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Effect of xanthone derivatives on animal models of depression.

Zhao X, Chen Q, Liu Y, Xia C, Shi J, Zheng M - Curr Ther Res Clin Exp (2014)

Bottom Line: The oral acute toxicity studies of 2 xanthone derivatives (1101 and 1105) did not show any toxic effect until the dose at 1000 mg/kg body weight, and xanthone derivatives 1101 and 1105 resulted in a significant decrease of the immobility period (in seconds) compared with the untreated control group during the forced swim test with rats (dose = 12 mg/kg; P < 0.05) and mice (dose = 25 mg/kg; P < 0.001).At lower doses, derivatives 1101 and 1105 also decreased the immobility period of rats and mice during the forced swim test but significant differences were only found in mice compared with the untreated control group (P < 0.05).Compared with the positive venlafaxine control group, no differences were found between those treated with either derivative 1101 or derivative 1105 and venlafaxine (P > 0.05).

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Nanjing University of Technology, Nanjing, China.

ABSTRACT

Background: Extracts of the plant Hypericum perforatum L. have been traditionally used in folk medicine for the treatment of depressive disorders. Xanthone, a component of Hypericum perforatum L., has been shown to be effective in animal models of depression.

Objective: We investigated if 2 xanthone derivatives (1101 and 1105) were as effective as venlafaxine, which is a serotonin-norepinephrine reuptake inhibitor and was used as a positive control, in animal models of depression.

Methods: A series of derivatives from xanthone were designed and synthesized. After preliminary experiments, 2 xanthone derivatives (1101 and 1105) were considered to be effective in our mouse depression model. To further determine their effects on depression, classical behavioral despair animal models (forced swim and tail suspension tests) were used to assess the efficacies of these derivatives, whereas venlafaxine hydrochloride was used as a positive control. Oral acute toxicity studies were used to determine if the derivatives were toxic in mice.

Results: The oral acute toxicity studies of 2 xanthone derivatives (1101 and 1105) did not show any toxic effect until the dose at 1000 mg/kg body weight, and xanthone derivatives 1101 and 1105 resulted in a significant decrease of the immobility period (in seconds) compared with the untreated control group during the forced swim test with rats (dose = 12 mg/kg; P < 0.05) and mice (dose = 25 mg/kg; P < 0.001). At lower doses, derivatives 1101 and 1105 also decreased the immobility period of rats and mice during the forced swim test but significant differences were only found in mice compared with the untreated control group (P < 0.05). No difference was found between the groups treated with xanthone derivatives and the positive control group during the swimming period in both mice (dose = 25 mg/kg) and rats (dose = 12 mg/kg) (P > 0.05). In the tail suspension test, derivatives 1101 and 1105 produced marked effects with regard to the motion of mice (P < 0.01 or 0.001, respectively) and the derivatives were also noted to have some effects on rats at a dose of 12 mg/kg (P < 0.05). Compared with the positive venlafaxine control group, no differences were found between those treated with either derivative 1101 or derivative 1105 and venlafaxine (P > 0.05).

Conclusions: Within certain dose ranges, xanthone derivatives 1101 and 1105 have similar effects to venlafaxine hydrochloride in the treatment of depression as suggested by behavioral despair animal models using rats and mice.

No MeSH data available.


Related in: MedlinePlus

Antidepressant-like effect of xanthone derivatives in mice following forced swim test. Data are represented as the mean seconds (SEM) of the total swim period during a 6-minute session. Xanthone derivatives 1101 and 1105 were administered 1 hour before testing and venlafaxine hydrochloride was administered 45 minutes before testing. Each group contained 8 to 9 mice. *P < 0.05; †P < 0.01; ‡P < 0.001 versus vehicle-treated mice; §P < 0.05; ǁP < 0.01 versus venlafaxine hydrochloride-treated mice.
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f0010: Antidepressant-like effect of xanthone derivatives in mice following forced swim test. Data are represented as the mean seconds (SEM) of the total swim period during a 6-minute session. Xanthone derivatives 1101 and 1105 were administered 1 hour before testing and venlafaxine hydrochloride was administered 45 minutes before testing. Each group contained 8 to 9 mice. *P < 0.05; †P < 0.01; ‡P < 0.001 versus vehicle-treated mice; §P < 0.05; ǁP < 0.01 versus venlafaxine hydrochloride-treated mice.

Mentions: Our experiment was carried out according to a previously described method.13 After the initial 2 to 3 minutes of vigorous activity, the animals displayed a period of immobility and floated with minimal movements. Some animals remained floating passively in the water in a slightly hunched but upright position with the nose above the surface of the water. All of the administered substances investigated in our study, including venlafaxine hydrochloride, increased the swimming period in mice (in seconds) compared with the negative control group in mouse FSTs. Figure 2 and Table I show that venlafaxine hydrochloride (16 mg/kg) significantly increased the swimming period of mice (P < 0.001). The tested substances 1101 and 1105 significantly prolonged the swimming period of mice also within a dose range of 6.25 to 25 mg/kg (P < 0.05 or 0.001). No difference was found between the mice treated with substances 1105 or 1101 (25 mg/kg) and the positive control group (P > 0.05).


Effect of xanthone derivatives on animal models of depression.

Zhao X, Chen Q, Liu Y, Xia C, Shi J, Zheng M - Curr Ther Res Clin Exp (2014)

Antidepressant-like effect of xanthone derivatives in mice following forced swim test. Data are represented as the mean seconds (SEM) of the total swim period during a 6-minute session. Xanthone derivatives 1101 and 1105 were administered 1 hour before testing and venlafaxine hydrochloride was administered 45 minutes before testing. Each group contained 8 to 9 mice. *P < 0.05; †P < 0.01; ‡P < 0.001 versus vehicle-treated mice; §P < 0.05; ǁP < 0.01 versus venlafaxine hydrochloride-treated mice.
© Copyright Policy - CC BY-NC-SA
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109418&req=5

f0010: Antidepressant-like effect of xanthone derivatives in mice following forced swim test. Data are represented as the mean seconds (SEM) of the total swim period during a 6-minute session. Xanthone derivatives 1101 and 1105 were administered 1 hour before testing and venlafaxine hydrochloride was administered 45 minutes before testing. Each group contained 8 to 9 mice. *P < 0.05; †P < 0.01; ‡P < 0.001 versus vehicle-treated mice; §P < 0.05; ǁP < 0.01 versus venlafaxine hydrochloride-treated mice.
Mentions: Our experiment was carried out according to a previously described method.13 After the initial 2 to 3 minutes of vigorous activity, the animals displayed a period of immobility and floated with minimal movements. Some animals remained floating passively in the water in a slightly hunched but upright position with the nose above the surface of the water. All of the administered substances investigated in our study, including venlafaxine hydrochloride, increased the swimming period in mice (in seconds) compared with the negative control group in mouse FSTs. Figure 2 and Table I show that venlafaxine hydrochloride (16 mg/kg) significantly increased the swimming period of mice (P < 0.001). The tested substances 1101 and 1105 significantly prolonged the swimming period of mice also within a dose range of 6.25 to 25 mg/kg (P < 0.05 or 0.001). No difference was found between the mice treated with substances 1105 or 1101 (25 mg/kg) and the positive control group (P > 0.05).

Bottom Line: The oral acute toxicity studies of 2 xanthone derivatives (1101 and 1105) did not show any toxic effect until the dose at 1000 mg/kg body weight, and xanthone derivatives 1101 and 1105 resulted in a significant decrease of the immobility period (in seconds) compared with the untreated control group during the forced swim test with rats (dose = 12 mg/kg; P < 0.05) and mice (dose = 25 mg/kg; P < 0.001).At lower doses, derivatives 1101 and 1105 also decreased the immobility period of rats and mice during the forced swim test but significant differences were only found in mice compared with the untreated control group (P < 0.05).Compared with the positive venlafaxine control group, no differences were found between those treated with either derivative 1101 or derivative 1105 and venlafaxine (P > 0.05).

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Nanjing University of Technology, Nanjing, China.

ABSTRACT

Background: Extracts of the plant Hypericum perforatum L. have been traditionally used in folk medicine for the treatment of depressive disorders. Xanthone, a component of Hypericum perforatum L., has been shown to be effective in animal models of depression.

Objective: We investigated if 2 xanthone derivatives (1101 and 1105) were as effective as venlafaxine, which is a serotonin-norepinephrine reuptake inhibitor and was used as a positive control, in animal models of depression.

Methods: A series of derivatives from xanthone were designed and synthesized. After preliminary experiments, 2 xanthone derivatives (1101 and 1105) were considered to be effective in our mouse depression model. To further determine their effects on depression, classical behavioral despair animal models (forced swim and tail suspension tests) were used to assess the efficacies of these derivatives, whereas venlafaxine hydrochloride was used as a positive control. Oral acute toxicity studies were used to determine if the derivatives were toxic in mice.

Results: The oral acute toxicity studies of 2 xanthone derivatives (1101 and 1105) did not show any toxic effect until the dose at 1000 mg/kg body weight, and xanthone derivatives 1101 and 1105 resulted in a significant decrease of the immobility period (in seconds) compared with the untreated control group during the forced swim test with rats (dose = 12 mg/kg; P < 0.05) and mice (dose = 25 mg/kg; P < 0.001). At lower doses, derivatives 1101 and 1105 also decreased the immobility period of rats and mice during the forced swim test but significant differences were only found in mice compared with the untreated control group (P < 0.05). No difference was found between the groups treated with xanthone derivatives and the positive control group during the swimming period in both mice (dose = 25 mg/kg) and rats (dose = 12 mg/kg) (P > 0.05). In the tail suspension test, derivatives 1101 and 1105 produced marked effects with regard to the motion of mice (P < 0.01 or 0.001, respectively) and the derivatives were also noted to have some effects on rats at a dose of 12 mg/kg (P < 0.05). Compared with the positive venlafaxine control group, no differences were found between those treated with either derivative 1101 or derivative 1105 and venlafaxine (P > 0.05).

Conclusions: Within certain dose ranges, xanthone derivatives 1101 and 1105 have similar effects to venlafaxine hydrochloride in the treatment of depression as suggested by behavioral despair animal models using rats and mice.

No MeSH data available.


Related in: MedlinePlus