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.

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.

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.