Abstract
Glycyrrhizin has a role in immune regulation in the central nervous system, but its impact on sciatic nerve injury had not previously been reported. In this study, a BALB/c mouse model of sciatic nerve injury was used to explore the role of glycyrrhizin in sciatic nerve repair and its underlying mechanism. Glycyrrhizin with intragastric gavage of 10 and 20 mg/kg weight per day (mid- and high-dose, respectively) inhibited p75 neurotrophin receptor (p75NTR) expression at the protein and mRNA levels versus the 5 mg/kg (low-dose) group and control (0.9% NaCl solution) at one, two, four and eight weeks following sciatic nerve injury, and simultaneously improved the action potential amplitude and motor nerve conductive velocity. Combined Marsland, Glees and Erikson’s silver stain and Luxol fast blue staining results indicated that high- and mid-dose glycyrrhizin promoted improved sciatic nerve myelination compared with the low-dose or control groups eight weeks after injury. Immunofluorescence staining demonstrated that glycyrrhizin had an inhibitory effect to a certain degree on local hypertrophic scar and inflammatory responses in the mouse model. In conclusion, glycyrrhizin can promote sciatic nerve regeneration and functional repair, in which doses of 10 and 20 mg/kg per day are more effective than lower doses, and such regeneration is associated with the downregulation of p75NTR.
Highlights
Glycyrrhizin, a naturally occurring licorice flavonoid glycoside extracted from licorice (Glycyrrhiza uralensis Fisch) root has been reported to have multiple functions [1,2,3]; it can scavenge free radicals, have anti‐bacterial, anti‐inflammatory, antiviral and anti‐ulcer effects and protect cytochrome enzymes as an antioxidant [1,2,3,4,5,6]
The present study explored the reparative effects of glycyrrhizin on sciatic nerve injury and the p75 neurotrophin receptor (p75NTR)‐associated immune inflammatory response in a BALB/c mouse model
The functional recovery of the sciatic nerves was determined by the action potential amplitude and Motor nerve conductive velocity (MNCV) (Table I)
Summary
Glycyrrhizin, a naturally occurring licorice flavonoid glycoside extracted from licorice (Glycyrrhiza uralensis Fisch) root has been reported to have multiple functions [1,2,3]; it can scavenge free radicals, have anti‐bacterial, anti‐inflammatory, antiviral and anti‐ulcer effects and protect cytochrome enzymes as an antioxidant [1,2,3,4,5,6]. Studies have shown that glycyrrhizin can regulate the secretion of various cytokines and the functioning of immunomodulatory effects in the central nervous system [6,7]. During 20 years of anti‐inflammatory application for the treatment of liver diseases, glycyrrhizin has not generated any toxicity or side-effects [10,11,12]. The effects of glycyrrhizin on functional recovery following peripheral nerve injury are not well understood. The p75 neurotrophin receptor (p75NTR), one of the nerve signaling proteins, plays a significant role in neuronal survival, apoptosis and axonal growth in the peripheral and central nervous systems. The present study explored the reparative effects of glycyrrhizin on sciatic nerve injury and the p75NTR‐associated immune inflammatory response in a BALB/c mouse model
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