The efficacy and active compounds of Chaihuang Qingyi Huoxue granule to Ameliorate intestinal mucosal barrier injury in rats with severe acute pancreatitis by suppressing the HMGB1/TLR4/NF-κB signaling pathway

被引:1
作者
Liu, Jian-Qin [1 ,3 ,4 ]
Hao, Wei-An [1 ,3 ,4 ]
Liu, Ya-Li [1 ,3 ,4 ]
Yang, Dan [3 ,4 ]
Wang, Hong-Lian [1 ,3 ,4 ]
Zhao, Long [3 ,4 ,5 ,6 ]
Chen, Hui [3 ,4 ,5 ,6 ]
Li, Li [3 ,4 ,5 ,6 ]
Jiang, Chao-Li [3 ,4 ,5 ]
Zhou, Xin [1 ,3 ,4 ,5 ,6 ]
Fu, Juan [3 ,4 ,5 ]
Li, Zhi [1 ,2 ,3 ,4 ,6 ]
机构
[1] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Res Ctr Integrated Chinese & Western Med, Luzhou 646000, Peoples R China
[2] North Sichuan Med Coll, Sch Integrated Tradit Chinese & Western Clin Med, Nanchong 637000, Peoples R China
[3] Southwest Med Univ, Coll Integrated Chinese & Western Med, Luzhou 646000, Peoples R China
[4] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Luzhou 646000, Peoples R China
[5] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Dept Spleen & Stomach, Luzhou 646000, Peoples R China
[6] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Key Lab Integrated Tradit Chinese & Western Med Pr, Luzhou 646000, Peoples R China
关键词
CHQY; Severe acute pancreatitis; Intestinal barrier injury; HMGB1; NF-kappa B signaling; Paeoniflorin sulfite; Chrysin-7-O-glucuronide; KAPPA-B; INFLAMMATION; CHRYSIN;
D O I
10.1016/j.intimp.2024.113632
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Intestinal mucosal barrier injury represents a critical complication of severe acute pancreatitis (SAP) without effective treatment. This study investigated the efficacy, underlying mechanism, and responsible active compounds of the traditional Chinese medicinal prescription Chaihuang Qingyi Huoxue granule (CHQY) in treating SAP-induced intestinal mucosal barrier injury. SAP was established in Sprague-Dawley rats via intrapancreaticobiliary duct infusion of sodium taurocholate, followed by oral CHQY administration (3.15 g/kg every 6 h for 12 and 24 h). Blood and tissues were harvested to assess the severity of pancreatitis, intestinal mucosal barrier integrity, and extent of inflammatory injury. Intestine-absorbing compounds were identified using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLCHRMS). Our results showed that CHQY treatment effectively mitigated SAP-induced intestinal mucosal injury, as evidenced by improved intestinal epithelial structure, decreased serum levels of intestinal injury markers (Dlactic acid, diamine oxidase, I-FABP, and Zonulin), restored expression of the tight junction protein ZO-1, and reduced serum endotoxin levels. Furthermore, CHQY administration suppressed the expression of proinflammatory mediator HMGB1, its receptor TLR4, and downstream NF-kappa B signaling in the intestine, leading to downregulated intestinal IL-1 beta expression and reduced circulating TNF-alpha and IL-6. UHPLC-HRMS analysis identified 15 intestine-absorbing compounds in CHQY, of which paeoniflorin sulfite and chrysin-7-O-glucuronide independently inhibited TNF-alpha-induced tight junction loss in IEC-6 cells and mitigated intestinal mucosal barrier injury in SAP rats through suppressing NF-kappa B signaling. In summary, CHQY ameliorates SAP-induced intestinal mucosal barrier injury by downregulating the proinflammatory HMGB1/TLR4/NF-kappa B signaling, with efficacy partially attributed to its active compounds paeoniflorin sulfite and chrysin-7-O-glucuronide.
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页数:17
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