Protective role of β-patchoulene from Pogostemon cablin against indomethacin-induced gastric ulcer in rats: Involvement of anti-inflammation and angiogenesis

• Published in: Phytomedicine (Stuttgart) 2018-01, Vol.39, p.111-118
• Main Authors: Wu, Jia-Zhen, Liu, Yu-Hong, Liang, Jia-Li, Huang, Qiong-Hui, Dou, Yao-Xing, Nie, Juan, Zhuo, Jian-Yi, Wu, Xue, Chen, Jian-Nan, Su, Zi-Ren, Wu, Qi-Duan
• Format: Article
• Language: English
• Subjects: Angiogenesis Inducing Agents - pharmacology; Animals; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Ulcer Agents - pharmacology; Antiulcer; Dinoprostone - metabolism; Drugs, Chinese Herbal - pharmacology; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gastric Mucosa - pathology; Gastric ulcer; Indomethacin; Indomethacin - adverse effects; Male; Pogostemon - chemistry; Pogostemon cablin; Protective Agents - pharmacology; Rats, Sprague-Dawley; Sesquiterpenes - pharmacology; Stomach Ulcer - chemically induced; Stomach Ulcer - drug therapy; Stomach Ulcer - pathology; Tumor Necrosis Factor-alpha - metabolism; β-patchoulene
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2017.12.024

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 E2. 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. [Display omitted]