Naringin Activates AMPK Resulting in Altered Expression of SREBPs, PCSK9, and LDLR To Reduce Body Weight in Obese C57BL/6J Mice.

Previous investigations have shown molecular cross-talk among activated adenosine monophosphate-activated protein kinase (AMPK), proprotein convertase subtilisin/kexin type 9 (PCSK9), sterol regulatory element-binding proteins (SREBPs), and low-density lipoprotein receptor (LDLR) and that it may be an innovative pharmacologic objective for treating obesity. We scrutinized the beneficial effect of naringin, a flavanone-7- O-glycoside, on obesity and the mechanisms in the present study. We arbitrarily divided 50 mice into five groups ( n = 10): 25 or 50 or 100 mg/kg/day naringin-treated obese mice (gavage for 8 weeks), untreated obese mice, and C57BL/6J control. After 8 weeks, body weight was 51.8 ± 4.4 in the untreated obese mice group, while the weights were 41.4 ± 4.1, 34.6 ± 2.2, and 28.0 ± 2.3 in 25, 50,100 mg/kg naringin groups, respectively. Moreover, naringin treatment significantly decreased plasma 8-isoprostane (an indicator of the oxidative stress) level, fat weight, liver weight, hepatic total cholesterol concentration, hepatic triglyceride concentration, plasma leptin level, plasma insulin content, plasma low-density lipoprotein cholesterol level, and plasma PCSK9 production concomitantly with down-regulated expression of SREBP-2, PCSK9, and SREBP-1, and up-regulated expression of p-AMPKα and LDLR. The present results suggest that naringin activates AMPK resulting in altered expression of SREBPs, PCSK9, and LDLR to reduce the body weight of obese C57BL/6J mice.

Kaempferol modulates Angiopoietin-like protein 2 expression to lessen the mastitis in mice.

BACKGROUND: Mastitis is inflammation of a breast (or udder). Angiopoietin-like protein 2 (ANGPTL2) has been found as a key inflammatory mediator in mastitis. Purpose of this research was to investigate the mechanisms about repressing effect of kaempferol on mastitis. METHODS: Forty mice were randomly divided into 4 groups (n=10): C57BL/6J control mice, untreated murine mastitis, 10mg/kg kaempferol treated murine mastitis (ip), and 30mg/kg kaempferol treated murine mastitis (ip). Primary cultured mouse mammary epithelial cells (MMEC) were indiscriminately divided into seven groups including control group, 10mmol/L vehicle of kaempferol group, 10µmol/L kaempferol treated group, 20µg/mL LPS treated group, 1µmol/L kaempferol plus LPS treated group, 3µmol/L kaempferol plus LPS treated group, and 10µmol/L kaempferol plus LPS treated group. RESULTS: In murine mastitis, kaempferol (10 or 30mg/kg) treatment prevented mastitis development, decreased myeloperoxidase (MPO) production, interleukin (IL)-6 level, tumour necrosis factor-α (TNF-α) concentration, and ANGPTL2 expression. In MMEC, kaempferol (1, 3 or 10µM) reduced MPO production, TNF-α concentration, IL-6 level, and ANGPTL2 expression. CONCLUSIONS: The results in present study show that kaempferol modulates the expression of ANGPTL2 to lessen the mastitis in mice.

Phillyrin lowers body weight in obese mice via the modulation of PPAR/-ANGPTL 4 pathway.

OBJECTIVE: Previous investigations have shown that the peroxisome proliferator activated receptor beta/delta (PPAR/)-angiopoietin-like protein 4 (ANGPTL4) pathways may be a new pharmacologic target for treatment of obesity. The present study was conducted to test the effect of phillyrin, a glucoside, on obesity in mice. METHOD: Fifty mice were randomly divided into 5 groups (n=10): control group (C57BL/6J mice), obese mice group, two groups of obese mice treated with phillyrin (15 or 45mg/kg/day), one group of obese mice treated with PPAR/ agonist GW0742 (3mg/kg/day). Twelve weeks after treatment, body weight, liver weight, fat weight, lipid levels in the liver, serum levels of tumour necrosis factor-(TNF-), leptin, and insulin, expression of PPAR/, ANGPTL4, and AMP-activated protein kinase (AMPK) were determined. RESULTS: Treatment with phillyrin (15 or 45mg/kg) significantly decreased body weight, liver weight, fat weight, hepatic total cholesterol, free fatty acid, and triglyceride concentrations, serum levels of TNF-, leptin, and insulin concomitantly with up-regulated expression of PPAR/, ANGPTL4, and p-AMPK-. In addition, GW0742 has similar effect of phillyrin. CONCLUSIONS: The present results suggest that phillyrin could regulate the PPAR/-ANGPTL 4 pathway to lower body weight in obese C57BL/6J mice.

Elevated Levels of ADMA Are Associated with Lower DDAH2 and Higher PRMT1 in LPS-Induced Endometritis Rats.

Chronic endometritis is a continuous inflammation of uterine endometrium. Recent research has shown that higher asymmetric dimethylarginine (ADMA) levels contribute to endothelial dysfunction. In the present study, we tested whether there is a correlation between endometritis and ADMA in LPS-induced endometritis rat and the mechanisms involved. Thirty-six rats were divided into two groups: blank control group and rat model of endometritis group. The entire infused uterus were removed to observe the changes of histopathology, production of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, 8-isoprostane, and reactive oxygen species (ROS), and gene expression of dimethylarginine dimethylaminohydrolase 2 (DDAH2), protein-methyl transferase 1 (PRMT1), TNF-α, and IL-6. In endometritis rat group, characteristic histopathologic changes in uteri were observed. The uterine 8-isoprostane, ROS, MPO activity, IL-6 and TNF-α concentrations, PRMT1, IL-6, and TNF-α expressions were significantly elevated, and DDAH2 expression was notably reduced in endometritis group compared with control group. The present findings suggest that elevated levels of ADMA are associated with lower DDAH2 and higher PRMT1 in LPS-induced endometritis rat.

Icariin improves eNOS/NO pathway to prohibit the atherogenesis of apolipoprotein E-null mice.

Impaired endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway induces atherogenesis. The present study examined whether icariin improves the eNOS/NO pathway to prohibit the atherogenesis of apolipoprotein E-null (ApoE-/-) mice. In vitro, primary human umbilical vein endothelial cells (HUVECs) were randomly divided into 7 groups: control; vehicle; icariin 10; lyphosphatidylcholine (LPC) group; LPC + icariin 1; LPC + icariin 3; and LPC + icariin 10. In vivo, 80 mice were separated randomly into 4 groups (n = 20): control, ApoE-/-, ApoE-/- + icariin 10, and ApoE-/- + icariin 30. ApoE-/- mice had significantly more atherosclerosis in the aortic root together with increased aortic ROS production, body mass, plasma triglyceride (TG) and total cholesterol (TC) concentration, decreased aortic eNOS expression, and plasma NO concentration. LPC (10 µg/mL) treatment induced a big decline in NO level in the conditioned medium and eNOS expression, and an increase in intracellular reactive oxygen species (ROS) production in HUVECs. Icariin treatment decreased atherogenesis, ROS production, body mass, plasma TG concentration, and plasma TC concentration, and increased NO concentration and eNOS expression. These findings suggested icariin could improve eNOS/NO-pathway to prohibit the atherogenesis of apolipoprotein E-null mice by restraining oxidative stress.