Catalpol induces autophagy and attenuates liver steatosis in ob/ob and high-fat diet-induced obese mice.

Impaired autophagy has been implicated in the pathogenesis of nonalcoholic fatty liver disease. Catalpol (CAT), a bioactive compound from Rehmannia (Di Huang) glutinosa, is known to ameliorate insulin resistance and the histological NAFLD spectrum in obese mice. Here, we investigated the effects of CAT on hepatic steatosis and autophagy in ob/ob and high-fat diet-induced obese mice, as well as in hepatocytes. In ob/ob mice, CAT reduced liver weight, liver triglyceride and cholesterol content, and hepatic lipogenic enzyme levels and increased fatty acid oxidase levels. In addition, CAT administration increased LC3-II levels and decreased SQSTM1/P62 levels in ob/ob mice. Similar effects on hepatic steatosis and autophagy were observed in high-fat diet-induced mice after administration of CAT. Additionally, we found that CAT stimulated AMPK and increased nuclear translocation of transcription factor EB (TFEB) in obese mice and hepatocytes. Inhibition of AMPK completely blocked the effects of CAT on TFEB nuclear localization, hepatic autophagy, and liver steatosis. These findings revealed that diminished AMPK/TFEB-dependent autophagy is involved in the pathogenesis of liver steatosis in obesity, and that CAT might be a novel therapeutic candidate for treatment of this condition.

Glaucoma Drainage Device Coated with Mitomycin C Loaded Opal Shale Microparticles to Inhibit Bleb Fibrosis.

Excessive fibrosis is the topmost factor for the defeat of surgical glaucoma drainage device (GDD) implantation. Adjuvant drug approaches are promising to help reduce the scar formation and excessive fibrosis. Opal shale (OS), as a natural state and noncrystalline silica substance with poriferous nature and strong adsorbability, is highly likely to undertake drug loading and delivery. Here, we employed OS microparticles (MPs) by ultrasound and centrifugation and presented an innovative and improved GDD coated with OS MPs, which were loaded with mitomycin C (MMC). MMC-loaded OS MPs were physically absorbed on the Ahmed glaucoma valve surface through OS' adsorbability. About 5.51 µg of MMC was loaded on the modified Ahmed glaucoma valve and can be released for 18 days in vitro. MMC-loaded OS MPs inhibited fibroblast proliferation and showed low toxicity to primary Tenon's fibroblasts. The ameliorated drainage device was well tolerated and effective in reducing the fibrous reaction in vivo. Hence, our study constructed an improved Ahmed glaucoma valve using OS MPs without disturbing aqueous humor drainage pattern over the valve surface. The modified Ahmed glaucoma valve successfully alleviated scar tissue formation after GDD implantation surgery.

Mori Cortex extract ameliorates nonalcoholic fatty liver disease (NAFLD) and insulin resistance in high-fat-diet/streptozotocin-induced type 2 diabetes in rats.

Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg-1·d-1) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.

Glycemic index, glycemic load, and glycemic response to pomelo in patients with type 2 diabetes.

Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D). Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.

Chemiluminescence detection of superoxide anion release and superoxide dismutase activity: modulation effect of Pulsatilla chinensis.

A novel flow-injection chemiluminescence-based method has been developed for determination of superoxide dismutase (SOD) activity. An in-vitro superoxide anion generation xanthine/xanthine oxidase stable source was established on line with FIA/CL-detection apparatus, for measuring SOD activity. This method can detect SOD in the linear range of 0.002-2.00 U mL(-1) with a detection limit of 0.001 U mL(-1). Another method for detection of superoxide anion is based on the luminol-FeCl(3) chemiluminescence (CL) reaction. This method was used to evaluate superoxide release and SOD activity in rats treated with the traditional Chinese herb Pulsatilla chinensis, which resulted in high clearance of hepatitis B virus (HBV) after treatment of a hepatitis B patient. Interestingly, we found that treatment with Pulsatilla chinensis can specifically increase superoxide release by liver tissues and, at the same time, slightly increase extracellular SOD (ECSOD) activity in plasma; in particular it can markedly increase MnSOD activity in mitochondria in liver tissue. This work revealed a possible mechanism whereby Pulsatilla chinensis prevents possible infection (for example HBV) by specifically increasing superoxide release in the liver and increasing MnSOD activity to minimize superoxide-mediated toxicity.