Pharmacology Department, Biosciences Institute, Universidade Estadual Paulista - UNESP, Botucatu, Brazil.
Pharmacology Department, Faculty of Medical Sciences, University of Campinas - UNICAMP, Campina, Brazil.
PLoS One. 2014 Jan 21;9(1):e86686. doi: 10.1371/journal.pone.0086686. eCollection 2014.
The aim of this research was to investigate the anti-apoptotic, antioxidant and anti-inflammatory properties of menthol against ethanol-induced gastric ulcers in rats. Wistar rats were orally treated with vehicle, carbenoxolone (100 mg/kg) or menthol (50 mg/kg) and then treated with ethanol to induce gastric ulcers. After euthanasia, stomach samples were prepared for histological slides and biochemical analyses. Immunohistochemical analyses of the cytoprotective and anti-apoptotic heat-shock protein-70 (HSP-70) and the apoptotic Bax protein were performed. The neutrophils were manually counted. The activity of the myeloperoxidase (MPO) was measured. To determine the level of antioxidant functions, the levels of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD) were measured using ELISA. The levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the anti-inflammatory cytokine interleukin-10 (IL-10) were assessed using ELISA kits. The menthol treated group presented 92% gastroprotection compared to the vehicle-treated group. An increased immunolabeled area was observed for HSP-70, and a decreased immunolabeled area was observed for the Bax protein in the menthol treated group. Menthol treatment induced a decrease in the activity of MPO and SOD, and the protein levels of GSH, GSH-Px and GR were increased. There was also a decrease in the levels of TNF-α and IL-6 and an increase in the level of IL-10. In conclusion, oral treatment with menthol displayed a gastroprotective activity through anti-apoptotic, antixidant and anti-inflammatory mechanisms.
本研究旨在探讨薄荷醇对乙醇诱导的大鼠胃溃疡的抗凋亡、抗氧化和抗炎特性。Wistar 大鼠经口给予载体、卡波氯铵(100mg/kg)或薄荷醇(50mg/kg),然后用乙醇处理诱导胃溃疡。安乐死后,制备胃组织切片和生化分析样本。进行细胞保护和抗凋亡热休克蛋白 70(HSP-70)和凋亡 Bax 蛋白的免疫组织化学分析。手动计数中性粒细胞。测量髓过氧化物酶(MPO)的活性。为了确定抗氧化功能的水平,使用 ELISA 测定谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽还原酶(GR)和超氧化物歧化酶(SOD)的水平。使用 ELISA 试剂盒评估促炎细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)以及抗炎细胞因子白细胞介素-10(IL-10)的水平。与载体处理组相比,薄荷醇处理组的胃保护率为 92%。薄荷醇处理组 HSP-70 的免疫标记面积增加,Bax 蛋白的免疫标记面积减少。MPO 和 SOD 的活性降低,GSH、GSH-Px 和 GR 的蛋白水平增加。TNF-α 和 IL-6 的水平降低,IL-10 的水平升高。总之,口服薄荷醇通过抗凋亡、抗氧化和抗炎机制显示出胃保护活性。
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