Histones are critical toxic factors in gut lymph of severe acute pancreatitis: Neutralization by baicalin and baicalein for protection

作者：Shiyu Liu, Qiqi Wang, Wenjuan Luo, Lijia Huang, Lan Li, Yongzi Wu, Wenhao Cai, Jiwon Hong, Anthony Philips, David G. Fernig, Robert M. Sutton, John A. Windsor, Peter Szatmary, Tingting Liu, Wei Huang, Qing Xia · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156474 · 被引用次数：6 · 研究领域：Pancreatitis Pathology and Treatment、Pancreatic and Hepatic Oncology Research、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

BACKGROUND: Whether circulating histones in gut lymph contribute to organ failure and impact of chaiqin chengqi decoction (CQCQD) on histones in severe acute pancreatitis (SAP) remain elusive. PURPOSE: To verify the role of histones in gut lymph of SAP and evaluate the effect of the CQCQD on them. METHODS: Sodium taurocholate was retrogradely infused into pancreatobiliary duct to induce SAP in rodents. Various regimens of CQCQD were administered intragastrically or via duodenum followed by dynamic gut lymph collection in rats. The impact of gut lymph and histones on endothelial cell viability and lymphocytes was determined. Components of CQCQD in gut lymph were identified by UHPLC-MS and their binding activities with histones were quantified by biolayer interferometry followed by validation in vitro and in vivo in mice. RESULTS: The histone level was significantly increased in gut lymph of SAP at various time points assessed, closely correlating with multiple organ injury (MOI) indices and contemporary cell viability. Inhibition of histones reduced cytotoxicity induced by SAP-conditioned gut lymph. CQCQD reduced apoptotic cell death in mesenteric lymph nodes, histone level, and cytotoxicity of gut lymph, alleviating MOI parameters. Baicalin and baicalein were amongst top 13 identified CQCQD components absorbed into gut lymph to actively bind histones, block membrane disruption and calcium influx of lymphocytes, and inhibit their cytotoxicity. Both baicalin and baicalein mitig...