Jian-Guang Luo

Chimonanthus salicifolius leaves (CSL), a traditional She medicine, are used both as food and medicine. Conventionally, tender leaves are used as tea beverages, while mature leaves serve as medicinal materials. However, their difference in chemistry and activity remains unknown. In this study, HPLC fingerprints of 20 batches of both tender and mature CSL were established, revealing a shared metabolite backbone, yet hierarchical cluster analysis clearly split the two stages into discrete chemotypes. DPPH and ABTS assays demonstrated that mature leaves possessed significantly higher antioxidant capacity than tender leaves. Integration of Pearson correlation analysis and partial least squares regression analysis uncovered the spectrum–bioactivity relationship, guiding three flavonoid glycosides, isoquercitrin (IQ), kaempferol‐7‐O‐rutinoside, and nicotiflorin, as antioxidant quality markers (Q‐markers). Moreover, the quantitation of Q‐markers illustrated that IQ emerged as the pivotal differential compound: Its abundance in mature leaves was 1.7‐fold higher than in tender leaves, whereas the content of the three glycosides was nearly twice as high in tender leaves. The established strategy for identifying antioxidant Q‐markers, based on HPLC fingerprinting and spectrum–effect relationships, effectively reveals quality differences between mature and tender leaves and provides a robust scientific basis for the tailored exploitation of CSL in both medicinal and nutraceutical applications.

Background: The immunosuppressive microenvironment and limited immune cell infiltration into the tumor bed contribute to the proliferation, metastasis, and invasion of breast cancer (BC) cells. Reprogramming the tumor immune microenvironment has emerged as a promising therapeutic target for BC, but remains challenging in clinical practice. Artemisia annua, a medicinal plant, has shown immune-enhancing and anti-tumor activities, although its potential therapeutic applications in BC remain underexplored. Methods: Extracellular vesicles (EVs) were isolated from fresh Artemisia annua using gradient centrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), Zetasizer Nano ZS90, ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS), and high-performance liquid chromatography (HPLC). Single-cell RNA sequencing (scRNA-seq) analysis was performed to investigate the mechanism of AEVs on tumor growth in vivo and mRNA sequencing (mRNA-seq) was employed to further explore the mechanism of AEVs-induced polarization shift from M2-like to M1-like macrophages. In vitro and in vivo assays were conducted to assess the polarization of macrophages and recruitment of T lymphocytes into the tumor bed. Results: AEVs were successfully isolated and characterized. In vivo, AEVs inhibited tumor growth by shifting macrophage polarization from the M2-like to the M1-like phenotype, and synergistically enhancing the recruitment of CD8⁺ and CD4⁺ T cells into the tumor microenvironment. AEVs activated the NF-κB signaling pathway while inhibiting the PPARγ pathway, thereby promoting the M1-like polarization of macrophages. Polarized M1-like macrophages secreted chemokines (CCL5 and CCL3), which facilitated T lymphocyte infiltration into the tumor bed. Notably, AEVs reshaped the BC immune microenvironment without inducing systemic toxicity. Conclusions: AEVs from Artemisia annua efficiently reprogrammed the immune microenvironment of breast cancer by inducing macrophage polarization and enhancing T lymphocyte infiltration. This study lays the foundation for using AEVs as a potential immunotherapy for BC and highlights the medicinal value of Artemisia annua in cancer treatment.

Ferroptosis suppressor protein 1 (FSP1), a key regulator of ferroptosis that functions independently of glutathione, has become a vital therapeutic target in ferroptosis research. However, the discovery of FSP1 inhibitors remains a significant challenge, particularly given the absence of natural FSP1 inhibitors. In this study, surface plasmon resonance (SPR)-guided fractionation of the fruit extract of Tetradium ruticarpum (FTR) led to the isolation of 12 quinolone alkaloids, including ten known compounds (1-10) and two new ones (11 and 12). Compounds 1-9 all inhibited FSP1, among which 2-4 were the most potent (IC₅₀ = 0.47 ± 0.12, 0.29 ± 0.17, and 0.52 ± 0.98 μM, respectively), exceeding the positive control icFSP by more than 50-fold. This study represents the first identification of natural FSP1 inhibitors. Our findings highlight the potential of quinolone alkaloids as novel agents targeting FSP1 and underscore the importance of exploring natural products for the development of new ferroptosis modulators.