Antidepressant-like activity of adhyperforin, a novel constituent of Hypericum perforatum L

Abstract

Adhyperforin is a novel constituent of Hypericum perforatum L., but its antidepressant-like activity remains unclear. To explore that, several well-validated animal models of depression as well as neurotransmitter reuptake and transporter binding assays were conducted. The results showed adhyperforin could reduce the immobility time of mice in the forced swimming test and tail suspension assay, antagonize the behaviors induced by reserpine, and have no effect on locomotor activity. Furthermore, following establishment of a chronic unpredictable mild stress model, adhyperforin increased the number of crossings and rearings in rats in the open field test and increased the sucrose consumption. Finally, adhyperforin inhibited uptake of serotonin, norepinephrine, and dopamine, and displayed robust binding affinities for the serotonin and norepinephrine transporters. Overall, the current study provides the first evidence that adhyperforin is a novel, active ingredient of Hypericum perforatum L. with robust antidepressant-like activity.

Figure 1. Effects of adhyperforin on the immobility times of mice in the forced swimming and tail suspension tests.

The animals were administered adhyperforin at doses of 8 and 16 mg/kg or FLU at 3.3 mg/kg by gavage, and then the immobility times of animals in the forced swimming test (A) and tail suspension test (B) were recorded. The data are presented as the mean ± SD (n = 8).

Figure 2. Effects of adhyperforin on spontaneous locomotor activity in mice.

The animals were administered adhyperforin at doses of 8 and 16 mg/kg or FLU at 3.3 mg/kg by gavage, and the OPT was used to detect the effects of the tested compounds on spontaneous locomotor activity. The data are presented as the mean ± SD (n = 8). *: p < 0.05, compared with the vehicle group.

Figure 3. Effects of adhyperforin on sucrose consumption in CUMS rats.

The CUMS model was established, the animals were treated with adhyperforin at doses of 8 and 16 mg/kg or FLU at 3.3 mg/kg by gavage, and then the sucrose consumptions of the animals were recorded and analyzed. The number of rats in each group was 12. The data are presented as the mean ± SD (n = 8). *: p < 0.05, compared with the control group; ^#: p < 0.05, compared with the CUMS-model group.

Figure 4. Effects of adhyperforin on the numbers of crossings and rearings by CUMS rats in the open field test.

The CUMS model was established, the animals were treated with adhyperforin at doses of 8 and 16 mg/kg or FLU at 3.3 mg/kg by gavage, and then the numbers of crossings and rearings of animals were observed. The data are presented as the mean ± SD (n = 8). *: p < 0.05, compared with the control group; ^#: p < 0.05, compared with the CUMS-model group.

Figure 5. Effects of adhyperforin on the uptake of 5-HT, NE, and DA.

Synaptosomes were prepared and incubated with ^[3H] 5-HT, ^[3H] NE or ^[3H] DA in the absence or presence of the test or reference compounds. The samples were terminated and rinsed and then detected by a scintillation counter. The data are presented as the mean ± SD (n = 3).

Figure 6. The binding affinities of adhyperforin for the hSERT, hNET and hDAT.

The cell membrane overexpressed hSERT, hNET, or hDAT were incubated with ^[3H] imipramine, ^[3H] nisoxetine, or ^[3H] BTCP, and then the samples were counted for radioactivity after complete rinsing. The data are presented as the mean ± SD (n = 3).