Metabolic dysfunction-associated steatohepatitis (MASH)-induced liver cancer (MALC) is a global public health challenge. This study aims to analyze the epidemiological characteristics of MALC from 1990 to 2021 and project future trends up to 2050 in China. Data on MALC were obtained from the Global Burden of Disease Study (GBD) 2021, including incidence, deaths, and disability-adjusted life-years (DALYs). The burden of MALC in China and trends in age-standardized rate (ASR) were analyzed using estimated annual percentage changes (EAPCs). Additionally, the attributable risk factors for MALC-related deaths and DALYs in China were assessed, and Bayesian age-period-cohort models were used to predict trends in ASR up to 2050. Compared to 1990, the number of MALC incidence, deaths, and DALYs in China more than doubled by 2021. From 1990 to 2021, the age-standardized incidence rate (ASIR) [EAPC: 0.72; 95% confidence interval (CI) 0.52 to 0.92] and age-standardized mortality rate (ASMR) (EAPC: 0.33; 95% CI 0.13 to 0.53) of MALC showed an upward trend. The ASIR, ASMR, and age-standardized DALYs rate (ASDR) in males consistently exceeded those in females. In 2021, the burden of MALC incidence, deaths, and DALYs in China was predominantly concentrated in the 65–69 age group. Among the risk factors recorded in GBD 2021, age-standardized MALC mortality in China in 2021 was primarily attributable to high fasting plasma glucose and smoking. It was also found that the proportion of risk factors for MALC in China was similar to those in high-middle SDI regions and World Bank upper-middle-income regions. Furthermore, predictive models estimate that by 2050, the ASIR and ASMR of MALC in both male and female patients in China will show a declining trend. The burden of MALC in China exhibits age and gender disparities. Although its future burden is expected to improve, it remains a significant public health challenge in China. Targeted intervention strategies must be developed based on its epidemiological characteristics and risk factors to mitigate the burden of MALC in China.

Objective Rosmarinic acid (RosA) is a natural polyphenol compound that has been shown to be effective in the treatment of inflammatory disease and a variety of malignant tumors. However, its specific mechanism for the treatment of lung adenocarcinoma (LUAD) has not been fully elucidated. Therefore, this study aims to clarify the mechanism of RosA in the treatment of LUAD by integrating bioinformatics, network pharmacology and in vivo experiments, and to explore the potential of the active ingredients of traditional Chinese medicine in treating LUAD. Methods Firstly, the network pharmacology was used to screen the RosA targets, and LUAD-related differential expressed genes (DEGs) were acquired from the GEO database. The intersection of LUAD regulated by RosA (RDEGs) was obtained through the Venn diagram. Secondly, GO and KEGG enrichment analysis of RDEGs were performed, and protein–protein interaction networks (PPIs) were constructed to identify and visualize hub RDEGs. Then, molecular docking between hub RDEGs and RosA was performed, and further evaluation was carried out by using bioinformatics for the predictive value of the hub RDEGs. Finally, the mechanism of RosA in the treatment of LUAD was verified by establishing a xenograft model of NSCLC in nude mouse. Results Bioinformatics and other analysis showed that, compared with the control group, the expressions of MMP-1, MMP-9, IGFBP3 and PLAU in LUAD tissues were significantly up-regulated, and the expressions of PPARG and FABP4 were significantly down-regulated, and these hub RDEGs had potential predictive value for LUAD. In vivo experimental results showed that RosA could inhibit the growth of transplanted tumors in nude mice bearing tumors of lung cancer cells, reduce the positive expression of Ki67 in lung tumor tissue, and hinder the proliferation of lung tumor cells. Upregulated expression of PPARG and FABP4 by activating the PPAR signaling pathway increases the level of ROS in lung tumor tissues and promotes apoptosis of lung tumor cells. In addition, RosA can also reduce the expression of MMP-9 and IGFBP3, inhibit the migration and invasion of lung tumor tissue cells. Conclusions This study demonstrated that RosA could induce apoptosis by regulating the PPAR signaling pathway and the expression of MMP-9, inhibit the proliferation, migration and invasion of lung cancer cells, thereby exerting anti-LUAD effects. This study provides new insight into the potential mechanism of RosA in treating LUAD and provides a new therapeutic avenue for treatment of LUAD.