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Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 2: 268 - 276

DOI: https://doi.org/10.19852/j.cnki.jtcm.20240203.005

Emodin suppresses alkali burn-induced corneal inflammation and neovascularization by the vascular endothelial growth factor receptor 2 signaling pathway

  • Xueying ZHENG ,
  • Liang GUO ,
  • Siyi LAI ,
  • Fengyue LI ,
  • Mingli LIANG ,
  • Wanting LIU ,
  • Chun MENG ,
  • Guanghui LIU
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  • 1 Department of Bioengineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou 350104, China
    2 Department of Bioengineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou 350104, China; Eye Institute of Integrated Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350004, China
    3 Department of Ophthalmology, Affiliated People's Hospital (Fujian Provincial People's Hospital), Fujian University of Traditional Chinese Medicine, Fuzhou 350004, China
    4 Eye Institute of Integrated Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350004, China

Received date: 2022-11-22

  Accepted date: 2023-04-27

  Online published: 2024-02-03

Supported by

Fujian Major Research Grants for Young and Middle-aged Health Professionals(Research and Development of Anti-Keratitis Protein Drug Sgp130)(2021ZQNZD012);National Natural Science Foundation of China(Study on Mechanism of Yijing Decoction in Preventing Microvascular Damage of Early Diabetic Retinopathy based on MMPs/TIMPs)(81774369)

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Abstract

OBJECTIVE: To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.

METHODS: The ability of emodin to target vascular endothelial growth factor receptor 2 (VEGFR2) was predicted by molecular docking. The effects of emodin on the invasion, migration, and proliferation of human umbilical vein endothelial cells (HUVEC) were determined by cell counting kit-8, Transwell, and tube formation assays. Analysis of apoptosis was performed by flow cytometry. CD31 levels were examined by immunofluorescence. The abundance and phosphorylation state of VEGFR2, protein kinase B (Akt), signal transducer and activator of transcription 3 (STAT3), and P38 were examined by immunoblot analysis. Corneal alkali burn was performed on 40 mice. Animals were divided randomly into two groups, and the alkali-burned eyes were then treated with drops of either 10 μM emodin or phosphate buffered saline (PBS) four times a day. Slit-lamp microscopy was used to evaluate inflammation and corneal neovascularization (CNV) in all eyes on Days 0, 7, 10, and 14. The mice were killed humanely 14 d after the alkali burn, and their corneas were removed and preserved at －80 ℃ until histological study or protein extraction.

RESULTS: Molecular docking confirmed that emodin was able to target VEGFR2. The findings revealed that emodin decreased the invasion, migration, angiogenesis, and proliferation of HUVEC in a dose-dependent manner. In mice, emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali burn. Compared to those of the PBS-treated group, lower VEGFR2 expression and CD31 levels were found in the emodin-treated group. Emodin dramatically decreased the expression of VEGFR2, p-VEGFR2, p-Akt, p-STAT3, and p-P38 in VEGF-treated HUVEC.

CONCLUSION: This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization. Emodin might be a promising new therapeutic option for corneal alkali burns.

Key words： alkali burn; emodin; corneal inflammation; corneal neovascularisation; vascular endothelial growth factor receptor-2; signal transduction

Cite this article

Xueying ZHENG , Liang GUO , Siyi LAI , Fengyue LI , Mingli LIANG , Wanting LIU , Chun MENG , Guanghui LIU . Emodin suppresses alkali burn-induced corneal inflammation and neovascularization by the vascular endothelial growth factor receptor 2 signaling pathway[J]. Journal of Traditional Chinese Medicine, 2024 , 44(2) : 268 -276 . DOI: 10.19852/j.cnki.jtcm.20240203.005

References

1. Sharma N, Kaur M, Agarwal T, Sangwan VS, Vajpayee RB. Treatment of acute ocular chemical burns. Surv Ophthalmol 2018; 63: 214-35.
2. Bakunowicz-?azarczyk A, Urban B. Assessment of therapeutic options for reducing alkali burn-induced corneal neovascularization and inflammation. Adv Med Sci 2016; 61: 101-12.
3. Arima T, Uchiyama M, Nakano Y, et al. Peroxisome proliferator-activated receptor alpha agonist suppresses neovascularization by reducing both vascular endothelial growth factor and angiopoietin-2 in corneal alkali burn. Sci Rep 2017; 7: 17763.
4. Peach CJ, Mignone VW, Arruda MA, et al. Molecular pharmacology of VEGF-A isoforms: binding and signalling at VEGFR2. Int J Mol Sci 2018; 19: 1264.
5. Claesson-Welsh L, Welsh M. VEGFA and tumour angiogenesis. J Intern Med 2013; 273: 114-27.
6. Dong X, Fu J, Yin X, et al. Emodin: a review of its pharmacology, toxicity and pharmacokinetics. Phytother Res 2016; 30: 1207-18.
7. Xia S, Ni Y, Zhou Q, et al. Emodin attenuates severe acute pancreatitis via antioxidant and anti-inflammatory activity. Inflammation 2019; 42: 2129-38.
8. Du HX, Zhu JQ, Chen J, Zhou HF, Yang JH, Wan HT. Revealing the therapeutic targets and molecular mechanisms of emodin-treated coronavirus disease 2019 via a systematic study of network pharmacology. Aging 2021; 13: 14571-89.
9. Ji C, Xin G, Duan F, Huang W, Tan T. Study on the antibacterial activities of emodin derivatives against clinical drug-resistant bacterial strains and their interaction with proteins. Ann Transl Med 2020; 8: 92.
10. Ding Y, Liu P, Chen ZL, et al. Emodin attenuates lipopolysaccharide-induced acute liver injury via inhibiting the tlr 4 signaling pathway in vitro and in vivo. Front Pharmacol 2018; 9: 962.
11. Sun Y, Wang X, Zhou Q, et al. Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo. Oncol Rep 2015; 33: 338-46.
12. Dai G, Ding K, Cao Q, et al. Emodin suppresses growth and invasion of colorectal cancer cells by inhibiting VEGFR2. Eur J Pharmacol 2019; 859: 172525.
13. Xu K, Li B, Zhang S, et al. DCZ3301, An aryl-guanidino agent, inhibits ocular neovascularization via PI3K/AKT and ERK1/ 2 signaling pathways. Exp Eye Res 2020; 201: 108267.
14. Herbert SP, Stainier DY. Molecular control of endothelial cell behaviour during blood vessel morphogenesis. Nat Rev Mol Cell Biol 2011; 12: 551-64.
15. Cha TL, Chuang MJ, Tang SH, et al. Emodin modulates epigenetic modifications and suppresses bladder carcinoma cell growth. Mol Carcinog 2015; 54: 167-77.
16. Jia X, Yu F, Wang J, et al. Emodin suppresses pulmonary metastasis of breast cancer accompanied with decreased macrophage recruitment and M2 polarization in the lungs. Breast Cancer Res Treat 2014; 148: 291-302.
17. Jelassi B, Anchelin M, Chamouton J, et al. Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2X7 receptors. Carcinogenesis 2013; 34: 1487-96.
18. Chen GL, Zhang JJ, Kao X, Wei LW, Liu ZY. Emodin ameliorates lipopolysaccharides-induced corneal inflammation in rats. Int J Ophthalmol 2015; 8: 665-9.
19. Caligiuri G. CD31 as a therapeutic target in atherosclerosis. Circ Res 2020; 126: 1178-89.
20. Jackson JR, Bolognese B, Hillegass L, et al. Pharmacological effects of SB 220025, a selective inhibitor of P38 mitogen-activated protein kinase, in angiogenesis and chronic inflammatory disease models. J Pharmacol Exp Ther 1998; 284: 687-92.
21. Chen WL, Chen YM, Chu HS, et al. Mechanisms controlling the effects of bevacizumab (avastin) on the inhibition of early but not late formed corneal neovascularization. PLoS One 2014; 9: e94205.
22. Arulanandam R, Batenchuk C, Angarita FA, et al. VEGF-mediated induction of prd1-bf1/blimp1 expression sensitizes tumor vasculature to oncolytic virus infection. Cancer Cell 2015; 28: 210-24.
23. Kamran MZ, Gude RP. Pentoxifylline inhibits melanoma tumor growth and angiogenesis by targeting STAT3 signaling pathway. Biomed Pharmacother 2013; 67: 399-405.
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