Korean J Physiol Pharmacol.  2014 Jun;18(3):233-239. 10.4196/kjpp.2014.18.3.233.

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

• El-Bakly W
• Hasanin AH

• KMID: 2285515
• DOI: http://doi.org/10.4196/kjpp.2014.18.3.233

Abstract

The present study was designed to investigate the effect Hypericum Perforatum (HP), on behavioral changes, corticosterone, TNF-alpha levels and tryptophan metabolism and disposition in bilateral ovariectomized rats compared to 17alpha -ethinylestradiol. Behavioral analysis by measuring immobility time in forced swimming test and open field test, serum and hippocampal corticosterone and TNF-alpha 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 17alpha-ethinylestradiol 30 microg/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-alpha 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 17alpha-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-alpha 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-alpha 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-alpha and corticosterone could contribute in its antidepressant effect in this animal model by other ways than their effects on tryptophan-kynurenine metabolism pathway.

Keyword

Corticosterone; Hypericum perforatum; Kyninurenine; TNF-alpha; Tryptophan

MeSH Terms

Animals
Corticosterone*
Depression
Hippocampus*
Hypericum*
Kynurenine
Metabolism
Models, Animal
Physical Exertion
Rats*
Tryptophan
Tumor Necrosis Factor-alpha*
Corticosterone
Kynurenine
Tryptophan
Tumor Necrosis Factor-alpha

Figure

• 

  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.

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