Integrating Strategies of Herbal Metabolomics, Network Pharmacology, and Experiment Validation to Investigate Frankincense Processing Effects

In-depth research on processing can promote the globalization of processed herbs. The purpose of this study is to propose an improved strategy for processing effect investigation. Frankincense and processed frankincense were used as research subjects. First, high-speed countercurrent chromatography (HSCCC) and preparation high-performance liquid chromatography (PHPLC) techniques were used for major compounds isolation and minor compounds concentration. Processed frankincense was subjected to two stepwise solvent systems, namely, n-hexane:ethanol:water (6:5:1) and n-hexane:methyl-acetate:acetonitrile:water (4:4:3:4), to yield 12 fractions, and 18 compounds were further separated. Second, a comprehensive metabolomic analysis conducted by ultrahigh-performance liquid-chromatography/electrospray-ionization mass spectrometry (UHPLC-Qtof-MS) coupled with multivariate statistics was performed to fully characterize the chemical components and discover the potential biomarkers between frankincense and processed frankincense. In total, 81 metabolites, including the 18 separated compounds, were selected as potential biomarkers between frankincense and processed frankincense among 153 detected compounds for their VIP values of greater than one. The tirucallane-type compounds and components with 9,11-dehydro structures clearly occurred at high levels in the processed frankincense, while lupine-type compounds and those with 11-keto structures were significantly higher in frankincense. Then, a network pharmacology model was constructed to decipher the potential mechanisms of processing. Intestinal absorption properties prediction indicated the possibility of processing-related absorption enhancement. A systematic analysis of the constructed networks showed that the C-T network was constructed with 18 potential biomarkers and 69 targets. TNF and IL-1β were among the top-ranked and were linked by 8 and 7 pathways, which were mainly involved in inflammation. The arachidonic acid metabolism pathway exhibited the highest number of target connections. Finally, the prediction was validated experimentally by an intestinal permeability and efficacy assay. The experiments provided convincing evidence that processed frankincense harbored stronger inhibition effects toward TNF-α-, IL-1β- and arachidonic acid-induced platelet aggregation. The processing procedure leads to changes of the chemical metabolites, which triggers the enhancement of absorption and cure efficiency. The global change of the metabolites, absorption and pharmacological effects of processing were depicted in a systematic manner

Systems-Mapping of Herbal Effects on Complex Diseases Using the Network-Perturbation Signatures

The herbs have proven to hold great potential to improve people's health and wellness during clinical practice over the past millennia. However, herbal medicine for the personalized treatment of disease is still under investigation owing to the complex multi-component interactions in herbs. To reveal the valuable insights for herbal synergistic therapy, we have chosen Traditional Chinese Medicine (TCM) as a case to illustrate the art and science behind the complicated multi-molecular, multi-genes interaction systems, and how the good practices of herbal combination therapy are applicable to personalized treatment. Here, we design system-wide interaction map strategy to provide a generic solution to establish the links between diseases and herbs based on comprehensive testing of molecular signatures in herb-disease pairs. Firstly, we integrated gene expression profiles from 189 diseases to characterize the disease-pathological feature. Then, we generated the perturbation signatures from the huge chemical informatics data and pharmacological data for each herb, which were represented the targets affected by the ingredients in the herb. So that we could assess the effects of herbs on the individual. Finally, we integrated the data of 189 diseases and 502 herbs, yielding the optimal herbal combinations for the diseases based on the strategy, and verifying the reliability of the strategy through the permutation testing and literature verification. Furthermore, we propose a novel formula as a candidate therapeutic drugs of rheumatoid arthritis and demonstrate its therapeutic mechanism through the systematic analysis of the influencing targets and biological processes. Overall, this computational method provides a systematic approach, which blended herbal medicine and omics data sets, allowing for the development of novel drug combinations for complex human diseases

MOESM1 of Application of a strategy based on metabolomics guided promoting blood circulation bioactivity compounds screening of vinegar

Additional file 1: Table S1. The content of TMPZ in RV and WV. Table S2. The peak area and the relative peak area value of four potential biomarkers in different aging period. Table S3. The levels and factors investigated in BBD. Figure S1. HPLC chromatogram of TMPZ. Figure S2. The results of bioactivity screening. Figure S3. Diagnostic efficacy evaluation using ROC curves of the four potential biomarker metabolites in two different vinegar. Figure S4. Trends of time-series analysis graphs of four potential biomarkers. (A) TMPZ (MAPE: 2.05853, MAD: 1.67627, fitted curve: Yt = 60.81+5.089xt); (B) Dihydroergotamine (MAPE: 1.63096, MAD: 0.15345, fitted curve: Yt = 6.726+0.7121xt); (C) Harmine (MAPE: 1.72704, MAD: 0.01711, fitted curve: Yt = 0.7764+0.05780xt); (D) 1,2,3,4-tetrahydroharmine (MAPE: 3.76071, MAD: 0.04998, fitted curve: Yt = 0.9695+0.0910xt). Figure S5. Response surfaces estimated from the full factorial design for the content of total alkaloids

MOESM2 of Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health

Additional file 2: Table S2. Alkaloids, coumarins, limonoids, carotenoids and phenolic acids isolated from Citrus species. The table summarized alkaloids, coumarins, limonoids, carotenoids and phenolic acids from Citrus species including C. aurantifolia, C. aurantium, C. bergamia, C. canaliculata, C. clementina, C. grandis, C. hassaku, C. junos, C. kinokuni, C. leiocarpa, C. limon, C. limonimedica, C. maxima, C. microcarpa, C. myrtifolia, C. paradisi,, C. reticulate,C. sinensis, C. tachibana and C. unshiu

MOESM1 of Citrus fruits as a treasure trove of active natural metabolites that potentially provide benefits for human health

Additional file 1: Table S1. Flavonoids isolated from Citrus species. The table summarized flavones (including polymethoxylated flavones), flavonols, flavanones and flavanonols from Citrus species including C. aurantifolia, C. aurantium, C. canaliculata, C. clementina, C. erythrosa, C. grandis, C. hassaku, C. hystrix, C. junos, C. kinokuni, C. leiocarpa, C. limon, C. limonimedica, C. medica, C. microcarpa, C. paradisi, C. reticulate, C. sinensis, C. suhuiensis, C. tachibana, C. tamurana and C. unshiu