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Monoester‐diterpenoid alkaloids are the main bioactive components of Sini decoction, which is a well‐known traditional Chinese medicine formula for the treatment of myocardial infarction (MI) and heart failure in China. In this work, an ultra‐high‐performance liquid chromatography–mass spectrometry combined with microdialysis method was successfully established and applied for investigating for the first time comparative plasma pharmacokinetics of three monoester‐diterpenoid alkaloids (benzoylmesaconitine, benzoylaconitine and benzoylhypacoitine) in normal and MI rats after oral administration of Sini decoction. The statistical results of pharmacokinetic parameters demonstrated that benzoylmesaconitine, benzoylaconitine and benzoylhypacoitine showed lower peak concentration, longer half‐life, smaller area under the concentration–time curve, slower clearance, time to peak concentration and mean residence time in MI rats than in normal rats (p < 0.05), which indicated that monoester‐diterpenoid alkaloids exhibited lower systemic exposure and slower elimination in the MI rats. The results provided the experimental basis for understanding the metabolic fate and therapeutic effects of Sini decoction. [ABSTRACT FROM AUTHOR]

Sini Decoction (SND) has been proven to be an effective formula to alleviate cardiac injury of myocardial infarction (MI). However, the potential mechanism of SND remains unclear. In this study, the MI rat model was established by ligating the left anterior descending coronary artery. A total of 17 SND-distributed components in heart were identified by using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOFMS). The combination of four-dimensional (4D) proteomics and network pharmacology was employed to find the potential targets for therapeutic intervention, and molecular docking and cellular thermal shift assay (CETSA) were used to reveal the interactions between the potential targets and the potential active components distributed in heart of SND. 33 SND-effected proteins were identified by 4D proteomics, which was involved in carbon metabolism, fatty acid metabolism, valine, leucine and isoleucine degradation, tricarboxylic acid (TCA) cycle and PPAR signaling pathway. 17 potential SND-targeted direct proteins were screened by comparing SND-effected proteins generated from 4D proteomics with the MI-related proteins obtained from disease database. The potential relationships between 17 components and 17 potential SND-targeted direct proteins were established by molecular docking analysis, in which songorine, benzoylhypaconine, hypaconine, formononetin, and liquiritigenin could be bound to the surrounding amino acid residues in the binding pocket of Mtor, Parp1, Acadm, Crat, and Aldh2. Then, CETSA analysis further confirmed that songorine and benzoylhypaconine could increase the heat stability of Mtor and Parp1 in cardiac tissue lysate, respectively, which suggested that there existed direct interactions between songorine and Mtor, and benzoylhypaconine and Parp1. In summary, this work concluded that SND produced cardioprotective effects mainly through preserving energy metabolism, also demonstrated that the combination of 4D proteomics and network pharmacology was a promising tool for uncovering the molecular mechanisms of multi-components multi-targets effects of TCM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Small cell lung cancer (SCLC) is a subtype of lung cancer with a poor prognosis, with bone metastasis being one of the main causes of treatment failure. Therefore, investigating new biomarkers associated with bone metastasis may result in positive treatment outcomes. The present study detected the expression levels of annexin A1 (ANXA1) in the serum of 82 patients with SCLC using ELISA. ANXA1 expression in patients with SCLC with bone metastasis was significantly higher compared with that in patients without bone metastasis. Receiver operating characteristic analysis revealed that ANXA1 expression was significant in the diagnosis of bone metastasis in SCLC. ANXA1 was inhibited in SBC-5 cells and overexpressed in SBC-3 cells. Results revealed that ANXA1 was able to enhance SCLC cell proliferation, invasion, migration and bone adhesion in vitro . In vivo xenograft bone metastasis assays indicated that ANXA1 had the potential to promote the bone-metastasis ability of SCLC cells in NOD/SCID mice. Furthermore, ANXA1 increased parathyroid hormone-related protein secretion and enhanced Smad2 phosphorylation following TGF-β treatment in SCLC cells. Overall, ANXA1 may be involved in the pathogenesis of bone metastasis in SCLC and may be a potential biomarker for the diagnosis of SCLC., (Copyright: © Chen et al.)

High-performance liquid chromatography with diode array detection (HPLC-DAD), time-of-flight mass spectrometry (HPLC-TOFMS) and quadrupole ion trap mass spectrometry (HPLC-QITMS) were used for separation and identification of multi-components in Psoralea corylifolia. Benefiting from combining the accurate mass measurement of HPLC-TOFMS to generate elemental compositions, the complementary multilevel structural information provided by HPLC-QITMS and the characteristic UV spectra obtained from HPLC-DAD, 24 components in P. corylifolia were identified. The five groups of isomers were differentiated based on the fragmentation behaviors in QITMS and UV spectra. It can be concluded that an effective method based on the combination of HPLC-DAD, HPLC-TOFMS and HPLC-QITMS for identification of chemical components in P. corylifolia was established. The results provide essential data for further pharmacological and clinical studies of P. corylifolia and facilitate the rapid quality control of the crude drug., (© Crown copyright 2015.)