Ameliorative Effects & Mechanism Of Sangjing Capsule And Its Separated Recipes On Animals With Type 2 Diabetes Mellitus

The term Diabetes Mellitus describes a metabolic disorder of multiple aetiologiescharacterized by chronic hyperglycemia with disturbances of carbohydrate, fat and proteinmetabolism, resulting from defects in insulin secretion, insulin action, or both. At present,the prevalence of diabetes mellitus is increasing, which is a serious disease damaginghuman being's health. Type 2 diabetes mellitus (T2DM) is the most prevalent form ofdiabetes accounting for about 90% of all diabetes cases. And its incidence rate with thesocio-economic development and lifestyle changes was an upward trend year after year,becoming second only to cardio-cerebral vascular diseases and tumors of a serious threat tohuman health, the third largest non-communicable diseases. According to the InternationalDiabetes Federation (IDF)'s statistics, there were 100 milli(?)n diabetic patients about theworld in the 20th century, however, the case number has rapidly increased to 246 million by2007, is expected 380 million diabetic people will be plagued by diabetes in the world bythe year 2025. At present, China has become second largest country of diabetes second onlyto India, patients with nearly 40 million. With the aging of population and the changes inlifestyle, our country's prevalence, disability and mortality of diabetes showed a clearupward trend.Type 2 diabetes is a heterogeneous disease, its development requires the presence of two fundamental defects: insulin resistance (IR) and pancreaticβ-cell failure. Insulinresistance, characterized by reduced responsiveness to the normal circulating insulin intarget tissues, is now considered as a fundamental aspect of etiology of type 2 diabetesmellitus, only IR alone is not sufficient to lead to T2DM. Longitudinal studies have shownthat significant hyperglycemia with pancreaticβ-cell function decline in the secretion,β-cell dysfunction in T2DM is a necessary condition. Pancreaticβ-cell failure is the resultof the development of T2DM as well as the driving force in T2DM condition worsened.Exploring the molecular mechanism of insulin resistance and searching for drugs thatprotectedβcells and improved insulin resistance has appeared to be a focus in globalmedical research.At present, many scientists focus on investigating the mechanism of traditional Chinesemedicinal herbs and its components in treating diabetes, and expect it can bring a thought indeveloping new drugs with more safe and effective for treating diabetes. Mulberry,Mulberry Leaf, Ramulus Mori and Mori Cortex are commonly used Chinese medicinalherbs. Modern pharmacological research showed that they can be used to treat type 2diabetes mellitus and have many advantages especially in diabetes and its complicationssuch as mild, broad and durable role and few side effects features and so on. SangjingCapsule is constituted of Mulberry, Mulberry Leaf, Ramulus Mori and Mori Cortex whichaccording to the clinical experience of Prof. Lu Fu-er. This research aimed to exploreantidiabetic effect of Sangjing Capsule on animals with type 2 diabetes mellitus and itspossible mechanism.The rats with T2DM were induced by the intravenous injection of low-dosestreptozotocin (STZ, 25mg/kg) and high sucrose-fat diet. The development of this animalmodel was similar to that of human suffered from type 2 diabetes mellitus. In this animalmodel, the low dose streptozotocin injection could damage pancreaticβ-cells slightly andlead to glucose intolerance and serum insulin reduction. On this basis, a high sucrose-fatdiet was followed to induce obesity and led to dyslipidemia, insulin resistance, which elevates serum insulin level in feedback.These experimental results showed that, Sangjing Capsule could decrease bloodglucose, correct impaired glucose tolerance, improve dyslipidemia, and ameliorate insulinresistance of type 2 diabetes mellitus. Furthermore, it is suggested by the present resultsthat the therapeutic effects of Sangjing Capsule on T2DM might be related to its ability toscavenge free radical, restore pancreatic islets viability and increase IRS-1, PI-3K andGLUT4 protein expression and-improve insulin signal transduction in adipose and skeletalmuscle tissues of T2DM rats.To investigate which herb plays the major role in Sangjing Capsule, Mulberry,Mulberry Leaf, Ramulus Mori and Mori Cortex were chosen as study objects. The resultsshowed that all of these herbs not only have hypoglycemic property, but also modulate theblood lipids. Its mechanism may be related to the balance of serum pro-inflammatorycytokines and anti-inflammatory cytokines levels and raise the activity of antioxidantenzymes, thereby protecting pancreatic tissue morphology and functions. But itsmechanism is different, each with its own characteristic. The results prove the reasonabilityof Sangjing Capsule in composition manner from this regard. SectionⅠAmeliorative Effect of Sang]ing Capsule on blood glucoseand lipid metabolism in T2DM rats induced by low-dose STZ andhigh sucrose-fat diet【OBJECTIVE】To investigate the effects of Sangjing Capsule on blood glucose and lipid metabolismof experimental T2DM rats.【METHODS】The rats with T2DM were induced by the intravenous injection of low-dosestreptozotocin (STZ, 25mg/kg) and high sucrose-fat diet. Then modeled diabetic animalswere divided into model, metformin and Sangjing Capsule group. Normal rats fed withcommon chow were designated as normal group. Eight weeks later, the oral glucosetolerance test (OGTT) was performed in all animals, the changes of murine body weight,fasting blood glucose (FBG), fasting insulin (FINS), Triglyceride (TG), Total Cholesterol(TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density LipoproteinCholesterol(LDL-C), Apolipoprotein A I (ApoA I), Apolipoprotein B(ApoB), Free FattyAcid (FFA) were routinely determined.【RESULTS】Compared with the model group, the result of OGTT in Sangjing Capsule group wasimproved. The levels of the body weights and FBG, FINS, TG, TC, LDL-C, ApoB and FFAdecreased, while HDL-C and ApoA I protein increased obviously.【CONCLUSION】Sangjing Capsule not only has hypoglycemic property, but also modulates the plasmalipids. SectionⅡEffect of Sangjing Capsule on T2DM rats induced bylow-dose STZ and high sucrose-fat diet and its possible mechanism【OBJECTIVE】To investigate the antidiabetoc effect of Sangjing Capsule on the rats with T2DMinduced by low-dose STZ and high sucrose-fat diet, and to explore its possible mechanism.【METHODS】The rats with T2DM were induced by the intravenous injection of low-dose ofstreptozotocin (STZ, 25mg/kg) and high sucrose-fat diet. Then modeled diabetic animalswere divided into model, metformin and Sangjing Capsule group. Normal rats fed withcommon chow were designated as normal group. Eight weeks later, the effects of SangjingCapsule on glucose metabolic parameters, factors related to oxidative stress, anti-injuryfactors of pancreatic islets and some key proteins in insulin signal transduction pathwaywere observed.【RESULTS】Intragastric administration of Sangjing Capsule significantly decreased FBG and FINSlevels in diabetic rats. Furthermore, Sangjing Capsule treatment significantly blocked theincrease of MDA and NO levels, increased SOD and GSH-px levels in diabetic rats.Histopathological scores showed that Sangjing Capsule had restored the damage ofpancreas tissues in rats with T2DM. Decreased IRS-1, PI 3-kinase p85 and GLUT4 proteinexpression in diabetes were significantly improved by Sangjing Capsule treatment. Theincreased serine phosphorylation level of IRS-1 (pSer307) was significantlydown-regulated in adipose and skeletal muscle tissues of T2DM rats treated with SangjingCapsule.【CONCLUSION】It is suggested that Sangjing Capsule could significantly inhibit the progression ofdiabetes induced by low-dose STZ and high sucrose-fat diet, and its inhibitory effect ondiabetes might be associated with its hypoglycemic effec and its ability to scavenge freeradical, restore pancreatic islets viability and enhance insulin signaling. SectionⅢComparison of Effects of Sangjing Capsule's SeparatedRecipes on T2DM Rats Induced by Low-dose STZ and HighSucrose-fat Diet and its Possible Mechanism【OBJECTIVE】To investigate the antidiabetic effect of Sangjing Capsule's separated recipes on therats with T2DM induced by low-dose STZ and high sucrose-fat diet, and to explore itspossible mechanism.【METHODS】The rats with T2DM were induced by the intravenous injection of low-dose ofstreptozotocin (STZ, 25mg/kg) and high sucrose-fat diet. Then modeled diabetic animalswere divided into into model, metformin, Mulberry leaf, Mulberry, Ramulus Mori and MoriCortex group. Normal rats fed with common chow were designated as normal group. Eightweeks later, the changes of rat body weight, and the effects of Mulberry, Mulberry leaf,Ramulus Mori and Mori Cortex on glucose and lipid metabolic parameters, factors relatedto inflammation and oxidative stress and anti-injury factors of pancreatic islets wereobserved.【RESULTS】Compared with the model group, the result of OGTT in every herbs group wasimproved. The levels of the body weights and FBG, FINS, TG, TC, LDL-C, ApoB and FFAdecreased, while HDL-C and ApoA I protein increased obviously also. Furthermore,Sangjing Capsule treatment significantly blocked the increase of CRP, TNF-α, IL-1β, IL-6,ICAM-1, VCAM-1, MDA and NO levels, increased IL-4, IL-10, SOD and GSH-px levels in diabetic rats. Histopathological scores showed that Sangjing Capsule had restored thefunction of pancreas tissues in rats with T2DM.【CONCLUSION】The results showed that all of these herbs not only have hypoglycemic property, butalso modulate the blood lipids. Its mechanism may be related to the balance of serumpro-inflammatory cytokines and anti-inflammatory cytokines levels and raise the activity ofantioxidant enzymes, thereby protecting pancreatic tissue morphology and functions. Butits mechanism is different, each with its own figures.