Honeyberry (Lonicera caerulea) has been used for medicinal purposes for thousands of years. Its predominant anthocyanin, cyanidin-3-O-glucoside (C3G), possesses antioxidant and many other potent biological activities. We aimed to investigate the effects of honeyberry extract (HBE) supplementation on HepG2 cellular steatosis induced by free fatty acids (FFA) and in diet-induced obese mice. HepG2 cells were incubated with 1 mM FFA to induce lipid accumulation with or without HBE. Obesity in mice was induced by a 45% high fat diet (HFD) for 6 weeks and subsequent supplementation of 0.5% HBE (LH) and 1% HBE (MH) for 6 weeks. HBE suppressed fatty acid synthesis and ameliorated lipid accumulation in HepG2 cells induced by FFA. Moreover, HBE also decreased lipid accumulation in the liver in the supplemented HBE group (LH, 0.5% or MH, 1%) compared with the control group. The expressions of adipogenic genes involved in hepatic lipid metabolism of sterol regulatory element-binding protein-1 (SREBP-1c), CCAAT/enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid synthase (FAS) were decreased both in the HepG2 cells and in the livers of HBE-supplemented mice. In addition, HBE increased mRNA and protein levels of carnitine palmitoyltransferase (CPT-1) and peroxisome proliferator-activated receptor α (PPARα), which are involved in fatty acid oxidation. Furthermore, HBE treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and Acetyl CoA Carboxylase (ACC). Honeyberry effectively reduced triglyceride accumulation through down-regulation of hepatic lipid metabolic gene expression and up-regulation of the activation of AMPK and ACC signaling in both the HepG2 cells as well as in livers of diet-induced obese mice. These results suggest that HBE may actively ameliorate non-alcoholic fatty liver disease.

Blue honeysuckle (BH, Lonicera caerulea) is used as a traditional medicine in Russia, Japan and China, but is not commonly considered as an edible berry in Europe, USA or Korea. BH has been revealed to decrease serum cholesterol and triacylglycerol (triglyceride or TG) levels through the activation of AMP-activated protein kinase (AMPK), thus it is expected to be a health functional food and pharmaceutical agent for the prevention of non-alcoholic liver damage, in addition to effects as a suppressor of hyperlipidemia and as an anti-obesity agent. In the present study, the pharmacological activity of BH extract (BHe) was observed in high-fat diet (HFD)-fed mice. Significant increases in fat pad weight, body weight, fat accumulation (body and abdominal fat density, and thickness of the periovarian and abdominal wall) and serum biochemical levels (aspartate transaminase, alanine amino-transferase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyltransferase, total cholesterol, low-density lipoprotein and TG, with the exception of high-density lipoprotein) were observed in HFD-fed mice. In addition, increases in adipocyte hypertrophy, the area of steatohepatitis and hepatocyte hypertrophy were observed, whereas decreased zymogen content was identified upon histopathological observation. Increased deterioration of the endogenous antioxidant defense system (liver catalase, glutathione and superoxide dismutase) and hepatic lipid peroxidation was observed. In addition, there were decreases in hepatic glucokinase activity, AMPKα1 and AMPKα2 mRNA expression, adipose tissue uncoupling protein 2 expression, and adiponectin mRNA expression, increases in phosphoenolpyruvate carboxykinase and glucose-6-phosphatase activity, hepatic acetyl-CoA carboxylase 1 mRNA expression, and the expression of leptin, CCAAT/enhancer-binding protein (C/EBP) α, C/EBPβ and sterol-regulatory-element-binding protein 1c mRNA in the periovarian tissue. Furthermore, non-alcoholic fatty liver disease (NAFLD) and obesity were significantly inhibited by the continuous administration of BHe for 84 days. These results revealed that BHe may be a promising novel drug or functional food candidate for the treatment of obesity and NAFLD.

Emerging evidence suggests that probiotics are beneficial in non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the effects of two Lactobacillus plantarum strains, ATG-K2 and ATG-K6 (isolated from Korean fermented cabbage), in a rat model of high fat/high fructose (HF/HF) diet-induced NAFLD. Rats with NAFLD were randomized into four groups (HF/HF diet control, (HC); HF/HF diet with silymarin, (PC); HF/HF diet with ATG-K2, (K2); and HF/HF diet with ATG-K6, (K6)) with healthy rats on a normal diet serving as the negative control. After treatment, histopathological and biochemical analyses of the blood and liver tissue were conducted. In addition, fecal microbiota was analyzed using the MiSeq platform. Compared with HC rats, K2 and K6 rats experienced significantly lower body weight gain, displayed decreased hepatic lipid accumulation, had lower serum levels of aspartate aminotransferase and alanine aminotransferase, and showed increased antioxidant enzyme activities. Moreover, de novo lipogenesis-related genes were downregulated following K2 and K6 administration. The fecal microbiota of K2 and K6 rats contained a higher proportion of Bacteriodetes and a lower proportion of Fimicutes than that of HC rats. Taken together, our results suggest that L. plantarum strains ATG-K2 and ATG-K6 are potential therapeutic agents for NAFLD.Nutrients 2020, 12, 542 2 of 16 of the transcription factors, such as sterol regulatory element binding protein 1c (SREBP-1c) and CCAAT/enhancer-binding protein alpha (C/EBPα), which in turn regulate the expression of hepatic gluconeogenesis and DNL genes [6]. It follows that fructose intake increases liver gluconeogenesis and DNL and elevates blood glucose and TG levels in humans [8,9] Another cause of NAFLD is oxidative stress. Fat deposition occurring in the liver results in lipid peroxidation, and it promotes a variety of responses such as inflammation and fibrosis. Thus, antioxidants (e.g., silymarin, vitamin E) are proposed as candidates for NAFLD treatment [10,11]; however, there are no standard pharmacological therapeutic agents for NAFLD yet. Recently, emerging evidence suggests that the gut-liver axis is strongly related to NAFLD. There are several reports published clinical trials applying probiotics on NAFLD patients [12]. Lactobacillus bulgaricus and Streptococcus thermophiles treatment improved liver aminotransferases levels in adult NAFLD patients [13]. In addition, probiotic capsules containing Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium bifidum, and Lactobacillus rhamnosus, as a supplement also decreased liver aminotransferases levels in obese children with NAFLD [14]. These results indicate that the intake of certain probiotics has a beneficial effect on NAFLD.Lactobacillus plantarum, which plays a key role in the production of various fermented foods, is one of the most important species of lactic acid bacteria (LAB). L. plantarum is found in diverse environments, such as the soil and the human gut, and is considered a potential pro...

BACKGROUND/OBJECTIVESTiming of almond intake during a day may result differently in the perspectives of body composition and changes of lipid profile. The current study was conducted to compare the effects of daily almond intake as a preload versus as a snack on body composition, blood lipid profile, and oxidative and inflammation indicators among young Korean adults aged 20–39 years old.SUBJECTS/METHODSParticipants were randomly assigned to one of three groups: a pre-meal almond group (PM), a snack almond group (SN) in which participants were instructed to consume 56 g of almonds either as a preload before meals or as a snack between meals, respectively, and a control group (CL) in which participants were provided high-carbohydrate iso-caloric control food. Measurements were performed at baseline, weeks 8 and 16.RESULTSA total of 169 (M 77/F 92) out of the 227 participants completed the study between June 2014 and June 2015 (n = 58 for PM; 55 for SN; and 56 for CL). A significant decrease in body fat mass was observed in the PM group at both weeks 8 and 16 compared with the CL. There were significant intervention effects on changes of body fat mass (P = 0.025), body fat percentages (P = 0.019), and visceral fat levels (P < 0.001). Consuming almonds as a daily snack reduced the levels of total cholesterol (P = 0.043) and low-density lipoprotein (LDL) cholesterol (P = 0.011) without changing high-density lipoprotein (HDL) cholesterol compared with the CL.CONCLUSIONAlmond consumption as a preload modified body fat percentages, whereas snacking on almonds between meals improved blood lipid profiles. This trial was registered at ClinicalTrials.gov as NCT03014531.

The purpose of this study was to investigate the gastroprotective effects of bovine milk on an acidified ethanol (HCl-ethanol) mixture that induced gastric ulcers in a mouse model. Mice received different doses of commercial fresh bovine milk (5, 10, and 20 mL/kg of body weight) by oral gavage once a day for 14 d. One hour after the last oral administration of bovine milk, the HCl-ethanol mixture was orally intubated to provoke severe gastric damage. Our results showed that pretreatment with bovine milk significantly suppressed the formation of gastric mucosa lesions. Pretreatment lowered gastric myeloperoxidase and increased gastric mucus contents and antioxidant enzymes catalase and superoxide dismutase. Administration of bovine milk increased nitrate/nitrite levels and decreased the malondialdehyde levels and the expression of proinflammatory genes, including transcription factor nuclear factor-κB, cyclooxygenase-2, and inducible nitric oxide synthase in the stomach of mice. These results suggest that bovine milk can prevent the development of gastric ulcer caused by acid and alcohol in mice.

The objective of this study was to evaluate the hepatoprotective effects of blue honeysuckle (BH) on carbon tetrachloride (CCl4)‐induced acute hepatic damage in mice. The experiment used a total of 60 ICR mice, which were divided into six groups. Except for the intact control groups, all groups received a single intraperitoneal injection of CCl4 after a 7 day pre‐treatment period with distilled water, BH extracts, or silymarin. Twenty‐four hours after the CCl4 injection, the following observations, representative of classical oxidative stress‐mediated centrolobular necrotic acute liver injuries, were observed: decreased body weight; small nodule formation and enlargement on the gross inspections with related liver weight increase; elevation of serum AST and ALT, increases in hepatic lipid peroxidation and related depletion of endogenous antioxidants and antioxidative enzymes; centrolobular necrosis; increases in apoptotic markers, lipid peroxidation markers, and oxidative stress markers. However, liver damage was significantly inhibited by the pre‐treatment with BH extracts. The present study demonstrated that oral administration of BH extracts prior to exposure to CCl4 conferred favorable hepatoprotective effects. These results demonstrated that BHe possessed suitable properties for use as a potent hepatoprotective medicinal food.

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