PDF(Pubmed)
Abstract：
BACKGROUND: Postoperative ileus (POI) is a common obstruction of intestinal content passage caused by almost all abdominal operations that seriously strokes the quality of life of patients. Kuanchang-Shu granule (KCSG), a classic modified prescription based on \"Da-Cheng-Qi Decoction\", has obtained satisfactory efficacy in the clinical therapeutics of POI. However, its material basis and holistic molecular mechanism against POI have not been revealed.
METHODS: The chemical ingredients of KCSG were first characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Subsequently, an integration strategy of the network pharmacology and molecular docking based on above identified ingredients was performed to unveil the potential targets involved in the treatment of KCSG on POI. Finally, intestinal manipulation induced rat POI model was constructed to verify the efficacy and predicted mechanism of KCSG against POI.
RESULTS: In total, 246 ingredients mainly including organic acids, flavonoids, quinones, alkaloids, terpenoids, phenylpropanoids and phenols were identified. 41 essential ingredients, 24 crucial targets as well as 15 relevant signaling pathways were acquired based on network pharmacology analysis. Pharmacodynamic research showed that KCSG treatment could protect intestinal histological damage, promote the recovery of measurement of gastrointestinal transit disorder and inhibit the secretion of myeloperoxidase in the distal ileum tissues. The up-regulated expression of p-AKT and down-regulated expression of p-eNOS and HSP9OAA1 predicted by molecular docking and validated by western blotting showed that AKT/eNOS/HSP90AA1 pathway may be one of the crucial mechanisms that mediates the protective effect of KCSG.
METHODS: The chemical ingredients of KCSG were first characterized by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Subsequently, an integration strategy of the network pharmacology and molecular docking based on above identified ingredients was performed to unveil the potential targets involved in the treatment of KCSG on POI. Finally, intestinal manipulation induced rat POI model was constructed to verify the efficacy and predicted mechanism of KCSG against POI.
RESULTS: In total, 246 ingredients mainly including organic acids, flavonoids, quinones, alkaloids, terpenoids, phenylpropanoids and phenols were identified. 41 essential ingredients, 24 crucial targets as well as 15 relevant signaling pathways were acquired based on network pharmacology analysis. Pharmacodynamic research showed that KCSG treatment could protect intestinal histological damage, promote the recovery of measurement of gastrointestinal transit disorder and inhibit the secretion of myeloperoxidase in the distal ileum tissues. The up-regulated expression of p-AKT and down-regulated expression of p-eNOS and HSP9OAA1 predicted by molecular docking and validated by western blotting showed that AKT/eNOS/HSP90AA1 pathway may be one of the crucial mechanisms that mediates the protective effect of KCSG.
摘要：
背景：术后肠梗阻（POI）是由几乎所有腹部手术引起的肠内容物通道的常见阻塞，严重影响患者的生活质量。宽昌舒颗粒（KCSG），基于“大承气汤”的经典改良处方，在POI的临床治疗中取得了满意的疗效。然而,其抗POI的物质基础和整体分子机制尚未揭示。
方法：首先通过超高效液相色谱-四极杆飞行时间质谱（UHPLC-QTOF-MS）表征KCSG的化学成分。随后，基于上述确定的成分,实施了网络药理学和分子对接的整合策略,以揭示在POI上治疗KCSG的潜在靶点.最后,构建经肠操作诱导的大鼠POI模型,验证KCSG抗POI的疗效及预测机制。
结果：总计，246种成分主要包括有机酸，黄酮类化合物，醌,生物碱，萜类化合物,苯丙素类和酚类被鉴定。41种必需成分,基于网络药理学分析获得了24个关键靶标以及15个相关信号通路。药效学研究表明,KCSG治疗对肠道组织学损伤具有保护作用,促进胃肠道转运障碍测量的恢复，并抑制远端回肠组织中髓过氧化物酶的分泌。通过分子对接预测并通过蛋白质印迹验证的p-AKT的上调表达和p-eNOS和HSP9OAA1的下调表达表明，AKT/eNOS/HSP90AA1通路可能是介导KCSG保护作用的关键机制之一。
方法：首先通过超高效液相色谱-四极杆飞行时间质谱（UHPLC-QTOF-MS）表征KCSG的化学成分。随后，基于上述确定的成分,实施了网络药理学和分子对接的整合策略,以揭示在POI上治疗KCSG的潜在靶点.最后,构建经肠操作诱导的大鼠POI模型,验证KCSG抗POI的疗效及预测机制。
结果：总计，246种成分主要包括有机酸，黄酮类化合物，醌,生物碱，萜类化合物,苯丙素类和酚类被鉴定。41种必需成分,基于网络药理学分析获得了24个关键靶标以及15个相关信号通路。药效学研究表明,KCSG治疗对肠道组织学损伤具有保护作用,促进胃肠道转运障碍测量的恢复，并抑制远端回肠组织中髓过氧化物酶的分泌。通过分子对接预测并通过蛋白质印迹验证的p-AKT的上调表达和p-eNOS和HSP9OAA1的下调表达表明，AKT/eNOS/HSP90AA1通路可能是介导KCSG保护作用的关键机制之一。
