Abstract Anoectochilus roxburghii (Wall.) Lindl., Orchidaceae, is a Chinese medicinal plant which can be effective for some diseases such as hepatitis, nephritis, pneumonia. Its active ingredient is kinsenoside. The mechanisms of kinsenoside on the liver-protective effect have not been fully explored until today. The present study was aimed to investigate the protective effect and mechanism of kinsenoside on acute alcoholic liver injury. The protected activity of kinsenoside (10, 20 and 40 mg/kg) were investigated on acute alcoholic liver injury in mice. Male C57BL/6 J mice were fed with non-fat feed for 30 days and oral administrated 14 ml/kg bw of ethanol (50%) on the 31st day. The activities of serum aspartate aminotransferase, serum alanine aminotransferase, triacylglyceride and very low density lipoprotein were determined in serum. The hepatic levels of oxidative stress as glutathione, malondialdehyde were measured in liver homogenates. The levels of cytochrome P450 2E1 (CYP2E1) were measured by immunohistochemistry. Furthermore, histopathological observations were carried out on the separated livers of mice. It was suggested that the trends of acute hepatic injury and fatty degeneration induced by alcohol were reduced in the ethanol group after kinsenoside treatment. Compared to ethanol groups, triacylglyceride, malondialdehyde, very low density lipoprotein, reduced glutathione, serum alanine aminotransferase and serum aspartate aminotransferase levels of kinsenoside (20, 40 mg/kg) groups were decreased (p < 0.05). Meanwhile kinsenoside significantly decreased the level of protein CYP2E1. In conclusion, kinsenoside enhances antioxidant capacity of mice and antagonizes alcohol-induced lipid metabolism disorders. Besides, kinsenoside inhibits alcohol-caused hepatocyte apoptosis, reduces oxidative stress, and relieves hepatocyte death, which may be a mechanism of kinsenoside in the treatment of alcoholic liver.

Objective: The role of epigenetic modifications on leptin expression during the development of obesity has not been clearly determined. This study aimed to investigate changes in the expression of DNA methyltransferases (DNMTs) at the leptin promoter and their effect on gene transcription during the development of obesity. Methods: Using a high-fat diet (HFD)-induced obese (DIO) mouse model, we examined adipose expression of leptin, its promoter associated DNMTs and the methyl CpG-binding domain protein 2 (MBD2) at different time points after HFD feeding. Results: The leptin expression levels in epididymal fat were significantly increased after feeding the mice a HFD for 4, 8, 12 and 18 weeks (w), as opposed to feeding them a standard diet (SD). However, the CpG promoter methylation fractions were significantly reduced at 8 w with a decreased association of MBD2 and DNMT1, and increased at 12 w and 18 w with an increased association of MBD2, DNMT3A and DNMT3B, after HFD feeding. Additionally, the binding of RNA polymerase II was increased at 8 w and decreased at 18 w after HFD feeding compared with SD feeding. Conclusions: These data indicate that time-specific changes in promoter associated DNMTs may be associated with the regulation of leptin expression, indicating that a complex and dynamic epigenetic mechanism underlies aberrant leptin expression during the development of obesity.

Objetivo: El objetivo de las modificaciones epigenéticas sobre la expresión de la leptina durante el desarrollo de obesidad no ha podido ser claramente establecido. Este estudio tiene por objetivo investigar los cambios en la expresión de ADN-metiltransferasas (ADNMTs) en el promotor de leptina y su efecto sobre la trascripción génica durante el desarrollo de obesidad. Métodos: Empleando un modelo de ratones con obesidad inducida por dieta rica en grasa (DRG), examinamos la expresión adiposa de leptina, su promotor asociado ADNMTs y la proteína 2 con dominio de unión a metil-CpG (MBD2) en diferentes momentos tras la alimentación DRG. Resultados: Los niveles de expresión de leptina en grasa epididimal aumentaron significativamente tras la alimentación de los ratones con una dieta DRG durante 4, 8, 12 y 18 semanas (s), contrariamente a la alimentación con dieta estándar (DE). Sin embargo, las fracciones de metilación del promotor CpG se redujeron significativamente en la s8 con una menor asociación de MBD2 y DNMT1, y aumentaron en la s12 y s18 con una mayor asociación de MBD2, DNMT3A y DNMT3B, tras la DRG. Además, la unión de ARN polimerasa II aumentó en la s8 y disminuyó en la s18 tras la DRG en comparación con la alimentación de DE. Conclusiones: Estos datos indican que los cambios en puntos temporales específicos en ADNMTs en relación con un promotor podrían estar relacionados con la regulación de la expresión de leptina, indicando que existe un mecanismo epigenético dinámico y complejo subyacente en la expresión de leptina aberrante durante el desarrollo de obesidad.