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Objective: Huidouba (HDB) is a Chinese folk medicine used to treat diabetes in Sichuan Province, China. Therefore, we investigated the anti-diabetic effects of HDB and its underlying mechanisms. We hypothesized that HDB treatment could enhance glucose tolerance and insulin sensitivity, and thus prevent a hyperglycemia state. Methods: To test the hypothesis, streptozotocin (STZ)-induced diabetic mice and db/db mice, widely used models of hyperglycemia and insulin-resistant diabetes, were either treated with HDB, metformin, or acarbose. Blood glucose, oral glucose tolerance test, insulin tolerance test, pancreatic histopathology and serum biochemistry were detected to assess the hypoglycemic effect of HDB. Results: HDB treatments were found to show the effect in reducing glucose levels. HDB also resulted in a significant reduction in body weight and food intake in the STZ-induced diabetic mouse model. Furthermore, it significantly improved glucose and insulin tolerance in the two diabetic mouse models. Importantly, insulin, glucagon, pancreatic polypeptide, and somatostatin immunohistochemistry revealed that HDB treatment improved the function and the location of the cells in the islets compared with the other two treatments. HDB treatment resulted in significant restoration of islet function. Our results illustrated the underlying mechanism of HDB in the progression of diabetes, and HDB can be an effective agent for the treatment of diabetes. Conclusion: The results of this study suggested that HDB can reduce blood glucose levels in STZ-induced hyperglycemic mice and db/db mice.
ABSTRACT
Objective:From a new perspective，to explore therapeutic effect of Huidouba (HDB) on alleviating kidney oxidative damage in rats with diabetic nephropathy (DN) and provide a scientific basis for developing HDB as a potential Tibetan medicine for treatment of DN. Method:Rats were fed with high-fat diet (HFD) and injected with streptozocin (STZ, 65 mg·kg-1) intraperitoneally to induce DN model, while rats in Blank group were injected with an equal volume of vehicle and fed with normal chow. The successfully modeling DN rats were randomly divided into three groups, 8 rats per group, DN model group (10 mL·kg-1·d-1), Metformin group (0.045 g·kg-1·d-1) and HDB group (0.18 g·kg-1·d-1). Monitor body weight (BW) and fasting blood glucose (FBG) weekly, and collect 24 hours urine before and after medication to examine microalbuminuria (mAlb). Calculate kidney index (KI) after sacrificing, analyze mAlb, serum creatinine (SCr) and blood urea nitrogen (BUN) with a fully automatic biochemical analyzer. Histopathology of kidney was observed by Masson staining. Lipid peroxidation malondialdehyde (MDA) assay kit was used to examine MDA content in kidney tissue. Nox4, as a subtype of triphosphopyridine nucleotide (NADPH) oxidase family was determined by Western blot and immunofluorescence assay of kidney tissue. Result:Compared with blank group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in DN model group were increased (P<0.01), tissue damage was obvious and Nox4 expression in glumeruli was increased significantly (P<0.01). Compared with DN model group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in drug administration groups were decreased (P<0.01), kidney injury was alleviated and Nox4 expression was down-regulated（P<0.01）. Conclusion:HDB as a Yiqiyangyin Tibetan medicine, could ease oxidative stress injury of kidney and reduce proteinuria in DN rats, thus prevent the development of DN. Its mechanism is closely related to down-regulating Nox4 expression of kidney tissue in DN rats.
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AIM To study the efficacy of different extractions of Huidouba,a Tibetan medicine to mice with type Ⅱ diabetic kidney disease (DKD).METHODS The type Ⅱ DKD mice models induced by the injection of streptozotocin (STZ) on base of high glucose and high fat diet subsequently treated with different extractions of Huidouba were studied to investigate the protective effects of Huidouba on renal injury.The mice were given high dose (200 mg/kg) and low dose (100 mg/kg) of Huidouba ethanol extract,Huidouba water extract and Huidouba polysaccharide respectively for 8 weeks.Their serum creatinine (SCr),blood urea nitrogen (BUN),urine protein (mg/24 h),glycosylated serum protein (Gsp) and advanced glycation end products (AGEs),their histological changes of renal pathology were detected and analyzed.Meanwhile their protein levels of fibronectin (FN),intercellular adhesion factor (ICAM-1) and transforming growth factor (TGF-β1) were identified by Western blot.RESULTS The different extractions of Huidouba,demonstrating a portfolio of capacity in decreasing levels of serum glucose and AGEs,inhibiting the expression of target protein,alleviating the glomerular basement membrane thickening,improving mesangial matrix,renal tubular and epithelial cells degeneration and other pathological conditions,improved the renal function of DKD mice.CONCLUSION The three extractions of Huidouba highlight the renal improvements in type Ⅱ DKD mice.
ABSTRACT
Diabetes is a metabolic disorder characterized by insulin resistance and progressive failure of β cell. It becomes a major disease and causes much attention because of high incidence, high disability, and high morbidity. Traditional Chinese medicine and ethical minority medicine have certain effects on diabetes, such as regulating lipid and losing weight, improving insulin resistance, and reducing hypoglycemia risk, and also have obvious advantage in therapy for vascular complication. Studies show that Tibetan Huidouba can improve metabolism of blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), activity of superoxide dismutase (SOD) and malondialdehyde (MDA) content in diabetic animal. The metabolism includes inhibiting α-glycosidase enzyme, activating peroxisome proliferators activated receptors (PPAR), and inhibiting nicotinamide adenine dinucleotide phosphate coenzyme II (NADPH) oxidase.