The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
Phytomedicine. 2018 Jan 15;39:111-118. doi: 10.1016/j.phymed.2017.12.024. Epub 2017 Dec 25.
Non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used as effective anti-inflammatory agents. However, their clinical application brings about inevasible gastrointestinal side effects. Pogostemon cablin is a traditional herbal medicine used for the treatment of gastrointestinal diseases in China. One of its representative components, the tricyclic triterpenoid β-patchoulone (β-PAE) has demonstrated great anti-inflammatory activity and gastroprotective effect against ethanol-induced gastric injury, but its protective effect against gastric ulcer induced by indomethacin is still unknown.
To assess the protective effect of β-PAE against ulcer produced by indomethacin and reveal the underlying pharmacological mechanism.
We used an indomethacin-induced gastric ulcer model of rats in vivo.
Gastroprotective activity of β-PAE (10, 20, 40 mg/kg, i.g.) was estimated via indomethacin-induced gastric ulcer model in rats. Histopathological and histochemical assessment of ulcerated tissues were performed. Protein and mRNA expression were determined by Elisa, Western blotting and qRT-PCR.
β-PAE could inhibit ulcer formation. Histopathological and histochemical assessment macroscopically demonstrated that β-PAE alleviates indomethacin-induced gastric ulceration in dose-dependent manner. After administration of β-PAE, elevated tumor necrosis factor -α level was significantly decreased and the phosphorylation of JNK and IκB was markedly inhibited. β-PAE suppressed the levels of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule and monocyte chemoattractant protein 1, as well as myeloperoxidase. Meanwhile, β-PAE increased cyclooxygenase enzyme activities (COX-1 and COX-2) to enhance the production of prostaglandin E. Proangiogenic protein, vascular endothelial growth factor and its receptor fms-like tyrosine kinase-1 mRNA expression were promoted while anti-angiogenic protein, endostatin-1 and its receptor ETAR mRNA expression were decreased.
β-PAE may provide gastroprotection in indomethacin-induced gastric ulcer in rats by reducing inflammatory response and improving angiogenesis.
非甾体抗炎药（NSAIDs）是最广泛使用的有效抗炎药。然而，它们的临床应用不可避免地会带来胃肠道副作用。广藿香是中国用于治疗胃肠道疾病的传统草药。其代表性成分之一，三环三萜 β-石竹烯（β-PAE）具有很强的抗炎活性和对乙醇诱导的胃损伤的胃保护作用，但它对吲哚美辛诱导的胃溃疡的保护作用尚不清楚。
评估 β-PAE 对吲哚美辛诱导的溃疡的保护作用，并揭示其潜在的药理机制。
我们在体内使用了吲哚美辛诱导的大鼠胃溃疡模型。
通过吲哚美辛诱导的大鼠胃溃疡模型评估 β-PAE（10、20、40mg/kg，ig）的胃保护活性。对溃疡组织进行组织病理学和组织化学评估。通过 ELISA、Western blot 和 qRT-PCR 测定蛋白和 mRNA 表达。
β-PAE 可抑制溃疡形成。组织病理学和组织化学评估宏观上表明，β-PAE 以剂量依赖的方式缓解吲哚美辛诱导的胃溃疡。给予 β-PAE 后，肿瘤坏死因子-α水平显著降低，JNK 和 IκB 的磷酸化明显受到抑制。β-PAE 抑制 E-选择素、P-选择素、细胞间黏附分子-1、血管细胞黏附分子和单核细胞趋化蛋白 1 的水平，以及髓过氧化物酶。同时，β-PAE 增加环加氧酶酶活性（COX-1 和 COX-2）以增强前列腺素 E 的产生。促血管生成蛋白血管内皮生长因子及其受体 fms 样酪氨酸激酶-1 的 mRNA 表达增加，而抗血管生成蛋白内皮抑素-1 及其受体 ETAR 的 mRNA 表达减少。
β-PAE 可能通过减轻炎症反应和改善血管生成来提供吲哚美辛诱导的大鼠胃溃疡的胃保护作用。
