The model polysaccharide potato galactan is actually a mixture of different polysaccharides.

Commercially-supplied potato galactan (PG) is widely used as a model polysaccharide in various bioactivity studies. However, results using this galactan are not always consistent with the stated composition. Here, we assessed its composition by fractionating this commercial PG and purified its primary components: PG-A, PG-B and PG-Cp with weight-averaged molecular weights of 430, 93, and 11.3 kDa, respectively. PG-Cp consists of free ß-1,4-galactan chains, whereas PG-A and PG-B are type I rhamnogalacturonans with long ß-1,4-galactan side chains of up to 80 Gal residues and short ß-1,4-galactan side chains of 0 to 3 Gal residues that display a "trees in lawn" pattern. Structures of these polysaccharides correlate well with their activities in terms of galectin-3 binding and gut bacterial growth assays. Our study clarifies the confusion related to commercial PG, with purified fractions serving as better model polysaccharides in bioactivity investigations.

Therapeutic mechanisms of the medicine and food homology formula Xiao-Ke-Yin on glucolipid metabolic dysfunction revealed by transcriptomics, metabolomics and microbiomics in mice.

BACKGROUND: In recent decades, the prevalence of metabolic diseases, particularly diabetes, hyperlipidemia, obesity, and non-alcoholic fatty liver disease (NAFLD), has increased dramatically, causing great public health and economic burdens worldwide. Traditional Chinese medicine (TCM) serves as an effective therapeutic choice. Xiao-Ke-Yin (XKY) is a medicine and food homology TCM formula consisting of nine "medicine and food homology" herbs and is used to ameliorate metabolic diseases, such as insulin resistance, diabetes, hyperlipidemia and NAFLD. However, despite its therapeutic potential in metabolic disorders, the underlying mechanisms of this TCM remain unclear. This study aimed to evaluate the therapeutic effectiveness of XKY on glucolipid metabolism dysfunction and explore the potential mechanisms in db/db mice. METHODS: To verify the effects of XKY, db/db mice were treated with different concentrations of XKY (5.2, 2.6 and 1.3 g/kg/d) and metformin (0.2 g/kg/d, a hypoglycemic positive control) for 6 weeks, respectively. During this study, we detected the body weight (BW) and fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), daily food intake and water intake. At the end of the animal experiment, blood samples, feces, liver and intestinal tissue of mice in all groups were collected. The potential mechanisms were investigated by using hepatic RNA sequencing, 16 S rRNA sequencing of the gut microbiota and metabolomics analysis. RESULTS: XKY efficiently mitigated hyperglycemia, IR, hyperlipidemia, inflammation and hepatic pathological injury in a dose dependent manner. Mechanistically, hepatic transcriptomic analysis showed that XKY treatment significantly reversed the upregulated cholesterol biosynthesis which was further confirmed by RT-qPCR. Additionally, XKY administration maintained intestinal epithelial homeostasis, modulated gut microbiota dysbiosis, and regulated its metabolites. In particular, XKY decreased secondary bile acid producing bacteria (Clostridia and Lachnospircaeae) and lowered fecal secondary bile acid (lithocholic acid (LCA) and deoxycholic acid (DCA)) levels to promote hepatic bile acid synthesis by inhibiting the LCA/DCA-FXR-FGF15 signalling pathway. Furthermore, XKY regulated amino acid metabolism including arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and tryptophan metabolism likely by increasing Bacilli, Lactobacillaceae and Lactobacillus, and decreasing Clostridia, Lachnospircaeae, Tannerellaceae and Parabacteroides abundances. CONCLUSION: Taken together, our findings demonstrate that XKY is a promising "medicine food homology" formula for ameliorating glucolipid metabolism and reveal that the therapeutic effects of XKY may due to its downregulation of hepatic cholesterol biosynthesis and modulation of the dysbiosis of the gut microbiota and metabolites.

Renal denervation ameliorates post-infarction cardiac remodeling in rats through dual regulation of oxidative stress in the heart and brain.

BACKGROUND: Myocardial remodeling is the key step in the development of ischemic cardiomyopathy. We aimed to compare effects of renal denervation (RDN) with those of angiotensin receptor neprilysin inhibitors (ARNi) on cardiac remodeling after myocardial infarction (MI), and explore underlying mechanism. METHODS: Sprague-Dawley rats (n = 40; male) were subjected to ligation of left anterior descending coronary artery to induce MI; six rats served as controls. ARNi was administered at a dose of 60 mg/kg/day for 4 weeks starting 1 week after MI. An RDN/Sham-RDN procedure was performed 1 week after MI. Rats in all groups were studied 5 weeks after MI. Echocardiography was used to evaluate cardiac function. Masson staining and TUNEL staining were used to determine the extent of cardiac remodeling. Indicators of oxidative stress in heart and brain were used to analyze the potential mechanisms involved. RESULTS: Five weeks after MI, both RDN and ARNi significantly improved cardiac function and cardiac remodeling; however, RDN was superior to ARNi at attenuating myocardial apoptosis. Compared to ARNi, RDN was also more effective at decreasing the abnormal oxidative stress caused by MI; this was especially true in case of the brain and was confirmed by evaluating the changes in reactive oxygen species (ROS) levels and other oxidative stress parameters following MI. CONCLUSIONS: RDN is not inferior to ARNi with respect to the improvement of cardiac remodeling in rats with ischemic cardiomyopathy. The effect of RDN might be associated with effective inhibition of oxidative stress in both the heart and brain.

Selective effects of ginseng pectins on galectin-3-mediated T cell activation and apoptosis.

Galectin-3 (Gal-3) can induce T-cell activation and apoptosis and plays a role in tumor immune tolerance. Here, we demonstrate that ginseng pectins selectively inhibit Gal-3-induced T-cell apoptosis, while not affecting T-cell activation. This finding stands in contrast to that from the use of modified citrus pectin (MCP) and potato galactan (P-galactan) that inhibit both. Whereas PKC/ERK and ROS/ERK pathways are involved in both T-cell activation and apoptosis, the Ras/PI3K/Akt pathway is unique to T-cell activation. Ginseng pectins selectively inhibit the ROS/ERK pathway. Using the Sarcomar-180 mouse model in which Gal-3 expression is increased, we found that ginseng pectins (but not MCP or P-galactan) significantly promote T-cell proliferation and IL-2 expression, and inhibit tumor growth by 45%. These in vivo data correlate well with selective effects of pectins on Gal-3-mediated T-cell apoptosis and activation. Our study suggests a novel approach for the development of polysaccharide-based agents that target Gal-3 function.

Mesoporous silica nanoparticle-based H2O2 responsive controlled-release system used for Alzheimer's disease treatment.

Metal ions play important roles in amyloid aggregation and neurotoxicity. Metal-ion chelation therapy has been used in clinical trials for Alzheimer's disease (AD) treatment. However, clinical trial studies have shown that long-term use of metal chelator can cause adverse side effect, subacute myelo-optic neuropathy. Nanoparticle engineering processes have become promising approaches for efficiently drugs delivery. A series of modified mesoporous silica nanoparticles (MSNs) using redox, pH, competitive binding, light, and enzyme as actuators have been demonstrated. Recently, significant advances in sensing oxidative stress have been made by taking advantage of specific chemistry between cellular oxidants such as H(2) O(2) . Here we report a biocompatible delivery platform by using H(2) O(2) responsive controlled-release system to realize target delivery of AD therapeutic metal chelator. The advantage of this novel strategy is that metal chelator can only be released by the increased levels of H(2) O(2) , thus, it would not interfere with the healthy metal homeostasis and can overcome strong side effect of metal chelator after long-term use. By taking advantage of the good biocompatibility, cellular uptake properties, and efficient intracellular release of metal chelators, the delivery system is promising for future in vivo controlled-release biomedical applications.

Rapid and efficient screening of Alzheimer's disease ß-amyloid inhibitors using label-free gold nanoparticles.

Herein we report that a visual, label-free gold nanoparticle-based assay for rapid and efficient screening of Alzheimer's disease ß-amyloid inhibitors.