Gandou decoction (GDD), a well-known traditional Chinese medicine (TCM) formula, has been widely used for decades to treat Wilson's disease (WD) in China due to its remarkable clinical effects. However, the chemical constituents of GDD still remain unclear because of their complexity. In this work, a reliable and sensitive strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MSE) and UNIFI informatics platform was applied to investigate the chemical components in GDD. In total, 96 compounds including anthraquinones, alkaloids, protostane triterpenoids, flavonoids, triterpenoid saponins, tannins, curcuminoids, etc, were identified or tentatively characterized from GDD by comparing their retention time, accurate mass within 5 ppm error and MSE fragmentation patterns. Among them, eleven compounds were confirmed unambiguously with reference standards. Representative compounds in different chemical structure types were analyzed in fragmentation patterns and characteristic ions. Moreover, to better understand the chemical contribution of individual herbs to the whole decoction, the corresponding each herb in GDD was also detected. This study developed a rapid method for characterizing the chemical constituents in GDD, which could not only be used for chemical standardization and quality control, but also be helpful for further research of GDD in vivo.

Atherosclerosis (AS) is associated with a high incidence of cardiovascular events, yet the mechanisms underlying this association remain unclear. Our previous study found that Atherosclerotic endothelial injury is closely associated with ferroptosis in ApoE^-/- mice. Ferroptosis is a novel mode of cell death induced by decreased antioxidant capacity of the organism and accumulation of reactive oxygen species. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is an important regulator of sudden ferroptosis in cells. However, the role of NCOA4 in AS and the exact mechanism by which it regulates the ferritinophagy response remain unclear. Herein, we report that NCOA4 expression is elevated in ApoE^-/- mice and endothelial cells and is significantly correlated with AS. NCOA4 expression promoted ferroptosis, and was positively correlated with ferritinophagy response. Mechanistically, our findings indicate that LOX-1 is a key upstream target that influences the function of NCOA4. The specific pathway is related to the activation of cGAS-STING signaling to upregulate NCOA4 expression. Moreover, our findings demonstrate the "Gualou-Xiebai" herb pair can regulate LOX-1 to inhibit ferroptosis. Collectively, our results provide evidence of a connection between NCOA4-mediated promotion of AS and suggest that targeting upstream molecules regulating NCOA4 could be a potential therapy for AS.

Background: Lymphatic formations that effectively eradicate the virus in the lymphatic system will be therapeutically advantagous in hepatitis B virus (HBV) infection. Lipid-based formulation is often used to deliver drug via the lymphatic system. Baicalin nanoemulsion may be a promising drug delivery system for improved treatment of HBV infection. Objective:This study aimed to prepare, characterize and evaluate a lipid-based nanoemulsion containing baicalin for lymphatic system absorption. Method: The presence of a nanoemulsion region was studied by pseudo-ternary phase diagrams. The physicochemical properties of a baicalin-loaded nanoemulsion were investigated. The oral bioavailability of the baicalin-loaded nanoemulsion was compared to that of a baicalin suspension. A chylomicron flow blocking model was used to examine the extent of lymphatic uptake. The lymph node distribution of baicalin was measured to investigate the lymphatic transport ability of the nanoemulsion compared to the suspension. Results: Compared to the baicalin suspension, the AUC_0-t and C_max values of the baicalin nanoemulsion were increased by 10.5- and 3.12-fold, respectively. Compared with the saline-treated rats that were orally administered the baicalin nanoemulsion, the AUC_0-t and C_max values of the nanoemulsion for the rats pretreated with cycloheximide were reduced from 23.076 ± 1.244 mg/L·h to 9.236 ± 0.940 mg/L·h and from 3.010 ± 0.119 mg/L to 1.567 ± 0.220 mg/L, respectively. In comparing baicalin in W/O nanoemulsion with suspension, the C_max value was found to be 11.5-fold higher in the lymph nodes of the rats treated with the nanoemulsion. Conclusion: The results indicated that a baicalin-loaded W/O nanoemulsion may be a promising drug delivery system for the treatment of chronic hepatitis B.