Hordenine, a single compound produced during barley germination, inhibits melanogenesis in human melanocytes.

Melanin plays an important role protecting skin against ultraviolet light injury. However, increased production and accumulation of melanin results in a large number of skin disorders. Here, we identified hordenine as an active compound from germinated barley (Hordeum vulgare L.) and investigated the effects of hordenine on melanogenesis and its mechanisms of action in human epidermal melanocytes. We measured melanin content, tyrosinase activity, expression of melanogenesis-related proteins, and cAMP production. Melanin content was significantly inhibited by hordenine. The intracellular cAMP level was also reduced by hordenine. In addition, expression of microphthalmia-associated transcription factor (MITF), an upstream transcription factor of tyrosinase as well as tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2, was inhibited by hordenine. Taken together, these results show that hordenine inhibited melanogenesis by suppressing cAMP production, which is involved in the expression of melanogenesis-related proteins and suggest that hordenine may be an effective inhibitor of hyperpigmentation.

Artemisinic acid is a regulator of adipocyte differentiation and C/EBP δ expression.

Adipocyte dysfunction is associated with the development of obesity. In this study, artemisinic acid, which was isolated from Artemisia annua L., inhibited adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSCs) and its mechanism of action was determined. The mRNA levels of peroxidase proliferation-activated receptor (PPAR) γ and CCAAT/enhancer binding protein (C/EBP) α, late adipogenic factors, were reduced by artemisinic acid. Moreover, the mRNA levels of the PPAR γ target genes lipoprotein lipase, CD36, adipocyte protein, and liver X receptor were down-regulated by artemisinic acid. Artemisinic acid reduced expression of the C/EBP δ gene without impacting C/EBP ß. In addition, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that reduced expression of the C/EBP δ gene was mediated by inhibiting Jun N-terminal kinase (JNK). Additionally, artemisinic acid also reduced the expression of the adipogenesis-associated genes glucose transporter-4 and vascular endothelial growth factor. In addition to the interference of artemisinic acid with adipogenesis, artemisinic acid significantly attenuated tumor necrosis factor-α-induced secretion of interleukin-6 by undifferentiated hAMSCs, thus influencing insulin resistance and the inflammatory state characterizing obesity. Taken together, these findings indicate that inhibiting adipogenic differentiation of hAMSCs by artemisinic acid occurs primarily through reduced expression of C/EBP δ, which is mediated by the inhibition of JNK and suggest that aremisinic acid may be used as a complementary treatment option for obesity associated with metabolic syndrome.

Immature Citrus sunki peel extract exhibits antiobesity effects by ß-oxidation and lipolysis in high-fat diet-induced obese mice.

The peel of Citrus sunki HORT. ex TANAKA has been widely used in traditional Asian medicine for the treatment of many diseases, including indigestion and bronchial asthma. In this study, we investigated the antiobesity activity of immature C. sunki peel extract (designated CSE) using high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. In the animal study, body weight gain, adipose tissue weight, serum total cholesterol, and triglyceride in the CSE-administered group decreased significantly compared to the HFD group. Also, CSE supplementation reduced serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and lactate dehydrogenase. Moreover, it significantly decreased the accumulation of fatty droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Dietary supplementation with CSE reversed the HFD-induced decrease in the phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which are related to fatty acid ß-oxidation, in the epididymal adipose tissue. Also, CSE increased AMPK and ACC phosphorylation in mature 3T3-L1 adipocytes. CSE also enhanced lipolysis by phosphorylation of cAMP-dependent protein kinase (PKA) and hormone-sensitive lipase (HSL) in mature 3T3-L1 adipocytes. These results suggest that CSE had an antiobesity effect via elevated ß-oxidation and lipolysis in adipose tissue.

A water-soluble extract of Petalonia binghamiae inhibits the expression of adipogenic regulators in 3T3-L1 preadipocytes and reduces adiposity and weight gain in rats fed a high-fat diet.

We previously showed that an ethanolic extract of the edible brown algae Petalonia binghamiae promotes the differentiation of 3T3-L1 preadipocytes and decreases hyperglycemia in streptozotocin-induced diabetic mice. Here, we report that a water-soluble extract of P. binghamiae thalli, prepared by enzymatic digestion, inhibits preadipocyte differentiation and adipogenesis in a dose-dependent manner. In differentiating 3T3-L1 preadipocytes, the extract (designated PBEE) decreased the expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding proteins α and ß, and fatty acid-binding protein aP2. It also inhibited the mitotic clonal expansion process of adipocyte differentiation, and it inhibited insulin-stimulated uptake of glucose into mature 3T3-L1 adipocytes by reducing phosphorylation of insulin receptor substrate-1. In rats with high-fat diet (HFD)-induced obesity, PBEE exhibited potent anti-obesity effects. In this animal model, increases in body weight and fat storage were suppressed by the addition of PBEE to the drinking water at 500 mg/L for 30 days. PBEE supplementation reduced serum levels of glutamic pyruvic and glutamic oxaloacetic transaminases and increased the serum level of high-density lipoprotein cholesterol. Moreover, it significantly decreased the accumulation of lipid droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Taken together, these data demonstrate that PBEE inhibits preadipocyte differentiation and adipogenesis in cultured cells and in rodent models of obesity.

Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice.

The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor gamma (PPARgamma) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPARgamma luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes.