At present, due to the limitations of drug therapy targets for atherosclerosis, some patients fail to achieve satisfactory efficacy. Cholesterol efflux dysfunction and endothelial cell inflammation are considered to be important factors in the development of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ), a promising therapeutic target for atherosclerosis, plays a dual role in regulating cholesterol efflux and endothelial cell inflammation. However, the use of PPARγ agonist in clinical practice is greatly limited as it could lead to water and sodium retention and hence result in congestive heart failure. Qihuang Zhuyu Formula (QHZYF) is a hospital preparation of Jiangsu Province Hospital of Chinese Medicine which has definite effect in the treatment of atherosclerosis, but its pharmacological mechanism has not been clear. In this study, we successfully predicted that QHZYF might regulate cholesterol efflux and endothelial inflammation via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways by using UPLC-Q-TOF/MS, network pharmacology, bioinformatics analysis, and molecular docking technology. Subsequently, we confirmed in vivo that QHZYF could attenuate atherosclerosis in ApoE−/− mice and regulate the expression levels of related molecules in PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways of ApoE−/− mice and C57BL/6 wild-type mice. Finally, in in vitro experiments, we found that QHZYF could reduce lipid content and increase cholesterol efflux rate of RAW 264.7 cells, inhibit the inflammatory response of HUVECs, and regulate the expression levels of related molecules in the two pathways. In addition, the above effects of QHZYF were significantly weakened after PPARγ knockdown in the two kinds of cells. In conclusion, our study revealed that QHZYF attenuates atherosclerosis via targeting PPARγ-mediated PPARγ/LXRα/ABCA1-ABCG1 and PPARγ/NF-κB p65 pathways to regulate cholesterol efflux and endothelial cell inflammation. More importantly, our study offers a promising complementary and alternative therapy which is expected to make up for the limitation of current drug treatment methods and provide a valuable reference for new drugs development in the future.

Aim of the Review. This study aims to summarize the therapeutic effect of luteolin on the pathogenesis of viral pneumonia, explore its absorption and metabolism in the human body, evaluate the possibility of luteolin as a drug to treat viral pneumonia, and provide a reference for future research. Materials and Methods. We searched MEDLINE/PubMed, Web of Science, China National Knowledge Infrastructure, and Google Scholar and collected research on luteolin in the treatment of viral pneumonia and related diseases since 2003. Then, we summarized the efficacy and potential of luteolin in directly inhibiting viral activity, limiting inflammatory storms, reducing pulmonary inflammation, and treating pneumonia complications. Results and Conclusion. Luteolin has the potential to treat viral pneumonia in multiple ways. Luteolin has a direct inhibitory effect on coronavirus, influenza virus, and respiratory syncytial virus. Luteolin can alleviate the inflammatory factor storm induced by multiple factors by inhibiting the function of macrophages or mast cells. Luteolin can reduce pulmonary inflammation, pulmonary edema, or pulmonary fibrosis induced by multiple factors. In addition, viral pneumonia may cause multisystem complications, while luteolin has extensive protective effects on the gastrointestinal system, cardiovascular system, and nervous system. However, due to the first-pass metabolism mediated by phase II enzymes, the bioavailability of oral luteolin is low. The bioavailability of luteolin can be improved, and its potential value can be further developed by changing the dosage form or route of administration.