Virtual screening of anti-angiogenesis quinolizidine alkaloids from Leguminosae plant / 中草药

Objective: To investigate the mechanism of quinacridine alkaloids based on the systematic of screening compounds that play antitumor effect. Methods: The virtual screening technique was used and collected 103 quinolizidine alkaloids from Leguminosae plants, and selected eight targets, which were closely related to angiogenesis. The compounds were screened by using the LibDock module in Discovery Studio 2.5 (DS 2.5) software. In addition, the small-molecule approved drugs of targets from DrugBank database have scores, the minimum score of each target's approved drugs as threshold and the original ligand scoring were set as a reference. Results: Nineteen compounds were screened out, which scores were higher than the minimum score of approved drugs as well as being in the top of 10%, and the mechanism of quinolizidine alkaloids anti-angiogenesis was preliminarily revealed. Conclusion: The results suggest that the quinolizidine alkaloids may inhibit angiogenesis to play the role of antitumor, diabetic vascular complications and so on. Compared with traditional screening, virtual screening technology saves a lot of time, energy and resources, provided a new method for the development of angiogenesis inhibitor drugs.

Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway / 中国天然药物

The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

Current Clinical Status and Vascular Complications among Patients with Type 2 Diabetes Mellitus at Tertiary Hospitals in Malaysia.

Objective: To assess the prevalence of diabetic vascular complications and cardiovascular risk factors control in type 2 diabetic patients at tertiary settings. Methods: This cross-sectional study was conducted among 313 patients diagnosed with type 2 diabetes mellitus (T2DM) at two tertiary referral hospitals in Malaysia. Data regarding socio-demographics, macro- and microvascular complications, family health history, blood pressure, anthropometric indices, glycaemic control, and lipid profile were obtained from medical records, face-to-face interview and physical examination. Results: The mean age of patients was 55.7±9.2 years, mean diabetes duration was 10.1±8.1 years, and 52.1% were females. Approximately 36.1% patients had cardiovascular disease (CVD). There were high prevalence of established coronary artery disease (30.7%), cerebrovascular disease (10.2%), and peripheral vascular disease (5.1%). Peripheral neuropathy, diabetic nephropathy and retinopathy were present in 41.5%, 17.6% and 15.0% patients respectively. Only 14.1% of the patients reached optimal HbA1c level and 21.1% patients achieved target fasting plasma glucose. The overall prevalence of dyslipidemia was 89.1%, hypertension was 80.2%, and obesity was 35.9% (BMI) and 86.5% (waist-to-hip ratio). Conclusions: Diabetic vascular complications were highly prevalent among the type 2 diabetic patients. Cardiovascular risk factors control was suboptimal. Both awareness and application of recommended guidelines need to be reinforced.

Reactive Oxygen and Nitrogen Species in Pathogenesis of Vascular Complications of Diabetes

Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in subjects with diabetes. Disorders of the physiological signaling functions of reactive oxygen species (superoxide and hydrogen peroxide) and reactive nitrogen species (nitric oxide and peroxynitrite) are important features of diabetes. In the absence of an appropriate compensation by the endogenous antioxidant defense network, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause cellular damage and contribute to the vascular complications of diabetes. It has recently been suggested that diabetic subjects with vascular complications may have a defective cellular antioxidant response against the oxidative stress generated by hyperglycemia. This raises the concept that antioxidant therapy may be of great benefit to these subjects. Although our understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. Thus, further investigation of therapeutic interventions to prevent or delay the progression of diabetic vascular complications is needed.

Change of puerarin on the dynamic equilibrium of ET-NO and ET-ANF of diabetic vascular complicatioin induced by streptozotocin / 中成药

AIM: To investigate the effect of puerarin on the alteration of ET and ANF in plasma, NO and NOS in serum of diabetic rats induced by streptozotocin(STZ). METHODS: Rat modeling was set up by means of intraperitoneal injection of ST2 with a dose of 60mg?kg -1. Four days later, blood glucose was measured by glucose oxygen kit. On the basis of present documents, the rats that blood glucose was over 16.7mM were accepted as diabetic ones, and then were divided randomly into five groups: diabetic mellitus (DM), aminoguanidine (AG 0.1g?kg -1,ig.), puel (0.5g?kg -1,ig.),pue2(0.25g?kg -1,ig.), pue3(0.125g?kg -1,ig.) and a normal group additionally. In order to set up a chronic model, we observed 12 weeks according to our past experiments. The FBS was measured at the twelfth week using the test kit. NO and NOS in serum were determined by checking their OD values, ET and ANF in plasma were determined by radio-immunization, respectively. RESULTS: In diabetic rats, Plasma ET and ANF levels increased obviously, NO and NOS levels decreased greatly (P