Aqueous Extract of Humulus japonicus Attenuates Hyperlipidemia and Fatty Liver in Obese Mice.

In this study, the effects of Humulus japonicus (HJ) aqueous extract on 3T3-L1 preadipocytes and HepG2 cells (in vitro model) as well as on C57BL/6 mice fed on high-fat diet (HFD) (in vivo model) were evaluated. Mice fed on HFD for 12-weeks were taken the HJ water extract (HJW) at various doses, 50, 150, and 250 mg/kg, orally for 8 weeks. We have noticed the accumulation of fat globules in preadipocytes and HepG2 cells using Oil Red O staining. In addition, supplementation with HJW considerably inhibited the weight gain, lipid accumulation, and adipogenesis and decreased the size of subcutaneous adipocytes in 3T3-L1 adipocytes. Furthermore, treatment with HJW improved hyperlipidemia via decreasing the levels of serum triglyceride (TG) and low-density lipoproteins as well as the atherogenic index. Supplementation with HJW could attenuate HFD-induced lipid accumulation, increase the mRNA expressions of fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD1), and would elevate the levels of serum aspartate aminotransferase and alanine aminotransferase in mice liver. The levels of TG and FAS mRNA in HepG2 cells treated with palmitate were reduced in a dose-dependent manner. In sum, HJW could alleviate the HFD-induced obesity and decrease the dyslipidemia profiles; the keys that could contribute to cardiovascular and nonalcoholic liver diseases.

Therapeutic Effects of Methanol Extract from Euphorbia kansui Radix on Imiquimod-Induced Psoriasis.

The roots of Euphorbia kansui, which belong to the family Euphorbiaceae, have been used as a traditional medicine for the treatment of various diseases such as diabetes, ascites, and leukemia. Recently, it was reported that the methylene chloride fraction of E. kansui radix (EKC) regulated the differentiation of Th17 cells and alleviated the symptoms of Th17-related inflammatory bowel disease. Imiquimod (IMQ), a TLR7/8 agonist, has been used to induce psoriasis in a mouse model. In this study, we evaluated the effect of EKC in an IMQ-induced psoriasis model. EKC effectively inhibited the production of interleukin-17A and interferon-γ in vitro. On this basis, EKC was administered to an animal model of psoriasis. Acanthosis and the infiltration of inflammatory cells into the dermis were significantly reduced by EKC. EKC also inhibited the expression of IL-17A, IL-22, IL-23, IL-12, and RAR-related orphan receptor gamma t (RORγt) in the spleen, skin-draining lymph nodes, and the skin. Additionally, EKC inhibited the activity of dendritic cells but not that of keratinocytes. In conclusion, EKC ameliorated the symptoms of psoriasis through inhibition of Th17 differentiation and activation of dendritic cells. These effects are expected to be beneficial in the treatment and prevention of psoriasis.

Effects of Aqueous Extract of Phyllostachyos Caulis in Taeniam on Longitudinal Bone Growth in Adolescent Rats.

This study examined whether treatment with Phyllostachyos Caulis in Taeniam aqueous extract improves longitudinal bone growth in adolescent male rats. Three-week-old male Sprague-Dawley rats were divided into three groups: a control group, a Phyllostachyos Caulis in Taeniam group (200 mg/kg, p.o.), and a recombinant human growth hormone group (20 µg/kg, s.c.). The total tibial length and the height of each growth plate zone were evaluated by radiography and histomorphometry. The total number of proliferative cells and 5-bromo-2'-deoxyuridine-positive cells were counted after 5-bromo-2'-deoxyuridine staining. Serum total osteocalcin levels were assayed using an enzyme-linked immunosorbent assay. The average total tibial length of the Phyllostachyos Caulis in Taeniam group was significantly longer than that of the control group. The heights of the proliferative and hypertrophic zones in the Phyllostachyos Caulis in Taeniam group were increased, and the ratio of 5-bromo-2'-deoxyuridine-positive to total cells in the proliferative zone was also increased. The serum osteocalcin, growth hormone, and insulin-like growth factor-1 levels were significantly increased in the Phyllostachyos Caulis in Taeniam group compared to the control group. Insulin-like growth factor-1 and insulin-like growth factor-1 receptor were highly expressed in the proliferative and hypertrophic zones in the Phyllostachyos Caulis in Taeniam group. The Phyllostachyos Caulis in Taeniam extract increased bone length, promoted cell proliferation, and activated the growth plate zones, which suggested that the extract could play an important role in longitudinal bone growth. Therefore, the Phyllostachyos Caulis in Taeniam extract might be a good alternative medicine to growth hormone therapy.

Beneficial Effects of Red Yeast Rice on High-Fat Diet-Induced Obesity, Hyperlipidemia, and Fatty Liver in Mice.

Obesity is a common cause of hyperlipidemia, which is a major coronary risk factor. Previous studies have shown red yeast rice (RYR) effectiveness in lowering low-density lipoprotein cholesterol. The aim of this study was to investigate the effects of RYR on obesity and hyperlipidemia. Mice were randomly separated into five groups: the control group with a normal diet, the high-fat diet (HFD) group fed a HFD without any treatment, and HFD-fed groups supplemented with RYR (1 g/kg/day for 8 weeks, 1 g/kg/day for 12 weeks, and 2.5 g/kg/day for 8 weeks). Body weight was recorded twice and food intake thrice weekly. Liver and fat pads were surgically removed and weighed. The levels of lipid parameters, liver enzymes, and leptin levels were measured. The HFD feeding resulted in obesity, which was associated with increases in body weight, liver weight, fat pad weight, liver enzymes, and plasma leptin levels with the development of hyperlipidemia. RYR prevented weight gain and fat pad weight in mice fed a HFD. RYR alleviated blood lipid parameters, liver enzymes, and leptin levels, and improved atherogenic index. These findings suggest that RYR has therapeutic potential in treating obesity and hyperlipidemia.

The role of phosphatidylcholine and deoxycholic acid in inflammation.

AIMS: Phosphatidylcholine with deoxycholic acid (PC/DA) is widely used to reduce localized fat deposits with mild adverse effects. We previously demonstrated that PC induces lipolysis with mild PMN infiltration, while DA induces adipose tissue damage. Therefore, the aim of this study was to extend our understanding of the pro-inflammatory responses of PC, DA, and PC/DA. MAIN METHODS: We evaluated the level of edema and polymononuclear (PMN) infiltration by histopathological examination. Myeloperoxidase (MPO) activity was analyzed using an MPO activity assay kit. Levels of inflammatory cytokines (IL-1ß and IL-6) and PGE2 were measured by ELISA. KEY FINDINGS: A low and high dose of PC failed to induce an inflammatory response, whereas DA led to an intense inflammatory response in a dose dependent manner. Combined PC/DA treatment resulted in a mild inflammatory response that was notably less severe than higher DA. Together, these results demonstrated that DA plays a role in inflammation caused by combined PC/DA. Histopathological examination and measurement of MPO activity indicated that DA was the primary cause of edema and PMN infiltration. Further, increased levels of cytokines (IL-1ß and IL-6) and PGE2 demonstrated that DA might directly induce inflammation, whereas PC alone has no effect on inflammation. SIGNIFICANCE: These results indicate that DA rather than PC is responsible for inflammation, and that PC may not aggravate inflammatory responses induced by DA. Thus, the results of this study suggest that the adverse effects of PC/DA during localized fat treatment may be solely due to DA.

Inhibitory effects of polysaccharide-rich extract of Phragmites rhizoma on atopic dermatitis-like skin lesions in NC/Nga mice.

AIMS: Phragmites rhizoma was reported to have anti-oxidative and free radical scavenging activity. It also has been traditionally used to suppress inflammation. In the present study, we aimed to evaluate the topical effects of the polysaccharide-rich extract of P. rhizoma (PEP) on atopic dermatitis. MAIN METHODS: We induced AD-like skin lesions by an extract of the house-dust mite Dermatophagoides farinae (Dfb) in NC/Nga mice, and then performed macroscopic analysis, immunohistochemical staining and measurement of total serum IgE and cytokine production by ELISA. KEY FINDINGS: Topically applied PEP suppressed dermatitis with a decrease in dermatitis score and scratch number. The histological manifestations of atopic skin lesions including thickened epidermis and increased numbers of mast cells, polymorphonuclear leukocytes and nerve fibers were significantly attenuated. The activation of IgE and the levels of cytokines such as IFN-γ IL-4 and IL-10 were also decreased. SIGNIFICANCE: Our results indicated that PEP might have an inhibitory effect on atopic dermatitis-like lesion and be a promising natural resource in the treatment of atopic dermatitis.

Inhibition of lung carcinogenesis and effects on angiogenesis and apoptosis in A/J mice by oral administration of green tea.

Oral administration of tea (Camellia sinensis) has been shown to inhibit the formation and growth of several tumor types in animal models. The present study investigated the effects of treatment with different concentrations of green tea on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in female A/J mice. Two days after a single dose of NNK (100 mg/kg body weight, i.p.), the mice were given 0.1, 0.2, 0.4, and 0.6% green tea solution (1, 2, 4, and 6 g of tea solids, respectively, dissolved in 1 l of water), 0.02% caffeine, or water as the sole source of drinking fluid until the termination of the experiment. Only the treatment with 0.6% tea preparation significantly reduced lung tumor multiplicity (mean +/- SE, 6.07 +/- 0.77 vs. 8.60 +/- 0.50 tumors per mouse, P = 0.018). Treatment with 0.6% tea also inhibited angiogenesis, as indicated by the lower microvessel density (number of blood vessels/mm2) based on immunostaining for the von Willebrand factor antigen (81.9 +/- 9.5 vs. 129.4 +/- 8.2, P = 0.0018) and anti-CD31 antibody staining (465.3 +/- 61.4 vs. 657.1 +/- 43.6, P = 0.0012). Significantly lower vascular endothelial growth factor immunostaining scores were also observed in the 0.6% tea-treated group (0.98 +/- 0.17 vs. 1.43 +/- 0.07, P = 0.006). The apoptosis index was significantly higher in lung adenomas from 0.6% tea-treated mice based on morphological analysis of cell apoptosis (2.51 +/- 0.18% vs. 1.57 +/- 0.11%, P = 0.00005), and the result was further confirmed using the TUNEL method. Inhibition of angiogenesis and the induction of apoptosis by green tea may be closely related to the inhibition of pulmonary carcinogenesis.

The mechanism of iron transport after intratracheal instillation of iron in rats.

OBJECTIVES: Iron (Fe) is an essential element in biological processes; however excessive Fe is harmful to human health. Some air pollutants contain a high level of Fe, and the human lung could therefore be over-exposed to Fe through inhaled air pollutants. This study was performed to investigate the role of metal transporters (divalent metal transporter 1, DMT1, and metal transporter protein 1, MTP1) in the lung under the environments of Fe deficiency in the body and Fe over-exposure in the lung. METHODS: Rats were fed Fe deficient (FeD, 2-6 mg Fe/kg) or Fe supplemented (FeS, 120 mg Fe/kg) diet for 4 weeks, followed by a single intratracheal instillation of ferrous sulfate at low (10 mg/kg) or high (20 mg/kg) dose. Fe concentration was analyzed in the serum, lung and liver, and histopathological findings were observed in the lung at 24 hours after Fe administration. The level of DMT1 and MTP1 expression in the lung was analyzed by RT-PCR. Also, the effect of Fe deficiency in the body was evaluated on the level of Fe concentration and metal transporters compared to FeS-diet fed rats at the end of 4-week FeD or FeS diet. RESULTS: The 4-week FeD diet in rats induced an Fe deficiency anemia with decreased serum total Fe, increased unsaturated Fe binding capacity and hypochromic microcytic red blood cells. The concentration of Fe in the lung and liver was lower in the FeD-diet fed rats than in the FeS-diet fed rats. The level of metal transporters mRNA expression was higher in the FeD-diet fed rats than in the FeS-diet. The concentration of Fe in the lung was increased in a dose-dependent pattern after intratracheal instillation of Fe into the rats, while the level of Fe in the serum and liver was not increased in the low-dose Fe administered rats. Therefore, DMT1 and MTP1 mRNA was highly expressed in both FeD-diet and FeS-diet fed rats, after intratracheal instillation of Fe. CONCLUSIONS: DMT1 and MTP1 mRNA were more highly expressed in FeD-diet fed rats than in FeS-diet fed rats. The over-exposure of Fe intratracheally induced high expression of metal transporters and increased Fe deposition in the lung in both FeD-diet and FeS-diet fed rats, but did not increase the Fe level of the serum and liver in low-dose Fe administered rats. These results suggest that the role of metal transporters in the lung might be different in a part from the duodenum under the environment of over-exposure to Fe.

Manganese distribution in brains of Sprague-Dawley rats after 60 days of stainless steel welding-fume exposure.

Welders working in a confined space, as in the shipbuilding industry, are at risk of being exposed to high concentrations of welding fumes and developing pneumoconiosis or other welding-fume exposure related diseases. Among such diseases, manganism resulting from welding-fume exposure remains a controversial issue, as the movement of manganese into specific brain regions has not yet been clearly established. Accordingly, to investigate the distribution of manganese in the brain after welding-fume exposure, male Sprague-Dawley rats were exposed to welding fumes generated from manual metal arc-stainless steel (MMA-SS) at concentrations of 63.6 +/- 4.1 mg/m(3) (low dose, containing 1.6 mg/m(3) Mn) and 107.1 +/- 6.3 mg/m(3) (high dose, containing 3.5 mg/m(3) Mn) total suspended particulate (TSP) for 2 h per day in an inhalation chamber over a 60-day period. Blood, brain, lung, and liver samples were collected after 2 h, 15, 30, and 60 days of exposure and the tissues analyzed for their manganese concentrations using an atomic absorption spectrophotometer. Although dose- and time-dependent increases in the manganese concentrations were found in the lungs and livers of the rats exposed for 60 days, only slight manganese increases were observed in the blood during this period. Major statistically significant increases in the brain manganese concentrations were detected in the cerebellum after 15 days of exposure and up until 60 days. Slight increases in the manganese concentrations were also found in the substantia nigra, basal ganglia (caudate nucleus, putamen, and globus pallidus), temporal cortex, and frontal cortex, thereby indicating that the pharmacokinetics and distribution of the manganese inhaled from the welding fumes were different from those resulting from manganese-only exposure.