Anti-inflammatory and antioxidative effects of gallic acid on experimental dry eye: in vitro and in vivo studies

Eye and Vision

Research

Xingyi Li¹  Qianwen Gong²  Zhiqiang Xu²  Fan Lu²  Kexin Li²  Yixuan Tong²  Meng Lin²  Kaiyan Huang²  Bin Lu²  Liang Hu²  Tinashe Emmanuel Mutsvene² 

[1] Institute of Biomedical Engineering, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, 325027, Wenzhou, People’s Republic of China;National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, 325027, Wenzhou, People’s Republic of China;National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, 325027, Wenzhou, People’s Republic of China;State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, 325027, Wenzhou, People’s Republic of China;

关键词: Corneal epithelial cells;    Macrophages;    Gallic acid;    Dry eye;    Inflammation;    Oxidative stress;   

DOI  :  10.1186/s40662-023-00334-5

 received in 2022-08-07, accepted in 2023-02-22,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTo investigate the anti-inflammatory and antioxidative effects of gallic acid (GA) on human corneal epithelial cells (HCECs) and RAW264.7 macrophages as well as its therapeutic effects in an experimental dry eye (EDE) mouse model.MethodsA cell counting kit-8 (CCK-8) assay was used to test the cytotoxicity of GA. The effect of GA on cell migration was evaluated using a scratch wound healing assay. The anti-inflammatory and antioxidative effects of GA in vitro were tested using a hypertonic model (HCECs) and an inflammatory model (RAW264.7 cells). The in vivo biocompatibility of GA was detected by irritation tests in rabbits, whereas the preventive and therapeutic effect of GA in vivo was evaluated using a mouse model of EDE.ResultsIn the range of 0–100 μM, GA showed no cytotoxicity in RAW264.7 cells or HCECs and did not delay the HCECs monolayer wound healing within 24 h. Ocular tolerance to GA in the in vivo irritation test was good after seven days. In terms of antioxidative activity, GA significantly reduced the intracellular reactive oxygen species (ROS) in lipopolysaccharide (LPS) activated RAW264.7 macrophages and HCECs exposed to hyperosmotic stress. Furthermore, after pre-treatment with GA, the expression levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase-1 (NQO-1) were significantly upregulated in RAW264.7 macrophages. GA also exhibits excellent anti-inflammatory properties. This is mainly demonstrated by the ability of GA to effectively downregulate the nuclear transcription factor-κB (NF-κB) pathway in LPS-activated RAW264.7 macrophages and to reduce inflammatory factors, such as nitric oxide (NO), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). In vivo efficacy testing results in a mouse model of EDE showed that GA can effectively prevent and inhibit the apoptosis of corneal epithelial cells (CECs), reduce inflammatory factors in the cornea and conjunctiva as well as protect goblet cells.ConclusionIn vitro and in vivo results indicate that GA possesses potent anti-inflammatory and antioxidative properties with no apparent cytotoxicity within the range of 0–100 μM. It is a promising eye drop formulation for the effective prevention and treatment of dry eye disease (DED).

【 授权许可】

CC BY   
© The Author(s) 2023

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