Zhao Mincong, Liu Li, Zheng Yating, Liu Guangrong, Che Biao, Li Penghui, Chen Huixiong, Dong Changzhi, Lin Li, Du Zhiyun
Institute of Natural Medicine & Green Chemistry, School of Biomedical and Pharmaceutical Engineering, Guandong University of Technology Guangzhou 510006 China
Infinitus (China) Company Ltd Jiangmen 529156 China.
RSC Adv. 2019 Apr 29;9(23):12998-13006. doi: 10.1039/c8ra09060b. eCollection 2019 Apr 25.
Dry eye disease (DED) is characterized by increased osmolality of tears due to a lack of production or increased evaporation of tears. Hyperosmolarity is involved in DED pathogenesis, which damages ocular surface cells and leads to inflammation of the ocular surface. We investigated the anti-inflammatory effect of paeoniflorin (PF) from Pall. on human corneal epithelial (HCE) cells and its molecular mechanisms, and its therapeutic effects on a mouse model of experimental dry eye (EDE). HCE cells were treated with PF-1 (PF prepared ; 0.01%, 0.1% and 1.0%). Protein production/activity was determined by Western blotting, RT-PCR and immunofluorescent staining. Meanwhile, eye drops containing 0.01%, 0.1% and 1.0% of PF-2 (PF prepared ) were applied to the EDE, and the tear volume, corneal fluorescein-staining score, detachment of the corneal epithelium, and immunohistochemical staining were measured after 28 days of treatment. PF reduced expression of proinflammatory factors such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α in HCE cells, and significantly improved dry-eye signs, including tear volume, desquamation of the corneal epithelium and ocular surface inflammation in mice treated with 1.0% PF-2. Further study showed that PF improved EDE by inhibiting mitogen-activated protein kinase (MAPK), phosphorylated (p)-c-Jun N-terminal kinase (JNK) and pp-38, and nuclear factor kappa B (NF-κB) signaling pathways. These data suggest that PF can improve dry-eye symptoms and reduce expression of proinflammatory mediators. Hence, eye drops containing PF could be used as an adjunctive treatment for DED.
干眼症（DED）的特征是由于泪液分泌不足或蒸发增加导致泪液渗透压升高。高渗参与了干眼症的发病机制，它会损害眼表细胞并导致眼表炎症。我们研究了芍药苷（PF）对人角膜上皮（HCE）细胞的抗炎作用及其分子机制，以及其对实验性干眼症（EDE）小鼠模型的治疗效果。用PF-1（制备的PF；0.01%、0.1%和1.0%）处理HCE细胞。通过蛋白质印迹法、逆转录-聚合酶链反应（RT-PCR）和免疫荧光染色来测定蛋白质的产生/活性。同时，将含有0.01%、0.1%和1.0% PF-2（制备的PF）的眼药水应用于EDE小鼠，在治疗28天后测量泪液体积、角膜荧光素染色评分、角膜上皮脱离和免疫组织化学染色。PF降低了HCE细胞中白细胞介素（IL）-1、IL-6和肿瘤坏死因子（TNF）-α等促炎因子的表达，并显著改善了干眼症症状，包括用1.0% PF-2处理的小鼠的泪液体积、角膜上皮脱屑和眼表炎症。进一步的研究表明，PF通过抑制丝裂原活化蛋白激酶（MAPK）、磷酸化（p）-c-Jun氨基末端激酶（JNK）和pp-38以及核因子κB（NF-κB）信号通路来改善EDE。这些数据表明PF可以改善干眼症症状并降低促炎介质的表达。因此，含有PF的眼药水可作为干眼症的辅助治疗药物。
