GLP-1 receptor agonists for the treatment of obesity: Role as a promising approach.

Obesity is a complex disease characterized by excessive fat accumulation which is caused by genetic, environmental and other factors. In recent years, there has been an increase in the morbidity, disability rate,and mortality due to obesity, making it great threat to people's health and lives, and increasing public health care expenses. Evidence from previous studies show that weight loss can significantly reduce the risk of obesity-related complications and chronic diseases. Diet control, moderate exercise, behavior modification programs, bariatric surgery and prescription drug treatment are the major interventions used to help people lose weight. Among them, anti-obesity drugs have high compliance rates and cause noticeable short-term effects in reducing obese levels. However, given the safety or effectiveness concerns of anti-obesity drugs, many of the currently used drugs have limited clinical use. Glucagon-like peptide-1 receptor (GLP-1R) agonists are a group of drugs that targets incretin hormone action, and its receptors are widely distributed in nerves, islets, heart, lung, skin, and other organs. Several animal experiments and clinical trials have demonstrated that GLP-1R agonists are more effective in treating or preventing obesity. Therefore, GLP-1R agonists are promising agents for the treatment of obese individuals. This review describes evidence from previous research on the effects of GLP-1R agonists on obesity. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop obesity treatments based on GLP-1R agonists.

Ginsenoside Re Improves Isoproterenol-Induced Myocardial Fibrosis and Heart Failure in Rats.

Objective. Panax ginseng is used widely for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of P. ginseng. We aimed to investigate the protective effect of ginsenoside Re on isoproterenol-induced myocardial fibrosis and heart failure in rats. Methods. A model of myocardial fibrosis and heart failure was established by once-daily subcutaneous injection of isoproterenol (5 mg/kg/day) to rats for 7 days. Simultaneously, rats were orally administrated ginsenoside Re (5 or 20 mg/kg) or vehicle daily for 4 weeks. Results. Isoproterenol enhanced the heart weight, myocardial fibrosis, and hydroxyproline content in rat hearts. Ginsenoside Re inhibited (at least in part) the isoproterenol-induced increase in heart weight, myocardial fibrosis, and hydroxyproline content. Compared with the isoproterenol group, treatment with ginsenoside Re ameliorated changes in left ventricular systolic pressure, left ventricular end diastolic pressure, and the positive and negative maximal values of the first derivative of left ventricular pressure. Ginsenoside Re administration also resulted in decreased expression of transforming growth factor (TGF)-ß1 in serum and decreased expression of Smad3 and collagen I in heart tissue. Conclusion. Ginsenoside Re can improve isoproterenol-induced myocardial fibrosis and heart failure by regulation of the TGF-ß1/Smad3 pathway.

[Effect of anti-androgen and progesterone on development of regrowth antlers in 6 year old sika deer].

To investigate the effects of anti-androgen drugs and melengestrol acetate (MGA) on development of regrowth antlers in 6 year old sika deer, twenty healthysika deerwith similar body weight and antler weightwere randomly divided into five groups by using single factor test design: flutamide (n=4), bicalutamide (n=4), progesterone acetate (CPA, n=4), melengestrol acetate (MGA, n=4), control(n=4). All deer were fed with same diets and were housed outside together in an opened fence of 15 m×30 m with free access to water and feed. Treatment groups were injected subcutaneously sustained-release agents of the four drugs respectively when two-branched antlers were harvested. The control group had no special treatment. In the experiment period of 60 d, blood sampleswere collected for 4 times for each deer. The concentration of testosterone in plasma was tested and analyzed to compare the changes between different groups. Development of regrowth antlers was observed. At the end of the experiment, regrowth antlers were weighted and analyzed. The resultsshowed that the weights of regrowth antlers in treatment groups were significantly greater than those from control group and the weight gain (as compared with the control group) was 100.50%, 64.46%, 87.16% and 117.46% respectively in flutamide group, bicalutamide group, progesterone acetate group and melengestrol acetate group. For plasma testosterone concentration, it was not significantly different in the early stage (in the first 35 d), but at the end of the experimen, it was significantly higher than that of earlier stage (P<0.01) in various groups. Testosterone concentration of flutamide treated group was significantly lower than that of the other groups (P<0.01), while the level inbicalutamide and MGA treated groups was significantly higher than that in other groups (P<0.01). The results showed that both anti-androgen drugs and MGA treatment promoted the development of regrowth antlers and increased the weight of regrowth antlers, where the effect was most significant by MGA treatment. From the morphological observation of the antlers, it was found that anti-androgen and MGA treatments prolonged the growth period of regrowth antlers through delaying the ossification of antlers. However, plasma testosterone concentration was not affected by the treatments.

Ginsenoside Re Attenuates Isoproterenol-Induced Myocardial Injury in Rats.

Objective. Panax ginseng is widely used for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of Panax ginseng. This study aimed to investigate the protective effect of Ginsenoside Re on isoproterenol-induced myocardial injury in rats. Methods. Male Wistar rats were orally given Ginsenoside Re (5, 20 mg/kg) daily for 7 days. Isoproterenol was subcutaneously injected into the rats for two consecutive days at a dosage of 20 mg/kg/day (on 6th and 7th day). Six hours after the last isoproterenol injection, troponin T level and creatine kinase-MB (CK-MB) activity were assayed. Histopathological examination of heart tissues was performed. The levels of malondialdehyde (MDA) and glutathione (GSH) in heart tissues were measured. The nuclear factor erythroid 2-related factor 2 (Nrf2) content in nucleus and the proteins of glutathione cysteine ligase catalytic subunit (GCLC) and glutathione cysteine ligase modulatory subunit (GCLM) in heart tissues were assayed by western blotting method. Results. Treatment with Ginsenoside Re at dose of 5, 20 mg/kg reduced troponin T level and CK-MB activity of rats subjected to isoproterenol. The cardioprotective effect of Ginsenoside Re was further confirmed by histopathological examination which showed that Ginsenoside Re attenuated the necrosis and inflammatory cells infiltration. Ginsenoside Re inhibited the increase of MDA content and the decrease of GSH in heart tissues. Moreover, the Nrf2 content in nucleus and the expressions of GCLC and GCLM were significantly increased in the animals treated with Ginsenoside Re. Conclusion. These findings suggested that Ginsenoside Re possesses the property to attenuate isoproterenol-induced myocardial ischemic injury by regulating the antioxidation function in cardiomyocytes.