A long period of studies on carbohydrates such as glycans and carbohydrate moieties of glycoconjugates has brought us a lot of understandings on various biological phenomena in the molecular level. Many of biological phenomena, such as cell-cell recognition, clearance of glycoproteins in blood, infection of pathogens, and initiation of innate immunity, are now recognized as those triggered via carbohydrate recognition. These studies have developed not only understandings on biological rolls of carbohydrate moieties of glycoconjugates but also established glycotechnology including glycan analyses, modification of oligosaccharide structure in glycoconjugates, and creation of novel glycosylated substances. Nowadays, glycotechnology and knowledge on carbohydrate-related biological phenomena are applied in a wide range of fields, especially medical science.This issue carries a series of articles including reviews on immunomodulation by polysaccharides and advanced technologies for structural analysis of glycans as well as some original studies on carbohydrate-related biological functions aiming medical use. These biochemical and/or physiological understandings on carbohydrates or glycoconjugates are expected to progress new approaches to overcome diseases. Finally, I express my gratitude to Dr. Fengshan Wang, Shandong University, Ji'nan, China, for his active management of these articles.
In recent years, there has been a great effort devoted to the investigation of the roles of carbohydrates in various essential biological processes and the development of carbohydrates to therapeutic drugs. This review summarizes the carbohydrate drugs which have been recorded in several pharmacopoeias, marketed, and under development. A prospect of the future development of carbohydrate drugs is discussed as well.
Aluminium-based adjuvants remain the only adjuvants approved for human use in the USA for over 80 years because of alum's simplicity, tolerability, safety and cost-efficiency. Recent development of vaccines, especially the increasing applications of recombinant subunit and synthetic vaccines, makes aluminium adjuvants cannot stimulate enough immunity to the antigens, since aluminium adjuvants can only induce Th2 type immune responses. So, novel adjuvants are urgent to make up the disadvantages of aluminium adjuvants. However, some major hurdles need to be overcome, not only the scientific knowledge of adjuvants but also unacceptable side-effects and toxicity. A number of carbohydrate-based polysaccharides from plant, bacterial, yeast and synthetic sources can act as pathogen-associated molecular patterns (PAMPs) and recognize pattern recognition receptors (PRRs) on immune cells, followed by triggering innate immunity and regulating adaptive immunity. What is more, polysaccharides are safe and biodegradable without tissue deposits as observed in aluminium adjuvants. Therefore, polysaccharide-based compounds and formulations are potential vaccine adjuvant candidates. Here, we mainly review polysaccharide-based adjuvants investigated in recent years.
Sweet medicines are a relatively untapped source of new drugs. Their biological activities are closely correlated to their chemical characteristics. However, accurately defining the chemical characteristics of glycans is a challenge due to their chemical heterogeneity and diversity. Gas chromatography-mass spectrometry (GC-MS) is an excellent technique for the analysis of glycans even though the preparation of adequate derivatives is necessary. We reviewed and discussed the most important methodologies currently used for glycan analysis in sweet medicines based on GC-MS, including the derivatization for monosaccharide analysis, hydrolysis methods for polysaccharide analysis, glycosidic linkage analysis based on methylation, and pyrolysis gas chromatography in carbohydrate analysis. Finally a strategy for quality control of sweet medicines based on quantification analysis is proposed.
A novel polysaccharide (LCPA50-S1) with immunomodulatory activity was extracted with simulated gastric medium from Litchi chinensis, and purified by DEAE-52 cellulose column, Sephadex G-50 column and Sephacryl S-300 HR chromatography. The structural characteristics of LCPA50-S1 were expounded through complete acid hydrolysis, partial acid hydrolysis, methylation and instrumental analysis. The results demonstrated that LCPA50-S1 is a heteropolysaccharide with a molecular weight of 1.58 × 105 Da. The backbone was composed of (1→4)-linked β-D-glucopyranosyl residues, (1→6)-linked β-D-galactopyranosyl, (1→3,6)-linked β-D-galactopyranosyl residues, (1→4,6)-linked α-D-glucopyranosyl residues and branched at O-6. The branches were consisted of (1→2)-linked α-L-rhamnopyranosyl residues, (1→4)-linked β-D-glucopyranosyl residues, and (1→6)-linked β-D-galactopyranosyl, terminated with (1→)-linked α-L-arabinopyranosyl residues and (1→)-linked β-D-galactopyranosyl residues, respectively. The immunoregulatory activity of LCPA50-S1 was evaluated through determination the effect of LCPA50-S1 on nitric oxide (NO) production of RAW264.7 macrophages and spleen lymphocyte proliferation as well as its cytokines secretion level. The results demonstrated that LCPA50-S1 increased NO and TNF-α production in RAW264.7 macrophages significantly, enhanced the proliferation as well as the interleukin-2 (IL-2) production of splenocytes. The data indicated that LCPA50-S1 had the potential to be explored as a novel natural immunomodulator for application in functional foods and medicine.
Two polysaccharides, LCP70S-1 and LCP70W, were isolated from the pulp tissues of Litchi chinensis by anion-exchange chromatography and gel-filtration chromatography, while the structure of LCP70S-1 was elucidated and its physico-chemical properties was analyzed. The results demonstrated that LCP70S-1 is composed of L-rhamnose, L-arabinose and D-galactose in the ratio of 1.06:6.39:4.21, and the main chain of the heteropolysaccharide possess (1→3,6)-linked galactopyranosyl branches at O-6. The three branches consist of (1→3)-linked rhamnopyranosyl residues, (1→3,6)-linked galactopyranosyl and (1→5)-linked arabinopyranosyl residues, and terminated with (1→)-linked arabinopyranosyl residues, respectively. The two polysaccharides were further evaluated with 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and their reducing power in vitro. The results showed that LCP70W and LCP70S-1 possessed significant antioxidant activities, especially for LCP70S-1. As such, LCP70S-1 could potentially serve as an antioxidant and would value further study for human healthcare.
Glycosylation is useful for improving the chemical properties and physiological functions of biologically and pharmacologically important compounds. The glycosylation of phenolic compounds can increase their solubility and stability in water. The addition of galactose residue has special meaning as it facilitates targeted delivery of drugs to the liver cancer cells with abundant galactose acceptors on the cell surface. In this work, the engineered β-galactosidase W980F from Lactobacillus bulgaricus L3 was utilized for the glycosylation of caffeic acid, a well-known phenolic phytochemical with broad bioactivities. The reaction was performed by incubation of the enzyme with 200 mM of lactose and 100 mM of caffeic acid at 45°C for 1 h. The product was purified and analyzed by MS and NMR spectra. The MS revealed a signal of [M-H]‒ at m/z 341.09, suggesting monogalactosylated products of caffeic acid (Mr 342). The NMR spectra further identified the products to be caffeic acid 3'-O-β- galactopyranoside and caffeic acid 4'-O-β-galactopyranoside in a ratio of 1:3. This was the first discovery that caffeic acid could be galactosylated by the engineered glycosidase.
Cancer cells express various aberrant glycoconjugates. Several kinds of carbohydrate antigens have been used for the serological tumor markers. In particular, the serological level of sialylated carbohydrate antigens, which contain the sialic acid residue in their structure, showed effectiveness in diagnosing cancer behavior. Although large number of carbohydrate antigens in serum of cancer patients was elevated broadly in various cancers, each tumor marker has different sensitivity and specificity for each cancer. Therefore, the combined use of several tumor markers which have different characteristics is effective for better sensitivity in diagnosing cancer behavior. The mechanism of synthesizing cancer- associated carbohydrate antigens is not fully understood because it is very complex. In addition, new cancer-associated carbohydrate antigens are also identified by molecular oncological studies. Those investigations are considered to develop more effective tumor markers to diagnose cancer behavior.
We advocate the use of silkworm larvae, Bombyx mori, as an animal model for discovery of drug candidates. We have established several disease models using silkworms, which offer technical advantages in drug development and the study of host-pathogen interaction. This mini review briefly describes recent trends in the use of silkworm larvae as a non-mammalian model for drug discovery and it offers suggestions regarding the potential for silkworm use in pharmaceutical-biomedical research.
Curcumin has been extensively reported as a potential natural antioxidant. However, there was no data on activity comparison as well as the biological interactions of curcumin with other natural antioxidants. The aim of the present study was to investigate the antioxidant power of curcumin in comparison with three important natural antioxidants; gallic acid, ascorbic acid, and xanthone on free radical scavenging action and their combination effects on this activity. The results indicated that the activities of these compounds were dose-dependent. The 50% effective concentration (EC50) of curcumin was found to be 11 μg/mL. Curcumin showed significantly higher antioxidant activity than ascorbic acid and xanthone but less than gallic acid. Interestingly, curcumin revealed synergistic antioxidant effect when combined with gallic acid whereas the antagonistic effect occurred in curcumin combination with ascorbic acid or xanthone. These results suggest that curcumin-gallic acid combination is the potential antioxidant mixture to be used in place of the individual substance whereas using of curcumin in combination with ascorbic acid or xanthone should be avoid.
Crizotinib is an oral small-molecule anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor for the treatment of ALK-positive non-small-cell lung cancer (NSCLC). A 63-year old woman with postoperative relapsed ALK-positive NSCLC was treated with crizotinib. Erythema multiforme (EM) occurred one week after initiation of crizotinib therapy. Skin biopsy specimen showed compatible drug eruption. The discontinuation of crizotinib improved her eruption within one week. This report presented the first case of crizotinib-associated EM, which is the preclinical stage of Stevens-Johnson syndrome. Although crizotinib is clinically available, we should be aware of its potential severe skin adverse event.
Forensic toxicology is aimed at identifying the relationship between drugs or poison and the cause of death or crime. In the authors' toxicology laboratory at Chiba University, the authors analyze almost every body for drugs and poisons. A simple inspection kit was used in an attempt to ascertain drug abuse. A mass spectrometer is used to perform highly accurate screening. When a poison is detected, quantitative analyses are required. A recent topic of interest is new psychoactive substances (NPS). Although NPS-related deaths may be decreasing, use of NPS as a cause of death is difficult to ascertain. Forensic institutes have recently begun to perform drug and poison tests on corpses. However, this approach presents several problems, as are discussed here. The hope is that highly accurate analyses of drugs and poisons will be performed throughout the country.