LICACHALCONE A AND ITS DERIVATIVES PROMOTE NEURONAL DIFFERENTIATION OF AN EMBRYONIC STEM CELL LINE

The etiology and incidence of neurodegenerative illness have reached their pinnacle in
the realm of modern medicine. The main factor behind the neurodegenerative disease is
neuronal loss. The current treatment is focused on the induction of neuronal differentiation as
a therapeutic solution to promote neuronal regeneration. Small molecules promoting the
neuronal differentiation of embryonic stem cells in the central nervous system (CNS) can be
used as regenerative medicine. Licochalcone A (1) is a major polyphenolic compound from
Glycyrrhiza inflata (licorice). Licochalcone A exerts multiple biological activities such as antioxidative,
neuroprotective, antibacterial, anti-stroke, osteogenic, anti-inflammatory activity,
and antidepressant activity. These findings suggest that Licochalcone A is an ideal candidate
for treating neurological and neurodegenerative diseases. Although the crystal structure of LA
has been revealed, there have been few attempts to modify its structure for improving its
neuritogenic and anti-neurodegenerative activity. To the best of our knowledge, we report for
the first time that Licochalcone A (1) and its derivatives (2) or (3) or their combination induced
the differentiation of mammalian P19 embryonic stem cells to neuronal cell lines in vitro
[Durairajan et al. 2019 Indian Patent Appl. 201941038499]. By screening a series of
Licochalcone A synthetic analogs 2 or 3 or 4, we identified only 1, 2, and 3 but not 4 induced
neuronal differentiation of pluripotent P19 cells at 5 μM concentration of each compound from
1 to 7th day. The present study thus provides an effective method for reprogramming mouse
embryonic stem cells toward neuronal cells, using Licochalcone-A and/or its derivatives.
Keywords: Neurodegenerative diseases, Licachalcone A, Neurogenesis, Neuronal
Differentiation, ERK pathway.