Location: Animal Parasitic Diseases LaboratoryTitle: Ellagitannin Punicalagin Disrupts the Pathways Related to Bacterial Growth and Affects Multiple Pattern Recognition Receptor Signaling by Acting as a Selective Histone Deacetylase Inhibitor
|LIU, F - Zhengzhou University|
|Wang, Thomas - Tom|
|YANG, H - Zhengzhou University|
Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/24/2023
Publication Date: 3/14/2023
Citation: Liu, F., Smith, A.D., Wang, T.T., Pham, Q., Yang, H., Li, R.W. 2023. Ellagitannin Punicalagin Disrupts the Pathways Related to Bacterial Growth and Affects Multiple Pattern Recognition Receptor Signaling by Acting as a Selective Histone Deacetylase Inhibitor. Journal of Agricultural and Food Chemistry. 71(12):5016-5026. https://doi.org/10.1021/acs.jafc.2c08738.
Interpretive Summary: As a key polyphenol and ellagitannin abundant in pomegranate, punicalagin possess wide-ranging biological activities, including antimicrobial and antiparasitic properties. However, the mechanisms underlying these biological activities are poorly understood. The extent of punicalagin regulates the global gene expression and cellular metabolome in both eukaryotic and bacterial cells have not been systematically evaluated. In this study, we adopted an innovative bioinformatic analysis in multiple cell types to understand biological processes via which punicalagin exerts its biological function. Our findings suggest that punicalagin acts as a potent selective histone deacetylase inhibitor, which can facilitate the development of its potential application in managing gastrointestinal disorders.
Technical Abstract: Punicalagin (PA) is a key ellagitannin abundant in pomegranate with wide-ranging biological activities. In this study, we examined the biological processes via which PA regulated bacterial growth and inflammation in human cells using multi-omics and molecular docking approaches. PA promoted macrophage mediated bacterial killing and inhibited the growth of Citrobacter rodentium by inducing a distinct metabolome pattern. PA acted as a selective regulator of histone deacetylases (HDAC) and affected 37 pathways in human macrophages, including signaling mediated by pattern recognition receptors, Toll-like, NOD-like, and RIG-I-like. In silico simulation shows that PA can bind with high affinity to HDAC7. PA downregulated HDAC7 at both mRNA and protein levels in human enterocytes and resulted in a net reduction in histone 3 lysine 27 acetylation. Our findings provided strong evidence that PA exerts its biological effects via multiple pathways, which can be exploited in developing this bioactive food ingredient for disease management.