Antihypernociceptive, Anxiolytic, and Antidepressant Properties of Aqueous and Ethanol Extracts of Dissotis thollonii Cogn. (Melastomataceae) in Mice

Abstract

Diabetic neuropathy, which affects 7 to 9% of the world's population and that is usually accompanied by anxiety and depression, is chronic pain that results from impaired function of the central or peripheral nervous system. This study aimed at evaluating the antihypernociceptive, antiallodynic, anxiolytic, and antidepressant effects of Dissotis thollonii extracts. Diabetic neuropathy was induced by intraperitoneal injection of streptozotocin (200 mg/kg) in mice. The aqueous and ethanol extracts (250 and 500 mg/kg) were administered orally. Hyperalgesia (thermal and chemical), allodynia (mechanical and thermal), anxiety (high plus labyrinth, light-dark box, and social interaction), and depression (open field test, suspension test tail, and forced swimming test) were evaluated, and then the levels of some cytokines and growth factors were determined. The aqueous and ethanol extracts of Dissotis thollonii demonstrated significant antihypernociceptive (inhibition of hyperalgesia and allodynia), anxiolytic, and antidepressant activities in mice made diabetic by STZ. The extracts also significantly inhibited (p < 0.001) the levels of TNF-α, IL-1β, and IL-6 in the blood as well as the levels of TNF-α, IL-1β, IL-6, IGF, and NGF in the sciatic nerve. This study shows that the extracts of Dissotis thollonii have antihypernociceptive and neuroprotective effects which could be linked to the inhibition of proinflammatory cytokines and growth factors in the blood and the sciatic nerve.

Figure 1

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on mechanical allodynia induced by Von Frey. Values are expressed as mean ± SEM for six animals and analyzed by two-way ANOVA followed by Bonferroni post hoc test. ^αp < 0.05, ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control.

Figure 2

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on cold allodynia induced by acetone. Values are expressed as mean ± SEM for six animals and analyzed by two-way ANOVA followed by Bonferroni post hoc test. ^αp < 0.05, ^βp < 0.01, ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control.

Figure 3

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on thermal hyperalgesia induced by hot plate. Values are expressed as mean ± SEM for six animals and analyzed by two-way ANOVA followed by Bonferroni post hoc test. ^βp < 0.01, ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^cp < 0.001 when compared with the diabetic control.

Figure 4

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on hyperalgesia induced by formalin. Values are expressed as mean ± SEM for six animals and analyzed by one-way ANOVA followed by the Tukey post hoc test. ^αp < 0.05, ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control.

Figure 5

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on the levels of TNF-α, IL-1β, and IL-6 in the serum of diabetic mice. Values are expressed as mean ± SEM for six animals and analyzed by one-way ANOVA followed by the Tukey post hoc test. ^αp < 0.05, ^βp < 0.01, ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control.

Figure 6

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on the levels of TNF-α, IL-1β, and IL-6 in the sciatic nerve of diabetic mice. Values are expressed as mean ± SEM for six animals and analyzed by one-way ANOVA followed by the Tukey post hoc test. ^αp < 0.05, ^βp < 0.01, ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control.

Figure 7

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on the levels of IGF and NGF in the sciatic nerve of diabetic mice. Values are expressed as mean ± SEM for six animals and analyzed by one-way ANOVA followed by the Tukey post hoc test. ^βp < 0.01, ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control.

Figure 8

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on the absolute time spent in the open arms (a) and close arms (b) during 6 min of exposure to the elevated plus maze. Values are expressed as mean ± SEM for six animals and analyzed by two-way ANOVA followed by Bonferroni post hoc test. ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control; s: seconds.

Figure 9

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on the absolute time spent in the open arms (light) compartment during 5 min of exposure to the light-dark box test. Values are expressed as mean ± SEM for six animals and analyzed by two-way ANOVA followed by Bonferroni post hoc test. ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control; s: seconds.

Figure 10

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on the absolute time spent for social interaction during 5 min. Values are expressed as mean ± SEM for six animals and analyzed by two-way ANOVA followed by Bonferroni post hoc test. ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^cp < 0.001 when compared with the diabetic control; s seconds.

Figure 11

Effects the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on the immobility time in the force swimming test during 5 min. Values are expressed as mean ± SEM for six animals and analyzed by two-way ANOVA followed by Bonferroni post hoc test. ^βp < 0.01, ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control; s: seconds.

Figure 12

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on the immobility time of mice in the tail suspension test during 5 min. Values are expressed as mean ± SEM for six animals and analyzed by two-way ANOVA followed by Bonferroni post hoc test. ^αp < 0.05, ^βp < 0.01, ^λp < 0.001 when compared with the normal control and ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 when compared with the diabetic control; s seconds.

Figure 13

Effects of the aqueous (AE) and ethanol (EE) extracts of Dissotis thollonii on the locomotor activity of mice in the open field test during 5 mins. Values are expressed as mean ± SEM for six animals and analyzed by two-way ANOVA followed by Bonferroni post hoc test. ^αp < 0.05, ^βp < 0.01, ^λp < 0.001 when compared with the normal control.