RESUMO
Si-Jun-Zi decoction (SJZD) with ginseng as the principal medicinal herb is a traditional Chinese Medicine multi-herb prescription that commonly employed to treat colorectal cancer etc. Previous studies showed that nearly half of the commercial ginseng was sulfur-fumigated, one of the postharvest processing methods that commonly causes sulfur-dioxide (SO2) residue and chemical composition transformation in medical herbs. In this study, the effect of sulfur-fumigated ginseng on global quality of SJZD was evaluated by UPLC-QTOF-MS/MS based metabolomics and multiple chromatographic techniques based glycomics strategies. For non-saccharides components, sulfur-fumigated ginseng led to the emergence of sulfur-containing derivatives and alteration of saponins and flavonoids in SJZD. For saccharide components, sulfur-fumigated ginseng decreased the total contents and molecular weights of polysaccharides, changed the monosaccharide composition of polysaccharides, and increased the contents of oligosaccharides and free monosaccharides of SJZD. The alterations of SJZD were aggravated with the sulfur-fumigated content of ginseng. Those phenomena might be attributed to 1) sulfur-fumigation caused the generation of sulfur-containing derivatives in ginseng, which further transferred to SJZD, and 2) sulfur-fumigation caused the residue of SO2 in ginseng, which reduced the pH value and further changed the dissolution of saponins and flavonoids and accelerated the degradation of the polysaccharides to oligosaccharides and/or monosaccharides in SJZD. Furthermore, although storage reduced the SO2 residue in sulfur-fumigated ginseng, it couldn't recover the alterations of chemical profiles in SJZD. In conclusion, sulfur-fumigated ginseng altered the global quality of SJZD, which promoted that extra attention must be paid during the application of herbal formulas that containing sulfur-fumigated herbs.
Assuntos
Medicamentos de Ervas Chinesas , Panax , Saponinas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Flavonoides , Fumigação , Glicômica , Monossacarídeos , Panax/química , Prescrições , Enxofre/química , Espectrometria de Massas em Tandem/métodosRESUMO
Codonopsis Radix, a popular food homology medicine, is widely used in clinical traditional Chinese medicine and food supplement, raw products and three types of processed products are the main forms of decoction pieces in China. However, there is no scientific basis for comprehensive chemical characterization of raw and three types of processed products. Herein, we investigated qualitatively and quantificationally secondary and primary metabolites in raw Codonopsis Radix and three types of processed products by metabolomics and glycomics employing multiple chromatography-mass spectrometry technology combined with chemometric analysis further to look for differential compounds and propose the processing-induced chemical mechanisms. The results indicated that Codonopsis Radix became dark-colored and the smell of burnt incense odor was observed after processing. The principal component analysis demonstrated that secondary metabolome and glycome were significantly altered between raw and processed products, and 36 differential secondary metabolites and 11 differential primary metabolites were finally screened through orthogonal partial least-squares-discriminant analysis. The main types of compounds are alkaloids, terpenoids, glycosides, amino acids, monosaccharides, oligosaccharides, and furfural derivatives. Meanwhile, Chemical mechanisms could be involved, including oxidation, glycosidic hydrolysis, esterification, dehydration, and Maillard reaction. This work supplies a chemical basis for the application of various types of Codonopsis Radix decoction pieces.
Assuntos
Codonopsis , Medicamentos de Ervas Chinesas , Cromatografia , Cromatografia Líquida de Alta Pressão , Codonopsis/metabolismo , Medicamentos de Ervas Chinesas/análise , Glicômica , Glicosídeos , Espectrometria de Massas , Metabolômica , TecnologiaRESUMO
BACKGROUND: SLC39A8, a gene located on chromosome 4q24, encodes for the manganese (Mn) transporter ZIP8 and its detrimental variants cause a type 2 congenital disorder of glycosylation (CDG). The common SLC39A8 missense variant A391T is associated with increased risk for multiple neurological and systemic disorders and with decreased serum Mn. Patients with SLC39A8-CDG present with different clinical and neuroradiological features linked to variable transferrin glycosylation profile. Galactose and Mn supplementation therapy results in the biochemical and clinical amelioration of treated patients. RESULTS: Here, we report clinical manifestations, neuroradiological features and glycophenotypes associated with novel SLC39A8 variants (c.1048G > A; p.Gly350Arg and c.131C > G; p.Ser44Trp) in two siblings of the same Italian family. Furthermore, we describe a third patient with overlapping clinical features harbouring the homozygous missense variant A391T. The clinical phenotype of the three patients was characterized by severe developmental disability, dystonic postural pattern and dyskinesia with a more severe progression of the disease in the two affected siblings. Neuroimaging showed a Leigh syndrome-like pattern involving the basal ganglia, thalami and white matter. In the two siblings, atrophic cerebral and cerebellum changes consistent with SLC39A8-CDG were detected as well. Serum transferrin isoelectric focusing (IEF) yielded variable results with slight increase of trisialotransferrin isoforms or even normal pattern. MALDI-MS showed the presence of hypogalactosylated transferrin N-glycans, spontaneously decreasing during the disease course, only in one affected sibling. Total serum N-glycome depicted a distinct pattern for the three patients, with increased levels of undergalactosylated and undersialylated precursors of fully sialylated biantennary glycans, including the monosialo-monogalacto-biantennary species A2G1S1. CONCLUSIONS: Clinical, MRI and glycosylation features of patients are consistent with SLC39A8-CDG. We document two novel variants associated with Leigh syndrome-like disease presentation of SLC39A8-CDG. We show, for the first time, a severe neurological phenotype overlapping with that described for SLC39A8-CDG in association with the homozygous A391T missense variant. We observed a spontaneous amelioration of transferrin N-glycome, highlighting the efficacy of MS-based serum glycomics as auxiliary tool for the diagnosis and clinical management of therapy response in patients with SLC39A8-CDG. Further studies are needed to analyse more in depth the influence of SLC39A8 variants, including the common missense variant, on the expression and function of ZIP8 protein, and their impact on clinical, biochemical and neuroradiological features.
Assuntos
Defeitos Congênitos da Glicosilação , Doença de Leigh , Defeitos Congênitos da Glicosilação/genética , Glicosilação , Humanos , Manganês , PolissacarídeosRESUMO
Sulfur fumigation and heating desulfurization are used together in the post-harvest processing of many medicinal herbs. However, little is known about the effects of sulfur fumigation on saccharide components, nor about the effects of heating desulfurization on all herbal constituents. In this study, metabolomics and glycomics were integrated to investigate the effects of these two processes on the chemistry of Codonopsis Radix (CR) as a pilot study. The results showed that both sulfur fumigation and heating desulfurization significantly changed the non-saccharide small-molecule metabolome and the glycome of CR in different ways. Chemical mechanisms, such as esterification, glycosidic hydrolysis, esterolysis, amide bond hydrolysis, oxidation and dehydration, are proposed to be involved. These facts strongly inspire that, in addition to investigations of how sulfur fumigation impacts non-saccharide small-molecule metabolites, researches on heating desulfurization and saccharides should be conducted so as to enable accurate, comprehensive evaluation of the quality of sulfur-fumigated herbs.
Assuntos
Codonopsis , Medicamentos de Ervas Chinesas , Plantas Medicinais , Fumigação , Glicômica , Calefação , Metabolômica , Projetos Piloto , EnxofreRESUMO
Glycomics is a rapidly emerging subspecialty of system sciences that evaluates the structures and functions of glycans in biological systems. Moreover, glycomics informs allied scholarships such as systems glycobiology and personalized glycomedicine that collectively aim to explain the role of glycans in person-to-person and between-population variations in disease susceptibility and response to health interventions such as drugs, nutrition, and vaccines. For glycomics to make greater, systems-scale, contributions to biology and medical research, it is facing a new developmental challenge: transition from single omics to multiomics integrative technology platforms. A comprehensive map of all possible connections between glycomics and other omics types has not yet been developed. Glycomics aims to discover a complex interplay of molecular interactions; however, little is known about the regulatory networks controlling these complex processes. In addition, the glycomics knowledgebase is presently scattered across various publications and databases, and therefore does not enable a holistic or systems view of this study field. Therefore, researchers are not always aware, for example, that a given analyzed genetic locus is linked with glycans, and that there are also glycomics determinants of complex phenotypes in health and biology. This review presents several published examples of glycomics science in association with other omics levels, such as genomics, transcriptomics, proteomics, metabolomics, epigenomics, ncRNomics, lipidomics, and interactomics. I also highlight the salient knowledge gaps and suggest future research directions. Understanding the interconnections of glycomics with other omics technologies will facilitate multiomics science and knowledge integration, enhance development of systems glycobiology and personalized glycomedicine.
Assuntos
Glicômica/métodos , Medicina de Precisão/métodos , Animais , Genômica/métodos , Humanos , Biologia de Sistemas/métodosRESUMO
Morindae Officinalis Radix (MOR), the dried root of Morinda officinalis F.C. How (Rubiaceae), is a popular food supplement in southeastern China for bone protection, andrological, and gynecological healthcare. In clinical use, 3-4 year old MOR is commonly used and the xylem is sometimes removed. However, there is no scientific rationale for these practices so far. In this study, metabolomics and glycomics were integrated using multiple chromatographic and mass spectrometric techniques coupled with multivariate statistical analysis to investigate the qualitative and quantitative variations of secondary metabolome and glycome in different growth years (1-7 years) and tissues (xylem and cortex) of MOR. The results showed that various types of bioactive components reached a maximum between 3 and 4 years of growth and that the xylem contained more potentially toxic constituents but less bioactive components than the cortex. This study provides the chemical basis for the common practice of using 3-4 year old MOR with the xylem removed.
Assuntos
Medicamentos de Ervas Chinesas/química , Morinda/crescimento & desenvolvimento , Raízes de Plantas/química , China , Medicamentos de Ervas Chinesas/metabolismo , Glicômica , Metabolômica , Morinda/química , Morinda/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Fatores de Tempo , Xilema/química , Xilema/metabolismoRESUMO
Bovine colostrum is a rich source of bioactive components which are important in the development of the intestine, in stimulating gut structure and function and in preparing the gut surface for subsequent colonization of microbes. What is not clear, however, is how colostrum may affect the repertoire of receptors and membrane proteins of the intestinal surface and the post-translational modifications associated with them. In the present work, we aimed to characterize the surface receptor and glycan profile of human HT-29 intestinal cells after exposure to a bovine colostrum fraction (BCF) by means of proteomic and glycomic analyses. Integration of label-free quantitative proteomic analysis and lectin array profiles confirmed that BCF exposure results in changes in the levels of glycoproteins present at the cell surface and also changes to their glycosylation pattern. This study contributes to our understanding of how milk components may regulate intestinal cells and prime them for bacterial interaction.
Assuntos
Colostro/fisiologia , Enterócitos/química , Glicômica/métodos , Proteômica/métodos , Animais , Bovinos , Colostro/química , Feminino , Glicoproteínas/análise , Células HT29 , Humanos , Lectinas/análise , Polissacarídeos/análise , Receptores de Superfície Celular/análiseRESUMO
Angelica radix (Danggui in Chinese) used in China and Japan is derived from two species of Angelica, namely Angelica sinensis and Angelica acutiloba, respectively. The differences in quality between A. sinensis radix (ASR) and A. acutiloba radix (AAR) should be therefore investigated to guide the medicinal and dietary applications of these two species. Secondary metabolites and carbohydrates have been demonstrated to be the two major kinds of bioactive components of Danggui. However, previously, quality comparison between ASR and AAR intensively concerned secondary metabolites but largely overlooked carbohydrates, thus failing to include or take into consideration an important aspect of the holistic quality of Danggui. In this study, untargeted/targeted metabolomics and glycomics were integrated by multiple chromatography-based analytical techniques for qualitative and quantitative characterization of secondary metabolites and carbohydrates in Danggui so as to comprehensively evaluate and compare the quality of ASR and AAR. The results revealed that not only secondary metabolites but also carbohydrates in ASR and AAR were different in type and amount, which should collectively contribute to their quality difference. By providing more comprehensive chemical information, the research results highlighted the need to assess characteristics of both carbohydrates and secondary metabolites for overall quality evaluation and comparison of ASR and AAR.
Assuntos
Angelica sinensis/química , Angelica/química , Medicamentos de Ervas Chinesas/química , Angelica/metabolismo , Angelica sinensis/metabolismo , Carboidratos/química , Cromatografia , Glicômica , Metabolômica , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Controle de Qualidade , Metabolismo SecundárioRESUMO
The health-promoting effects of milk fat globule membrane (MFGM) glycoconjugates has attracted curiosity especially with regard to the challenges encountered to unravel the glycan complexities of MFGM glycoproteins and glycosphingolipids. In this context, we characterized glycans present in buffalo milk and colostrum fat globule membranes by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis by adopting chemoselective glycoblotting technique. Unlike human and bovine MFGM glycoproteins, the variations were obvious with respect to their number, size, heterogeneity, and abundance among the samples analyzed. Among N-linked glycans, mono-, di-, and trisialyl glycans were apparent in colostrum, while MFGM predominantly contained mono- and disialyl glycans, in addition to neutral and high-mannose glycoforms. The structural assignments of major glycans were confirmed by TOF/TOF analysis. Core 1 O-glycans were more common in both samples, and the major glycosphingolipids were GM3 and GD3 irrespective of the samples analyzed. The colostrum N-glycans, being effective antibacterials against human pathogens, established the structure-function relationship of oligosaccharides in early milk in providing innate protection to the newborn.
Assuntos
Colostro/química , Glicolipídeos/química , Glicoproteínas/química , Leite/química , Animais , Búfalos , Bovinos , Glicômica , Humanos , Gotículas Lipídicas , Proteínas do Leite/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
It is well-recognized that multiple components, the majority of which are secondary metabolites and carbohydrates, collectively contribute to the therapeutic effects of herbal medicines. The chemical characterization of herbal medicines has focused extensively on secondary metabolites but has largely overlooked carbohydrates. Here, we proposed an integrated chromatographic technique based targeted glycomics and untargeted metabolomics strategy simultaneously determining carbohydrates and secondary metabolites for the overall chemical profiling of herbal medicines; this strategy was successfully exemplified in an investigation of processing chemistry of Rehmanniae Radix (RR), a Chinese medicinal herb. It was demonstrated that the integrated strategy holistically illuminated the variations in the glycome and metabolome of RR samples processed by the traditionally-adopted nine cycles of steaming and drying, and further elucidated the processing-induced chemical transformation mechanisms of carbohydrates and secondary metabolites, and thereby revealed the inherent chemical connections between carbohydrates and secondary metabolites. The result suggested that the proposed strategy meets the technical demands for the overall chemical characterization of herbal medicines, and therefore could serve as a powerful tool for deciphering the scientific basis of herbal medicines.