BackgroundEssential hypertension (EH) is a complex disease as a consequence of interaction between environmental factors and genetic background, but the pathogenesis of EH remains elusive. The emerging tools of network medicine offer a platform to explore a complex disease at system level. In this study, we aimed to identify the key proteins and the biological regulatory pathways involving in EH and further to explore the molecular connectivities between these pathways by the topological analysis of the Protein-protein interaction (PPI) network.ResultThe extended network including one giant network consisted of 535 nodes connected via 2572 edges and two separated small networks. 27 proteins with high BC and 28 proteins with large degree have been identified. NOS3 with highest BC and Closeness centrality located in the centre of the network. The backbone network derived from high BC proteins presents a clear and visual overview which shows all important regulatory pathways for blood pressure (BP) and the crosstalk between them. Finally, the robustness of NOS3 as central protein and accuracy of backbone were validated by 287 test networks.ConclusionOur finding suggests that blood pressure variation is orchestrated by an integrated PPI network centered on NOS3.

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Pingxiao capsule (PXC) is a herbal medicine used for adjuvant therapy in breast cancer. However, the constituents and absorbed components of the formula and their related metabolites have not been elucidated to date. PXC is a typical traditional Chinese medicine formula consisting ofStrychnos nux‐vomicaL.,Curcuma wenyujinY. H.,Agrimonia pilosaLedeb.,Toxicodendron vernicifluum,Trogopterusdung, alumen, potassium nitrate (saltpeter) andCitrus aurantiumL. In this study, a ultra‐high performance liquid chromatography system equipped with high resolution Q‐Orbitrap mass spectrometry (MS) and comparative Global Natural Product Social molecular networking together with the Compound Discoverer software were used to identify metabolites of PXCin vitroandin vivo.Based on untargeted data‐dependent MS2and data‐mining techniques, 89 peaks of alkaloids, flavonoids, organic acid and phenolic compounds were identified in a PXC 70% methanol extract. Furthermore, 15 absorbed prototype compounds and their metabolites were rapidly confirmed in rat blood. Glucuronidation, oxidation, methylation and hydroxylation were the main metabolic pathways. We fully clarified the chemical constituents of PXC and provided a scientific and efficient strategy for rapid discovery and identification of prototypes and their metabolites in rat plasma using high‐resolution MS aided by Global Natural Product Social and Compound Discoverer software.

Introduction The roots of Polygonum multiflorum (PM) serve as a classical traditional Chinese medicine (TCM), which has multiple biological activities. However, many cases of hepatotoxicity in PM have been reported in recent years. Processing PM with black beans decoction is one of the typical processing methods to reduce the hepatotoxicity of PM since ancient times. Objectives To find potential effective constituents, as well as the optimal variety and origin of black beans for the processing of PM. Methods Based on ultrahigh‐performance liquid chromatography Q‐Orbitrap mass spectrometry (UHPLC‐Q‐Orbitrap‐MS) analysis, we measured the contents of the two potential toxic compounds (emodin‐8‐O‐glucoside and torachrysone‐O‐hexose) in raw PM (R‐PM), PM processed with big black beans (B‐PM) and PM processed with small black beans (S‐PM). The flow cytometry method analysed the effects of different processed products of PM on apoptosis of L02 cells in different drug concentration. Proton nuclear magnetic resonance (1H‐NMR) and UHPLC‐Q‐Orbitrap‐MS together with multivariate statistical analysis were used to systematically analyse the different components between small black beans (Small‐BB) and big black beans (Big‐BB) from 30 different habitats. Results The toxicity was ranked from small to large: S‐PM < B‐PM < R‐PM. Processing PM with black beans could significantly decrease the apoptosis rate of L02 cells, especially when the drug concentration is 80 μg/mL. Besides, we find five differential compounds (α‐arabinose, α‐galactose, proline, isomer of daidzein and isomer of genistein) may be potential active ingredients. In terms of the black beans collected from 30 producing areas, we find that Small‐BB from Weifang in Shandong province was optimum to processing PM, followed by Shangqiu in Henan province, Jilin and Liaoning province. Conclusion The ingredients that affect the processing of PM may be attributed to α‐arabinose, α‐galactose, proline, isomer of daidzein and isomer of genistein in black beans. When the drug concentration is higher, the effect of reducing the hepatotoxicity of PM is better. Besides, Small‐BB was more effective than Big‐BB for reducing the toxicity of PM, especially Small‐BB from Weifang in Shandong, Shangqiu in Henan province and northeast China.

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