weight/day) (S+G). Immobilization stress reduced the body weight gain and thymus weight by 50.2% and 31.3%, respectively, compared to the control group. The levels of serum aspartate transaminase, alanine transaminase, and corticosterone were significantly higher in the stress group, compared to the control group. Moreover, immobilization stress elevated the mRNA levels of tyrosine hydroxylase (Th), dopamine beta-hydroxylase (Dbh), and cytochrome P450 side-chain cleavage (P450scc), which are related to catecholamine and corticosterone synthesis in the adrenal gland. HPG administration also increased the body weight gain and thymus weight by 12.7% and 16.6%, respectively, compared to the stress group. Furthermore, the mRNA levels of Th, Dbh, phenylethanolamine-N-methyltransferase, and P450scc were elevated by the HPG treatment when compared to the stress group. These results suggest that HPG would have antistress effects partially via the reversal of stress-induced physiological changes and suppression of mRNA expression of genes related to corticosterone and catecholamine synthetic enzymes.

The Inhibitory Effect of Tartary Buckwheat Extracts on Adipogenesis and Inflammatory Response.

Tartary buckwheat (Fagopyrum tataricum) has been established globally as a nutritionally important food item, particularly owing to high levels of bioactive compounds such as rutin. This study investigated the effect of tartary buckwheat extracts (TBEs) on adipogenesis and inflammatory response in 3T3-L1 cells. TBEs inhibited lipid accumulation, triglyceride content, and glycerol-3-phosphate dehydrogenase (GPDH) activity during adipocyte differentiation of 3T3 L1 cells. The mRNA levels of genes involved in fatty acid synthesis, such as peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α (CEBP-α), adipocyte protein 2 (aP2), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoylcoenzyme A desaturase-1 (SCD-1), were suppressed by TBEs. They also reduced the mRNA levels of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), and inducible nitric oxide synthase (iNOS). In addition, TBEs were decreased nitric oxide (NO) production. These results suggest that TBEs may inhibit adipogenesis and inflammatory response; therefore, they seem to be beneficial as a food ingredient to prevent obesity-associated inflammation.