Anti-Depressant Like Effect of Methyl Gallate Isolated from Acer barbinerve in Mice

Abstract

In the present study, the anti-depressant like effect of methyl gallate (MG) isolated from the stem bark of Acer barbinerve was examined in ICR mice. Body weight (BDW) and blood glucose (BDG) levels significantly decreased in the repeated restraint stress (RRS) group (2 h/day for 14 days) compared to the no stress (NS) group. To examine the effect of MG on RS-induced BDW loss and hypoglycemia, MG (10 mg/kg) and the anti-depressant fluoxetine (10 mg/kg) were administered daily for 14 days. Orally administered MG and fluoxetine significantly attenuated the RS-induced BDW loss and hypoglycemia. Interestingly, MG administered mice showed increased BDG levels in the normal and glucose feeding condition. Chronic RS-subjected mice showed immobilized and depressed behaviors. The effect of MG on the depressed behaviors was evaluated using the tail-suspension test (TST) and the forced swimming test (FST). In both tests, RS-induced immobilized behaviors were significantly reversed in MG and fluoxetine administered groups. Taken together, MG significantly attenuated the RS-induced BDW loss, hypoglycemia, and depressed behaviors. Considering that decreased BDG levels (hypoglycemia) can cause depression, MG may exert its anti-depressant like effect by preventing hypoglycemia. Our results suggest that MG isolated from A. barbinerve can exert anti-depressant like effect, and could be used as a new and natural anti-depressant therapy.

Keywords: Acer barbinerve; Anti-depressant; Hypoglycemia; Methyl gallate; Restraint stress.

Fig. 1

Structure of methyl gallate and experimental design. (A) Structure of methyl gallate (MG). (B) Experimental design. Mice were subjected to RS (2 h/day for 14 days). Mice were orally fed with MG (10 mg/kg) and fluoxetine (10 mg/kg) daily up to 14 days. Body weight (BDW) and blood glucose (BDG) levels were measured on day before RS exposure at every day or every 3 days.

Fig. 2

Effect of MG on RS-induced BDW loss. (A) BDW was measured every 3 days in NS and RS (2 h/day for 14 days) groups. (B) Mice were orally fed with MG (10 mg/kg) and fluoxetine (10 mg/kg) daily up to 14 days. BDW was measured on day 14 before RS exposure. Values are mean±SEM (A: ^***p<0.001; compared to each NS group, n=12, B: ^**p<0.01; compared to NS group, ⁺p<0.05; RS+VHC vs RS+fluoxetine, RS+VHC vs RS+MG, n=8).

Fig. 3

Effect of MG on RS-induced hypoglycemia. (A) BDG level was measured every 3 days in NS and RS (2 h/day for 14 days) groups. (B) Mice were orally fed with MG (10 mg/kg) and fluoxetine (10 mg/kg) daily up to 14 days. BDG level was measured on day 14 before RS exposure. (C) Mice were orally fed with MG (10 mg/kg) daily up to 21 days. BDG level was measured on day before RS exposure every 3 days. Values are mean±SEM (A: ^***p<0.001; compared to each NS group, n=14, B: ^*p<0.05, ^**p<0.01; compared to NS group, ⁺p<0.05; RS-VHC vs RS-fluoxetine, RS-VHC vs RS-MG, n=7, C: ^**p<0.01; compared to each NS group, ⁺p<0.05; RS+VHC vs RS+MG, n=6).

Fig. 4

Effect of MG on BDG level in OGTT. Mice were administered orally with D-glucose (2 g/kg) at 30 min after orally pretreatment with MG (10 and 20 mg/kg). The BDG level was measured at 30, 60, and 120 min after D-glucose feeding. Values are mean±SEM (^*p<0.05; compared to VHC+D-Glu group, n=5).

Fig. 5

Effect of MG on RS-induced depressive behaviors. (A) Experimental design for behavioral analyses. Mice were subjected to RS (2 h/day for 14 days). Mice were orally treated with MG (10 mg/kg) and fluoxetine (10 mg/kg) daily for up to 14 days. Total immobilized time was measured on day 14 after final RS exposure using tail-suspension test (TST) (B) and forced swimming test (FST) (C). Values are mean±SEM (B and C: ^*p<0.05, ^***p<0.001; compared to NS group, ⁺p<0.05, ⁺⁺p<0.01, ⁺⁺⁺p<0.001; RS-VHC vs RS-fluoxetine, RS-VHC vs RS-MG, n=10).