Aidoo Douglas B, Obiri David D, Osafo Newman, Antwi Aaron O, Essel Leslie B, Duduyemi Babatunde M, Ekor Martins
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science & Technology, KNUST, Kumasi, Ghana.
Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri, Kansas City, USA.
Adv Pharmacol Sci. 2019 Feb 3;2019:6097349. doi: 10.1155/2019/6097349. eCollection 2019.
Bergapten (5-methoxypsoralen, 5-MOP) is a plant-derived furocoumarin with demonstrated anti-inflammatory action. The present study investigated its effects on allergic inflammation in two related pathways of mast cell degranulation. Compound 48/80 and lipopolysaccharide (LPS) were used to activate the IgE-independent pathway while bovine serum albumin (BSA) was used as allergen for the IgE-dependent pathway. The modulatory effect of bergapten on mast cell degranulation, neutrophil extravasation, protein concentration, lung histopathology, and oxidative stress was assessed. Bergapten at 10, 30, and 100 g/ml for 15 min stabilized mast cells in rat mesenteric tissue from disruption and when administered at 3, 10, and 30 mg kg for 1 h protected mice from fatal anaphylaxis induced by compound 48/80. Similarly, treatment of LPS-challenged mice with bergapten (3, 10, and 30 mg kg) for 24 h significantly decreased neutrophil infiltration into bronchoalveolar lavage fluid, mean protein concentration, and inflammatory cell infiltration of pulmonary tissues when compared to the saline-treated LPS-challenged control. In addition, lung histology of the bergapten-treated LPS-challenged mice showed significantly less oedema, congestion, and alveolar septa thickening when compared to the saline-treated LPS-challenged disease control. LPS-induced oxidative stress was significantly reduced through increased tissue activities of catalase and superoxide dismutase and reduced malondialdehyde levels on treatment with bergapten. In the triple antigen-induced active anaphylaxis, daily administration of bergapten at 3, 10, and 30 mg kg for 10 days, respectively, protected previously sensitized and challenged mice against anaphylactic shock. Overall, our study demonstrates the ability of bergapten to attenuate allergic airway-induced hypersensitivity in murine models of inflammation, suggesting its possible therapeutic benefit in this condition.
补骨脂素（5-甲氧基补骨脂素，5-MOP）是一种源自植物的呋喃香豆素，具有抗炎作用。本研究调查了其在肥大细胞脱颗粒的两个相关途径中对过敏性炎症的影响。化合物48/80和脂多糖（LPS）用于激活非IgE依赖性途径，而牛血清白蛋白（BSA）用作IgE依赖性途径的过敏原。评估了补骨脂素对肥大细胞脱颗粒、中性粒细胞渗出、蛋白质浓度、肺组织病理学和氧化应激的调节作用。10、30和100μg/ml的补骨脂素作用15分钟可稳定大鼠肠系膜组织中的肥大细胞，防止其破裂，当以3、10和30mg/kg给药1小时时，可保护小鼠免受化合物48/80诱导的致命过敏反应。同样，与盐水处理的LPS攻击对照组相比，用补骨脂素（3、10和30mg/kg）处理LPS攻击的小鼠24小时，可显著减少中性粒细胞向支气管肺泡灌洗液中的浸润、平均蛋白质浓度以及肺组织中的炎性细胞浸润。此外，与盐水处理的LPS攻击疾病对照组相比，补骨脂素处理的LPS攻击小鼠的肺组织学显示水肿、充血和肺泡间隔增厚明显减轻。补骨脂素处理后，通过增加过氧化氢酶和超氧化物歧化酶的组织活性以及降低丙二醛水平，显著降低了LPS诱导的氧化应激。在三联抗原诱导的主动过敏反应中，分别以3、10和30mg/kg的剂量每日给予补骨脂素10天，可保护先前致敏并受到攻击的小鼠免受过敏性休克。总体而言，我们的研究证明了补骨脂素在小鼠炎症模型中减轻过敏性气道诱导的超敏反应的能力，表明其在这种情况下可能具有治疗益处。
