Anti-arthritic effects of Schisandra chinensis extract in monosodium iodoacetate-induced osteoarthritis rats.

The present study aimed to investigate the therapeutic effects of Schisandra chinensis (SC) extract on clinical symptoms of osteoarthritis and the modulating effect on the mechanisms associated with the progression of osteoarthritis in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. Osteoarthritis-induced rats were randomized into four groups: MIA injection control (MC), MIA injection with celecoxib (PC), MIA injection with SC extract 100 mg/kg (SC100), and MIA injection with SC extract 200 mg/kg (SC200). Another healthy group received a saline injection as a negative control (NC). During the treatment, weight-bearing measurements were performed once a week for 4 weeks. Histopathological and biochemical analyses of the joints, blood, and chondrocyte tissue were performed following the completion of treatment. Compared with MC rats, SC rats demonstrated significantly alleviated pain behavior, bone erosion, and cartilage degradation. SC reduced serum levels of matrix metalloproteinases and pro-inflammatory cytokines. SC treatment also reversed the levels of biomarkers such as Collagen II and ADAMTS4 in the cartilage tissue. Moreover, SC administration inhibited the phosphorylation levels of nuclear factor kappa B (NF-κB) and NF-κB Inhibitor alpha. This study demonstrates that SC ameliorated osteoarthritis at in vivo level. Our results suggest that SC might be a potential therapeutic agent for osteoarthritis.

Honeysuckle Berry (Lonicera caerulea L.) Inhibits Lipase Activity and Modulates the Gut Microbiota in High-Fat Diet-Fed Mice.

Honeysuckle berry (HB, Lonicera caerulea L.) is an oriental herbal medicine reported to have beneficial effects on metabolic disorders, such as obesity and non-alcoholic fatty liver disease. The fruit part of HB is rich in anthocyanin, a type of polyphenol. Most studies credit the antioxidant and anti-inflammatory properties of HB as the mechanisms of its effectiveness. This study investigated the inhibitory effects of HB on lipase using an in vitro assay and the modulatory effect of HB on gut microbiota in high-fat diet (HFD)-fed mice. HB inhibited pancreatic lipase activity with IC50 values of approximately 0.47 mg/mL. The fecal triglyceride (TG) levels were higher from the HFD of the HB-fed mice than they were for the control mice. Moreover, the fecal microbiota from the HFD of the HB-fed mice had relatively lower Firmicutes and higher Bacteroidetes than that from the HFD-only mice. These results suggest that HB modulates gut microbiota composition, which may contribute to body fat reduction. Hence, HB could present a useful agent for treating metabolic diseases through lower TG uptake and the regulation of gut microflora.

Anti-Sarcopenic Obesity Effects of Lonicera caerulea Extract in High-Fat Diet-Fed Mice.

Sarcopenic obesity is a combination of sarcopenia and obesity. Although several herbal extracts showed improvement on sarcopenia and obesity, respectively, there are few studies on sarcopenic obesity. Lonicera caerulea (honeysuckle berry, HB) can ameliorate metabolic disorders including obesity. However, its effects on sarcopenic obesity have not been reported yet. Thus, the aim of this study was to investigate whether HB extract might have any beneficial effects on sarcopenic obesity in high-fat diet-induced mice. Forty-eight mice were classified into six groups and treated for eight weeks: (1) NC, normal diet control; (2) HC, high-fat diet control; (3) PC, high-fat diet with orlistat; (4) HB100, high-fat diet with HB extract at 100 mg/kg; (5) HB200, high-fat diet with HB extract at 200 mg/kg; and (6) HB400, high-fat diet with HB extract at 400 mg/kg. Body weight, fat accumulation, muscle mass, muscle strength, and mRNA expression of muscle atrophy were monitored. Compared with the HC group, HB administration showed anti-obesity properties. It reduced body weight gain and modulated serum biochemical parameters and tissue antioxidant enzymes. HB also increased muscle strength and muscle mass of hind legs. In addition, it decreased mRNA expression levels of Atrogin1 and MuRF1 as markers of muscle atrophy but increased PGC1α and SIRT1 as markers of muscle growth. These results suggest that HB might be effective in preventing sarcopenia associated with obesity.

Ameliorative effects of black ginseng on nonalcoholic fatty liver disease in free fatty acid-induced HepG2 cells and high-fat/high-fructose diet-fed mice.

BACKGROUND: Black ginseng (BG) is a type of Korean ginseng prepared by steaming and drying raw ginseng to improve the saponin content. This study examined the effects of BG on nonalcoholic fatty liver disease (NAFLD) in HepG2 cells and diet-induced obese mice. METHODS: HepG2 cells were treated with free fatty acids to induce lipid accumulation before supplementation with BG. NAFLD-induced mice were fed different doses (0.5%, 1%, and 2%) of BG for 8 weeks. RESULTS: BG significantly reduced lipid accumulation and expression of lipogenic genes, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, sterol regulatory element-binding protein-1c, and fatty acid synthase in HepG2 cells, and the livers of mice fed a 45% high-fat diet with 10% fructose in the drinking water (HFHF diet). BG supplementation caused a significant reduction in levels of aspartate aminotransferase and alanine aminotransferase, while antioxidant enzymes activities were significantly increased in 45% high-fat diet with 10% fructose in the drinking water diet-fed mice. Expression of proliferator-activated receptor alpha and carnitine palmitoyltransferase I were upregulated at the transcription and translation levels in both HepG2 cells and diet-induced obese mice. Furthermore, BG-induced phosphorylation of AMP-activated protein kinase and acetyl CoA carboxylase in both models, suggesting its role in AMP-activated protein kinase activation and the acetyl CoA carboxylase signaling pathway. CONCLUSION: Our results indicate that BG may be a potential therapeutic agent for the prevention of NAFLD.

Beneficial Effects of Lactobacillus plantarum Strains on Non-Alcoholic Fatty Liver Disease in High Fat/High Fructose Diet-Fed Rats.

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.

Phellinus baumii enhances the immune response in cyclophosphamide-induced immunosuppressed mice.

Phellinus species is a mushroom used as traditional medicine in Eastern Asia. Research on Phellinus baumii (PB) is relatively limited; however, it has been reported to have antioxidant, DNA damage-protecting, immunostimulating, and antidiabetic activities. In our previous study on anti-inflammatory properties in lipopolysaccharide-stimulated RAW 264.7 cells and the various bioactive components of PB, we propose that PB could exert immune enhancing effects. Therefore, our current study aimed to investigate the immune-enhancing effect on immunosuppressed mice. Different concentrations of PB extract (0, 50, 100, 200, and 400 mg/kg body weight) were given to mice via oral gavage for 6 weeks accompanied by intraperitoneal cyclophosphamide administration to induce immunosuppression. A bone marrow micronucleus test was performed in mice to screen for potential genotoxic compounds. Splenocyte viability and proliferation, splenic and peritoneal natural killer cell activities, and hematological markers were then measured. Cytokines in the spleen and serum, as well as splenic mRNA levels of nuclear factor-κB; interferon-γ; tumor necrosis factor-α; and interleukin (IL)-1ß, IL-6, and IL-12, were determined in mice. As a result, PB ameliorated T- and B-lymphocyte proliferation, splenic and peritoneal NK cell activities, bone marrow cells, hematological markers, cytokine levels, and T-lymphocyte numbers. Moreover, serum and spleen cytokine levels and mRNA expression were elevated in the PB groups compared to controls. Our results suggest that the PB extract can be used as a potent immunomodulator under immunosuppressive conditions. Thus, PB may be used as a potent biofunctional and pharmaceutical material to potentially enhance human immunity.

Lonicera caerulea Extract Attenuates Non-Alcoholic Fatty Liver Disease in Free Fatty Acid-Induced HepG2 Hepatocytes and in High Fat Diet-Fed Mice.

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.

Hepatoprotective effects of blue honeysuckle on CCl4-induced acute liver damaged 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.

Evaluation of in vitro anti-oxidant and anti-inflammatory activities of Korean and Chinese Lonicera caerulea.

BACKGROUND/OBJECTIVES: The honeysuckle berry (HB) contains ascorbic acid and phenolic components, especially anthocyanins, flavonoids, and low-molecular-weight phenolic acids. In order to examine the potential of HB as a hepatoprotective medicinal food, we evaluated the in vitro anti-oxidant and anti-inflammatory activities of Korean HB (HBK) and Chinese HB (HBC). MATERIALS/METHODS: Antioxidant and anti-inflammatory effects of the extracts were examined in HepG2 and RAW 264.7 cells, respectively. The anti-oxidant capacity was determined by DPPH, SOD, CAT, and ARE luciferase activities. The production of nitric oxide (NO) as an inflammatory marker was also evaluated. The Nrf2-mediated mRNA levels of heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase [quinone] 1 (Nqo1), and glutamate-cysteine ligase catalytic subunit (Gclc) were measured. The concentrations of HB extracts used were 3, 10, 30, 100, and 300 µg/mL. RESULTS: The radical scavenging activity of all HB extracts increased in a concentration-dependent manner (P < 0.01 or P < 0.05). SOD (P < 0.05) and CAT (P < 0.01) activities were increased by treatment with 300 µg/mL of each HB extract, when compared to those in the control. NO production was observed in cells pretreated with 100 or 300 µg/mL of HBC and HBK (P < 0.01). Treatment with 300 µg/mL of HBC significantly increased Nqo1 (P < 0.01) and Gclc (P < 0.05) mRNA levels compared to those in the control. Treatment with 300 µg/mL of HBK (P < 0.05) and HBC (P < 0.01) also significantly increased the HO-1 mRNA level compared to that in the control. CONCLUSIONS: Thus, the Korean and Chinese HBs were found to possess favorable in vitro anti-oxidant and anti-inflammatory activities. Nrf2 and its related anti-oxidant genes were associated with both anti-oxidant and anti-inflammatory activities in HB-treated cells. Further studies are needed to confirm these in vivo effects.

Anti-obesity and fatty liver-preventing activities of Lonicera caerulea in high-fat diet-fed mice.

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 AMP­activated protein kinase (AMPK), thus it is expected to be a health functional food and pharmaceutical agent for the prevention of non­alcoholic liver damage, in addition to effects as a suppressor of hyperlipidemia and as an anti­obesity agent. In the present study, the pharmacological activity of BH extract (BHe) was observed in high­fat 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 aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ­glutamyltransferase, total cholesterol, low­density lipoprotein and TG, with the exception of high­density lipoprotein) were observed in HFD­fed 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 glucose­6­phosphatase activity, hepatic acetyl­CoA carboxylase 1 mRNA expression, and the expression of leptin, CCAAT/enhancer­binding protein (C/EBP) α, C/EBPß and sterol­regulatory­element­binding protein 1c mRNA in the periovarian tissue. Furthermore, non­alcoholic 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.

Protective effect of bovine milk against HCl and ethanol-induced gastric ulcer in mice.

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 effects of daily intake timing of almond on the body composition and blood lipid profile of healthy adults.

BACKGROUND/OBJECTIVES: Timing 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/METHODS: Participants 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. RESULTS: A 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. CONCLUSION: Almond 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.