Plateau hyperuricemia is a common disease in the plateau area, and the incidence is much higher than that in the plain area. Dioscin (DIO) and its active metabolite Diosgenin (DG) exert therapeutic effects on hyperuricemia through oxidative stress and inflammation. In this study, DIO and its active metabolite DG were taken as the research objects to explore their therapeutic effects on high-altitude hyperuricemia in rats. To evaluate the therapeutic effect of DIO on the rat model of high-altitude hyperuricemia, the evaluation indexes include blood biochemical indexes, renal histopathology, oil red O staining of the kidney, rat kidney index, and rat renal inflammatory factors. Transcriptomics was used to analyze the control group, model group, and drug-administered group to preliminarily explore the protective mechanism of DIO in rats with high-altitude hyperuricemia. An HK-2 high-altitude hyperuricemia cell injury model was established to verify the therapeutic mechanism of DIO in rats with high-altitude hyperuricemia. Western blot was used to detect the expression of related proteins in renal tissues and cell models. The results showed that DIO and its active metabolite DG regulate renal lipid metabolism through the EPHX2 gene, attenuate renal inflammatory reaction, and then promote the excretion of uric acid and reduce its reabsorption, which ultimately achieves the effect of treating plateau hyperuricemia.

Myocardial injury is a common disease in the plateau, especially in the lowlanders who have migrated to the plateau, in which the pathogenesis is not well understood. Here, we established a cohort of lowlanders comprising individuals from both low-altitude and high-altitude areas and conducted plasma proteomic profiling. Proteomic data showed that there was a significant shift in energy metabolism and inflammatory response in individuals with myocardial abnormalities at high altitude. Notably, integrin alpha-Ⅱb (ITGA2B) emerged as a potential key player in this context. Functional studies demonstrated that ITGA2B upregulated the transcription and secretion of interleukin-6 (IL-6) through the integrin-linked kinase (ILK)/nuclear factor-κB (NF-κB) signaling axis under hypoxic conditions. Moreover, ITGA2B disrupted mitochondrial structure and function, increased glycolytic capacity, and aggravated energy reprogramming from oxidative phosphorylation to glycolysis. Leveraging the therapeutic potential of traditional Chinese medicine in cardiac diseases, we discovered that tanshinone ⅡA (TanⅡA) effectively alleviated the myocardial injury caused by the abnormally elevated expression of ITGA2B and hypobaric hypoxia exposure in mice, thus providing a novel candidate therapeutic strategy for the prevention and treatment of high-altitude myocardial injury.

The toxicity of herbal medicine combinations is critical to the clinical safety of traditional Chinese medicine(TCM). Current assessment methods are often inefficient and costly, creating an urgent need for new strategies to evaluate herbal medicine toxicity. We conducted research based on the commonly used TCM, Psoraleae Fructus(PF), and its formulations, Er Shen Pills(ESP) and Si Shen Pills(SSP). Therefore, We will conduct a series of analyses on Drosophila and Vibrio fischeri. In Drosophila experiments, ESP and SSP groups showed longer survival times, with male flies being more sensitive, making them more suitable for toxicity studies. Enzyme assays indicated a decreasing toxicity trend for ESP and SSP compared to PF, with significant changes observed in female flies. The qPCR analysis revealed that the upregulation of cpr and cyp6a8, along with the downregulation of keap1, hsp22, hsp68, gstD6, and hsp83, can assess the toxicity changes of PF, ESP, and SSP. The primary detoxification pathway involves the metabolism of xenobiotics by cytochrome P450. In the Vibrio fischeri assay, the IC50(50% inhibition;) value of ESP was the highest, indicating reduced toxicity compared to PF. Screening for toxic components revealed that PF had 4, ESP had 16, and SSP had 22 components, primarily acting on LuxD, LuxE, and LuxG.