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Gallic and vanillic acid suppress inflammation and promote myelination in an in vitro mouse model of neurodegeneration

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Abstract

Neuroinflammation affects millions of people around the world as a result of injury or stress. Neuroinflammation represents almost all types of neurological diseases such as multiple sclerosis and Alzheimer’s disease. Neurodegenerative diseases comprise demyelination and synaptic loss. The inflammatory response is further propagated by the activation of glial cells and modulation of constitutively expressed extracellular matrix proteins. The aim of the present study was to identify the anti-inflammatory effects of purified compounds gallic acid (GA, 1.0 µM) and vanillic acid (VA, 0.2 µM) on the lysolecithin (LPC, 0.003%)-induced model of inflammation. Hippocampal neurons were co-cultured with glial cells, and LPC was added to induce inflammation. Neurite outgrowth was measured by morphometry software. The level of myelination and demyelination was identified by immunostaining and sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting techniques using different antibodies. Whole-cell patch clamp recordings were used to observe the sustained repetitive firing pattern. The data showed that GA and VA significantly increased the neurite outgrowth after 48 h in culture. Both compounds significantly reduced the expression of cyclooxygenase-2, NFκB, tenascin-C, chondroitin sulfate proteoglycans and glial fibrillary acidic protein in astrocytes in the LPC-induced model of inflammation. The level of myelin protein in neurites and oligodendrocyte cell bodies was significantly upregulated by GA and VA treatment. The reduction in sustained repetitive firing in the LPC-induced model of inflammation was reversed by both GA and VA treatment. This study supports the hypothesis that VA and GA have anti-inflammatory activities and could be regarded as potential treatments for neurodegenerative disease.

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Acknowledgements

The authors are gratified for the Research Grant # 2680 provided by Higher Education Commission (HEC) of Pakistan.

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Authors and Affiliations

  1. Institute of Biomedical Sciences, Dow University of Health Sciences, Karachi, Pakistan

    Sonia Siddiqui

  2. Department of Neuroscience, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Sonia Siddiqui, Aisha Kamal & Faisal Khan

  3. Department of Surgery, Dow University of Health Sciences, Karachi, Pakistan

    Khawar Saeed Jamali

  4. HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Zafar Saeed Saify

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  1. Sonia Siddiqui
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Correspondence to Sonia Siddiqui.

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The experiments were performed to the Protocol 2015-0007, assigned by Advisory Committee on Animal Standards, ICCBS, University of Karachi.

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11033_2018_4557_MOESM1_ESM.tif

Supplementary material 1 (TIF 4782 KB) Supplementary Fig. 1 Dose–response effects of gallic and vanillic acid on hippocampal neurite outgrowth. a–d Neurons were cultured in the presence of different concentrations of GA and VA acid (µM: 0.1, 0.2, 0.5, 1, 1.5) for 48 h. a, c Mean average lengths of the 10 longest neurites from each group. b, d Sum of all neurite lengths was calculated as the sum of all neurites in each group (n = 180). Neurite lengths were measured by tracing the entire length of the neurite from the cell body. The results are shown as the means ± SD. Statistical differences were revealed by Mann–Whitney U-test. **p < 0.001

11033_2018_4557_MOESM2_ESM.tif

Supplementary material 2 (TIF 5956 KB). Supplementary Fig. 2 Expression of proteins. a and b Primary oligodendrocytes were stained with antibodies against TN-C and CSPGs. Asterisks shows the oligodendrocytes. Scale bar = 50 µm. c Neurons were stained with antibody against neurofilament. d Cortical astrocytes were stained with antibody against GFAP. Arrows represents neurons or astrocytes. Scale bar = 25 µm. e and f Neuroglial co-culture immunostained with antibodies against LN and CSPGs. Arrows represents neurons and arrowheads represents neurites. Scale bar = 25 µm. g and h Neurons were stained with antibodies against CSPG and TN-C. Asterisks shows neurons. Scale bar = 50 µm. i and j Astrocytes were stained with antibodies with LN and TN-C. Asterisks shows the astrocytes. Scale bar = 50 µm

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Siddiqui, S., Kamal, A., Khan, F. et al. Gallic and vanillic acid suppress inflammation and promote myelination in an in vitro mouse model of neurodegeneration. Mol Biol Rep 46, 997–1011 (2019). https://doi.org/10.1007/s11033-018-4557-1

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