| Obesity, a systemic low-level inflammation, is chronic disease. It’s embodied in some degree of significantly overweight or thick fat layer, refers to a particular state of the body caused by excessive accumulation of triglycerides. Obesity can induce metabolism changes, which cause human pathological and physiological changes or latent. Obesity leads to disease and hazards public health. It is a risk factor for leading to diabetes, coronary heart disease, fatty liver, hypertension, stroke, arthritis and other diseases, but also with an increased incidence of pancreatic cancer and other related cancers. It not only affects the quality of life, but also brings a heavy burden to the social-health service system. At present, the clinical treatment of obesity includes diet, exercise, and medicine. The clinical weight loss drugs generally have resistance and side effects, and its therapeutic effect is still not satisfactory. Therefore, it’s is necessary to develop and research a new weight loss drug, immediately. Chinese medicine treatment of obesity has a long clinical history. And Rhizoma Coptidis has been widely used in clinical treatment of lipid-lowering or weight-loss. Modern research shows that Huanglian Jiedu soup can effectively improve the BMI index of type Ⅱ diabetes. Berberine, as one of the main components of Rhizoma Coptidis, can influence the gut flora, down-regulate LPS levels, reduce inflammation, relieve the symptoms of obesity. Coptisine is an isoquinoline derivative alkaloid in Rhizoma Coptidis as well as berberine. Thus they have the similar physiological activity. Both of them have antibacterial, hypoglycemic, lipid-lowering effects. Recent studies have reported coptisine has lipid-lowering and weight loss effects. Therefore, this project mainly aimed at preliminarily study the obese mice’s lose weight of coptisine and explore its potential mechanism.The main contents and results of this project as follow:(1) Preliminarily study on coptisine lowering body weight effect of high-fat and high-cholesterol(HFHC) diet induced obese golden hamsters. Results found that HFHC diet could lead to a significant increase of body weight, serum lipids(TC, LDL-c, VLDL-c), TG and Apo B. Each group found no obviously changes in food intake, after treatment with drugs for a moth. And coptisine had good biological activities of weight loss and lipid-lowering activity. Especially, coptisine at high dosage group(CopH) effectively improved the Lee’s index of obese hamsters. Coptisine significantly reduced the levels of TC, TG, LDL-c, VLDL-c and ApoB, it’s reduced by 27.6%, 10.0%, 21.7%, 36.2% and 23.8%, respectively(P<0.01 or P<0.05). In addition, CopH could significantly increase the level of HDL-c and insulin(P <0.05).(2) In experiment of exploring the effect of coptisine on the weight of liver and adipose tissue of obese hamsters with induced by HFHC diet. CopH significantly decreased the accumulation of perirenal fat and epididymal fat, liver weight was significantly reduced. Liver oil red O staining experiments showed that CopH relieved the fatty liver condition; it’s also significantly reduced the lipid droplets’ quantity and size in liver tissue. Epididymal adipose tissue HE staining experiment showed that CopH could inhibit the expansion of adipocytes. It demonstrated that coptisine probably reduced body weight by inhibiting the size of adipocytes rather than quantity.(3) Real-time quantitative PCR and ELISA were used to detect mRNA expression and protein expression of the endotoxin and inflammation-related factors. Results indicated that CopH effectively decreased serum levels of LPS, LBP, IL-6 and TNF-α, compared with HFHC group. Likewise, CopH notably down-regulated the expression level of liver protein and mRNA of TLR-4, as well as CD14. Pearson’s correlation analysis was used to analyze the correlation between LPS and LBP, IL-6 and TNF-α, respectively. The results showed that LPS had strong positive correlation with LBP, IL-6 and TNF-α. It demonstrated that CopH could reduce obese hamsters’ serum LPS levels, reduced the secretion of inflammatory cytokines by effectively inhibit LPS/TLR-4 pathway.(4) Intestinal permeability was detected by lactulose/mannitol method. HFHC group was found an increase on intestinal permeability of hamsters, compared with normal control group. But CopH could reverse the HFHC group’s status.(5) Preliminary study on coptisine affects the intestinal flora of obese C57BL/6J mice with induced by HFHC diet. It was found that obese C57BL/6J mice reduced the intestinal flora species and increased in proteobacteria categories intestinal microflora, compared with normal control group. Compared with HFHC group, coptisine group decreased proteobacteria’s relative abundance of intestinal microbial, body weight of mice was reduced by 22.0%(P<0.05). It meant that coptisine could improve the change of the amount and type of intestinal flora in HFHC diet induced obese mice. Coptisine reduced the relative abundance of the gram-negative bacteria and decreased the body weight of obese C57BL/6J mice.(6) In experiment of exploring the effect of coptisine on anti-Enterobacter cloacae and anti-endotoxin in vitro. The results showed that the minimum inhibitory concentration of coptisine against Enterobacter cloacae was 60 μg/mL. And 4 μg/mL coptisine had significant anti-endotoxin activity. It demonstrated coptisine had a good antibacterial effect of anti-Enterobacter cloacae and an activity of anti-endotoxin.In conclusion, coptisine may be a potential weight loss drug. Its mechanism might have a certain anti-endotoxin activity in vitro, improved intestinal flora’s structure and quantity, decreased intestinal permeability and inhibited the quantity of Enterobacter cloacae to reduce and to absorb of LPS. Coptisine improved the body’s inflammatory state to achieve the purpose of reducing weight by decreasing the serum level of LPS, blocking the stimulation signals across the membrane and transmission and reducing the secretion of cytokines. |
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