Studies On The Anxiolytic Effects Of Riboflavin Tetrabutyrate

Aim To investigate the anxiolytic effects of riboflavin tetrabutyrate (RTB) and to explore the mechanisms of its anxiolytic activities preliminarily.Methods1. The pharmacodynamic studies of RTB on anxiety modelsSeveral behavioral pharmacological models were used to evaluate anxiolytic effects of RTB, including elevated plus-maze (EPM) test, light-dark box test, the staircase test, the novel food consumption test, and the holeboard test.2. The effects of RTB on muscle coordination and motor coordination of miceRotarod test, traction test, and sloping panel test on mice were utilized to determine whether or not RTB has impairment on muscle coordination and motor coordination.3. The effects of RTB on central nervous systemThe mice spontaneous locomotor acitivity test was used to investigate the side effect of RTB on central nervous system.4. The effects of RTB on behavior of mice in acute stress+EPM testExperimental mice were stimulated with electric shock on feet for 3 days to form a state of anxiety disorder, then were tested in EPM to further verify anxiolytic effects of RTB under acute stress circumstance.5. The mechanisms of anxiety effects of RTBThe contents of norepinephrine (NE) in the cerebrums and nitric oxide (NO) in the serums of the mice tested in the acute stress+EPM model were measured to explore the mechanisms of anxiolytic effects of RTB preliminarily.Result1. The results from the behavioral pharmacological studies showed that RTB had anxiolytic effect. In the EPM test, RTB did not change the total arm entries (OE+OT) of mice at 20,40, and 80 mg·kg-1. Whereas, OT% of the group administered with 20 mg·kg-1 of RTB increased significantly compared with the blank control group, so did OE% and OT% of the group with 40 mg·kg-1 of RTB. Furthermore, RTB at the dose of 40 mg·kg-1 increased the head-dipping counts and rearing counts significantly compared with the blank control group. In light-dark box test, the mice administered with 40 mg·kg-1 of RTB crossed more lattices in light box and transited more between light and dark box than those in the blank control group. Additionally, RTB at the dose of 20 and 40 mg·kg-1 increased the time spent in light box signifficantly. In the staircase test, RTB at the dose of 20 and 40 mg·kg-1 decreased the number of rearing significantly compared with the blank control group. In the novel food consumption test, the mice administered 80 mg·kg-1 of RTB consumed more novel food (mg·kg-1) than those having in the blank control group. In the holeboard test, RTB did not display effect on head-dipping behavior of mice, but at the dose of 40 mg·kg-1, RTB increased the rearing duration, and at 20 and 40 mg·kg-1, increased rearing counts significantly compared with the blank control.2. The results from the rotarod test, the traction test, and the sloping panel test showed that RTB did not impair muscle and sports coordination of mice. In the rotarod test, the rate of falling of mice from rotarod had no differences between groups having 20,40, and 80 mg·kg-1 of RTB and blank control group. In the traction test, the treatment with 20,40, and 80 mg·kg-1 of RTB had no significant effects on mice. In the sloping panel test, the reference drugs, DZP and Buspirone, significantly decreased the inclined angle of the sloping panel, but RTB did not.3. The results from mice spontaneous locomotor activity test displayed that RTB had no inhibitory or excitant effects on central nervous system in mice.4. In the acute stress+EPM test, RTB can improve the behaviors of acute-stressed mice in EPM at the dose of 20,40 and 80 mg·kg-1. OE% and OT% increased significantly compared with those of the model group.5. The contents of norepinephrine in the cerebrums of the acute-stressed mice in RTB groups were lower than those in the blank control group. However, the contents of nitric oxide in serum did not change significantly after mice were administered with RTB.ConclusionRTB showed anxiolytic activity on mice. Meanwhile, RTB did not impair muscle and sports coordination, and did not inhibit or excite central nervous system of mice. So RTB can be used as a novel anti-anxiety drug without obvious toxic and side effects.