Purpose: Pseudoephedrine (PSE) has rapid absorption and metabolism, which limits its pharmacologic actions. We postulated that pseudoephedrine nanoparticles (PSE-NPs) with high bioavailability could overcome this limitation. The defensive function of PSE-NPs nanoparticles against adriamycin-induced reproductive toxicity in mice was studied. Methods: We encapsulated PSE in polylactide-polyglycolide nanoparticles (PLGA-NPs) and verified their protective activity against testicular injury in vivo and in vitro. Results: We report a promising delivery system that loads PSE into PLGA-NPs and finally assembles it into a nanocomposite particle. In vitro, PSE-NPs reduced the adriamycin-induced apoptosis of GC-1 cells significantly, improved mitochondrial energy metabolism and promoted expression of the proteins related to the gonadotropin-releasing hormone (GnRh) receptor signaling pathway. In vivo, evaluation of sperm indices and histology showed that adriamycin could induce testicular toxicity. PSE-NPs significantly increased the sperm motility of mice, reduced the percent apoptosis and oxidative stress of testes, increased serum levels of GnRh, activated the GnRhR signaling pathway in testes and promoted expression of meiosis-related factors. Conclusion: In view of their safety and efficiency, these PSE-NPs have potential applications in alleviating adriamycin-induced reproductive toxicity. Graphical Abstract:

Lipid deposition in the kidney can cause serious damage to the kidney, and there is an obvious epithelial–mesenchymal transition (EMT) and fibrosis in the late stage. To investigate the interventional effects and mechanisms of phenolic compounds from Mori Cortex on the EMT and fibrosis induced by sodium oleate-induced lipid deposition in renal tubular epithelial cells (NRK-52e cells), and the role played by CD36 in the adjustment process, NRK-52e cells induced by 200 μmol/L sodium oleate were given 10 μmoL/L moracin-P-2″-O-β-d-glucopyranoside (Y-1), moracin-P-3′-O-β-d-glucopyranoside (Y-2), moracin-P-3′-O-α-l-arabinopyranoside (Y-3), and moracin-P-3′-O-[β-glucopyranoside-(1→2)arabinopyranoside] (Y-4), and Oil Red O staining was used to detect lipid deposition. A Western blot was used to detect lipid deposition-related protein CD36, inflammation-related protein (p-NF-κB-P65, NF-κB-P65, IL-1β), oxidative stress-related protein (NOX1, Nrf2, Keap1), EMT-related proteins (CD31, α-SMA), and fibrosis-related proteins (TGF-β, ZEB1, Snail1). A qRT-PCR test detected inflammation, EMT, and fibrosis-related gene mRNA levels. The TNF-α levels were detected by ELISA, and the colorimetric method was used to detects SOD and MDA levels. The ROS was measured by flow cytometry. A high-content imaging analysis system was applied to observe EMT and fibrosis-related proteins. At the same time, the experiment silenced CD36 and compared the difference between before and after drug treatment, then used molecular docking technology to predict the potential binding site of the active compounds with CD36. The research results show that sodium oleate can induce lipid deposition, inflammation, oxidative stress, and fibrosis in NRK-52e cells. Y-1 and Y-2 could significantly ameliorate the damage caused by sodium oleate, and Y-2 had a better ameliorating effect, while there was no significant change in Y-3 or Y-4. The amelioration effect of Y-1 and Y-2 disappeared after silencing CD36. Molecular docking technology showed that the Y-1 and Y-2 had hydrogen bonds to CD36 and that, compared with Y-1, Y-2 requires less binding energy. In summary, moracin-P-2″-O-β-d-glucopyranoside and moracin-P-3′-O-β-d-glucopyranoside from Mori Cortex ameliorated lipid deposition, EMT, and fibrosis induced by sodium oleate in NRK-52e cells through CD36.

Purpose: Fatty oil of Descurainia Sophia (OIL) has poor stability and low solubility, which limits its pharmacological effects. We hypothesized that fatty oil nanoparticles (OIL-NPs) could overcome this limitation. The protective effect of OIL-NPs against monocrotaline-induced lung injury in rats was studied. Methods: We prepared OIL-NPs by wrapping fatty oil with polylactic-polyglycolide nanoparticles (PLGA-NPs) and conducted in vivo and in vitro experiments to explore its anti-pulmonary hypertension (PH) effect. In vitro, we induced malignant proliferation of pulmonary artery smooth muscle cells (RPASMC) using anoxic chambers, and studied the effects of OIL-NPs on the malignant proliferation of RPASMC cells and phospholipase C (PLC)/inositol triphosphate receptor (IP3R)/Ca²⁺ signal pathways. In vivo, we used small animal echocardiography, flow cytometry, immunohistochemistry, western blotting (WB), polymerase chain reaction (PCR) and metabolomics to explore the effects of OIL-NPs on the heart and lung pathological damage and PLC/IP3R/Ca²⁺ signal pathway of pulmonary hypertension rats. Results: We prepared fatty into OIL-NPs. In vitro, OIL-NPs could improve the mitochondrial function and inhibit the malignant proliferation of RPASMC cells by inhibiting the PLC/IP3R/Ca²⁺signal pathway. In vivo, OIL-NPs could reduce the pulmonary artery pressure of rats and alleviate the pathological injury and inflammatory reaction of heart and lung by inhibiting the PLC/IP3R/Ca²⁺ signal pathway. Conclusion: OIL-NPs have anti-pulmonary hypertension effect, and the mechanism may be related to the inhibition of PLC/IP3R/Ca²⁺signal pathway.