Metabolic profiling integrated with pharmacokinetics to reveal the material basis of Xiaokeyinshui extract combination in the treatment of type 2 diabetes in rats.

Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.

Hydrogen peroxide modification affects the structure and physicochemical properties of dietary fibers from white turnip (Brassica Rapa L.).

Turnip (Brassica rapa L.) is widely consumed as a vegetable and traditional Chinese medicine with high dietary fiber content. Soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) were obtained from white turnips, and the IDF was modified with alkaline hydrogen peroxide to obtain modified IDF (MIDF) and modified SDF (MSDF). The compositional, structural, and functional properties of the four samples were investigated. After modification, the modified dietary fibers (MDFs) showed smaller particle sizes and lower contents of pectin and polyphenol than those of unmodified dietary fibers (DFs) The results of scanning electron microscopy (SEM), Fourier transformed infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) showed that compared to the DFs, the MDFs were smaller and had more exposed hydroxyl groups. Analysis of the microrheological behaviors showed that the MDFs had higher viscosity than that of the DFs, with a looser structure for the MSDF and a stable structure for the MIDF. Therefore, due to structural changes, the physical and functional properties of the MDFs were improved compared to those of the unmodified DFs. Pearson correlation analysis showed that the particle size was positively correlated with the pectin content. The water holding capacity (WHC), oil adsorption capacity (OAC) and water swelling capacity (WSC) showed positive correlations with each other. This work indicated that white turnip could be a potential new source of DFs, which presented desirable functional properties after modification.

Foliar application is an effective method for incorporating selenium into peanut leaf proteins with antioxidant activities.

Proteins were extracted from Se-enriched peanut leaves, an agro-byproduct, and the foliar application of sodium selenite was indicated to be an effective method to incorporate Se into leaf selenoproteins with 75-80% incorporation rates. After trypsin digestion, the most abundant proteins from Se-enriched peanut leaf (PSPL) were identified as pathogenesis-related class 10 proteins, Ara h 8 allergen and its isoforms, using LC-MS/MS. The Se species in both the low Se PSPL and high Se PSPL were determined to be selenomethionine (SeMet), methylselenocysteine (MeSeCys) and selenocystine (SeCys2) with SeMet (15.6 mg/g) dominated the high Se PSPL. Their antioxidant activities were also evaluated using free radical scavenging assay, reducing power assay and ferric thiocyanate (FTC) test. As results, the PSPL exhibited potent DPPH radical (96.2%) and superoxide anion radical (98.4%) scavenging activities and showed strong reducing power in a Se-concentration-dependent manner, indicating that PSPL can be used as antioxidants and Se sources to improve health.

Chronic treatment with qiliqiangxin ameliorates aortic endothelial cell dysfunction in diabetic rats.

Qiliqiangxin (QL), a traditional Chinese medicine, has been shown to be beneficial for chronic heart failure. However, whether QL can also improve endothelial cell function in diabetic rats remains unknown. Here, we investigated the effect of QL treatment on endothelial dysfunction by comparing the effect of QL to that of benazepril (Ben) in diabetic Sprague-Dawley rats for 8 weeks. Cardiac function was evaluated by echocardiography and catheterization. Assays for acetylcholine-induced, endothelium-dependent relaxation (EDR), sodium nitroprusside-induced endothelium-independent relaxation, serum nitric oxide (NO), and nitric oxide synthase (NOS) as well as histological analyses were performed to assess endothelial function. Diabetic rats showed significantly inhibited cardiac function and EDR, decreased expression of serum NO and phosphorylation at Ser(1177) on endothelial NOS (eNOS), and impaired endothelial integrity after 8 weeks. Chronic treatment for 8 weeks with either QL or Ben prevented the inhibition of cardiac function and EDR and the decrease in serum NO and eNOS phosphorylation caused by diabetes. Moreover, either QL or Ben suppressed inducible NOS (iNOS) protein levels as well as endothelial necrosis compared with the diabetic rats. Additionally, QL prevented the increase in angiotensin-converting enzyme 1 and angiotensin II receptor type 1 in diabetes. Thus, chronic administration of QL improved serum NO production, EDR, and endothelial integrity in diabetic rat aortas, possibly through balancing eNOS and iNOS activity and decreasing renin-angiotensin system expression.