Over the centuries, Chinese herbal drugs have served as a major source of medicines for the prevention and treatment of diseases including diabetes mellitus (known as 'Xiao-ke'). It is estimated that more than 200 species of plants exhibit hypoglycaemic properties, including many common plants, such as pumpkin, wheat, celery, wax guard, lotus root and bitter melon. To date, hundreds of herbs and traditional Chinese medicine formulas have been reported to have been used for the treatment of diabetes mellitus. This paper provides a brief review of the antidiabetic drugs of plant origin that have been approved by the Chinese health regulatory agency for commercial use in China. It was believed, through pharmacological studies, that medicinal herbs were meticulously organized in these antidiabetic drug formulas such that polysaccharide containing herbs restore the functions of pancreatic tissues and cause an increase in insulin output by the functional beta cells, while other ingredients enhance the microcirculation, increase the availability of insulin and facilitate the metabolism in insulin-dependent processes. Pharmacological and clinical evaluations indicated that these drugs had a mild, but significant, blood glucose lowering effect and that the long-term use of these agents may be advantageous over chemical drugs in alleviating some of the chronic diseases and complications caused by diabetes. Additionally, the use of these natural agents in conjunction with conventional drug treatments, such as a chemical agent or insulin, permits the use of lower doses of the drug and/or decreased frequency of administration which decreases the side effects most commonly observed.

Background: Astragaloside IV (ASI) in Radix Astragali is believed to be the active component in treating heart failure. The present study aims to examine the effects of ASI on cardiovascular parameters in long-term heart failure in rats.

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The multiple physiological properties of glucagon-like peptide-1 (GLP-1) make it a promising drug candidate for the treatment of type 2 diabetes. However, the in vivo half-life of GLP-1 is short due to rapid degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. The poor stability of GLP-1 has significantly limited its clinical utility; however, many studies are focused on extending its stability. Fatty acid conjugation is a traditional approach for extending the stability of therapeutic peptides because of the high binding affinity of human serum albumin for fatty acids. However, the conjugate requires a complex synthetic approach, usually involving Lys and occasionally involving a linker. In the current study, we conjugated the GLP-1 molecule with fatty acid derivatives to simplify the synthesis steps. Human serum albumin binding assays indicated that the retained carboxyl groups of the fatty acids helped maintain a tight affinity to HSA. The conjugation of fatty acid-like molecules improved the stability and increased the binding affinity of GLP-1 to HSA. The use of fatty acid-like molecules as conjugating components allowed variant conjugation positions and freed carboxyl groups for other potential uses. This may be a novel, long-acting strategy for the development of therapeutic peptides.

1 The objective of this study was to evaluate the effects of three sulphydryl (SH) compounds, Nacetylcysteine (NAC), cysteine (Cys) and cystamine, on functional recovery and ventricular arrhythmias (VF) in stunned myocardium in the isolated perfused heart of the rat. 2 Hearts (n = 7-8 per group) were perfused by the Langendorff procedure for 20min to stabilize and then assigned to one of five groups: saline, sham, NAC, Cys and cystamine. After the stabilizing period, the drugs (at 3.6,uMmin-1) or their vehicle (saline) were infused into coronary vessels throughout the experimental period. Ten min after administration of drugs, the left anterior descending coronary artery (LAD) was ligatured for 20 min and then untied to reperfuse for 30 min. In the sham group, a ligature was placed around the LAD but not tied. 3 NAC and Cys had a significant effect in attenuating myocardial stunning: the percentage recovery of rate-pressure product measured 30min after reperfusion as an index of heart function, was improved with the NAC (98.3 + 4.5) and Cys groups (104.0 + 6.5) compared with the saline (only 73.6 + 3.8, P < 0.01) group. Cystamine did not show these beneficial effects. This may be due to the difference in chemical structure between NAC, Cys and cystamine since the latter does not have a free SH group with a disulphide bond formed. This phenomenon suggests that a free SH group is essential for the protective effects of compounds like NAC and Cys in myocardial injury. 4 NAC and Cys prevented the fall in coronary flow during the LAD occlusion and enhanced coronary flow during reperfusion but cystamine did not have such a beneficial effect. 5 The incidence of VF in the saline, cystamine, Cys and NAC groups was 6/8 (75.0%), 4/7 (57.1%), 3/8 (37.5%) and 2/7 (28.6%), respectively, and no significant differences (P > 0.05) were noted between the saline-and drug-treated groups. 6 An in vitro study with electron spin resonance indicated that Cys effectively scavenged the hydroxyl radical (-OH) generated by Fenton's reaction but did not scavenge superoxide generated in an irradiated riboflavin system. NAC and cystamine showed a scavenging effect on -OH to a certain extent but this effect did not reach statistical significance (P > 0.05 vs saline). 7 Our results demonstrate that NAC and Cys treatment before ischaemia and reperfusion can reduce myocardial stunning. This beneficial effect may be mainly due to their ability to preserve and enhance coronary flow during coronary occlusion and reperfusion and in part due to scavenging -OH and/or replenishing intracellular glutathione. The results also indicate that the condition of coronary perfusion can produce a great impact on postischaemic ventricular performance.

In order to solve the problems of receptor promiscuity and poor blood‐brain barrier (BBB) penetration in the treatment of glioblastomas (GBM), a novel dual‐functional nanocomplex drug delivery system is developed based on the strategy of peptide‐drug conjugates. In this study, SynB3‐PVGLIG‐PTX is designed and screened out by matrix metalloproteinase‐2 (MMP‐2), to which it exhibits the best affinity. The MMP‐2‐sensitive peptide (PVGLIG) and a cell‐penetration peptide (SynB3) are combined to form a dual‐functional peptide. Moreover, as a drug‐peptide nanocomplex, SynB3‐PVGLIG‐PTX exhibited a high potential to form an aggregation with good solubility that can release paclitaxel (PTX) through the cleavage of MMP‐2. From a functional perspective, it is found that SynB3‐PVGLIG‐PTX can specifically inhibit the proliferation, migration, and invasion of GBM cells in vitro in the presence of MMP‐2, in contrast to that observed in MMP‐2 siRNA transfected cells. Further investigation in vivo shows that SynB3‐PVGLIG‐PTX easily enters the brain of U87MG xenograft nude mice and can generate a better suppressive effect on GBM through a controlled release of PTX from SynB3‐PVGLIG‐PTX compared with PTX and temozolomide. Thus, it is proposed that SynB3‐PVGLIG‐PTX can be used as a novel drug‐loading delivery system to treat GBM due to its specificity and BBB permeability.

Permeability assessment is an important procedure in the drug development process, and drug partitioning in membrane bilayer is related to permeability. To investigate the pH dependence on drug partitioning, the process of different ionization state of ibuprofen passing across POPC bilayer was studied using molecular dynamics simulation. The results show that both atomic charge scheme and ionization state of the drug affect the value and shape of energy profile when passing across the POPC bilayer. The neutral ibuprofen (ibuprofen under acidic condition) has a much lower energy barrier as compared with the anionic ibuprofen (ibuprofen under basic condition). Meantime, hydrogen bond analysis also certifies that it is easy for neutral ibuprofen to pass from bulk water to bilayer center. Our calculation suggests that the ionization state of ibuprofen may be changed between neutral and anionic state when passing across membrane: it may be ionized outside the membrane and neutralized inside the membrane.