The Effect Of Bitter Melon Lyophilized Superfine Powder On Metabolic Syndrome

With the progress of human civilization and lifestyle changes, the metabolic syndrome represented by the obesity and type2diabetes has been one of the mainly non-infectious chronic diseases that affect human health. Now, various synthetic drugs are available to improve metabolic syndrome, but these drugs have certain side effects on human. Thus, screening safe and effective natural products is important for intervention in metabolic syndrome. Bitter melon(Momordica charantia L.) as a medicinal and edible food, is rich in various active ingredients and has been used to lose weight, lower lipid and treat diabetes. Bitter melon contains many active ingredients which have the glucose lowering effects, we may improve the nutritional values of bitter melon by physical means.In this paper, bitter melon was used as raw materials, freeze-drying technology and superfine grinding technology were selected to make bitter melon lyophilized superfine powder (BLSP), and we used the adipocytes cell model, obese rat model and type2diabetes rat model to study the effect and mechanism of BLSP on metabolic syndrome. The main contents and conclusions are presented as the following:1. The effects of freeze-drying and superfine grinding on main ingredients solubility of bitter melon were analyzed. The results showed that:(1) Superfine grinding could affect the main ingredients solubility of BLSP, the particle size of90%BLSP was≤25μm, and BLSP were homogeneous, the moisture content is2.66%, and the Aw is0.37. And the contents of soluble protein (2.99mg/g), soluble sugar (13.07mg/g), total phenolics (10.03mg/g), total flavonoids (5.27mg/g) and total saponins (2.74%) were higher than bitter melon hot air drying powder.(2) The main phenolics compounds of BLSP are catechinic acid (95.36μg/g) and gallic acid (87.15μg/g), the main flavonoid is lutin (7.00[μg/g), and the main amino acids are histidine (0.13%) and arginine (0.11%).2. The3T3-L1preadipocytes model was selected to study the effect of BLSP on adipocyte differentiation. The results showed that:the BLSP water extracts (BW) could significantly reduce the viability of3T3-L1preadipocyte, and the IC50value was5.45±0.04mg/mL; the BW could reduce the intracellular fat accumulation and the effect was better than metformin. Thence, BW could suppresse the differentiation of preadipocytes to adipocytes, 3. The obese rat model was selected to study the effect of BLSP on insulin resistance. The results showed that:(1) BLSP could reduce the body weight, Lee’s index and the fat content of obese rats. Meanwhile, the fasting blood glucose levels and the serum insulin levels was reduced, the glucose tolerance was improved, and the hepatic glycogen and the muscle glycogen was increased when treated with BLSP. So, BLSP could lower rate of increase of obese rats’ body weights, reverse the disorders of glucose metabolism and ameliorate the symptoms of insulin resistance in obese rats.(2) BLSP could reduce the serum TG and CHOL contents, increase the activity of liver LPL and HL, and reduce the serum AST, ACP and ALP contents of obese rats. Moreover, the steatosis of liver was inhibited in obese rats after treatment with BLSP. Therefore, BLSP could improve lipid metabolism in obese rats, protect the liver, and prevent the formation of fatty liver.(3) BLSP might increase the antioxidant capacity and up-regulate the protein expression of PI3K and AMPK in obese rats, and then ameliorate the symptoms of insulin resistance and improve glucose and lipid metabolism.(4) There were similarities and differences between BLSP and pioglitazone on the effects of insulin resistance in obese rats. BLSP and pioglitazone could both ameliorate the symptoms of insulin resistance and up-regulate the protein expression of PI3K and AMPK in obese rats; while pioglitazone showed no significant effect on body weight and the steatosis of liver in obese rats, but BLSP could lower rate of increase of obese rats’body weights and inhibit the steatosis of liver.4. High-fat diet and low dose STZ induced type2diabetes rat model was selected to study the anti-diabetic effect of BLSP. The results showed that:(1) BLSP could ameliorate the symptoms of emaciation, polydipsia and polyphagia, reduce fasting blood glucose levels, serum insulin levels and TG levels, and increase the serum HDL levels in type2diabetes rats. Hence, BLSP could regulate the disorders of glucose and lipid metabolism.(2) The liver index, kidney index and stomach index were close to the normal group, the levels of serum ALT, AST, ACP and BUN were reduced, the levels of liver SOD were restored, the damaged islets were renovated, and the islet cell mass was increased in type2diabetes rats after BLSP treatment. So BLSP was speculated to have antioxidant function, which could help to protect organs.(3) BLSP could active the expression of AMPK and inhibit the JNK/p38 mediated MAPK signaling pathway, which might help to restore normal lipid metabolism and correct glucose metabolism in type2diabetes rats.(4) BLSP and metformin could both ameliorate the disorders of glucose and lipid metabolism in type2diabetes rats, but there were some different effects between them:BLSP could renovate the damaged islets and inhibit the expression of p38, while there was no significant effect on the damaged islets and the expression of p38after metformin treatment.5. The effects of BLSP on gut microbiota of type2diabetes rats were studied using454pyrosequencing methods, and the links of BLSP-change of gut microbiota-the disorders of glucose and lipid metabolism were investigated. The results showed that:(1) The gut microbiota of type2diabetes rats was changed:the ratio of Firmicutes to Bacteroidetes was increased, the dominant family was Ruminococcaceae, and the dominant genera were Bacteroides and Ruminococcus when compared with normal rats. The results demonstrated that the gut microbial markers might be useful for classifying type2diabetes.(2) BLSP can modify the gut microbiota in type2diabetes rats without disturbing the normal population diversity:the ratio of Firmicutes to Bacteroidetes was significantly decreased, the dominant family was Lachnospiraceae which was beneficial for intestinal health, and the contents of Bacteroides and Ruminococcus were significantly decreased. We speculated that the gut microbiota may become a new target for BLSP treating type2diabetes.(3) Metformin could also change the gut microbiota in type2diabetes rats, but there were significant differences when compared with normal rats and type2diabetes rats:the dominant phyla were Firmicutes and Proteobacteria, the dominant family were Helicobacteraceae and unclassified, and the dominant genera were Anaeroplasma、Blautia、Helicobacter and TM7. We could conclude that the effects of BLSP and metformin on gut microbiota was different.