Effects of Anthocyanin Supplementation on Reduction of Obesity Criteria: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Anthocyanins, water-soluble flavonoids that produce red-to-blue pigment in plants, have antioxidant properties and have been developed as a functional food to fight obesity. In randomized controlled trials (RCTs), a systematic review with meta-analysis (SR-MA) was used to investigate these anti-obesity effects. Using search engines (PubMed, EMBASE, Cochrane-library, and CINAHL) and keywords (anthocyanins, BMI, WC, WHR, and inflammatory biomarkers), 11 out of 642 RCTs (28.3-500 mg/day of anthocyanins for 4 to 24 weeks) were included. The results showed a significant reduction in body mass index (BMI) (MD = -0.36, 95% CI = -0.58 to -0.13), but body weight (BW) and waist circumference (WC) did not change. Anthocyanins decreased BMI in the non-obese (non-OB) group in five RCTs (BMI ≤ 25; MD = -0.40 kg/m2; 95% CI = -0.64 to -0.16;) but did not affect BMI in the obese (OB) group. A subgroup analysis of six RCTs showed that fewer than 300 mg/day reduced BMI (MD = -0.37; 95% CI = -0.06 to -0.14), but ≥300 mg/day did not. A treatment duration of four weeks for four RCTs was sufficient to decrease the BMI (MD = -0.41; 95% CI = -0.66 to -0.16) as opposed to a longer treatment (6-8 or ≥12 weeks). An analysis of the effect of anthocyanins on the BMI showed a significant fall among those from the Middle East compared to those from Asia, Europe, South America, or Oceania. In conclusion, the anthocyanin supplementation of 300 mg/day or less for four weeks was sufficient to reduce the BMI and BW compared to the higher-dose and longer-treatment RCTs. However, further studies might be conducted regarding the dose- or period-dependent responses on various obese biomarkers.

L-Carnitine's Effect on the Biomarkers of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to assess L-carnitine supplements' influence on the biomarkers of metabolic syndrome (MetSyn). PubMed, EMBASE, Cochrane library, and CINAHL were used to collect RCT studies published prior to February 2020. RCT studies were included if they had at least one of the following biomarker outcome measurements: waist circumference (WC), blood pressure (BP), fasting blood sugar (FBS), triglyceride (TG), or high density lipoprotein-cholesterol (HDLc). Nine of twenty studies with adequate methodological quality were included in this meta-analysis. The dose of L-carnitine supplementation administered varied between 0.75 and 3 g/day for durations of 8-24 weeks. L-carnitine supplementation significantly reduced WC and systolic BP (SBP), with no significant effects on FBS, TG, and HDLc. We found that L-carnitine supplementation at a dose of more than 1 g/d significantly reduced FBS and TG and increased HDLc. In conclusion, L-carnitine supplementation is correlated with a significant reduction of WC and BP. A dose of 1-3 g/d could improve the biomarkers of MetSyn by reducing FBS and TG and increasing HDLc.

Anti-Inflammatory Potential of Cultured Ginseng Roots Extract in Lipopolysaccharide-Stimulated Mouse Macrophages and Adipocytes.

Wild ginseng, Panax ginseng Meyer, is a traditional medicine widely used in Asia. Due to low reward and high costs, wild ginseng is produced by a plant cell culture technique called cultured ginseng roots (GR). The health benefits of wild ginseng have been well studied, but the potential health effects of GR are largely unknown. Thus, we investigated the role of a GR extract (GRE) on inflammatory responses. We firstly investigated the anti-inflammatory potential of GRE in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. GRE (100 µg/mL) dampened pro-inflammatory gene expression, cytokine release, reactive oxygen species (ROS) production, and mitogen-activated protein kinase (MAPK) activation. These anti-inflammatory responses by GRE were confirmed in mouse bone marrow-derived macrophages (BMDMs), which showed that GRE could inhibit inflammation with the induction of antioxidant levels. LPS was recently reported to impair mitochondrial bioenergetics in mouse macrophages. We next measured the mitochondrial oxygen consumption rate (OCR), determining mitochondrial function. LPS treatment downregulated OCR; however, GRE partially restored the LPS-mediated energy homeostasis defects. Furthermore, GRE-pretreated conditioned media (CM) obtained from mouse macrophages decreased CM-mediated adipocyte inflammation. Collectively, these data suggested that GRE attenuated LPS-induced inflammation, and it might be partially involved in the protection from mitochondrial dysfunction in macrophages and adipocytes.

Laminaria japonica Extract Enhances Intestinal Barrier Function by Altering Inflammatory Response and Tight Junction-Related Protein in Lipopolysaccharide-Stimulated Caco-2 Cells.

In the normal physiological state, intestinal epithelial cells act as a defensive frontline of host mucosal immunity to tolerate constant exposure to external stimuli. In this study, we investigated the potential anti-inflammatory and gut permeability protective effects of Laminaria japonica (LJ) water extract (LJE) and three types of fermented Laminaria japonica water extracts (LJE-F1, LJE-F2, and LJE-F3) in lipopolysaccharide (LPS)-stimulated Caco-2, human intestinal epithelial cells. All four extracts significantly decreased the production of nitric oxide and interleukin-6 induced by LPS stimulus. In addition, LJE and the three types of LJE-Fs also inhibited LPS-induced loss of monolayer permeability, as assessed by changes in transepithelial electrical resistance. All four LJ extracts significantly prevented the inhibition of the protein levels of occludin, whereas LJE, LJE-F1, and LJE-F3 significantly attenuated the reduction in phosphorylation of adenosine monophosphate-activated protein kinase compared with the LPS-treated group in Caco-2 cells. In conclusion, LJE and its fermented water extracts appear to have potential gut health-promoting effects by reducing inflammation and partially regulating the tight junction-related proteins in human intestinal epithelial cells. Thus, additional studies are warranted to evaluate Laminaria japonica as a therapeutic agent for inflammatory bowel diseases.

Metabolomics Associated with Genome-Wide Association Study Related to the Basal Metabolic Rate in Overweight/Obese Korean Women.

A previous genome-wide association study (GWAS) on obese/overweight Korean women reported five new genetic loci associated with the basal metabolic rate (BMR) and body mass index (BMI), NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17. This metabolite GWAS (mGWAS) aimed to identify the key metabolites and metabolic pathways regulated by these genes. Potential metabolic pathways associated with leanness and obesity were identified by detecting metabolites in association with GWAS. Waist circumference, lean body mass, and body fat mass were strongly associated with BMI rather than BMR. However, plasma triglyceride and total cholesterol were significantly higher in obese individuals with low BMR than in lean individuals with high BMR. Upon analyzing NRG3, BCL2L2-PABPN1, and SLC22A17, uric acid, succinic acid, arginine, uridine, and aspartic acid were the metabolites positively associated with obesity. Uric acid and arginine were both identified through general metabolomics targeting of obesity genes classified on the basis of BMI or BMR. Metabolites associated with disruption in beta-oxidation, lipid metabolism, branched-chain amino acid and aromatic amino acid catabolism, the urea cycle, and purine/pyrimidine metabolism play important roles in obesity classified on the basis of either BMI or BMR in middle-aged Korean women. These results further the current understanding of obesity and the predictability of obesity-related risks using mGWAS.

Peanut Sprout Extracts Attenuate Triglyceride Accumulation by Promoting Mitochondrial Fatty Acid Oxidation in Adipocytes.

Peanut sprouts (PS), which are germinated peanut seeds, have recently been reported to have anti-oxidant, anti-inflammatory, and anti-obesity effects. However, the underlying mechanisms by which PS modulates lipid metabolism are largely unknown. To address this question, serial doses of PS extract (PSE) were added to 3T3-L1 cells during adipocyte differentiation. PSE (25 µg/mL) significantly attenuated adipogenesis by inhibiting lipid accumulation in addition to reducing the level of adipogenic protein and gene expression with the activation of AMP-activated protein kinase (AMPK). Other adipocyte cell models such as mouse embryonic fibroblasts C3H10T1/2 and primary adipocytes also confirmed the anti-adipogenic properties of PSE. Next, we investigated whether PSE attenuated lipid accumulation in mature adipocytes. We found that PSE significantly suppressed lipogenic gene expression, while fatty acid (FA) oxidation genes were upregulated. Augmentation of FA oxidation by PSE in mature 3T3-L1 adipocytes was confirmed via a radiolabeled-FA oxidation rate experiment by measuring the conversion of [³H]-oleic acid (OA) to [³H]-H2O. Furthermore, PSE enhanced the mitochondrial oxygen consumption rate (OCR), especially maximal respiration, and beige adipocyte formation in adipocytes. In summary, PSE was effective in reducing lipid accumulation in 3T3-L1 adipocytes through mitochondrial fatty acid oxidation involved in AMPK and mitochondrial activation.

Anti-Diabetic Effects and Anti-Inflammatory Effects of Laminaria japonica and Hizikia fusiforme in Skeletal Muscle: In Vitro and In Vivo Model.

Laminaria japonica (LJ) and Hizikia fusiforme (HF) are brown seaweeds known to have various health-promoting effects. In this study, we investigated the anti-diabetic effects and possible mechanism(s) of LJ and HF by using both in vitro and in vivo models. C2C12 myotubes, mouse-derived skeletal muscle cells, treated with LF or HF extracts were used for the in vitro model, and muscle tissues from C57BL/6N mice fed a high-fat diet supplemented with 5% LF or HF for 16 weeks were used for the in vivo model. Although both the LF and HF extracts significantly inhibited α-glucosidase activity in a dose-dependent manner, the HF extract had a superior α-glucosidase inhibition than the LF extract. In addition, glucose uptake was significantly increased by LJ- and HF-treated groups when compared to the control group. Phosphorylation of protein kinase B and AMP-activated protein kinase was induced by LJ and HF in both the vivo and in vitro skeletal muscle models. Furthermore, LJ and HF significantly decreased tumor necrosis factor-α whereas both extracts increased interleukin (IL)-6 and IL-10 production in lipopolysaccharide-stimulated C2C12 myotubes. Taken together, these findings imply that the brown seaweeds LJ and HF could be useful therapeutic agents to attenuate muscle insulin resistance due to diet-induced obesity and its associated inflammation.

PPARγ2 C1431T Polymorphism Interacts with the Antiobesogenic Effects of Kochujang, a Korean Fermented, Soybean-Based Red Pepper Paste, in Overweight/Obese Subjects: A 12-Week, Double-Blind Randomized Clinical Trial.

Kochujang, a Korean fermented soybean-based red pepper paste, has been reported to have beneficial health effects. The aim of this study was to examine the antiobesity effects of Kochujang as a supplement in overweight/obese subjects according polymorphisms in the obesity-linked gene, peroxisome proliferator activator receptor γ (PPARγ2). Sixty overweight/obese subjects, who had body mass indexes (BMI, kg/m2) ≥23 or waist/hip ratios (WHR) ≥0.90 for males or ≥0.85 for females, were randomly assigned to either taking 32 g/day of placebo or Kochujang for 12 weeks. Before and after the intervention, anthropometric and metabolic parameters and body fat distribution (by computed tomography) were measured. After PPARγ2 C1431T polymorphism was analyzed by PCR-restriction fragment length polymorphism, the differences among the four groups (wild and mutant alleles in Kochujang and placebo groups) were determined. Between the Kochujang (n = 26) and placebo (n = 27) groups, there were no differences in body composition, insulin resistance, or antioxidant biomarkers before and after intervention. Compared to placebo, Kochujang significantly decreased plasma triglyceride (TG), TG/high-density lipoprotein (HDL), and dietary intakes of protein, sodium, and potassium after age, sex, and BMI were adjusted. The beneficial effects of Kochujang on lowering of TG and TG/HDL were weakened in subjects with the PPARγ2 mutant T allele with increasing subcutaneous fat area. However, the interaction between Kochujang and the PPARγ2 T allele improved insulin sensitivity. The obesogenic variables affected by the T mutant allele of PPARγ2 C1431T SNP were different in overweight/obese subjects in response to Kochujang.

Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17ß-oestradiol.

Oestrogen and n-3 PUFA, especially EPA and DHA, have been reported to have beneficial effects on bone loss. Thus, the purpose of the present study was to investigate the synergistic bone-protective mechanism of combined treatments of EPA+DHA supplementation and oestrogen injection in ovariectomised rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0 %, 1 % or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and after a 1-week recovery period rats were injected with either 17ß-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Combined use of n-3 PUFA and E2 synergistically increased femoral cortical bone volume, bone mineral content and the bone expression of runt-related transcription factor 2 (RUNX2), but decreased the bone expression of IL-1ß. Both n-3 PUFA and E2 decreased the bone expressions of IL-7, TNF-α and PPAR-γ, and increased the bone expression of oestrogen receptor-α. n-3 PUFA in the presence of E2 and E2 alone significantly decreased the bone expressions of IL-1ß and IL-6 and increased the bone expression of RUNX2. E2 significantly decreased the serum levels of bone turnover markers and the bone expression of receptor activator of NF-κB ligand, but decreased the bone expression of osteoprotegerin. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective efficacy through up-regulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1ß.

Anthocyanin Rich-Black Soybean Testa Improved Visceral Fat and Plasma Lipid Profiles in Overweight/Obese Korean Adults: A Randomized Controlled Trial.

Anthocyanin-rich black soybeans have been used in traditional East Asian medicine to cure diseases related to oxidative stress and carcinogens, but not obesity. Our objective was to investigate the effects of anthocyanin-rich black soybean testa extracts (BBT), Glycine max (Chongja No. 3), on obesity. In total, 63 participants defined as overweight or obese by their body mass index (BMI >23) or waist circumference (WC >90 cm for males, >85 cm for females) were sorted into two groups: 32 receiving the trial medication (BBT, 2.5 g/d) and 31 receiving the placebo (starch, 2.5 g/d). Participants completed an 8-week, randomized, double-blinded, and placebo-controlled clinical trial. There were no significant differences between the two groups at the beginning of the trial, and both required the same safety assessments. Significant decreases in abdominal fat, described according to WC and hip circumference, and lipid profiles such as triacylglycerols (TG), low density lipoprotein cholesterol (LDLc), and non-high density lipoprotein cholesterol (non-HDLc) were observed in the BBT group at the conclusion of the clinical trial. The indicators for arteriosclerosis such as total cholesterol (TC)/HDLc and LDLc/HDLc were significantly decreased in the BBT group, but had not changed in the placebo group. With no difference between the two groups in energy-adjusted dietary intakes and physical activity, BBT was shown to strongly improve plasma lipid profiles, related to the reduction of WC (an indicator of abdominal fat) as long as high dietary fiber and low cholesterol diets were maintained. In conclusion, BBT can potentially be developed as a functional food for preventing abdominal obesity with high fiber and low cholesterol diets.

Effects of Mung Bean (Vigna radiata L.) Ethanol Extracts Decrease Proinflammatory Cytokine-Induced Lipogenesis in the KK-Ay Diabese Mouse Model.

Rapid increase in the prevalence of obesity-related metabolic inflammatory diseases has led to research focused on nutraceuticals for their treatment. This study investigated the effects of the ethanol extracts of mung bean testa (MBT) on the metabolic inflammation-induced lipogenesis in gastrocnemius muscle of KK-Ay diabese mice. Ethanol extracts of MBT were orally administered to diabese KK-Ay mice for 4 weeks after diet-induced obesity model was generated by feeding a 60% high-fat diet for 3 weeks. Although there were no changes in body weight gain, MBT treatments decreased total weight of white adipose tissue. MBT also decreased triacylglycerol and total cholesterol levels in the muscle by 30%, which was correlated with suppression of lipogenic genes such as ACC, C/EBP alpha, PGC-1 alpha, and PPAR gamma. In particular, decreased levels of p-ERK1/2, PPAR gamma, and C/EBP alpha in the MBT-treated groups suggest that MBT might inhibit adipogenesis and decrease differentiation via the MEK/ERK pathway. Furthermore, significantly lower amounts of plasma interleukin (IL)-6 and intramuscular tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein-1 (MCP-1) were detected in MBT groups, confirming the anti-inflammatory effect of mung bean. In addition, our in vitro pilot study with 3T3-L1 cells showed that vitexin, the functional chemical in MBT, inhibited inflammation-induced lipogenesis with significantly lower amounts of IL-6 and MCP-1 after 14 days of vitexin treatment. Thus, the functional compounds in the mung bean ethanol extracts such as vitexin and isovitexin may regulate intracellular lipogenesis and adipogenesis via anti-inflammatory mechanisms and MEK/ERK pathway in the KK-Ay mouse model.

Doenjang, a Korean fermented soy food, exerts antiobesity and antioxidative activities in overweight subjects with the PPAR-γ2 C1431T polymorphism: 12-week, double-blind randomized clinical trial.

We examined the antiobesity and antioxidant effects of supplementation with doenjang, a fermented soybean paste, in overweight Koreans with the PPAR-γ2 C1431T polymorphism. Sixty overweight subjects were randomly assigned to consume either 9.8 g/day of doenjang or placebo for 12 weeks. Before and after the intervention, anthropometric and metabolic parameters, along with abdominal fat distribution and PPAR-γ2 polymorphisms, were measured. Fifty-one subjects completed the study, doenjang (n=26) and placebo (n=25) groups. Relative frequencies of the PPAR-γ2 genotypes CC, TC, and TT were 70% (n=41), 25.9% (15), and 3.4% (2), whereas those of the PPAR-γ2 alleles C and T were 81.6% and 18.4%. Visceral fat area (VFA) was significantly decreased by doenjang supplementation in subjects with a mutant T allele of PPAR-γ2 compared to those with a C allele after adjusting for age, sex, and body mass index. Plasma free fatty acid, insulin, and homeostatic model assessment insulin resistance (HOMA-IR) levels were also significantly increased in the doenjang group. Doenjang pills significantly activated radical clearance capacity (ORAC and DNA tail length) in subjects with the C allele. The catalase (CAT) activity was increased twofold in the doenjang-treated group with the C allele, but this phenomenon was reversed in those with the T allele. Doenjang-treated subjects tended to have low dietary carbohydrate and sodium intakes compared with those given placebo. We found that doenjang supplementation decreased visceral fat accumulation and aging most effectively in subjects with PPAR-γ polymorphisms. This study suggests that doenjang has antiobesity and antioxidative effects in overweight individuals with mutant alleles of PPAR-γ2.

Combined treatment of mulberry leaf and fruit extract ameliorates obesity-related inflammation and oxidative stress in high fat diet-induced obese mice.

The aim of this study was to investigate whether a combined treatment of mulberry leaf extract (MLE) and mulberry fruit extract (MFE) was effective for improving obesity and obesity-related inflammation and oxidative stress in high fat (HF) diet-induced obese mice. After obesity was induced by HF diet for 9 weeks, the mice were divided into eight groups: (1) lean control, (2) HF diet-induced obese control, (3) 1:1 ratio of MLE and MFE at doses of 200 (L1:1), (4) 500 (M1:1), and (5) 1000 (H1:1) mg/kg per day, and (6) 2:1 ratio of MLE and MFE at doses of 200 (L2:1), (7) 500 (M2:1), and (8) 1000 (H2:1) mg/kg per day. All six combined treatments significantly lowered body weight gain, plasma triglycerides, and lipid peroxidation levels after the 12-week treatment period. Additionally, all combined treatments suppressed hepatic fat accumulation and reduced epididymal adipocyte size. These improvements were accompanied by decreases in protein levels of proinflammatory markers (tumor necrosis factor-alpha, C-reactive protein, interleukin-1, inducible nitric oxide synthase, and phospho-nuclear factor-kappa B inhibitor alpha) and oxidative stress markers (heme oxygenase-1 and manganese superoxide dismutase). M2:1 was the most effective ratio and dose for the improvements in obesity, inflammation, and oxidative stress. These results demonstrate that a combined MLE and MFE treatment ameliorated obesity and obesity-related metabolic stressors and suggest that it can be used as a means to prevent and/or treat obesity.

Vitamin D3 supplementation modulates inflammatory responses from the muscle damage induced by high-intensity exercise in SD rats.

Vitamin D is an important factor for calcium and phosphorus homeostasis. A negative relationship has been observed between vitamin D status and diseases such as cancer, arthritis, diabetes, and muscle fiber atrophy. However, the relationship between vitamin D and prevention of skeletal muscle damage has not been clearly elucidated. The purpose of this study was to investigate the effects of vitamin D on exercise-induced muscle changes. Rats were divided into 3 groups: (1) sedentary control (C: n=10), (2) high-intensity exercise (HE: n=10), and (3) high-intensity exercise with vitamin D supplementation (HED: n=10; i.p. 1000 IU/kg body weight). Rats were trained for 30 min/day on treadmills (5 days/week for 8 weeks) with the running speed gradually increased up to 30 m/min at a 3° incline. At the end of the training period, the running speed was 38 m/min at a 5° incline. The high-intensity exercise significantly increased plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity. In addition, IL-6 and TNF-α levels as well as phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB were significantly increased. Vitamin D-treated rats showed a significant decrease in plasma CK level, phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB, and gene expression of IL-6 and TNF-α. Furthermore, the protein expression of vitamin D receptor (VDR) was highly increased in the muscles of HED-treated rats, respectively. Therefore, we concluded that vitamin D may play a pivotal role in exercise-induced muscle damage and inflammation through the modulation of MAPK and NF-κB involved with VDR.

Supplementation of Korean fermented soy paste doenjang reduces visceral fat in overweight subjects with mutant uncoupling protein-1 allele.

The purpose of this study was to examine the hypothesis that the antiobesity effect of doenjang, a Korean fermented soy paste is different between the mutant and the wild-type alleles of a polymorphism upstream of the uncoupling protein-1 (UCP-1) gene in overweight subjects. In our randomized, double-blind, placebo-controlled trial, a total of 51 subjects with a body mass index of 23 kg/m(2) or greater and a waist-to-hip ratio of 0.90 or greater for men or 0.85 or greater for women were randomly assigned to take 9.9 g/d of either a placebo or doenjang for 12 weeks. The relative frequency of the mutant G allele of the UCP-1 polymorphism was 0.60 in the placebo group and 0.62 in the doenjang group. Supplementation of doenjang had no significant effect on the visceral fat area compared with that of the placebo group, but there was a significantly reduced amount of visceral fat in subjects with the G allele of UCP-1 polymorphism. Doenjang supplementation was found to significantly increase the free fatty acid concentration in subjects with both the A allele and the G allele. There was a significant association between visceral fat and age in study subjects with both the wild-type and mutant alleles of the UCP-1 gene. Doenjang supplementation significantly reduced visceral fat and increased the free fatty acid concentrations in subjects with the G allele of the UCP-1 polymorphism, which suggests that doenjang may be related to increased free fatty acid levels caused by elevated lipolysis in these subjects.

Antioxidant and apoptotic effects of korean white ginseng extracted with the same ratio of protopanaxadiol and protopanaxatriol saponins in human hepatoma HepG2 cells.

To investigate the antioxidative effects of ginsenosides [protopanaxadiol derivatives (PD):protopanaxatriol derivatives (PT) = 1:1] from the roots of Korean ginseng, cell viability, malondialdehyde (MDA) production, antioxidant enzyme activities, and expressions of apoptosis were analyzed after pretreatment of human hepatoma HepG2 cells with H(2)O(2). Cell death was increased through H(2)O(2) treatment dose dependently, and a dose of ginseng extract (PD:PT = 1:1) of 18.6 microg/mL was enough to derive it in reverse. MDA production was reduced through the administration of ginseng extracts even with more intensive H(2)O(2) treatments. Through the use of even low levels of ginseng extract (e.g., 1.86 microg/mL), catalase (CAT) activity was easily reduced from the plateau induced by H(2)O(2). The glutathione peroxidase activity was no better than that of CAT. We assume that ginseng extract acts as an antioxidant even when effective levels of ginseng differ. A ginseng extract dose of 18.6 microg/mL increased the apoptotic expression of oxidative stressed signals, such as c-Jun-N-terminal kinase and stress-activated protein kinase expressions, and mitochondrial cytochrome c released caspase-3 activation; however, these expressions changed with higher doses of ginseng.

Differential effects of dietary fatty acids on the regulation of CYP2E1 and protein kinase C in human hepatoma HepG2 cells.

We investigated the effects of different fatty acids (FAs) or with different degrees of unsaturation on cytochrome P450 2E1 (CYP2E1) induction and protein kinase C (PKC) activity in human hepatoma HepG2 cells. As the degree of unsaturation increased, the cell survival rate decreased for FAs with 18 carbons, but linolenic acid (LNA) or docosahexaenoic acid (DHA) groups were similar even through they have different degrees of unsaturation. Treatment with palmitic acid (PA), oleic acid (OA), linoleic acid (LA), LNA, and DHA resulted in respective cellular FA concentrations of C16:0 (43.1%), C18:1 (18.5%), C18:2 (7.4%), LNA (2.85%), and C22:6 (3.13%), which was highest for the FA that was used as the treatment, indicating that their incorporation within the cell is directly proportional to treatment. After 2 hours of cultivation, the lipid peroxide (LPO) in the DHA group increased 600% compared with control, and was much higher than in the groups treated with the other FAs, with LNA > LA > OA > PA. CYP2E1 induction increased with greater effect as the degree of unsaturation of OA, LA, and DHA increased. PA did not affect PKC activity, but DHA treatment increased PKC activity the most. The effects of LNA and LA were similar, but less than that of DHA, and that of OA was lower still, indicating that activity of PKC is proportional to the degree of unsaturation, and not the configuration of the FA. Increased plasma membrane concentrations of n-3 FA, such as DHA, might exert regulatory effects on PKC by increasing membrane fluidity, causing changes in CYP2E1, elevating levels of LPO, or producing oxidative stress.