Dietary Supplementation with Virgin Coconut Oil Improves Lipid Profile and Hepatic Antioxidant Status and Has Potential Benefits on Cardiovascular Risk Indices in Normal Rats.

Research findings that suggest beneficial health effects of dietary supplementation with virgin coconut oil (VCO) are limited in the published literature. This study investigated the in vivo effects of a 5-week VCO-supplemented diet on lipid profile, hepatic antioxidant status, hepatorenal function, and cardiovascular risk indices in normal rats. Rats were randomly divided into 3 groups: 1 control and 2 treatment groups (10% and 15% VCO-supplemented diets) for 5 weeks. Serum and homogenate samples were used to analyze lipid profile, hepatorenal function markers, hepatic activities of antioxidant enzymes, and malondialdehyde level. Lipid profile of animals fed VCO diets showed significant reduction in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels; high-density lipoprotein (HDL) level increased significantly (p < .05) compared to control; and there were beneficial effects on cardiovascular risk indices. The level of malondialdehyde (MDA), a lipid peroxidation marker, remarkably reduced and activities of hepatic antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were markedly increased in VCO diet-fed rats. The VCO diet significantly modulated creatinine, sodium (Na+), potassium (K+), chloride (Cl-), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) compared to control. The findings suggest a beneficial effect of VCO on lipid profile, renal status, hepatic antioxidant defense system, and cardiovascular risk indices in rats.

Inhibition of Toll-like receptor 4 ameliorates experimental postischemic injury in the cholestatic liver through inhibition of high-mobility group box protein b1 (HMGB1) signaling.

BACKGROUND: The objective of this study was to elucidate whether the inhibition of Toll-like receptor 4 attenuates liver injury ischemia/reperfusion in the cholestatic liver. METHOD: Rats were assigned into sham, bile duct ligation, sham ischemia/reperfusion (ischemia/reperfusion after laparotomy), and bile duct ligation ischemia/reperfusion (ischemia/reperfusion after bile duct ligation) groups. In some rats, TAK-242, an inhibitor of Toll-like receptor 4, was administered 15 minutes before ischemia/reperfusion. We measured intrahepatic Toll-like receptor 4 expression, serum hepatic marker expression, liver necrosis, gene expression of inflammation-associated factors, and serum high-mobility group box protein b1 levels. RESULTS: Intrahepatic Toll-like receptor 4 expression was significantly greater in the bile duct ligation group than in the sham group. Toll-like receptor 4 expression was further increased after ischemia/reperfusion in bile duct ligation ischemia/reperfusion groups. The levels of serum hepatic markers were significantly greater in both the sham ischemia/reperfusion and bile duct ligation ischemia/reperfusion groups than in the groups without ischemia/reperfusion. Liver necrosis was greater in the bile duct ligation group than in the sham group and was further increased in the bile duct ligation ischemia/reperfusion group. Genomic expression of inflammation-associated factors was also significantly greater in the bile duct ligation ischemia/reperfusion group than in the sham group. Serum high-mobility groups box protein b1 levels were greater in the bile duct ligation ischemia/reperfusion group than in the sham group (28.1 ng/ml versus 9.2 ng/ml, P = .011) and the bile duct ligation group (28.1 ng/ml versus 10.6 ng/ml, P = .017). These changes in the bile duct ligation ischemia/reperfusion group were significantly attenuated by preconditioning with TAK242. CONCLUSIONS: Toll-like receptor 4 inhibition has a potential to minimize severe injury after ischemia/reperfusion in the cholestatic liver through inhibition of high-mobility groups box protein b1.

Parenteral fish oil and liver function tests in hospitalized adult patients receiving parenteral nutrition: A propensity score-matched analysis.

BACKGROUND & AIMS: Intravenous fat emulsions are associated with liver disease and there is some evidence that the administration of intravenous fish oil (FO) may be useful in reversing it. The aim of our study was to assess whether there are differences in the changes of liver function tests (LFTs) in hospitalized adult patients with parenteral nutrition (PN) with FO and vegetal lipids vs patients without FO. The secondary aim was to study the relationship between impaired LFT and FO. METHODS: This was a 4-year, propensity score-matched analysis including patients aged ≥18 years treated with PN for ≥10 days. The exclusion criteria were previous liver disease, biliary disorders or pancreatic cancer, and altered initial LFT values. Patients were classified into 2 groups: FO cohort (patients who received FO - in addition to vegetal oil - after the first week of PN) and the vegetal oil cohort (patients who received only vegetal oil). A propensity score matched cohort design was developed. Univariate analyses were used to study the changes in LFTs. To evaluate whether LFT alterations vary with FO administration, four stepwise multiple linear regression models were conducted. RESULTS: 52 patients were included, 52% men, median 66 (55-75) years and 69 kg (61.7-78.8), with 18.5 (14-31.8) days of PN treatment. Maximum FO supplementation was 23%. During the first week with PN (none of the groups receiving FO), gammaglutamyl transferase (GGT), alkaline phosphatase (AP) and total bilirubin (BIL) increased significantly. Comparing LFT values at seven days of PN with at the end of PN treatment, the univariate analysis showed a better response for the FO group. The group without FO showed a significant increase for GGT and AP. In multivariate models, the percentage of FO administered was associated with a decrease in GGT, B = -0.33 [CI 95% = -0.54/-0.12], in AP, B = -0.12 [CI 95% = -0.20/-0.03] and ALT, B = -0.12 [CI 95% = -0.21/-0.024]. CONCLUSIONS: Lipid composition plays a significant role in LFT alteration associated with PN, and FO intravenous lipid emulsions (ILEs) minimize disturbance of LFTs in hospitalized adult patients.

Effects of Myrtus communis extract treatment in bile duct ligated rats.

BACKGROUND: The aim of our study was to investigate the antifibrotic and antioxidant effects of Myrtus communis subsp. communis (MC) extract against liver injury and fibrosis occurring in rats with biliary obstruction. MATERIALS AND METHODS: The rats were randomized into four groups (n = 8). Control group (C), MC-administrated group (MC), the bile duct ligation (BDL), and BDL + MC groups. MC was administered at a dose of 50 mg/kg a day orally for 28 days. In blood samples, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase levels, tumor necrosis factor-α, and interleukin-1ß measurement were measured. Oxidative injury was examined by measuring luminol and lucigenin chemiluminescence, malondialdehyde and glutathione levels, superoxide dismutase and myeloperoxidase activities. Transforming growth factor-beta and hydroxyproline levels were measured for analyzing fibrosis. The hepatic injury was also analyzed microscopically. RESULTS: Plasma total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, and interleukin-1ß levels were found significantly high in the BDL group, while these values significantly decreased in the BDL group treated with MC. On the other hand, the glutathione and superoxide dismutase values significantly decreased in the BDL group compared to the control group but increased markedly in BDL + MC group compared to the BDL group. Malondialdehyde levels, myeloperoxidase activity, tissue luminol, lucigenin, transforming growth factor-beta, and hydroxyproline levels when compared with the control group increased dramatically in the BDL group and reduced the MC + BDL group. CONCLUSIONS: Our results suggest that MC protects the liver tissues against oxidative damage following BDL via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration.

Construction of local gene network for revealing different liver function of rats fed deep-fried oil with or without resistant starch.

To study the mechanism underlying the liver damage induced by deep-fried oil (DO) consumption and the beneficial effects from resistant starch (RS) supplement, differential gene expression and pathway network were analyzed based on RNA sequencing data from rats. The up/down regulated genes and corresponding signaling pathways were used to construct a novel local gene network (LGN). The topology of the network showed characteristics of small-world network, with some pathways demonstrating a high degree. Some changes in genes led to a larger probability occurrence of disease or infection with DO intake. More importantly, the main pathways were found to be almost the same between the two LGNs (30 pathways overlapped in total 48) with gene expression profile. This finding may indicate that RS supplement in DO-containing diet may mainly regulate the genes that related to DO damage, and RS in the diet may provide direct signals to the liver cells and modulate its effect through a network involving complex gene regulatory events. It is the first attempt to reveal the mechanism of the attenuation of liver dysfunction from RS supplement in the DO-containing diet using differential gene expression and pathway network.

Lipid emulsions in the treatment and prevention of parenteral nutrition-associated liver disease in infants and children.

Long-term parenteral nutrition (PN) carries the risk of progressive liver disease in infants with intestinal failure. Although PN-associated liver disease (PNALD) is multifactorial in etiology, components of soybean oil lipid emulsions have been implicated in the disease's pathogenesis. Historically, infants with PNALD who were unable to wean from PN to full enteral feeding developed cirrhosis and end-stage liver disease, which require liver transplantation to survive. Over the past 2 decades, novel strategies for the management of parenteral lipids have improved morbidity and mortality from PNALD in infants with intestinal failure. Current strategies for the treatment of PNALD include restricting the dose of parenteral soybean oil lipid emulsion and/or replacing the soybean oil with a parenteral fish-oil lipid emulsion or emulsions of mixed-lipid sources. The purpose of this report is to review published data that evaluate these strategies in parenteral lipid management for the treatment and prevention of PNALD.

Mercuric chloride induced hepatotoxic and hematologic changes in rats: The protective effects of sodium selenite and vitamin E.

This study focuses on investigating the possible protective effect of sodium selenite (Na2SeO3) and/or vitamin E against mercuric chloride (HgCl2)-induced hepatotoxicity in rat. Male rats were given HgCl2 (1 mg/kg body weight (bw)) and HgCl2 plus Na2SeO3 (0.25 mg/kg bw) and/or vitamin E (100 mg/kg bw) daily via gavage for 4 weeks. HgCl2-treated groups had significantly higher white blood cell and thrombocyte counts than the control group. Serum activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl-transferase, and lactate dehydrogenase significantly increased and serum levels of total protein, albumin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly decreased in the HgCl2-treated groups compared with control group. Malondialdehyde level significantly increased and superoxide dismutase, catalase, and glutathione peroxidase activities decreased in liver tissue of HgCl2-treated rats. Also, HgCl2 exposure resulted in histopathological changes. Supplementation of Na2SeO3 and/or vitamin E provided partial protection in hematological and biochemical parameters that were altered by HgCl2 As a result, Na2SeO3 and/or vitamin E significantly reduced HgCl2-induced hepatotoxicity, but not protected completely.

Preservation of biochemical liver function with low-dose soy-based lipids in children with intestinal failure-associated liver disease.

OBJECTIVES: Intestinal failure-associated liver disease (IFALD) contributes to significant morbidity in pediatric patients with intestinal failure (IF); however, the use of parenteral nutrition (PN) with a fish oil-based intravenous (IV) emulsion (FO) has been associated with biochemical reversal of cholestasis and improved outcomes. Unfortunately, FO increases the complexity of care: because it can be administered only under Food and Drug Administration compassionate use protocols requiring special monitoring, it is not available as a 3-in-1 solution and is more expensive than comparable soy-based IV lipid emulsion (SO). Because of these pragmatic constraints, a series of patient families were switched to low-dose (1 g kg(-1) day(-1)) SO following biochemical resolution of cholestasis. The present study examines whether reversal of cholestasis and somatic growth are maintained following this transition. METHODS: The present study is a chart review of all children with IFALD who switched from FO to SO following resolution of cholestasis. Variables are presented as medians (interquartile ranges). Comparisons were performed using the Wilcoxon signed-rank test. RESULTS: Seven patients ages 25.9 (16.2-43.2) months were transitioned to SO following reversal of cholestasis using FO. At a median follow-up of 13.9 (4.3-50.1) months, there were no significant differences between pretransition and post-transition serum alanine and aspartate aminotransferases, direct bilirubin, and weight-for-age z scores. Because of recurrence of cholestasis, 1 patient was restarted on FO after 4 months on SO. CONCLUSIONS: Biochemical reversal of IFALD and growth were preserved after transition from FO to SO in 6 of 7 (86%) patients. Given the challenges associated with the use of FO, SO may be a viable alternative in select patients with home PN.

Synergistic effect of black tea and curcumin in improving the hepatotoxicity induced by aflatoxin B1 in rats.

Aflatoxin B1 (AFB1) is a toxic compound commonly found as a contaminant in human food. It is carcinogenic due its potential in inducing the oxidative stress and distortion of the most antioxidant enzymes. Since black tea possesses strong antioxidant activity, it protects cells and tissues against oxidative stress. Curcumin (CMN), a naturally occurring agent, has a combination of biological and pharmacological properties that include antioxidant activity. Therefore, the present study was carried out to investigate the possible role of separate and mixed supplementation of black tea extract and CMN in the hepatotoxicity induced by AFB1 in rats. A total of 48: adult male Sprague Dawley rats were randomly divided into eight groups with six rats in each group. Group 1 (normal control) includes rats that received no treatment. Groups 2, 3, and 4 (positive control) include rats that received olive oil, black tea extract, and CMN, respectively. Group 5 includes rats that received AFB1 at a dose of 750 µg/kg body weight (b.w.) dissolved in olive oil. Groups 6, 7, and 8 include rats that received AFB1 along with 2% black tea extract, CMN at a dose of 200 mg/kg b.w., and both black tea extract and CMN at the same previous doses, respectively. After 90 days, biochemical and histopathological examination was carried out for the blood samples and liver tissues. A significant decrease in the antioxidant enzymes and a significant increase in the lipid peroxidation and hydrogen peroxide in the rats treated with AFB1 were observed. Moreover, there were dramatic changes in the liver function biomarkers, lipid profile, and liver architecture. Supplementation of black tea extract or CMN showed an efficient role in repairing the distortion of the biochemical and histological changes induced by AFB1 in liver. This improvement was more pronounced when both CMN and black tea were used together.

Medium-chain TAG attenuate hepatic oxidative damage in intra-uterine growth-retarded weanling piglets by improving the metabolic efficiency of the glutathione redox cycle.

The present study investigated the effects of medium-chain TAG (MCT) on hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). At weaning (mean 21 (SD 1·06) d of age), twenty-four IUGR piglets and twenty-four normal-birth weight (NBW) piglets were selected according to their birth weight (BW; IUGR: mean 0·95 (SD 0·04) kg; NBW: mean 1·58 (SD 0·04) kg) and weight at the time of weaning (IUGR: mean 5·26 (SD 0·15) kg; NBW: mean 6·98 (SD 0·19) kg) and fed either a soyabean oil (SO) diet (containing 5% SO) or a MCT diet (containing 1% SO and 4% MCT) for 28 d. IUGR piglets exhibited poor (P<0·05) growth performance, lower (P<0·05) metabolic efficiency of hepatic glutathione (GSH) redox cycle, and increased (P<0·05) levels of reactive oxygen species, apoptosis and necrosis in hepatocytes compared with NBW piglets. The MCT diet increased (P<0·05) the average daily gain and feed efficiency of piglets during the first 4 weeks after weaning. Furthermore, MCT diet-fed piglets had a higher (P<0·05) GSH:oxidised glutathione ratio and increased (P<0·05) activities of glucose-6-phosphate dehydrogenase (G6PD) and GSH reductase. The expression of G6PD was up-regulated (P<0·05) by the MCT diet irrespective of BW. Moreover, malondialdehyde concentrations in the liver and apoptosis and necrosis levels in hepatocytes were decreased (P<0·05) by the MCT diet irrespective of BW. These results indicate that MCT might have auxiliary therapeutic potential to attenuate hepatic oxidative damage in IUGR offspring during early life, thus leading to an improvement in the metabolic efficiency of the hepatic GSH redox cycle.

Protective effects of ginsenoside Rb1 on septic rats and its mechanism.

This study aims to observe the protective effects of ginsenoside Rb1 on liver and lung in rats with septic shock and reveal its mechanism. Rats were randomly divided into three groups: sham, cecal ligation and puncture (CLP), and CLP with ginsenoside Rb1. Then, the survival rate, arterial blood pressure, TLR4 mRNA, and TNF-α levels were determined. The liver and lung tissues were stained with hematoxylin-eosin (HE). The overall survival rate of the Rb1 group was significantly higher than that of the CLP group. Mean arterial blood pressure went down in both the CLP and Rb1 groups after CLP, and there was a significant difference both in the sham and Rb1 groups when compared with the CLP group. The Rb1 treatment group had markedly lower TLR4 mRNA expression and TNF-α levels than the CLP group. In the CLP group, pathology showed swelling, degeneration, necrosis, and neutrophil infiltration in the liver and alveolar epithelial cells. However, in the Rb1 group, there was mild degeneration and slight neutrophil infiltration, but no obvious necrosis. Rb1 may improve the survival rate, ameliorate arterial blood pressure, and protect the liver and lung in septic shock rats by downregulating the expression of TLR4 mRNA and inhibiting the production of TNF-α.

Quercetin prevents ethanol-induced iron overload by regulating hepcidin through the BMP6/SMAD4 signaling pathway.

Emerging evidence has demonstrated that chronic ethanol exposure induces iron overload, enhancing ethanol-mediated liver damage. The purpose of this study was to explore the effects of the naturally occurring compound quercetin on ethanol-induced iron overload and liver damage, focusing on the signaling pathway of the iron regulatory hormone hepcidin. Adult male C57BL/6J mice were pair-fed with isocaloric-Lieber De Carli diets containing ethanol (accounting for 30% of total calories) and/or carbonyl iron (0.2%) and treated with quecertin (100 mg/kg body weight) for 15 weeks. Mouse primary hepatocytes were incubated with ethanol (100 mM) and quercetin (100 µM) for 24 h. Mice exposed to either ethanol or iron presented significant fatty infiltration and iron deposition in the liver; these symptoms were exacerbated in mice cotreated with ethanol and iron. Quercetin attenuated the abnormity induced by ethanol and/or iron. Ethanol suppressed BMP6 and intranuclear SMAD4 as well as decreased hepcidin expression. These effects were partially alleviated by quercetin supplementation in mice and hepatocytes. Importantly, ethanol caused suppression of SMAD4 binding to the HAMP promoter and of hepcidin messenger RNA expression. These effects were exacerbated by anti-BMP6 antibody and partially alleviated by quercetin or human recombinant BMP6 in cultured hepatocytes. In contrast, co-treatment with iron and ethanol, especially exposure of iron alone, activated BMP6/SMAD4 pathway and up-regulated hepcidin expression, which was also normalized by quercetin in vivo. Quercetin prevented ethanol-induced hepatic iron overload different from what carbonyl iron diet elicited in the mechanism, by regulating hepcidin expression via the BMP6/SMAD4 signaling pathway.

Soya phospholipid complex of mangiferin enhances its hepatoprotectivity by improving its bioavailability and pharmacokinetics.

BACKGROUND: Mangiferin is a xanthonoid present in Mangifera indica. It has been reported for a variety of pharmacological activities, including hepatoprotection. However, the major disadvantage of mangiferin is its reduced biological activity due to poor absorption, low bioavailability and rapid elimination from the body after administration. The aim of this study was to prepare a phospholipid complex of mangiferin to overcome these limitations and to investigate the impact of the complex on hepatoprotective activity and bioavailability. RESULTS: The results showed that the complex has an enhanced hepatoprotective and in vivo antioxidant activity as compared to pure mangiferin at the same dose level (30 and 60 mg kg⁻¹). The complex restored the levels of serum hepatic marker enzymes and liver antioxidant enzymes with respect to carbon tetrachloride-treated animals. The complex also increased the bioavailability of mangiferin in rat serum by 9.75-fold compared to pure mangiferin at the same dose level and enhanced the elimination half-life (t(1/2 el)) from 1.71 ± 0.12 h⁻¹ to 3.52 ± 0.27 h⁻¹. CONCLUSION: The results suggested that the complexation of mangiferin with soya phospholipid enhanced the hepatoprotection and in vivo antioxidant activity, which may be due to the improved bioavailability and pharmacokinetics of mangiferin in rat serum.

κ-Selenocarrageenan prevents microcystin-LR-induced hepatotoxicity in BALB/c mice.

Microcystins (MCs) are a family of cyclic heptapeptides that are produced by blooming algae Microcystis. MCs have been implicated in the development of liver cancer, necrosis and even intrahepatic bleeding. Effective prophylactic approaches and complete removal of MCs are urgently needed. Accumulating evidence suggests that microcystin-LR (MC-LR)-induced damage is accompanied by oxidative stress. Supplementation of Se can enhance resistance to oxidative stress. Therefore, in the present study, we investigated the protective effects of κ-Selenocarrageenan (Se-Car), a kind of organic Se compound, in Balb/c mice exposed to MC-LR. Our results proved that Se-Car could significantly ameliorate the hepatic damage induced by MC-LR, including serum markers of liver dysfunction, oxidative damages and histological alterations. Furthermore, Se-Car could significantly alleviate the up-regulation of the molecular targets indicating mitochondrial dysfunction and endoplasmic reticulum stress induced by MC-LR. In conclusion, Se-Car showed clear protection against toxicity induced by MC-LR. Thus, Se-Car could be useful as a new category of anti-MC-LR toxicity reagent.

Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion.

Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Curcumin is a natural phenolic compound with impressive antioxidant properties. What's more, curcumin is recently proved to exert its chemopreventive effects partly through the activation of nuclear factor (erythroid-2 related) factor 2 (Nrf2) and its antioxidant and phase II detoxifying enzymes. In vivo, we investigated the protective effects of curcumin against arsenic-induced hepatotoxicity and oxidative injuries. Our results showed that arsenic-induced elevation of serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) activities, augmentation of hepatic malonaldehyde (MDA), as well as the reduction of blood and hepatic glutathione (GSH) levels, were all consistently relieved by curcumin. We also observed the involvement of curcumin in promoting arsenic methylation and urinary elimination in vivo. Furthermore, both the hepatic Nrf2 protein and two typically recognized Nrf2 downstream genes, NADP(H) quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), were consistently up-regulated in curcumin-treated mice. Our study confirmed the antagonistic roles of curcumin to counteract inorganic arsenic-induced hepatic toxicity in vivo, and suggested that the potent Nrf2 activation capability might be valuable for the protective effects of curcumin against arsenic intoxication. This provides a potential useful chemopreventive dietary component for human populations.

Effect of decreased parenteral soybean lipid emulsion on hepatic function in infants at risk for parenteral nutrition-associated liver disease: a pilot study.

PURPOSE: We performed a pilot trial to compare reduced dose versus standard soybean lipid emulsion in neonates at risk for parenteral nutrition-associated liver disease. METHODS: A prospective randomized controlled trial was performed (2009-2011) enrolling surgical patients ≥ 26 weeks' gestation anticipated to require >50% of daily caloric intake from parenteral nutrition (PN) for at least 4 weeks. Randomization occurred into either reduced (1.0 g/kg/day) or standard (3g/kg/day) groups. Co-primary outcomes for interpretation of the results were conjugated bilirubin and total bile acids. Additional outcomes included ALT, AST, GGT, alkaline phosphatase, growth, and essential fatty acid levels. Outcomes were compared between treatment groups using Wilcoxon rank sums tests. RESULTS: Twenty-eight patients (47% enrollment rate) were included in the study with an average treatment duration of 5.4 weeks. Groups had similar PN calories and protein intake throughout the study. Total increase from baseline was smaller in the reduced vs. standard group for conjugated bilirubin (p=0.04) and total bile acids (p=0.02). Weight z-score increased more in the standard group, and no patient experienced essential fatty acid deficiency. CONCLUSION: Markers of cholestasis rose at a slower rate using reduced lipid doses. This pilot study demonstrates feasibility and need for a larger study evaluating the effects of reduced lipids in patients at risk for developing parenteral nutrition-associated liver disease.

Improvement of biochemical parameters in type 1 diabetic rats after the roots aqueous extract of yacon [Smallanthus sonchifolius (Poepp.& Endl.)] treatment.

The aim of this study was to evaluate the effect of yacon (Smallanthus sonchifolius) (Poepp.& Endl.) on clinical parameters under diabetic conditions. The aqueous extract of yacon tuberous roots (YRAE; 0.76 g fructan kg⁻¹ body weight) was prepared at the moment of each administration. Thirty-two male rats were divided into four groups (n=8): control group (C); group that received YRAE (Y); untreated diabetic group (DM1); and diabetic group treated with YRAE (Y-DM1). The diabetes mellitus was induced by streptozotocin (60 mg kg⁻¹ body weight). The animals from Y2 and Y-DM1 received YRAE by gavage, at 7-day intervals, for 30 days. The aqueous extract of yacon roots decreased (p<0.05) the water and food intake in diabetic rats (Y-DM1). YRAE treatment reduced (p<0.05) glycaemia, total cholesterol, VLDL-c, LDL-c and triacylglycerol levels in diabetic rats (YRAE). HDL, urea and creatinine levels did not differ (p>0.05) between the Y and Y-DM1 groups. YRAE normalised alanine aminotransferase (ALT) activity, when comparing DM1 and Y-DM1 rats, but had no effect on lactate dehydrogenase activity (LDH). In conclusion, YRAE was sufficient for controlling water and food consumption, hyperglycaemia and dyslipidaemia, and promote the reduction of the ALT, suggesting a hepatoprotective effect in rats with STZ-induced DM1.

Theacrine, a purine alkaloid obtained from Camellia assamica var. kucha, attenuates restraint stress-provoked liver damage in mice.

Theacrine (1,3,7,9-tetramethyluric acid), a purine alkaloid, has proven to be beneficial in maintaining several brain functions and is being studied for potential medicinal uses in recent years. In this study, we isolated theacrine from Camellia assamica var. kucha and investigated its protective effects on liver damage induced by restraint stress in mice. Results showed that 18 h of restraint stress could induce liver damage, with an obvious increase in levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). This finding was further confirmed by hepatic pathological examination, which showed inflammatory cell infiltration and focal necrosis of hepatocytes. However, oral administration of theacrine (10, 20, 30 mg/kg for 7 consecutive days) was found to decrease plasma ALT and AST levels, reduce hepatic mRNA levels of inflammatory mediators (IL-1ß, TNF-α, IL-6, and IFN-γ), and reverse the histologic damages in stressed mice. Simultaneously, theacrine also significantly decreased the content of malondialdehyde and increased oxygen radical absorbance capacity (ORAC) level in the plasma and liver of stressed mice. These results suggested that the protective effects of theacrine on stress-induced liver damage might be correlated with its antioxidative activity. The antioxidative capacity of theacrine was further evaluated by in vitro ORAC and cellular antioxidant activity assay. The results suggested that the antioxidative capacity of theacrine was not due to the direct action on free radical clearance. Moreover, the elevated activities and gene expressions of superoxide dismutase, catalase, and glutathione peroxidase, as well as the reduced activity of xanthine oxidase by theacrine treatment in stressed mice suggested that the antioxidative activity might be due to the strengthening of the antioxidant system in vivo. On the basis of the above results, theacrine is possibly a good candidate for protecting against or treating lifestyle diseases and might contribute to the study of natural products.

Dietary supplementation with geranylgeraniol suppresses lipopolysaccharide-induced inflammation via inhibition of nuclear factor-κB activation in rats.

PURPOSE: The isoprenoid geranylgeraniol (GGOH) inhibits nuclear factor-kappa B (NF-κB) activation in the liver, yet the mechanism remains unclear. We investigated the modulation and inhibition of lipopolysaccharide (LPS)-induced NF-κB signaling in the liver of rats fed a GGOH-supplemented diet. METHODS: Rats were fed a diet supplemented with or without GGOH for 10 days. Rats were then intraperitoneally injected with 0.5 mg/kg LPS or vehicle (sterilized saline) and fasted for 18 h. Plasma levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, and the liver damage indicators alanine and aspartate aminotransferases (ALT and AST) were assessed. Liver mRNA and proteins were assayed for changes in NF-κB target genes and signal transduction genes. RESULTS: Rats fed a high-dose, GGOH-supplemented diet showed significantly lower levels of plasma inflammatory cytokines and ALT and AST activities. In the liver, GGOH significantly suppressed NF-κB activation and mRNA expression of its pro-inflammatory target genes. Furthermore, GGOH supplementation substantially suppressed mRNA expression of signal transducer genes upstream of the IκB kinase complex. Western blotting of liver extracts further demonstrated the substantial decrease in total IL-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6), leading to lower signal transduction and inhibition of NF-κB after LPS. CONCLUSION: A 10-day, high-dose, GGOH-supplemented diet was sufficient to inhibit LPS-induced inflammation and activation of NF-κB in rat livers. GGOH significantly modulated NF-κB signaling molecules, inhibiting its signal transduction and activation in the liver, thus protecting against liver damage.