The protective effect of Lycium ruthenicum Murr. against radiation injury was examined in mice. Kunming mice were randomly divided into a control group, model group, positive drug group and L. ruthenicum high dose (8 g/kg), L. ruthenicum middle dose (4 g/kg), L. ruthenicum low dose (2 g/kg) treatment groups, for which doses were administered the third day, seventh day and 14th day after irradiation. L. ruthenicum extract was administered orally to the mice in the three treatment groups and normal saline was administered orally to the mice in the control group and model group for 14 days. The positive group was treated with amifostine (WR-2721) at 30 min before irradiation. Except for the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body at one time. Body weight, hemogram, thymus and spleen index, DNA, caspase-3, caspase-6, and P53 contents were observed at the third day, seventh day, and 14th day after irradiation. L. ruthenicum could significantly increase the total red blood cell count, hemoglobin count and DNA contents (p < 0.05). The spleen index recovered significantly by the third day and 14th day after irradiation (p < 0.05). L. ruthenicum low dose group showed a significant reduction in caspase-3 and caspase-6 of serum in mice at the third day, seventh day, and 14th day after irradiation and L. ruthenicum middle dose group experienced a reduction in caspase-6 of serum in mice by the seventh day after irradiation. L. ruthenicum could decrease the expression of P53. The results showed that L. ruthenicum had protective effects against radiation injury in mice.

(1) Background: High-altitude hypoxia has been shown to affect the pharmacokinetic properties of drugs. Although there is a high incidence of cardiovascular disease among individuals living in high-altitude areas, studies on the effect of high-altitude hypoxia on the pharmacokinetic properties of cardiovascular drugs are limited. (2) Methods: The aim of this study was to evaluate the pharmacokinetics of nifedipine, bosentan, simvastatin, sildenafil, and their respective main metabolites, dehydronifedipine, hydroxybosentan, simvastatin hydroxy acid, and N-desmethyl sildenafil, in rats exposed to high-altitude hypoxia. Additionally, the protein and mRNA expression of cytochrome P450 3A1 (CYP3A1), a drug-metabolizing enzyme, were examined. (3) Results: There were significant changes in the pharmacokinetic properties of the drugs in rats exposed to high-altitude hypoxia, as evidenced by an increase in the area under the curve (AUC) and the half-life (t_1/2z) and a decrease in total plasma clearance (CL_z/F). However, most of these changes were reversed when the rats returned to a normoxic environment. Additionally, there was a significant decrease in CYP3A1 expression in rats exposed to high-altitude hypoxia at both the protein and mRNA levels. (4) Conclusions: High-altitude hypoxia suppressed the metabolism of the drugs, indicating that the pharmacokinetics of the drugs should be re-examined, and the optimal dose should be reassessed in patients living in high-altitude areas.

Background: The blood-brain barrier is a major obstacle drug transport into the central nervous system. High-altitude hypoxia induces structural and functional alterations in the central nervous system, which in turn can influence drug metabolism and transport throughout the body. Methods: Rats and human brain microvascular endothelial cells (hCMEC/D ₃ ) were used as experimental models in this study. The effects of hypoxia on blood-brain barrier structure and function were assessed using Evans Blue staining and confocal laser scanning microscopy. Changes in the expression and activity of drug transporters and drug-metabolizing enzymes under hypoxic conditions were investigated using data-independent acquisition (DIA) proteomic sequencing, RT-qPCR, and western blot. Additionally, pharmacokinetic studies were conducted to evaluate drug concentrations across the blood-brain barrier. Results: High-altitude hypoxic environments significantly altered the cerebral distribution and trans-blood-brain barrier transport of drug substrates by upregulating the expression of the efflux transporter, ATP-binding cassette subfamily B member 1 (Abcb1), downregulating the expression of the drug-metabolizing enzyme CYP2B1, and increasing blood-brain barrier permeability. Moreover, the prolonged half-life (t₁/₂) and reduced total clearance (CL) observed for drug substrates indicate a significant deceleration in their in vivo metabolism under high-altitude hypoxia. Conclusion: Our findings preliminarily reveal the differential characteristics of drug metabolism under high-altitude hypoxic environments, implying potential differences in drug disposition between high-altitude and plain human populations. Accordingly, these findings provide novel theoretical insights into the molecular regulatory mechanism of drug metabolism in hypoxic plateau environments, and lay a valuable foundational reference for subsequent basic research on rational drug application in plateau areas.

Objectives: Prolonged and intense ultraviolet (UV) exposure can cause skin photoaging diseases. Therefore, there is a need for more natural and safe drugs to treat UV skin damage diseases. Methods: This study explored the mechanism of Sanhuang Erxiang Powder (SHEX) in the treatment of UV-induced skin through network pharmacology and verified the results by creating UV-induced injury models in BJ human fibroblasts and SD rats. Results: A total of 707 SHEX targets, 7244 UV damage targets, and 651 drug-disease targets were obtained by network pharmacology. The enrichment analysis suggested that SHEX may have a therapeutic role in UV damage through the MAPK signaling pathway. The in vitro model demonstrated that SHEX significantly increased BJ fibroblast viability as well as intracellular antioxidant enzyme levels. In vivo experiments showed that SHEX reduced the degree of skin damage in rats, increased the levels of antioxidant enzymes in skin tissues, and inhibited the release of p38 MAPK and MMP-1 in the MAPK signaling pathway. Conclusion: SHEX can be used to treat UV damage by a mechanism that may be related to antioxidant effects and the inhibition of p38 MAPK and MMP-1 release.