Differentiation in TCM patterns of chronic obstructive pulmonary disease by comprehensive metabolomic and lipidomic characterization.

Introduction: Chronic obstructive pulmonary disease (COPD) is a complex disease involving inflammation, cell senescence, and autoimmunity. Dialectical treatment for COPD with traditional Chinese medicine (TCM) has the advantage of fewer side effects, more effective suppression of inflammation, and improved immune function. However, the biological base of TCM pattern differentiation in COPD remains unclear. Methods: Liquid Chromatography-Quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap MS/MS) based metabolomics and lipidomics were used to analyze the serum samples from COPD patients of three TCM patterns in Lung Qi Deficiency (n=65), Lung-Kidney Qi Deficiency (n=54), Lung-Spleen Qi Deficiency (n=52), and healthy subjects (n=41). Three cross-comparisons were performed to characterize metabolic markers for different TCM patterns of COPD vs healthy subjects. Results: We identified 28, 8, and 16 metabolites with differential abundance between three TCM patterns of COPD vs healthy subjects, respectively, the metabolic markers included cortisol, hypoxanthine, fatty acids, alkyl-/alkenyl-substituted phosphatidylethanolamine, and phosphatidylcholine, etc. Three panels of metabolic biomarkers specific to the above three TCM patterns yielded areas under the receiver operating characteristic curve of 0.992, 0.881, and 0.928, respectively, with sensitivity of 97.1%, 88.6%, and 91.4%, respectively, and specificity of 96.4%, 81.8%, and 83.9%, respectively. Discussion: Combining metabolomics and lipidomics can more comprehensively and accurately trace metabolic markers. As a result, the differences in metabolism were proven to underlie different TCM patterns of COPD, which provided evidence to aid our understanding of the biological basis of dialectical treatment, and can also serve as biomarkers for more accurate diagnosis.

Chemical Identification and Antioxidant Screening of Bufei Yishen Formula using an Offline DPPH Ultrahigh-Performance Liquid Chromatography Q-Extractive Orbitrap MS/MS.

Chronic obstructive pulmonary disease (COPD) has high morbidity and mortality and presents a threat to human health worldwide. Numerous clinical trials have confirmed that Bufei Yishen formula (BYF), an herbal medicine, can alleviate the symptoms of COPD by reducing oxidative stress-mediated inflammation. However, the active components of BYF remain unclear. We developed an efficient ultrahigh-performance liquid chromatography Q-Extractive Orbitrap mass spectrometry method to identify the composition of BYF and determine its antioxidant profile through an offline screening strategy based on 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH)-liquid chromatography-mass spectrometry. In total, 189 compounds were identified in BYF extract, including 83 flavonoids, 24 lignans, 20 alkaloids, 15 saponins, 11 terpenoid, 10 saccharides, eight lipids, seven organic acids, two coumarins, two amino acids, and seven other compounds. Among them, 79 compounds were found to have a potential antioxidant activity. In vitro validation indicated that the free radical scavenging activities of rosmarinic acid and calycosin were similar to that of the positive control (DPPH IC50 = 25.72 ± 1.02 and 147.23 ± 25.12 µg/mL, respectively). Furthermore, calycosin had a high content in serum after the oral administration of BYF, indicating that calycosin might be the major antioxidant compound in BYF.

Identification of the active compounds and functional mechanisms of Jinshui Huanxian formula in pulmonary fibrosis by integrating serum pharmacochemistry with network pharmacology.

BACKGROUND: Jinshui Huanxian formula (JHF), a traditional Chinese medicine (TCM), has been demonstrated to attenuate idiopathic pulmonary fibrosis (IPF). The active compounds and underlying mechanisms of JHF, however, are unclear. PURPOSE: The purpose of This study was to aimed to identify the active compounds and pharmacological mechanism of JHF by integrating serum pharmacochemistry with a network pharmacology strategy. METHODS: JHF was orally administered to a rat model with bleomycin (BLM)-induced pulmonary fibrosis (PF). The pharmacodynamic effects and compounds present in the serum were identified. The targets and biological mechanisms of these compounds were revealed using network analysis and validated using in vitro experiments. RESULTS: JHF could significantly ameliorate BLM-induced PF by preventing extracellular matrix collagen deposition. Twenty-seven compounds that were found to be enriched in the serum samples collected 1 h after oral administration with JHF were identified as the candidate active compounds, and their 423 potential targets were identified as JHF targets. primarily related to the advanced glycation and products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway, phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or AKT) signaling pathway, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, etc. The 423 targets, 1145 IPF-related genes and their overlapped genes were applied to analyze, respectively. The results showed that these genes were primarily related to the advanced glycation end-products-receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, lipid and atherosclerosis pathology, phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or AKT) signaling pathway, and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. Furthermore, the affinity between serum JHF compounds and the main proteins in the above important pathways was investigated through molecular docking. As a result, Molecular docking analysis showed that, tangeretin, isosinensetin, and peimine were found to could bind to EGFR and AKT, and their inhibitory effect on EGFR and AKT were validated in fibroblast cell induced by transforming growth factor (TGF)TGF-ß. The results indicated that suppression of fibroblast activation by inhibiting the EGFR/PI3K/AKT signaling pathway might be an important mechanism of JHF may to treat PF. CONCLUSION: JHF may suppress fibroblast activation by inhibiting the EGFR/PI3K/AKT signaling pathway to ameliorate PF. Tangeretin, isosinensetin, and peimine may be the active compounds in JHF involved in the treatment of that have therapeutic effects on IPF.

Comprehensive determination of polycyclic aromatic hydrocarbons in Chinese herbal medicines by solid phase extraction and gas chromatography coupled to tandem mass spectrometry.

A simple and highly sensitive gas chromatography-tandem mass spectrometry (GC-MS/MS) method combined with solid-phase extraction cleanup was established for the comprehensive determination of 16 Environmental Protection Agency (EPA) polycyclic aromatic hydrocarbons (PAHs) in various kinds of Chinese herbal medicines (CHMs). A solid-phase extraction (SPE) purification strategy, including three parallel procedures, was developed depending on sample type, and satisfactory purification performances were achieved for all selected CHMs. The limits of detection ranged from 0.12 to 1.08 µg kg(-1) for the analyzed PAHs. The average recoveries were in the range of 65.9 % to 100.8 %, except for naphthalene (43.8 %-75.9 %), and the relative standard deviations were ≤12.8 %. The proposed method was successfully applied to the analysis of PAHs in 24 CHMs including five roots, three stems, four flowers, two fruits, four seeds, three leaves, and three barks. In the samples analyzed, all 16 PAHs are present. Their sum ranges from 21.1 to 2236.3 µg kg(-1). The entire procedure was shown to be effective and conveniently fast, and may serve as an alternative screening protocol for the determination of PAHs in CHMs.

Antioxidant effects of grape vine cane extracts from different Chinese grape varieties on edible oils.

This study involved the determination of the peroxide value (POV) as a measure of the resistance of the oxidation of edible oil with grape vine cane additives to assess their antioxidation potential. The study demonstrated that grape extracts of canes could effectively inhibit the lipid oxidation of edible oils and that this ability varied significantly due to the different extraction solvents employed, as well as to the different varieties of canes used. Lipid oxidation of edible oils was significantly reduced under an accelerated storage condition of 70 ± 1 °C in the presence of Vitamin C (VC), which was chosen as a synergist of grape vine cane extract. A 4:1 ratio of Victoria Blanc-ethyl acetate fraction (EAF) and VC led to a significant lowering of the peroxide value and indicated a better antioxidant effect. Thus, these results indicated that some varieties of grape vine cane extracts could be applied as natural antioxidants for elevation of the quality of edible oils in the food industry.

Plasma and hepatic cholesterol-lowering effects of tomato pomace, tomato seed oil and defatted tomato seed in hamsters fed with high-fat diets.

The cholesterol-lowering effects of tomato pomace (TP), tomato seed oil (TSO) and defatted tomato seed (DTS) were determined in male Golden Syrian hamsters. Hamsters fed high-fat diets containing 10% TSO or 18% DTS were compared to a diet containing 10% corn oil and 10% microcrystalline cellulose (control 1), 42% TP were compared to 25% microcrystalline cellulose (control 2). TP, TSO and DTS reduced hepatic total cholesterol (TC) content. DTS also lowered plasma TC and low-density lipoprotein cholesterol (LDL-C) concentrations. Fecal excretion of lipid, bile acid and cholesterol increased in the DTS group compared to control 1. DTS-fed hamsters had higher levels of hepatic CYP7A1, CYP51, ABCB11, and ABCG5 gene expression than control, suggesting both hepatic bile acid and cholesterol synthesis increased due to increased fecal excretion of bile acid and cholesterol. The results suggest that protein, dietary fibre or phenolic compounds in DTS may be responsible for plasma cholesterol decrease.

Study of optimal extraction conditions for achieving high yield and antioxidant activity of tomato seed oil.

UNLABELLED: Value of tomato seed has not been fully recognized. The objectives of this research were to establish suitable processing conditions for extracting oil from tomato seed by using solvent, determine the impact of processing conditions on yield and antioxidant activity of extracted oil, and elucidate kinetics of the oil extraction process. Four processing parameters, including time, temperature, solvent-to-solid ratio and particle size were studied. A second order model was established to describe the oil extraction process. Based on the results, increasing temperature, solvent-to-solid ratio, and extraction time increased oil yield. In contrast, larger particle size reduced the oil yield. The recommended oil extraction conditions were 8 min of extraction time at temperature of 25 °C, solvent-to-solids ratio of 5/1 (v/w) and particle size of 0.38 mm, which gave oil yield of 20.32% with recovery rate of 78.56%. The DPPH scavenging activity of extracted oil was not significantly affected by the extraction parameters. The inhibitory concentration (IC(50) ) of tomato seed oil was 8.67 mg/mL which was notably low compared to most vegetable oils. A 2nd order model successfully described the kinetics of tomato oil extraction process and parameters of extraction kinetics including initial extraction rate (h), equilibrium concentration of oil (C(s) ), and the extraction rate constant (k) could be precisely predicted with R(2) of at least 0.957. PRACTICAL APPLICATION: The study revealed that tomato seed which is typically treated as a low value byproduct of tomato processing has great potential in producing oil with high antioxidant capability. The impact of processing conditions including time, temperature, solvent-to-solid ratio and particle size on yield, and antioxidant activity of extracted tomato seed oil are reported. Optimal conditions and models which describe the extraction process are recommended. The information is vital for determining the extraction processing conditions for industrial production of high quality tomato seed oil.

Free-radical scavenging properties and reducing power of grape cane extracts from 11 selected grape cultivars widely grown in China.

Total phenolic contents (TPC), total flavonoid contents (TFC), related antioxidative and antiradical capabilities of grape cane extracts from 11 varieties (five V. vinifera cultivars and six Chinese wild grapes) widely grown in China were evaluated. Antioxidant properties were determined as DPPH and ABTS radical-scavenging abilities, superoxide anion and hydroxyl radical and hydrogen peroxide scavenging assays, as well as reducing power. Phenolic profiles of the extracts were characterized by using high-performance liquid chromatography (HPLC) techniques. All extracts exhibited strong antioxidant and effective free radical inhibition activities (EC(50) values), which generally correlated negatively with TPC (r = -0.804 to -0.918) and TFC (r = -0.749 to -0.888). In comparison with gallic acid, Trolox and tert-butylhydroquinone (positive controls), most grape cane extracts showed more efficient scavenging effects toward different reactive oxygen species. HPLC analysis revealed the presence of (+)-catechin, (-)-epicatechin, and trans-resveratrol as major phenolic components in the extracts. These results suggest that grape cane extracts may serve as a potential source of natural antioxidant for food and pharmaceutical application.