Characterization and Antioxidant Activity Determination of Neutral and Acidic Polysaccharides from Panax Ginseng C. A. Meyer.

Panax ginseng (P. ginseng) is the most widely consumed herbal plant in Asia and is well-known for its various pharmacological properties. Many studies have been devoted to this natural product. However, polysaccharide's components of ginseng and their biological effects have not been widely studied. In this study, white ginseng neutral polysaccharide (WGNP) and white ginseng acidic polysaccharide (WGAP) fractions were purified from P. ginseng roots. The chemical properties of WGNP and WGAP were investigated using various chromatography and spectroscopy techniques, including high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, and high-performance liquid chromatography with an ultra-violet detector. The antioxidant, anti-radical, and hydrogen peroxide scavenging activities were evaluated in vitro and in vivo using Caenorhabditis elegans as the model organism. Our in vitro data by ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid), reducing power, ferrous ion chelating, and hydroxyl radical scavenging activity suggested that the WGAP with significantly higher uronic acid content and higher molecular weight exhibits a much stronger antioxidant effect as compared to that of WGNP. Similar antioxidant activity of WGAP was also confirmed in vivo by evaluating internal reactive oxygen species (ROS) concentration and lipid peroxidation. In conclusion, WGAP may be used as a natural antioxidant with potent scavenging and metal chelation properties.

Mechanisms of interactions in pattern-recognition of common glycostructures across pectin-derived heteropolysaccharides by Toll-like receptor 4.

Complex pectin, originating from terrestrial plant cell walls has been attracting research attention as a promising source of a new innate immune modulator. Numerous bioactive polysaccharides associated with pectin are newly reported every year, but the general mechanism of their immunological action remains unclear owing to the complexity and heterogeneity of pectin. Herein, we systematically investigated the interactions in pattern-recognition for common glycostructures of pectic heteropolysaccharides (HPSs) by Toll-like receptors (TLRs). The compositional similarity of glycosyl residues derived from pectic HPS was confirmed by conducting systematic reviews, leading to molecular modeling of representative pectic segments. Via structural investigation, the inner concavity of leucine-rich repeats of TLR4 was predicted to act as a binding motif for carbohydrate recognition, and subsequent simulations predicted the binding modes and conformations. We experimentally demonstrated that pectic HPS exhibits the non-canonical and multivalent binding aspects for TLR4 resulting in receptor activation. Furthermore, we showed that pectic HPSs were selectively clustered with TLR4 during endocytosis, inducing downstream signals to cause phenotypic activation of macrophages. Overall, we have presented a better explanation for the pattern recognition of pectic HPS and further proposed an approach to understand the interaction between complex carbohydrates and proteins.

Multivalent Carbohydrate Nanocomposites for Tumor Microenvironment Remodeling to Enhance Antitumor Immunity.

Current cancer immunotherapeutic strategies mainly focus on remodeling the tumor microenvironment (TME) to make it favorable for antitumor immunity. Increasing attention has been paid to developing innovative immunomodulatory adjuvants that can restore weakened antitumor immunity by conferring immunogenicity to inflamed tumor tissues. Here, a galactan-enriched nanocomposite (Gal-NC) is developed from native carbohydrate structures through an optimized enzymatic transformation for effective, stable, and biosafe innate immunomodulation. Gal-NC is characterized as a carbohydrate nanoadjuvant with a macrophage-targeting feature. It is composed of repeating galactan glycopatterns derived from heteropolysaccharide structures of plant origin. The galactan repeats of Gal-NC function as multivalent pattern-recognition sites for Toll-like receptor 4 (TLR4). Functionally, Gal-NC-mediated TLR activation induces the repolarization of tumor-associated macrophages (TAMs) toward immunostimulatory/tumoricidal M1-like phenotypes. Gal-NC increases the intratumoral population of cytotoxic T cells, the main effector cells of antitumor immunity, via re-educated TAMs. These TME alterations synergistically enhance the T-cell-mediated antitumor response induced by αPD-1 administration, suggesting that Gal-NC has potential value as an adjuvant for immune checkpoint blockade combination therapies. Thus, the Gal-NC model established herein suggests a glycoengineering strategy to design a carbohydrate-based nanocomposite for advanced cancer immunotherapies.

Clinical Factors Affecting the Serum Retention of a Teratogenic Etretinate after the Acitretin Administration.

Etretinate, an acitretin metabolite, has a long retention duration in adipose tissues with a teratogenic potential. FDA advises a contraceptive period of at least three years after discontinuing acitretin. However, the effect of accumulated etretinate in adipose tissues on fetus is unknown. Although the teratogenic threshold for serum concentration of etretinate has been presented as higher than 2 ng/mL, that of acitretin is unknown. To examine factors affecting body retention of acitretin and etretinate, effects of acitretin dosage, acitretin-taking duration, elapsed time after stopping acitretin, age, sex, concomitant alcohol consumption, and foods and supplements rich in vitamin A intake on serum concentrations of acitretin and etretinate were analyzed in 14 acitretin-taken patients and 58 controls without taking acitretin or etretinate. Serum concentrations of acitretin, but not etretinate, tended to be inversely related to the discontinuation duration. They were also related to old age. Different from a published result that alcohol consumption could promote the metabolism of acitretin into etretinate, alcohol intake did not affect serum concentrations of etretinate. Unexpectedly, more frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum acitretin, whereas less frequent intake of vitamin A or provitamin A-rich food and supplements was associated with higher serum levels of etretinate in acitretin-taken patients. Despite preliminary data, inter-individual variations in serum retention of etretinate suggest the necessity of further research before applying the same guidelines to everyone to minimize unnecessary contraception.

Metabolomics Approach Based on Multivariate Techniques for Blood Transfusion Reactions.

Blood transfusions temporarily improve the physical state of the patient but exert widespread effects on immune and non-immune systems. Perioperative allogeneic blood transfusions (ABT) are associated with various risks, including coagulopathy, incompatibility, transmission of infectious agents, and allergic reactions. Nevertheless, little is known about the global metabolic alterations that reflect the possible reactions of blood transfusions. In this study, we investigated metabolite changes generated by ABT in a rat model using metabolomics technology. To further profile the "metabolome" after blood transfusions, we used both liquid chromatography-quadrupole time-of-flight high-definition mass spectrometry and gas chromatography-mass spectrometry. ABT promoted a stimulatory microenvironment associated with a relative increase in glucose transporter 1/4 (GLUT1/GLUT4) expression. Supporting this result, glucose metabolism-related enzyme IRS1 and interleukin-6 (IL-6) were abnormally expressed, and levels of lysophosphatidylcholine (LysoPC) and its related enzyme phospholipase A2 (PLA2) were significantly altered in allogeneic groups compared to those in autologous groups. Finally, amino acid metabolism was also altered following ABT. Taken together, our results show a difference between autologous and allogeneic blood transfusions and demonstrate correlations with cancer-associated metabolic changes. Our data provide endogenous information for a better understanding of blood transfusion reactions.