Scutellaria baicalensis Georgi is a traditional Chinese herbal medicine mainly containing flavonoids that contribute to its bioactivities. In this study, the distributions and dynamic changes of flavonoid levels in various organs of S. baicalensis at different development stages were investigated by UHPLC-QTOF-MS/MS and HPLC-DAD methods. The results indicated that the metabolic profiles of S. baicalensis changed with growth and development. During the initial germination stage, the seeds mainly contained flavonols. With growth, the main kinds of flavonoids in S. baicalensis changed from flavonols to flavanones and flavones. The results also revealed that the accumulation of flavonoids in S. baicalensis is organ-specific. The flavones without 4′-OH groups mainly accumulate in the root and the flavanones mainly accumulate in aerial organs. Dynamic accumulation analysis showed that the main flavonoids in the root of S. baicalensis accumulated rapidly before the full-bloom stage, then changed to a small extent. The results suggested the proper harvest time for the aerial parts was at the initial stage of reproductive growth and the flower buds should be collected before flowering. This study deepening the knowledge of S. baicalensis should provide valuable information for guiding the scientific cultivation of this plant and the development and utilization of S. baicalensis.

Introduction: Scutellaria barbata D. Don is a widely cultivated Chinese herbal medicine known for its medicinal properties. However, differences in the spatial distribution of metabolites, accumulation patterns of flavonoids, and pharmacological activities between the aerial parts and roots of S. barbata still remain unclear, posing challenges for its standardized cultivation and quality control. This study aimed to elucidate the quality differences between these plant parts and clarify their seasonal variations.Methods: The chemical profiles were qualitatively analyzed by UPLC-QTOF-MS/MS. The accumulation patterns of total flavonoids, scutellarin and baicalin in different parts of S. barbata were quantitatively analyzed by UV and HPLC respectively. The differences of pharmacological efficacy were evaluated by antioxidant assays and CCK-8 assay.Results: In this research, there were 46 compounds identified in S. barbata that included 44 flavonoids. The aerial parts primarily accumulate flavonoids with 4′-hydroxyl group, while the root mainly accumulate flavonoids without this group. Additionally, the accumulation and variation of flavonoid components were seasonally dependent, with the aerial parts reaching peak content in spring during vigorous vegetative growth and the roots accumulating most flavonoids in autumn. The extracts from both parts exhibited antioxidant activity and inhibitory effects on cancer cell proliferation, with notable differences between them.Discussion: This study provides valuable insights into the quality differences and seasonal dynamics of the different parts of S. barbata, offering a reference for standardized harvesting and quality control.

Taxanes play a crucial role in cancer treatment, particularly for non-small cell lung cancer and breast cancer. However, real-world studies examining drug-induced liver injury (DILI) associated with these drugs remain limited. Our study investigates the association between taxanes and DILI through analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database, alongside an exploration of potential hepatotoxicity mechanisms via network pharmacology. We collected DILI reports related to taxanes from the FAERS database between January 2004 and March 2024, employing disproportionality analyses with the reporting odds ratio (ROR) and 95% confidence intervals. Our findings revealed a significant association between paclitaxel (ROR = 2.35) and nab-paclitaxel (ROR = 3.14) with DILI, while docetaxel demonstrated no significant correlation (ROR = 0.68), although it was linked to higher mortality rates and earlier onset. Network pharmacology analysis uncovered that the mechanisms of liver injury induced by these two drugs may not be entirely congruent. Unique targets for docetaxel included BCL2, CNR2, and MAPK1, while the ‘Regulation of lipolysis in adipocytes’ pathway was specifically associated with docetaxel-induced DILI. Our findings indicate that taxanes exhibit differential hepatotoxic risks and hepatotoxicity mechanisms, emphasizing the need for enhanced drug safety monitoring strategies for cancer patients.

Breast cancer(BC) is a major cause of cancer-related mortality in women worldwide, with current therapies often limited by toxicity and drug resistance. Pachymic acid (PA), a natural compound, demonstrates antitumor potential with relatively low systemic toxicity. However, its mechanism in triple-negative breast cancer (TNBC) remains unclear. This study aims to deeply explore the anti-tumor effect of PA on TNBC. The intersection targets of PA and BC were screened through multiple databases, and the key genes were determined through TCGA survival analysis. The potential mechanism was simulated and studied through methods such as network pharmacology, molecular docking and molecular dynamics. Cell proliferation ability was evaluated by CCK-8 assay and colony formation assay. Cell migration and invasion abilities were detected by scratch assay and Transwell assay respectively. Gene expression levels were analyzed by qPCR and Western Blot, and the degree of lipid peroxidation was evaluated by malondialdehyde (MDA) assay. Through multi-database screening and TCGA survival analysis, PTGS2, NOS2 and ABCB1 were identified as key targets. The TNBC cell line MDA-MB-231 was used as the experimental model. PA significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells. Mechanistic studies demonstrated that PA concurrently upregulates PTGS2 and NOS2 expression while downregulating ABCB1. Notably, the upregulation of PTGS2 was significantly correlated with increased lipid peroxidation, suggesting its crucial role in ferroptosis. The coordinated upregulation of NOS2 and downregulation of ABCB1 further enhanced cellular sensitivity to ferroptosis. This study is the first to reveal that PA induces ferroptosis in TNBC cells by regulating the PTGS2/NOS2/ABCB1 signaling axis, providing new potential targets for TNBC treatment. However, this study has limitations, as validation has been conducted only at the cellular level and not yet confirmed in animal models or clinical samples. Future research should validate this mechanism in more TNBC models and across different molecular subtypes of breast cancer to promote the clinical application of PA.

PRCC-TFE3 rearranged renal cell carcinoma (PRCC-TFE3 rRCC) is a highly malignant renal malignancy with limited therapeutic options, underscoring the urgent need for novel treatment strategies. This study aimed to identify potential therapeutic compounds for PRCC-TFE3 rRCC through high-throughput screening and to elucidate the underlying oncogenic mechanisms that could be targeted. A high-throughput screening of a 1,823-compound library was conducted using UOK120. Promising candidates were further evaluated in a C57BL/6J mouse model. Mechanistic insights were gained through integrated bioinformatic and functional analyses. Our investigation revealed a novel oncogenic pathway driven by the PRCC-TFE3 fusion, which directly enhances the transcription of key glycolytic enzymes to promote lactate accumulation and upregulates the lactyltransferase KAT6A, leading to increased histone H3 lysine 9 lactylation (H3K9la). This epigenetic modification enhanced VEGFB transcription, thereby activating the VEGF-VEGFR2 signaling axis. From the initial screening, sanguinarine chloride (SGC) was identified as a potent inhibitor of this pathway. SGC exerts a dual mechanism of action: it directly antagonizes VEGFR2 on the cell membrane to block VEGFB autocrine signaling, and it suppresses VEGFB transcription via ROS/p-STAT3 axis. Furthermore, SGC treatment effectively inhibited the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) by reducing tumor-derived chemokine secretion, thereby reversing their pro-tumorigenic effects within the tumor microenvironment. This study uncovers a novel, lactylation-driven oncogenic pathway in PRCC-TFE3 rRCC through epigenetic activation of VEGFB-VEGFR2 signaling, and characterizes SGC as a promising therapeutic candidate that dually targets this pathway and modulates the tumor immune microenvironment.