Hypericum Perforatum Decreased Hippocampus TNF-α and Corticosterone Levels with No Effect on Kynurenine/Tryptophan Ratio in Bilateral Ovariectomized Rats

Abstract

The present study was designed to investigate the effect Hypericum Perforatum (HP), on behavioral changes, corticosterone, TNF-α levels and tryptophan metabolism and disposition in bilateral ovariectomized rats compared to 17α -ethinylestradiol. Behavioral analysis by measuring immobility time in forced swimming test and open field test, serum and hippocampal corticosterone and TNF-α along with hippocampal kynurenine/tryptophan ratio were determined in mature ovariectomized rats treated orally either by HP at three different doses 125, 250, and 500 mg/kg/day or by 17α-ethinylestradiol 30 µg/kg/day for 30 days. Ovariectomized rats showed significant increase in immobility time in the forced swimming test. Along with elevation in serum and hippocampal TNF-α and corticosterone levels associated with significant increase in hippocampal kynurenine/tryptophan ratio. Immobility time in the forced swimming test was decreased in rats treated by different doses of HP in a dose dependent manner and 17α-ethinylestradiol with no concomitant changes in the open field test. Only Rats treated with HP exhibited significant decrease in the elevated serum and hippocampal TNF-α and corticosterone, which couldn't explain the associated insignificant effect on hippocampaus kynurenine/tryptophan ratio in comparison to ovariectomized untreated rats. It is concluded that increased tryptophan metabolism toward kynurenine secondary to elevated corticosterone and TNF-α might be one of the pathohphysiological mechanisms that could explain depression like state observed in this rat model. Further, the observed attenuating effect of HP on TNF-α and corticosterone could contribute in its antidepressant effect in this animal model by other ways than their effects on tryptophan-kynurenine metabolism pathway.

Keywords: Corticosterone; Hypericum perforatum; Kyninurenine; TNF-α; Tryptophan.

Fig. 1

Effect of treatment with 17α-ethinylestradiol (30 µg/kg) and Hpericum Perforatum (HP; 125, 250, 500 mg/kg) on the number of squares crossed in open field test (OFT) (A) and on immobility time of forced swimming test (FST) in seconds (B) of ovariectomized rats (OVX). Correlation between body weights at the end versus immobility time in FST in the different groups (C). Data are mean±SD, number of animals=6. One way ANOVA followed by Tukey's Multiple Comparisons test: ^ap<0.05, compared to control sham operated group. ^bp<0.05 compared to OVX untreated group and ^cp<0.05 compared to 17α-ethinylestradiol treated group. r, Pearson's correlation coefficient.

Fig. 2

Correlation between serum versus hippocampus corticosterone level in the different group. r, Pearson's correlation coefficient, P significant level.

Fig. 3

Effects of treatment with 17α-ethinylestradiol (E; 30 µg/kg) and Hpericum Perforatum (HP; 125, 250, 500 mg/kg) on hippocampus. (A) Tryptophan, (B) kynurenine and (C) kynurenine/tryptophan ratio of OVX Wistar rats. Data are mean±SD, number of animals per group=6, OVX=ovariectomized. One way ANOVA followed by Tukey's Multiple Comparisons test: ^ap<0.05, compared to control sham operated group. ^bp<0.05 compared to OVX untreated group and ^cp<0.05 compared to 17α-ethinylestradiol treated group.