Hepatology|Kong Lingyi/Zhang Hao's team published a research paper on potential targets and naturally active molecules against NASH


Recently, Hepatology (IF: 17.298), a leading journal in hepatology, published online the latest research results of Prof. Kong Lingyi's team at the School of Traditional Chinese Medicine, China Pharmaceutical University - RNA helicase DEAD-box protein 5 alleviates Postdoctoral fellow Zhang Yanqiu and doctoral student Ye Shengtao are the co-first authors of the article, and Professors Kong Lingyi and Zhang Hao are the corresponding authors. The article was co-authored by postdoctoral fellow Yanqiu Zhang and doctoral student Shengtao Ye, with Professors Lingyi Kong and Hao Zhang as corresponding authors.


Non-alcoholic steatohepatitis (NASH) is a progressive stage of non-alcoholic fatty liver disease (NAFLD) that can progress to liver fibrosis, cirrhosis and liver cancer. Since its global incidence continues to rise and no anti-NASH drugs are available in clinical practice, the search for new anti-NASH targets and their active compounds has attracted much attention in the domestic and international pharmaceutical community and has become a major clinical need for the treatment of NASH disease. Professor Kong Lingyi's team discovered and elucidated the mechanism of action of DDX5, a potential new target, to inhibit the progression of NASH, and used it as a target to screen for the presence of m-benzotrienols, a natural active molecule of the medicinal plant Hypericum, which provides a new idea for the development of innovative anti-NASH drugs.


This study revealed that DDX5 inhibits the activation of mTORC1 signaling pathway by recruiting TSC complex to mTOR protein, which in turn improves lipid metabolism disorder, increases autophagy level, inhibits inflammation activation and alleviates NASH progression. Using DDX5 as a potential target and combining the advantages of traditional Chinese medicine and natural products in the treatment of NASH, we screened our natural product library and found that Hyperforcinol K (HK), a m-triol compound from Hypericum perforatum, upregulated DDX5 protein expression by blocking TRIM5-mediated ubiquitination degradation of DDX5, and thus showed good anti-NASH effects in various NASH models. The present study elucidated the effects of DDX5 regulation on the expression of DDX5 protein. This study elucidated the mechanism of DDX5 regulation of mTORC1 signaling pathway to reshape lipid metabolism and inflammation to inhibit NASH progression, and revealed the mechanism of action of HK, a natural active molecule, against NASH, which laid a solid foundation for the development of anti-NASH drugs.


The research work has been funded by the National Natural Science Foundation of China (NSFC), the Major New Drug Creation Science and Technology Special Project, the Innovation and Wisdom Program of Higher Education Institutions, the Natural Science Foundation of Jiangsu Province, the Basic Research Funds of the Central Universities, and the Double First-class Project of the university.


Article link: https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.32651



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