Paeonol, a major ingredient isolated from Moutan Cort, has various pharmacological effects. Our previous studies have shown that paeonol can exert antioxidant and anti-inflammatory therapeutic effects on ethanol-induced experimental gastric ulcer (GU). Therefore, in this study, we designed two GU models in rats induced by pyloric ligation (PL) and acetic acid and evaluated the protective effects of paeonol and gastroretention tablets of paeonol (GRT-Ps; 24, 48, and 96 mg/kg) on GU in rats and the effect of paeonol (48 mg/kg) on the intestinal flora. In vivo experiments showed that paeonol or GRT-Ps remarkably reduced gastric mucosal damage in a dose-dependent manner in the different types of models and improved the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content. And in fact, the sustained-release effect of GRT-Ps is more conducive to the improvement of GU compared with the rapid clearance of free drugs. In the PL-induced model, gastric secretion parameters, that is, pH and total acid, showed significant differences compared with the model group. In addition, paeonol treatment can improve the richness and diversity of the intestinal flora and increase the amount of beneficial bacteria, such as Lactobacillus. Paeonol and its stable sustained-release tablet GRT-Ps can promote ulcer healing by inhibiting oxidative stress and regulating the intestinal flora. This study can provide basis for the clinical treatment of GU with paeonol.

Graphical Abstract

从牡丹皮中分离出来的主要成分丹皮酚具有多种药理作用。我们之前的研究表明，丹皮酚对乙醇诱导的实验性胃溃疡（GU）具有抗氧化和抗炎的治疗作用。因此，在本研究中，我们设计了两种由幽门结扎 (PL) 和乙酸诱导的大鼠 GU 模型，并评估了丹皮酚和丹皮酚胃滞留片 (GRT-Ps; 24、48 和 96 mg/kg) 的保护作用。对大鼠 GU 和丹皮酚 (48 mg/kg) 对肠道菌群的影响。体内实验表明，丹皮酚或GRT-Ps在不同类型模型中以剂量依赖性方式显着减轻胃粘膜损伤，并提高超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量。而事实上，与游离药物的快速清除相比，GRT-Ps的缓释作用更有利于GU的改善。在PL诱导的模型中，胃分泌参数，即pH和总酸与模型组相比有显着差异。此外，丹皮酚治疗可以改善肠道菌群的丰富度和多样性，增加有益菌的数量，如乳酸杆菌. 丹皮酚及其稳定的缓释片 GRT-Ps 可通过抑制氧化应激和调节肠道菌群促进溃疡愈合。本研究可为临床应用丹皮酚治疗GU提供依据。

图形概要