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Combined metabolomics and proteomics to reveal beneficial mechanisms of Dendrobium fimbriatum against gastric mucosal injury.

ABSTRACT: As a dietary and medicinal plant, Dendrobium fimbriatum (DF) is widely utilized in China for improving stomach disease for centuries. However, the underlying mechanisms against gastric mucosal injury have not been fully disclosed. Here, metabolomics and proteomics were integrated to clarify the in-depth molecular mechanisms using cyclophosphamide-induced gastric mucosal injury model in mice. As a result, three metabolic pathways, such as creatine metabolism, arginine and proline metabolism, and pyrimidine metabolism were hit contributing to DF protective benefits. Additionally, γ-L-glutamyl-putrescine, cytosine, and thymine might be the eligible biomarkers to reflect gastric mucosal injury tatus, and DF anti-gastric mucosal injury effects were mediated by the so-called target proteins such as Ckm, Arg1, Ctps2, Pycr3, and Cmpk2. This finding provided meaningful information for the molecular mechanisms of DF and also offered a promising strategy to clarify the therapeutic mechanisms of functional foods.

SUBMITTER: Sun J

PROVIDER: S-EPMC9468276 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Combined metabolomics and proteomics to reveal beneficial mechanisms of <i>Dendrobium fimbriatum</i> against gastric mucosal injury.

Sun Jing J Liu Peng-Fei PF Liu Jia-Ni JN Lu Cong C Tong Li-Tao LT Wang Yong-Quan YQ Liu Jia-Meng JM Fan Bei B Wang Feng-Zhong FZ

Frontiers in pharmacology 20220830

As a dietary and medicinal plant, <i>Dendrobium fimbriatum</i> (DF) is widely utilized in China for improving stomach disease for centuries. However, the underlying mechanisms against gastric mucosal injury have not been fully disclosed. Here, metabolomics and proteomics were integrated to clarify the in-depth molecular mechanisms using cyclophosphamide-induced gastric mucosal injury model in mice. As a result, three metabolic pathways, such as creatine metabolism, arginine and proline metabolis ...[more]

PMID: 36110550

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Project description:Dendrobium fimbriatum is a perennial herb, and its stems are high-grade tea and nourishing medicinal materials. Various solvent extracts of D. fimbriatum were evaluated for their anti-inflammatory, anti-acetylcholinesterase (AChE), antioxidant, and anti-α-glucosidase properties. Acetone and EtOAc extracts showed significant antioxidant effects. Acetone, n-hexane, and EtOAc extracts revealed potent inhibition against α-glucosidase. EtOAc, n-hexane, and dichloromethane extracts displayed significant anti-AChE activity. Among the isolated constituents, gigantol, moscatin, and dendrophenol showed potent antioxidant activities in FRAP, DPPH, and ABTS radical scavenging tests. Moscatin (IC50 = 161.86 ± 16.45 μM) and dendrophenol (IC50 = 165.19 ± 13.25 μM) displayed more potent anti-AChE activity than chlorogenic acid (IC50 = 236.24 ± 15.85 μM, positive control). Dendrophenol (IC50 = 14.31 ± 3.17 μM) revealed more efficient anti-NO activity than quercetin (positive control, IC50 = 23.09 ± 1.43 μM). Analysis of AChE and iNOS inhibitory components was performed using molecular docking and/or the bioaffinity ultrafiltration method. In bioaffinity ultrafiltration, the binding affinity of compounds to the enzyme (acetylcholinesterase and inducible nitric oxide synthase) was determined using the enrichment factor (EF). Among the main components of the EtOAc extract from D. fimbriatum stem, moscatin, dendrophenol, gigantol, and batatasin III with acetylcholinesterase exhibited the highest binding affinities, with affinity values of 66.31%, 59.48%, 54.60%, and 31.87%, respectively. Moreover, the affinity capacity of the identified compounds with inducible nitric oxide synthase can be ranked as moscatin (88.99%) > dendrophenol (65.11%) > gigantol (44.84%) > batatasin III (27.18%). This research suggests that the bioactive extracts and components of D. fimbriatum stem could be studied further as hopeful candidates for the prevention or treatment of hyperglycemia, oxidative stress-related diseases, and nervous disorders.

Project description:The aim of this study was to investigate the chemical composition and antioxidant capacity of various polar fractions obtained from Dendrobium fimbriatum Hook (DH). First, a 90% ethanol-aqueous extract of DH (CF) was subjected to sequential fractionation using different organic solvents, resulting in the isolation of a methylene chloride fraction (DF), an ethyl acetate fraction (EF), an n-butanol fraction (BF), and a remaining water fraction (WF) after condensation. Additionally, the CF was also subjected to column chromatography via a D101 macroreticular resin column, eluted with ethanol-aqueous solution to yield six fractions (0%, 20%, 40%, 60%, 80%, and 100%). UPLC-Q-Exactive Orbitrap-MS/MS analysis identified a total of 47 chemical compounds from these polar fractions, including fatty acids, amino acids, phenolic acids, flavonoids, organic heterocyclic molecules, and aromatic compounds. Moreover, DF, EF, and the 60%, 80%, and 100% ethanol-aqueous fractions had higher total phenol content (TPC) and total flavonoid content (TFC) values and greater 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS-) and 1,1-diphenyl-2-picrylhydrazyl (DPPH)-scavenging abilities. In H2O2-induced HepG2 cells, the aforementioned fractions could increase the activities of antioxidative enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1), superoxide dismutase (SOD), heme oxygenase-1 (HO-1) and catalase (CAT), stimulate glutathione (GSH) synthesis by increasing the activities of glutamic acid cysteine ligase (GCL) and glutathione synthetase (GS), regulate GSH metabolism by increasing glutathione peroxidase (GSH-Px) and glutathione reductase (GR) activities, and reduce levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, the antioxidative stress effect of the DH fractions was found to be positively correlated with the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) protein and the presence of antioxidative chemical constituents. In conclusion, this study highlights the efficacy of both liquid–liquid extraction and macroporous resin purification techniques in the enrichment of bioactive compounds from natural food resources. The comprehensive analysis of chemical constituents and antioxidant effects of different polar fractions from Dendrobium fimbriatum Hook contributes to the understanding of its potential application in functional foods and nutraceuticals.

Project description:BackgroundCurrently available prognostic tools and focused therapeutic methods result in unsatisfactory treatment of gastric cancer (GC). A deeper understanding of human epidermal growth factor receptor 2 (HER2)-coexpressed metabolic pathways may offer novel insights into tumour-intrinsic precision medicine.MethodsThe integrated multi-omics strategies (including transcriptomics, proteomics and metabolomics) were applied to develop a novel metabolic classifier for gastric cancer. We integrated TCGA-STAD cohort (375 GC samples and 56753 genes) and TCPA-STAD cohort (392 GC samples and 218 proteins), and rated them as transcriptomics and proteomics data, resepectively. 224 matched blood samples of GC patients and healthy individuals were collected to carry out untargeted metabolomics analysis.ResultsIn this study, pan-cancer analysis highlighted the crucial role of ERBB2 in the immune microenvironment and metabolic remodelling. In addition, the metabolic landscape of GC indicated that alanine, aspartate and glutamate (AAG) metabolism was significantly associated with the prevalence and progression of GC. Weighted metabolite correlation network analysis revealed that glycolysis/gluconeogenesis (GG) and AAG metabolism served as HER2-coexpressed metabolic pathways. Consensus clustering was used to stratify patients with GC into four subtypes with different metabolic characteristics (i.e. quiescent, GG, AAG and mixed subtypes). The GG subtype was characterised by a lower level of ERBB2 expression, a higher proportion of the inflammatory phenotype and the worst prognosis. However, contradictory features were found in the mixed subtype with the best prognosis. The GG and mixed subtypes were found to be highly sensitive to chemotherapy, whereas the quiescent and AAG subtypes were more likely to benefit from immunotherapy.ConclusionsTranscriptomic and proteomic analyses highlighted the close association of HER-2 level with the immune status and metabolic features of patients with GC. Metabolomics analysis highlighted the co-expressed relationship between alanine, aspartate and glutamate and glycolysis/gluconeogenesis metabolisms and HER2 level in GC. The novel integrated multi-omics strategy used in this study may facilitate the development of a more tailored approach to GC therapy.

Dataset Information

Combined metabolomics and proteomics to reveal beneficial mechanisms of Dendrobium fimbriatum against gastric mucosal injury.

Publications

Combined metabolomics and proteomics to reveal beneficial mechanisms of <i>Dendrobium fimbriatum</i> against gastric mucosal injury.

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