Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood. The aims of the current study were: i) to investigate the regulation of adipose Nrg4 expression during obesity and the physiological signals involved, ii) to elucidate the mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid metabolism, and iii) to explore whether Nrg4 regulates adipose tissue secretome gene expression and adipokine secretion. We examined the correlation of adipose Nrg4 expression with obesity in a cohort of diet-induced obese mice and investigated the upstream signals that regulate Nrg4 expression. We performed metabolic cage and hyperinsulinemic-euglycemic clamp studies in Nrg4 transgenic mice to dissect the metabolic pathways regulated by Nrg4. We investigated how Nrg4 regulates hepatic lipid metabolism in the fasting state and explored the effects of Nrg4 on adipose tissue gene expression, particularly those encoding secreted factors. Adipose Nrg4 expression is inversely correlated with adiposity and regulated by pro-inflammatory and anti-inflammatory signaling. Transgenic expression of Nrg4 increases energy expenditure and augments whole body glucose metabolism. Nrg4 protects mice from diet-induced hepatic steatosis in part through activation of hepatic fatty acid oxidation and ketogenesis. Finally, Nrg4 promotes a healthy adipokine profile during obesity. Nrg4 exerts pleiotropic beneficial effects on energy balance and glucose and lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic therapeutics based on Nrg4 may improve both type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in patients.

Yukmijihwang-tang, a traditional herbal formula, has been used for treating disorder, diabetic mellitus and neurosis in China (Liu-wei-di-huang-tang in Chinese), Japan (Lokumijio-to in Japanese) and Korea for many years. In this study, we investigated the effects of Yukmijihwang-tang water extract (YJT) on the development of benign prostatic hyperplasia (BPH) using a rat model of testosterone propionate (TP)-induced BPH.

The fruit ofCornus officinalisSieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit ofC. officinalis(ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease. The use of immunomodulatory corticosteroids in AD treatment causes adverse side effects. Therefore, novel natural anti-inflammatory therapeutics are needed. The aim of the present study was to investigate the anti-allergic and anti-inflammatory activities of kuwanon G and morusin. To investigate the effect of kuwanon G and morusin on skin inflammation, enzyme-linked immunosorbent assays (ELISA) to quantitate secreted (RANTES/CCL5), thymus- and activation-regulated chemokine (TARC/CCL17), and macrophage-derived chemokine (MDC/CCL22) were performed, followed by Western blotting to measure the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and nuclear transcription factor-κB (NF-κB) p65 in tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-stimulated HaCaT keratinocytes. In order to evaluate the anti-allergic effects, ELISA to quantify histamine and leukotriene C₄ (LTC₄) production and Western blotting to measure 5-lipoxygenase (5-LO) activation were performed using PMA and A23187-stimulated MC/9 mast cells. Kuwanon G reduced the release of RANTES/CCL5, TARC/CCL17, and MDC/CCL22 via down-regulation of STAT1 and NF-κB p65 signaling in TNF-α and IFN-γ-stimulated HaCaT keratinocytes. Kuwanon G also inhibited histamine production and 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Morusin inhibited RANTES/CCL5 and TARC/CCL17 secretion via the suppression of STAT1 and NF-κB p65 phosphorylation in TNF-α and IFN-γ-stimulated HaCaT keratinocytes, and the release of histamine and LTC₄ by suppressing 5-LO activation in PMA and A23187-stimulated MC/9 mast cells. Kuwanon G and morusin are potential anti-inflammatory mediators for the treatment of allergic and inflammatory skin diseases such as AD.

Background: Artemisia capillaries Thunb. (AC) has been used to treat inflammatory and hepatic disorders such as hepatic injury, hepatic fibrosis and hepatitis. However, the efficacy of AC against atopic dermatitis (AD), an inflammatory disease, has not been examined. In the present study, AC was evaluated for anti-inflammatory and anti-AD effects using both in vitro and in vivo systems. Methods: The contents of six compounds (chlorogenic acid, caffeic acid, isochlorogenic acid A, hyperoside, isoquercitrin and scoparone) in AC were simultaneously assayed using HPLC system. To evaluate the anti-inflammatory effect of AC, NO production was measured in RAW264.7 cell stimulated with 1 μg/mL LPS. Histamine levels were assayed in MC/9 cells stimulated with 50 nM PMA and 1 μM A23187. To examine the role of AC in vivo, AC (10 mg/mouse/day) was topically applied for four weeks the back and ears of Dermatophagoides farinae-sensitized Nc/Nga mice. Protopic ointment (0.1% tacrolimus) was used as a positive control. Results: The contents of the six components in AC range from 0.44 to 43.14 mg/g. Chlorogenic acid (21.06 ± 0.08 mg/g) and isochlorogenic acid A (43.14 ± 0.12 mg/g) were major components in AC. AC inhibited NO and histamine production in cells respectively. In D. farinae-sensitized Nc/Nga mice, the topical application of AC reduced dermatitis scores, hemorrhage, hypertrophy and hyperkeratosis of the epidermis in the dorsal skin and ear. The treatment of AC also reduced the plasma levels of histamine (1.5 fold) and IgE (1.4 fold). Conclusions: Our results suggest that AC should be explored as a potential therapeutic agent to treat atopic dermatitis and analysis by HPLC will help to improve the quality of AC.