Yongrui Bao

Hepatocellular carcinoma (HCC) lacks effective therapies. Compound Muji Granules (MJ), a traditional Chinese medicine, shows potential anti‐HCC activity, but its material basis and synergistic mechanism with exosomal delivery remain unclear. Using UPLC‐Q‐TOF‐MS/MS, 98 compounds were identified in MJ, including 25 blood‐absorbed and 23 tissue‐distributed components, with gallic acid (GA) as the core active constituent. hUC‐MSC‐derived exosomes (hUC‐MSCs‐Exos) were prepared and combined with MJ or GA. In HepG2 cells and rat HCC organoids, exosome‐combined treatment significantly reduced IC50, increased apoptosis and necrosis, and inhibited ATP production. Transcriptomic analysis and qPCR revealed regulation of the IL‐17/MAPK/p53 axis, with downregulation of MEK1/2, CREB1, and IL17A, and activation of TP53. These findings indicate that MJ exerts anti‐HCC efficacy through multi‐component synergy, with GA as the main material basis, and hUC‐MSCs‐Exos enhance these effects by modulating IL‐17/MAPK/p53 signaling, inhibiting tumor proliferation and energy metabolism, and promoting apoptosis.

Heart failure (HF) is an end stage of cardiovascular diseases. Tongmai Qiangshen Medicinal Liquor (TMQSJ) is an over‐the‐counter traditional Chinese medicinal liquor, but its efficacy‐related material basis and mechanisms in HF remain unclear. In this study, UPLC‐Q‐TOF‐MS/MS was used to characterize TMQSJ constituents and prototype compounds in rat plasma. HPLC fingerprinting, spectrum‐effect relationship analysis, single‐compound activity evaluation, and integrative bioinformatics were combined to screen efficacy‐related candidate quality markers and HF‐associated candidate genes. A total of 223 compounds were characterized, including 33 prototype plasma components. Chemometric analysis identified caffeic acid, Epimedin A, Epimedin B, Epimedin C, and icariin as characteristic constituents. Spectrum‐effect analysis based on 10 batches of TMQSJ and validation in DOX‐injured AC16 cells highlighted Epimedin A, Epimedin B, and Epimedin C. Among them, Epimedin A and Epimedin C showed prototype plasma exposure and were prioritized as efficacy‐related candidate quality markers. Integration of predicted targets of prototype plasma components with HF transcriptomic data and machine‐learning analysis identified BCL2L1, STAT3, HIF1A, MAPK8, and ESR1 as five candidate core genes. Immune cell estimation and molecular docking provided computational clues. Overall, this study establishes an integrated framework linking chemical quality, pharmacological association, in vivo exposure, and mechanistic prediction for TMQSJ quality evaluation.

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with pro-tumor inflammation playing a critical role in its initiation and progression. Chronic inflammation acts as a major driving force and a distinct mechanism underlying tumorigenesis. Although previous studies have demonstrated the importance of the VEGF/p38MAPK and p38MAPK/HSP27 signaling pathways in CRC-associated inflammation, a comprehensive understanding of the entire pro-tumor inflammatory mechanism remains incomplete.Methods: This study combined network pharmacology analysis and in vivo pharmacodynamic experiments using a p38MAPK pathway inhibitor to systematically identify and validate the VEGF/p38MAPK/HSP27 pro-tumor inflammatory signaling pathway. Western blotting was used to confirm key target proteins. Molecular docking and microscale thermophoresis (MST) experiments were conducted to screen active compounds from Patrinia villosa (PV). Molecular dynamics (MD) simulations evaluated the stability and drug-likeness of compound-target interactions.Results: Key proteins VEGF, p38MAPK, and HSP27 were identified as critical components of the signaling pathway. Three active compounds rutin, nicotiflorin, and 4,5-dicaffeoylquinic acid (4,5-Dicqa) were found to bind these targets with high affinity. MD simulations supported the stability of these interactions and their potential as drug candidates.Conclusion: This study provides theoretical and experimental evidence for pharmacological targets involved in pro-tumor inflammation in CRC. The findings offer valuable insights for developing novel anti-inflammatory therapeutics targeting the VEGF/p38MAPK/HSP27 signaling pathway.

Introduction: The fruit of Sinopodophyllum hexandrum (FSH) is derived from Sinopodophyllum hexandrum (Royle) Ying, a plant belonging to the family Berberidaceae of the order Ranunculaceae. It is mainly distributed in the Himalayan alpine region, and born in the understory of forests, and wetlands at the edge of forests, thickets or grasses. FSH grows at an altitude of 2,200–4,300 meters above sea level. Its main pharmacological activities include anti-tumor, anti-inflammation, analgesia, heat clearing and detoxification. In the current experiment, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was adopted for investigating the chemical components contained in FSH, their transformation patterns in vivo and the potential anti-tumor components, so as to provide an experimental basis for the utilization and development of the resources of FSH.Methods: The chemical components of FSH and their transformation patterns in vivo were investigated by UPLC-Q-TOF-MS, and the potential anti-tumor active components were predicted from the in vivo transformed components of FSH by using a network pharmacology approach.Results: Totally 85 chemical components were identified in FSH, among which, 61 were flavonoids and 24 were lignans. The above components were transformed in vivo, including 36 prototype components and 13 transformed products. As revealed by the results of network pharmacology on the prediction of anti-tumor components of FSH, 17 compounds such as Kaempferol, Uralenol, and 8-Prenylquercetin in FSH were used as the potential anti-tumor components.Conclusion: In this study, the chemical composition, in vivo transformed components of FSH and their metabolites are investigated, and the in vivo transformed components are predicted to have potential anti-tumor pharmacological activities. This study provides the experimental bases for the utilization and development of the resources of FSH.

Inflammation is a well-known risk factor for tumor development. Intervening in chronic inflammation may be an effective approach to inhibit the progression of ulcerative colitis (UC) to colitis-associated colon cancer (CAC). Sophora japonica is a medicinal and food plant commonly used to treat hemorrhoids, bleeding, and inflammation, symptoms that coincide with those of patients with CAC. However, studies on using Sophora japonica to treat CAC are scarce. Therefore, this study aimed to investigate the anti-inflammatory and antitumor effects of Sophora japonica extract (SJE) using dextran sodium sulfate (DSS)-induced UC and azoxymethane (AOM)/DSS-induced CAC models. Furthermore, we employed ultraperformance liquid chromatographyquadrupole time-of-flighttandem mass spectrometry (UPLCQTOFMS/MS) technology to explore the metabolomics mechanism through which SJE inhibited the progression of UC to CAC. The results demonstrated that SJE significantly inhibited UC and CAC and alleviated symptoms such as bloody stools, colon shortening, inflammation, and intestinal tissue damage in model mice. Further, 57 differential metabolites were identified by UPLCQTOFMS/MS, which were composed mainly of lipids (fatty acids, glycerophospholipids, sterol lipids, pregnenolone lipids, etc.) and peptides (amino acids). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that SJE might inhibit the progression of UC to CAC by regulating lipid metabolic pathways such as arachidonic acid metabolism, primary bile acid biosynthesis, and linoleic acid metabolism. This study, for the first time, substantiated the inhibitory effect of SJE on CAC. Employing metabolomics techniques, the research delved into the potential pathways through which SJE may exert its inhibitory effects on CAC by suppressing the progression of UC. These findings contribute scientific evidence to the application of Sophora japonica in functional foods and the development of natural drugs for the prevention and treatment of UC and CAC.

Bufei Jianpi granule (BJG) is clinically effective for treating chronic obstructive pulmonary disease (COPD). At present, there is no report regarding the drug metabolism of BJG in vivo. This work developed an ultra‐high‐performance liquid chromatography coupled with triple quadrupole mass spectrometry method with high accuracy and sensitivity to determine drug metabolism of this compound in vivo. After continuous administration of BJG, the concentrations of 10 components in rat plasma, namely betaine, peimine, peiminine, astragaloside A, sinensetin, nobiletin, naringin, calycosin, formononetin, and magnolol, were determined at different time points. Meanwhile, the pharmacokinetic parameters and metabolic rules of these 10 components were evaluated: C_max, 8.624–574.645 ng/mL; T_max, 0.250–8.667 h; AUC_0–t, 17.640–8947.393 ng h/mL; T_1/2, 3.405–66.014 h; mean residence time (MRT), 6.893–11.223 h. All these components possessed anti‐inflammatory, antioxidant, and other biological activities to varying degrees, contributing to improving lung function, mitigating pneumonia and pulmonary fibrosis, and preventing and treating chronic obstructive pulmonary disease. Exploring the pharmacokinetic parameters and the laws of chemical components in BJG forms the scientific basis for applying the compound clinically and identifying quality markers for the control of the compound.

Fructus Aurantii (FA) is the dry and immature fruit of Citrus aurantium L. and its rutaceous cultivars. FA has been widely used to treat digestive system diseases since ancient China, and it promotes gastrointestinal (GI) motility in functional dyspepsia (FD), but its potential therapeutic mechanisms remain unclear. We examined the effects of FA ethanol extracts in an iodoacetamide (IA)-induced FD rat model. Firstly, key FA therapy targets for FD were gathered using systematic pharmacology. Combined with systemic pharmacological analyses, plasma metabolomics based on UPLC-QTOF-MS were conducted. Then, MetaboAnalyst was used to jointly analyze systemic pharmacology targets and metabolomic metabolites to select key metabolic pathways. Finally, the key path is verified by experiments. FA exerted distinct therapeutic effects in anti-inflammation and promoting gastrointestinal motility in our IA-induced FD rat model. When compared with the model group, FA down-regulated the inflammatory factors interleukin 1β and tumor necrosis factor-α. At the same time, FA up-regulated tight junction proteins in the intestinal epithelial barrier. Through the integrated analysis of metabolomics and systemic pharmacology, we conducted experimental verification on Fc epsilon RI signaling pathway. When compared with the model group, FA down-regulatedphospho-mitogen activated protein kinase, phospho-extracellular signal regulated kinase1/2, myosin light chain kinase, and phospho-myosin regulatory light chain protein levels. Thus, FA ameliorated FD by regulating the Fc epsilon RI signaling pathway. Our integrated strategy identified underlying FA mechanisms toward FD treatment and provided a foundation for FA development as a clinical agent for FD.