| Obesity affects the quality of human life seriously, and, is an important cause ofcardiovascular and cerebrovascular diseases, metabolic diseases in addition that obesityaccounted for a growing proportion of the world’s population, so how to treat obesity hasbecome one of the major topic in the area of medicine and pharmacology today. Five kindsof diet pills for weight-loss had been approved by FDA, they were: Atmospherefenfluramine, Right atmosphere fenfluramine, Temin, sibutramine and Orlist. Currently,four of them had been delisted because of the huge side effects, so Orlist is the only OTCpills for weight-loss now. But due to the presence of serious liver damage and even liverfailure leading to the risk of death, Orlist was warned by FDA the year before last year.Concerning the serious side effects and adverse reactions caused by chemical drugs forweight loss, the development of an safe, natural substance of active ingredients seems to bemore and more significant.Chitosan (CTS) is the only trona polysaccharides with a positive charge in the nature.CTS has good biocompatibility and biodegradability. What’s more, a large number ofhuman trials and animal experiments have proved that CTS has the pharmacologicalactivities of lowering blood lipids and losing weight. At present, chitosan has been widelyapplied in lowering blood lipids and losing weight, but its applications were limited due tothe excessive nausea, vomiting, constipation and other side effects caused by huge dosage.Chitosan microspheres (CTMS) has been prepared using modern pharmaceutical means byin the preliminary study of our team. CTMS improves the bioavailability of CTS to reducethe oral dosage so that to enhance the pharmacological effects of lowering blood pressureand lose weight while reducing the its side effects. Capsaicin, as the natural product ofcapsicum, has been proved its pharmacological activity of losing weight through animalexperiments and human studies. Capsaicin can promote the secretion of theneurotransmitter acetylcholine and norepinephrine in the human’s body, while the epinephrine plays a role in weight losing through sweating and burning fat.The CCMS (Capsian-loaded chitosan microspheres, CCMS) has been prepared usingiron cross linking combined spray-dried preparation in the preliminary study of our team.The entrapment efficiency and the drug loading efficiency are the main evaluation indexes.Results showed that the CCMS have a spherical shape, the particle size was4.50μm, theZate was+3.84mV; the drug entrapment efficiency was can reach to85.17%±0.78; thedrug loading efficiency was8.87%±0.08.CCMS has been determinated its median lethal(LD50) dose using the Bliss method.The experimental results showed that the LD50of CCMS was14.618g/kg which was actualnon-toxic substances. The dosage was greater than10g/Kg which means it’s safe to human.The weight loss efficacy of the CCMS was studied and compared with a single CTMSand CAP, as well as Orlist (The only OTC drug used in weight-losing permitted by FDA)invivo animal experiments. The pharmacodynamic eperimental results showed that CCMScould control the growth of rat body weight, body mass index, organ index, body fat andthe proportion of fat and body weight at normal levels or lower in rats at the same time hadno effect on the rats’ appetite so that achieved a good effect on weight lossing.The effect ofCCMS on controlling weight gain, body mass index wass particularly evident, even betterthan the Orlist. CCMS played a significantly better role in weight loss than CAP and CTMSto achieve the synergistic effect. CCMS significantly reduced the TC, TG and LDL tonormal levels, but reduced role than single CTMS or the CAP did not achieve thesynergistic effect. CCMS has a potential role in lowering blood lipids but not so as CTMS,CTS or CAP.In the further study of the mechanism, the expression of PPARα gene, PPARγ gene,Leptin gene, Adiponectin gene, UCP2gene, GPR120gene and FTO gene at mRNA levelswere assayed by real-time RT-PCR. CTMS was found regulating the expression of PPARαgene, PPARγ gene, Leptin gene, Adiponectin gene up and regulating the expression ofUCP2gene down. The result was confirmed on their protein content in the serum throughELISA. Slices showed that rats which had been given CCMS had thinner myocardium cellsand liver cells than that of the model group. Besides, there were less inflammatory cell infiltration and fatty degeneration of hepatocytes in the heart cells and liver cells ofCCMS-treated rats. CCMS-treated group also showed smaller subcutaneous fatty cells andmesentery fatty cells. Overall, CTMS has a good efficacy on reducing weight and apotential therapeutic effect on fatty liver and myocardium hypertrophy which were causedby obesity. Moreover, CTMS inhibited the growing of fat cells to a certain extent. Thepossible mechanism of weight-reducing efficacy of CTMS might be that CTMS regulatedPPARα-gene, Leptin-gene, Adiponectin-gene and UCP2-gene in effect.In summary, CCMS could be defined as an actual non-toxic substance which plays agood role in controlling obesity through the study of acute toxicity and pharmacologicalactivity. CCMS maybe achieved the effect of weight-losing by regulating the mRNA andserum protein expression of PPARα gene, PPARγ gene, Leptin gene, Adiponectin gene upand regulating the expression of UCP2gene down. CCMS could be considered as an safeand effective natual weight-loss substance with an clear mechanism. |
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