Lee Ba-Wool, Ha Ji-Hye, Ji Yeongseon, Jeong Seong-Hun, Kim Ju-Hong, Lee Jihye, Park Ji-Young, Kwon Hyung-Jun, Jung Kyungsook, Kim Jong-Choon, Ryu Young-Bae, Lee In-Chul
Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, South Korea.
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea.
Front Pharmacol. 2021 Feb 10;12:614442. doi: 10.3389/fphar.2021.614442. eCollection 2021.
(Spach) Rupr. (AH), a member of the Betulaceae family, is widely used in Eastern Asia of as a source of medicinal compounds for the treatment of hemorrhage, diarrhea, and alcoholism. In this study, we investigated the protective effects of a methanolic extract of AH branches against airway inflammation and mucus production in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in an ovalbumin (OVA)-challenged allergic asthma mouse model. Female BALB/c mice were injected with OVA (40 μg) and aluminum hydroxide (2 mg) on days 0 and 14 to induce allergic airway inflammation. The mice were then challenged with 1% OVA from days 21-23. Mice were treated with AH (50 and 100 mg/kg/day; 2% DMSO) or dexamethasone (positive control; 3 mg/kg/day) from days 18-23. AH treatment effectively attenuated airway resistance/hyperresponsiveness and reduced levels of T helper type 2 (Th2) cytokines, eotaxins, and number of inflammatory cells in bronchoalveolar lavage fluid, and immunoglobulin E in serums of OVA-challenged mice. In histological analysis, AH treatment significantly inhibited airway inflammation and mucus production in OVA-challenged mice. AH treatment downregulated the phosphorylation of I kappa B-alpha, p65 nuclear factor-kappa B (p65NF-κB), and mitogen-activated protein kinases with suppression of mucin 5AC (MUC5AC) in lung tissue. Moreover, AH treatment decreased the levels of pro-inflammatory cytokines and Th2 cytokines, as well as MUC5AC expression, and inhibited the phosphorylation of p65NF-κB in TNF-α-stimulated NCI-H292 cells. These results indicate that AH might represent a useful therapeutic agent for the treatment of allergic asthma.
桦木科植物糙皮桦（Rupr. (AH)）在东亚被广泛用作治疗出血、腹泻和酗酒的药用化合物来源。在本研究中，我们研究了糙皮桦树枝甲醇提取物对肿瘤坏死因子（TNF）-α刺激的NCI-H292细胞以及卵清蛋白（OVA）激发的过敏性哮喘小鼠模型中气道炎症和黏液产生的保护作用。雌性BALB/c小鼠在第0天和第14天注射OVA（40μg）和氢氧化铝（2mg）以诱导过敏性气道炎症。然后在第21至23天用1%OVA对小鼠进行激发。从第18至23天，小鼠接受糙皮桦（50和100mg/kg/天；2%DMSO）或地塞米松（阳性对照；3mg/kg/天）治疗。糙皮桦治疗有效减轻了气道阻力/高反应性，并降低了OVA激发小鼠支气管肺泡灌洗液中2型辅助性T细胞（Th2）细胞因子、嗜酸性粒细胞趋化因子的水平以及炎症细胞数量，以及血清中的免疫球蛋白E。在组织学分析中，糙皮桦治疗显著抑制了OVA激发小鼠的气道炎症和黏液产生。糙皮桦治疗下调了肺组织中IκB-α、p65核因子-κB（p65NF-κB）的磷酸化以及丝裂原活化蛋白激酶，并抑制了黏蛋白5AC（MUC5AC）。此外，糙皮桦治疗降低了促炎细胞因子和Th2细胞因子的水平以及MUC5AC的表达，并抑制了TNF-α刺激的NCI-H292细胞中p65NF-κB的磷酸化。这些结果表明，糙皮桦可能是治疗过敏性哮喘的一种有用的治疗剂。
