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Identification of geraldol as an inhibitor of aquaporin‑4 binding by NMO‑IgG

  • Authors:
    • Jie Wang
    • Shuai Wang
    • Meiyan Sun
    • Huijing Xu
    • Wei Liu
    • Deli Wang
    • Lei Zhang
    • Yan Li
    • Jiaming Cao
    • Fang Li
    • Miao Li
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, The Third Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China, Medical Examination College, Jilin Medical University, Jilin, Jilin 132013, P.R. China, Medical Examination College, Jilin Medical University, Jilin, Jilin 132013, P.R. China, Department of Neurosurgery, The Third Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1111-1118
    |
    Published online on: June 4, 2020
       https://doi.org/10.3892/mmr.2020.11212
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Abstract

Neuromyelitis optica (NMO) is a severe neurological demyelinating autoimmune disease that affects the optic nerves and spinal cord. There is currently no effective cure or therapy. Aquaporin‑4 (AQP4) is a known target of the autoimmune antibody NMO‑IgG. Therefore, binding of NMO‑IgG to AQP4, and subsequent activation of antibody‑mediated and complement‑dependent cytotoxicity (CDC), are thought to underlie the pathogenesis of NMO. In the present study, a cell‑based high‑throughput screening approach was developed to identify molecular inhibitors of NMO‑IgG binding to AQP4. Using this approach, extracts from the herb Petroselinum crispum were shown to have inhibitory effects on NMO‑IgG binding to AQP4, and the natural compound geraldol was purified from the herb extracts. Analytical high performance liquid chromatography, electrospray ionization‑mass spectrometry and nuclear magnetic resonance analyses confirmed the identity of the isolated compound as geraldol, a flavonoid. Geraldol effectively blocked binding of NMO‑IgG to AQP4 in immunofluorescence assays and decreased CDC in NMO‑IgG/complement‑treated FRTL‑AQP4 cells and primary astrocytes. Geraldol exhibited low cytotoxicity, with no effect on proliferation or apoptosis of FRTL‑AQP4 cells and primary astrocytes. Permeability assays indicated that geraldol did not alter the water transport function of AQP4 in either cell system. The present study suggests the potential therapeutic value of geraldol for NMO drug development.
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Copy and paste a formatted citation
Spandidos Publications style
Wang J, Wang S, Sun M, Xu H, Liu W, Wang D, Zhang L, Li Y, Cao J, Li F, Li F, et al: Identification of geraldol as an inhibitor of aquaporin‑4 binding by NMO‑IgG. Mol Med Rep 22: 1111-1118, 2020.
APA
Wang, J., Wang, S., Sun, M., Xu, H., Liu, W., Wang, D. ... Li, M. (2020). Identification of geraldol as an inhibitor of aquaporin‑4 binding by NMO‑IgG. Molecular Medicine Reports, 22, 1111-1118. https://doi.org/10.3892/mmr.2020.11212
MLA
Wang, J., Wang, S., Sun, M., Xu, H., Liu, W., Wang, D., Zhang, L., Li, Y., Cao, J., Li, F., Li, M."Identification of geraldol as an inhibitor of aquaporin‑4 binding by NMO‑IgG". Molecular Medicine Reports 22.2 (2020): 1111-1118.
Chicago
Wang, J., Wang, S., Sun, M., Xu, H., Liu, W., Wang, D., Zhang, L., Li, Y., Cao, J., Li, F., Li, M."Identification of geraldol as an inhibitor of aquaporin‑4 binding by NMO‑IgG". Molecular Medicine Reports 22, no. 2 (2020): 1111-1118. https://doi.org/10.3892/mmr.2020.11212
Copy and paste a formatted citation
x
Spandidos Publications style
Wang J, Wang S, Sun M, Xu H, Liu W, Wang D, Zhang L, Li Y, Cao J, Li F, Li F, et al: Identification of geraldol as an inhibitor of aquaporin‑4 binding by NMO‑IgG. Mol Med Rep 22: 1111-1118, 2020.
APA
Wang, J., Wang, S., Sun, M., Xu, H., Liu, W., Wang, D. ... Li, M. (2020). Identification of geraldol as an inhibitor of aquaporin‑4 binding by NMO‑IgG. Molecular Medicine Reports, 22, 1111-1118. https://doi.org/10.3892/mmr.2020.11212
MLA
Wang, J., Wang, S., Sun, M., Xu, H., Liu, W., Wang, D., Zhang, L., Li, Y., Cao, J., Li, F., Li, M."Identification of geraldol as an inhibitor of aquaporin‑4 binding by NMO‑IgG". Molecular Medicine Reports 22.2 (2020): 1111-1118.
Chicago
Wang, J., Wang, S., Sun, M., Xu, H., Liu, W., Wang, D., Zhang, L., Li, Y., Cao, J., Li, F., Li, M."Identification of geraldol as an inhibitor of aquaporin‑4 binding by NMO‑IgG". Molecular Medicine Reports 22, no. 2 (2020): 1111-1118. https://doi.org/10.3892/mmr.2020.11212
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