Vol.:(0123456789) 1 3
Molecular Biology Reports
https://doi.org/10.1007/s11033-018-4557-1
ORIGINAL ARTICLE
Gallic and vanillic acid suppress inflammation and promote
myelination in an in vitro mouse model of neurodegeneration
Sonia Siddiqui
1,2
· Aisha Kamal
2
· Faisal Khan
2
· Khawar Saeed Jamali
3
· Zafar Saeed Saify
4
Received: 3 May 2018 / Accepted: 6 December 2018
© Springer Nature B.V. 2018
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 lysoleci-
thin (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 repeti-
tive 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 sup-
ports the hypothesis that VA and GA have anti-inflammatory activities and could be regarded as potential treatments for
neurodegenerative disease.
Keywords Lysolecithin · CNS injury · Remyelination · GA · VA · ECM proteins
Introduction
Neuroinflammatory diseases are a significant problem and
a complicated multi-factorial process in the brain that is
believed to play a crucial role in the development of neu-
rodegenerative diseases. The extracellular matrix (ECM) is
a mesh work of intricate macromolecules that provide the
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s11033-018-4557-1) contains
supplementary material, which is available to authorized users.
* Sonia Siddiqui
siddisbs@yahoo.com
Aisha Kamal
aisha.kamal@iccs.edu
Faisal Khan
faisal.khan@iccs.edu
Khawar Saeed Jamali
khawarjamali@gmail.com
Zafar Saeed Saify
zssaify@gmail.com
1
Institute of Biomedical Sciences, Dow University of Health
Sciences, Karachi, Pakistan
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
3
Department of Surgery, Dow University of Health Sciences,
Karachi, Pakistan
4
HEJ Research Institute of Chemistry, International Center
for Chemical and Biological Sciences, University of Karachi,
Karachi 75270, Pakistan