Astragalus Ⅳ ameliorates the dry eye injury in rabbit model via MUC1-ErbB1 pathway

Submitted: 11 November 2020
Accepted: 18 February 2021
Published: 1 April 2021
Abstract Views: 944
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The therapeutic effects and potential mechanisms of astragaloside IV on a rabbits dry eye model induced by benzalkonium chloride (BAC) was examined. In our study, a BAC-induced dry eye rabbit model was treated with eye drops containing astragaloside IV (5, 10 μM) or solvent four times a day. The clinical evaluations, such as tear break-up time (BUT) and Schirmer tear test (STT), were performed on days 0, 7, 14, 21, and 28. On day 28, the cornea and bulbar conjunctiva tissues (left eye and right eye) were collected with histology, and immunofluorescent staining conducted. The levels of MUC1 and ErbB1in the corneas were determined by real-time quantitative PCR (qRT-PCR) and the proteins levels of MUC1 and ErbB1 were detected by Western blot. It was demonstrated that both astragaloside IV (5, 10 μM) treatments resulted in an increased STT and BUT on days 7, 14, 21 and 28. Additionally, the astragaloside IV (5, 10 μM)-treated group showed increasing PAS-positive goblet cells than model group (0 μM). Moreover, the MUC1 in model group (0 μM) was decreased, while the expression of MUC1 in astragaloside IV (5, 10 μM) group was increased. Furthermore, astragaloside IV had a protective effect on BAC-induced rabbits’ dry eye and demonstrated clinical improvements, which indicated that astragaloside IV served as a potential protective agent in the clinical treatment of dry eye.

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Calonge M, Enríquez–de–Salamanca A, Diebold Y, González–García MJ, Reinoso R, Herreras JM, et al. Dry eye disease as an inflammatory disorder. Ocul Immunol Inflamm 2010;18:244-53. DOI: https://doi.org/10.3109/09273941003721926
Craig JP, Nelson JD, Azar DT, Belmonte C, Bron AJ, Chauhan SK, et al. The TFOS dry eye workshop II: executive summary. Ocul Surf 2017;15:802-12. DOI: https://doi.org/10.1016/j.jtos.2017.08.003
Kovács I, Luna C, Quirce S, Mizerska K, Callejo G, Riestra A, et al. Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease. J Pain 2016;157:399-417. DOI: https://doi.org/10.1097/j.pain.0000000000000455
Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, et al. TFOS DEWS II definition and classification report. Ocul Surf 2017;15:276-83. DOI: https://doi.org/10.1016/j.jtos.2017.05.008
You H, Lu Y, Gui D, Peng A, Chen J, Gu Y. Aqueous extract of Astragali Radix ameliorates proteinuria in adriamycin nephropathy rats through inhibition of oxidative stress and endothelial nitric oxide synthase. J Ethnopharmacol 2011;134:176-82. DOI: https://doi.org/10.1016/j.jep.2010.11.064
Cheng X, Gu J, Zhang M, Yuan J, Zhao B, Jiang J, Ji X. Astragaloside IV inhibits migration and invasion in human lung cancer A549 cells via regulating PKC-α-ERK1/2-NF-κB pathway. Int J Immunopharmaco 2014;23:304-13. DOI: https://doi.org/10.1016/j.intimp.2014.08.027
Gui D, Huang J, Guo Y, Chen J, Chen Y, Xiao W, et al. astragaloside IV ameliorates renal injury in streptozotocin–induced diabetic rats through inhibiting NF-κB-mediated inflammatory genes expression. Cytokine 2013;61:970-7. DOI: https://doi.org/10.1016/j.cyto.2013.01.008
Zhang WJ, Hufnagl P, Binder BR, Wojta J. Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF–κB activation and adhesion molecule expression. Thromb Haemost 2003;89:904-14. DOI: https://doi.org/10.1160/TH03-03-0136
Schroeder JA, Thompson MC, Gardner MM, Gendler SJ. Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen–activated protein kinase activation in the mouse mammary gland. J Biol Chem 2001;276:13057-64. DOI: https://doi.org/10.1074/jbc.M011248200
Imbert Y, Darling DS, Jumblatt MM, Foulks GN, Couzin EG, Steele PS, et al. MUC1 splice variants in human ocular surface tissues: possible differences between dry eye patients and normal controls. Exp Eye Res 2006;83:493-501. DOI: https://doi.org/10.1016/j.exer.2006.01.031
Inatomi T, Spurr-Michaud S, Tisdale AS, Zhan Q, Feldman ST, Gipson IK. Expression of secretory mucin genes by human conjunctival epithelia. Invest Ophth Vis Sci 1996;37:1684-92.
Spicer AP, Parry G, Patton S, Gendler SJ. Molecular cloning and analysis of the mouse homologue of the tumor–associated mucin, MUC1, reveals conservation of potential O–glycosylation sites, transmembrane, and cytoplasmic domains and a loss of minisatellite–like polymorphism. J Biol Chem 1991;266:15099-109. DOI: https://doi.org/10.1016/S0021-9258(18)98592-3
Siegel PM, Ryan ED, Cardiff RD, Muller WJ. Elevated expression of activated forms of Neu/ErbB‐2 and ErbB‐3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer. Embo J 1999;18:2149-64. DOI: https://doi.org/10.1093/emboj/18.8.2149
Onn A, Correa AM, Gilcrease M, Isobe T, Massarelli E, Bucana CD, et al. Synchronous overexpression of epidermal growth factor receptor and HER2-neu protein is a predictor of poor outcome in patients with stage I non-small cell lung cancer. Clin Cancer Res 2004;10:136-43. DOI: https://doi.org/10.1158/1078-0432.CCR-0373-3
Qi Y, Gao F, Hou L, Wan C. Anti–inflammatory and immunostimulatory activities of astragaloside IVs. Am J Chinese Med 2017;45:1157-67. DOI: https://doi.org/10.1142/S0192415X1750063X
Yang J, Wang HX, Zhang YJ, Yang YH, Lu ML, Zhang J, et al. astragaloside IV attenuates inflammatory cytokines by inhibiting TLR4/NF-кB signaling pathway in isoproterenol–induced myocardial hypertrophy. J Ethnopharmacol 2013;150:1062-70. DOI: https://doi.org/10.1016/j.jep.2013.10.017
Zhou X, Sun X, Gong X, Yang Y, Chen C, Shan G, et al. astragaloside IV from Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting inflammation via TLR4/NF-кB in vivo and in vitro. Int Immunopharmacol 2017;42:18-24. DOI: https://doi.org/10.1016/j.intimp.2016.11.006
Zhang Z, Yang WZ, Zhu ZZ, Hu QQ, Chen YF, He H, et al. Therapeutic effects of topical doxycycline in a benzalkonium chloride-induced mouse dry eye model. Invest Ophth Vis Sci 2014;55:2963-74. DOI: https://doi.org/10.1167/iovs.13-13577
Toshida H, Nguyen DH, Beuerman RW, Murakami A. Neurologic evaluation of acute lacrimomimetic effect of cyclosporine in an experimental rabbit dry eye model. Invest Ophth Vis Sci 2009;50:2736-41. DOI: https://doi.org/10.1167/iovs.08-1880
Oh JY, In YS, Kim MK, Ko JH, Lee HJ, Shin KC, et.al. Protective effect of uridine on cornea in a rabbit dry eye model. Invest Ophth Vis Sci 2007;48:1102-9. DOI: https://doi.org/10.1167/iovs.06-0809
Gipson IK. Distribution of mucins at the ocular surface. Exp Eye Res 2004;78:379-88. DOI: https://doi.org/10.1016/S0014-4835(03)00204-5
Gipson IK, Argueso P. Role of mucins in the function of the corneal and conjunctival epithelia. Int Rev Cytol 2003;231:1-49. DOI: https://doi.org/10.1016/S0074-7696(03)31001-0
Watanabe H. Significance of mucin on the ocular surface. Cornea 2002;21:S17-22. DOI: https://doi.org/10.1097/00003226-200203001-00005
Baudouin C, Rolando M, Del Castillo JMB, Messmer EM, Figueiredo FC, Irkec M, et al. Reconsidering the central role of mucins in dry eye and ocular surface diseases. Prog Retin Eye Res 2019;71:68-87. DOI: https://doi.org/10.1016/j.preteyeres.2018.11.007
Johnson ME, Murphy PJ. Changes in the tear film and ocular surface from dry eye syndrome. Prog Retin Eye Res 2004;23:449-74. DOI: https://doi.org/10.1016/j.preteyeres.2004.04.003
Albietz JM. Dry eye: an update on clinical diagnosis, management and promising new treatments. Clin Exp Optom 2001;84:4-18. DOI: https://doi.org/10.1111/j.1444-0938.2001.tb04930.x
Zhang X, Qu Y, He X, Ou S, Bu J, Jia C, et.al. Dry eye management: targeting the ocular surface microenvironment. Int J Mol Sci 2017;18:1398. DOI: https://doi.org/10.3390/ijms18071398
Wolosin JM, Budak MT, Akinci MAM. Ocular surface epithelial and stem cell development. Int J Dev Biol 2004;48:981-91. DOI: https://doi.org/10.1387/ijdb.041876jw
Carraway KL, Ramsauer VP, Haq B, Carothers Carraway CA. Cell signaling through membrane mucins. Bioessays 2003;25:66-71. DOI: https://doi.org/10.1002/bies.10201
Li Y, Yu WH, Ren J, Chen W, Huang L, Kharbanda S, et al. Heregulin targets γ-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein. Mol Cancer Res 2003;1:765-75.
Muraoka-Cook RS, Feng SM, Strunk KE, Earp HS. ErbB4/HER4: role in mammary gland development, differentiation and growth inhibition. J Mammary Gland Biol Neoplasia 2008;13:235-46. DOI: https://doi.org/10.1007/s10911-008-9080-x

How to Cite

Chu, L., Ma, S., Chen, Z., & Cao, W. (2021). Astragalus Ⅳ ameliorates the dry eye injury in rabbit model <em>via</em> MUC1-ErbB1 pathway. European Journal of Histochemistry, 65(2). https://doi.org/10.4081/ejh.2021.3198