Antrodia cinnamomea and its compound dehydroeburicoic acid attenuate nonalcoholic fatty liver disease by upregulating ALDH2 activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disease, but currently has no specific medication in clinic. Antrodia cinnamomea (AC) is a medicinal fungus and it has been shown that AC can inhibit high fat diet (HFD)-induced lipid deposition in mouse livers, but the effective monomer in AC and mechanism against NAFLD remain unclear. It has been reported that aldehyde dehydrogenase 2 (ALDH2) activation shows protective effects on NAFLD. Our previous study demonstrates that AC and its monomer dehydroeburicoic acid (DEA) can upregulate the ALDH2 activity on alcoholic fatty liver disease mouse model, but it is not clear whether the anti-NAFLD effects of AC and DEA are mediated by ALDH2. AIM TO STUDY: To elucidate the active compound in AC against NAFLD, study whether ALDH2 mediates the anti-NAFLD effects of AC and its effective monomer. MATERIALS AND METHODS: WT mice, ALDH2-/- mice and ALDH2-/- mice re-expressed ALDH2 by lentivirus were fed with a methionine-choline deficient (MCD) diet or high fat diet (HFD) to induce NAFLD, and AC at the different doses (200 and/or 500 mg/kg body weight per day) was administrated by gavage at the same time. Primary hepatocytes derived from WT and ALDH2-/-mice were stimulated by oleic acid (OA) to induce lipid deposition, and the cells were treated with AC or DEA in the meantime. Lentivirus-mediated ALDH2-KD or ALDH2-OE were used to knock down or overexpress ALDH2 expression in HepG2 cells, respectively. Finally, the effects of DEA against NAFLD as well as its effects on upregulating liver ALDH2 and removing the harmful aldehyde 4-hydroxynonenal (4-HNE) were studied in the MCD diet-induced NAFLD mouse model. RESULTS: In WT mice fed with a MCD diet or HFD, AC administration reduced hepatic lipid accumulation, upregulated ALDH2 activity in mouse livers, decreased 4-HNE contents both in mouse livers and serum, inhibited lipogenesis, inflammation and oxidative stress and promoted fatty acid ß-oxidation. These effects were abolished in ALDH2 KO mice but could be restored by re-expression of ALDH2 by lentivirus. In primary hepatocytes of WT mice, AC and DEA inhibited OA-induced lipid accumulation and triglyceride (TG) synthesis, promoting the ß-oxidation of fatty acid in the meantime. However, these effects were lost in primary hepatocytes of ALDH2 KO mice. Moreover, the expression level of ALDH2 significantly affected the inhibitory effects of AC and DEA on OA-induced lipid deposition in HepG2 cells. The effects of AC and DEA on suppressing lipid deposition, inhibiting mitochondrial ROS levels, reducing TG synthesis, and promoting ß-oxidation of fatty acid were all enhanced with the overexpression of ALDH2 and reduced with the knockdown of ALDH2 expression. DEA showed dose-dependent effects on inhibiting liver lipid deposition, elevating ALDH2 activity and reducing 4-HNE levels in the livers of MCD diet-induced NAFLD mice. CONCLUSION: DEA is the effective compound in AC against NAFLD. The related anti-NAFLD mechanisms of AC and DEA were through upregulating ALDH2 expression and activity, thus enhancing the elimination of 4-HNE in the livers, and sequentially alleviating oxidative stress and inflammation, promoting fatty acid ß-oxidation and decreasing lipogenesis.

[Characteristics of nitrogen transportation in Castanea mollissima forest around the Fushi Reservoir watershed in north Zhejiang Province, China.] / æµ™æ±Ÿèµ‹çŸ³æ°´åº“é›†æ°´åŒºæ¿æ —æž—åœŸå£¤æ°®ç´ è¿ç§»ç‰¹å¾.

In this study, through setting runoff plots in Chinese chestnut (Castanea mollissima) fo-rest, the runoff water samples were collected and tested from January to October, 2013. Combining with soil nitrogen data before and after the rainy season, we analyzed the characteristics of soil nitrogen transportation in chestnut forest around the Fushi Reservoir watershed in north Zhejiang Pro-vince, China. The results showed that among the 10 surface runoff events of Chinese chestnut fo-rest, there exhibited a significant difference in runoff water volume of each runoff plot, and the maximum amount was 0.51 m3. Nitrogen was the major element associated with nutrient loss in the study region. The concentrations of nitrate nitrogen (NO3--N), ammonium nitrogen (NH4+-N), total nitrogen (TN) andchemical oxygen demend (CODMn) in the runoff water ranged from 0.02-1.87, 0.04-3.53, 1.69-5.33 and 5.30-14.07 mg·L-1, respectively. The water quality indexes were greatly affected by the runoff volume, and the relationship between the amount of nitrogen loss and runoff could be well fitted by using a linear equation. The difference in nitrogen contents of the soil in the upper, middle and lower part of the runoff plots was evident both before and after the rainy season. Moreover, the nitrogen content increased with the increasing altitude, but this trend decreased with increasing soil depth. Comparison of the difference between the four forms of soil nitrogen (NO3--N, NH4+-N, TN and hydrolyzable nitrogen Hydro-N of soil) before and after the rainy season showed that there existed significant differences in Hydro-N and TN, and the average diffe-rence values were 20.21 and 307.49 mg·kg-1, respectively. In this area, there was a great risk of nitrogen loss with runoff, and the potential non-point source pollution in Fushi Reservoir should be concerned.