2. Academic Validation
  3. 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

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

  • Int Immunopharmacol. 2025 Jan 10:144:113632. doi: 10.1016/j.intimp.2024.113632.
Jian-Qin Liu 1,  Wei-An Hao 1,  Ya-Li Liu 1,  Dan Yang 2,  Hong-Lian Wang 1,  Long Zhao 3,  Hui Chen 3,  Li Li 3,  Chao-Li Jiang 4,  Xin Zhou 5,  Juan Fu 6,  Zhi Li 7
Affiliations

Affiliations

  • 1 Research Center of Integrated Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University Luzhou, 646000, China; College of Integrated Chinese and Western Medicine and the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China.
  • 2 College of Integrated Chinese and Western Medicine and the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China.
  • 3 College of Integrated Chinese and Western Medicine and the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; Department of Spleen & Stomach, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou city, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Lu zhou, 646000, China.
  • 4 College of Integrated Chinese and Western Medicine and the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; Department of Spleen & Stomach, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China.
  • 5 Research Center of Integrated Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University Luzhou, 646000, China; College of Integrated Chinese and Western Medicine and the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; Department of Spleen & Stomach, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou city, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Lu zhou, 646000, China. Electronic address: [email protected].
  • 6 College of Integrated Chinese and Western Medicine and the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; Department of Spleen & Stomach, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China. Electronic address: [email protected].
  • 7 Research Center of Integrated Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University Luzhou, 646000, China; School of Integrated Traditional Chinese and Western Clinical Medicine, North Sichuan Medical College, Nanchong, 637000, China; College of Integrated Chinese and Western Medicine and the Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, 646000, China; The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou city, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Lu zhou, 646000, China. Electronic address: [email protected].
PMID: 39566389 DOI: 10.1016/j.intimp.2024.113632
Abstract

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 intra-pancreaticobiliary 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 (UHPLC-HRMS). 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 (d-lactic 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-κB signaling in the intestine, leading to downregulated intestinal IL-1β expression and reduced circulating TNF-α 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-α-induced tight junction loss in IEC-6 cells and mitigated intestinal mucosal barrier injury in SAP rats through suppressing NF-κB signaling. In summary, CHQY ameliorates SAP-induced intestinal mucosal barrier injury by downregulating the proinflammatory HMGB1/TLR4/NF-κB signaling, with efficacy partially attributed to its active compounds paeoniflorin sulfite and chrysin-7-O-glucuronide.

Keywords

CHQY; Chrysin-7-O-glucuronide; HMGB1; Intestinal barrier injury; NF-κB signaling; Paeoniflorin sulfite; Severe acute pancreatitis.

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