Eltrombopag is a small molecule TPO-R agonist that has been shown in our previous studies to inhibit tumor growth by targeting Human antigen R (HuR) protein. HuR protein not only regulates the mRNA stability of tumor growth-related genes, but it also regulates the mRNA stability of a variety of cancer metastasis-related genes, such as Snail, Cox-2, and Vegf-c. However, the role and mechanisms of eltrombopag in breast cancer metastasis have not been fully investigated. The purpose of this study was to investigate whether eltrombopag can inhibit breast cancer metastasis by targeting HuR. Our study first found that eltrombopag can destroy HuR-AU-rich element (ARE) complexes at the molecular level. Secondly, eltrombopag was found to suppress 4T1 cell migration and invasion and inhibit macrophage-mediated lymphangiogenesis at the cellular level. In addition, eltrombopag exerted inhibitory effects on lung and lymph node metastasis in animal tumor metastasis models. Finally, it was verified that eltrombopag inhibited the expressions of Snail, Cox-2, and Vegf-c in 4T1 cells and Vegf-c in RAW264.7 cells by targeting HuR. In conclusion, eltrombopag displayed antimetastatic activity in breast cancer in an HuR dependent manner, which may provide a novel application for eltrombopag, hinting at the multiple effects of HuR inhibitors in cancer therapy.

The neuroinflammation triggered by cellular demise plays a pivotal role in ameliorating the injury associated with ischemic stroke, which represents a significant global burden of mortality and disability. The compound SHPL-49, a derivative of rhodioloside, was discovered by our research team and has previously demonstrated neuroprotective effects in rats with ischemic stroke. This study aimed to elucidate the underlying mechanisms of SHPL-49’s protective effects. Preliminary investigations revealed that SHPL-49 effectively alleviates PMCAO-induced neuroinflammation. Further studies indicated that SHPL-49 downregulates the expression of the lysosomal protein LAMP-2 and reduces lysosomal activity, impeding the fusion of lysosomes and autophagosomes, thus inhibiting excessive autophagy and increasing the expression levels of the autophagy proteins LC3-II and P62. Furthermore, SHPL-49 effectively reverses the NF-κB nuclear translocation induced by the autophagy inducer rapamycin, significantly lowering the expression levels of the inflammatory factors IL-6, IL-1β, and iNOS. In a co-culture system of BV2 and PC12 cells, SHPL-49 enhanced PC12 cell viability by inhibiting excessive autophagy in BV2 cells and reducing the ratio of apoptotic proteins Bax and BCL-2. The overall findings suggest that SHPL-49 exerts its neuroprotective effects through the inhibition of excessive autophagy and the suppression of the NF-κB signaling pathway in microglia, thereby attenuating neuroinflammation.

Dragon’s Blood, from the Dracaena cochinchinensis plant, is known for enhancing blood circulation. Its main components are Dragon’s Blood phenolic extracts (DBE). To pinpoint the active DBE constituents that are effective against thrombosis and understand their mechanism of action, the PT-stroke model was employed to assess DBE’s antithrombotic effects on cerebral blood flow and platelet aggregation. This investigation demonstrates that DBE enhances cerebral blood flow and inhibits ADP-induced platelet aggregation in photothrombotic (PT) stroke models. An FeCl₃-induced carotid artery thrombosis model was developed to test the antithrombotic activity of four DBE fractions. Through screening with this model, the ethyl acetate (EA) and methanol fractions were identified as the principal active components that effectively reduced thrombus weight and improved hemodynamics. Furthermore, the EA fraction was found to preserve the integrity of the blood–brain barrier. Phytochemical isolation allowed for the identification of compounds in the EA fractions, and UHPLC-MS was performed to characterize DBE and its active components in the bloodstream. In vitro ADP-induced platelet aggregation assays highlighted the active compounds. Through phytochemical analysis, Loureirin D (compound 17) was identified as a predominant constituent present in plasma. In vitro assays revealed that compounds 1 and 17 possess strong antiplatelet activity, with Loureirin D being confirmed as a selective P2Y12 receptor antagonist via molecular docking and cellular thermal shift assays. These findings substantiate Loureirin D as a pivotal antithrombotic component in DBE and its potential as a P2Y12-targeting therapeutic agent for thrombosis treatment.