Song Shun-Zhe, Xie Jiang-Nan, Zhang Jing-Wen, Gong Ai-Xia
Digestive Endoscopy, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, 116000, China.
Chin J Integr Med. 2025 Jan 14. doi: 10.1007/s11655-025-3825-x.
To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification.
Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively.
UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10 to 10 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10 to 3 × 10 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10 to 10 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged.
BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
通过整合运用复方分析、网络药理学和实验验证，阐明半夏厚朴汤（BHD）治疗胃食管反流病（GERD）的机制。
采用超高效液相色谱-高分辨质谱（UPLC-HRMS）鉴定BHD中的主要成分。运用网络药理学检索靶基因。建立GERD大鼠模型，将32只SD大鼠用随机数字表法随机分为模型组、BHD低剂量组（3 g/kg）、BHD高剂量组（6 g/kg）和莫沙必利组（0.75 mg/kg），每组8只。选取8只未构建GERD模型的大鼠作为空白组。通过肉眼观察和组织病理学评估食管损伤情况。采用酶联免疫吸附测定（ELISA）法测定血清和食管下括约肌（LES）中5-羟色胺（5-HT）水平。用压力传感器测量LES收缩力，分别采用逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹法（Western blot）和免疫荧光染色法评估LES中5-羟色胺转运体（SERT）和5-HT4受体（5-HT4R）的表达。
UPLC-HRMS分析鉴定出BHD中的37个吸收峰和157种化合物。功能富集分析确定SERT是LES收缩力的重要靶点。组织病理学结果显示，与模型组相比，BHD高剂量组食管黏膜损伤较轻。虽然血清5-HT水平无显著差异，但BHD高剂量组LES组织中的5-HT浓度显著升高（P<0.05）。在10至10 mmol/L范围内，BHD高剂量组和莫沙必利组的LES收缩力显著增强（P<0.05）。在3×10至3×10 mmol/L 5-HT范围内，BHD高剂量组的LES收缩力增强（P<0.05）。在10至10 mmol/L 5-HT范围内未检测到显著差异。值得注意的是，通过RT-PCR、Western blot和免疫荧光染色评估，BHD高剂量组的SERT表达显著低于模型组（均P<0.01）；而5-HT4R表达无变化。
BHD可能通过抑制LES组织中SERT的表达来增强LES收缩力。
