Bano Samina, Dawood Shazia
Department of Biochemistry, Clinical Biochemistry and Psychopharmacology Research Unit, University of Karachi, Karachi-75270, Pakistan.
Pak J Pharm Sci. 2008 Jan;21(1):63-9.
Present study shows the effects of St John's Wort (SJW) (20 mg/kg) on swim stress induced changes in tryptophan (TRP) metabolism and disposition in rats. The results show that after forced swim test (FST) hepatic tryptophan pyrrolase (holo and total) activities were significantly decreased (P<0.001). Liver TRP was increased (P<0.001) while serum TRP was decreased (P<0.01). Brain TRP, 5-hydroxytryptamine (5-HT, Serotonin) and 5-hydroxyindole acetic acid (5-HIAA) concentrations were increased (P<0.001), similarly immobility time during swim test was also increased. SJW pretreated FS group of rats showed reduced holo enzyme activity (P<0.001) while increase in total and apo enzyme activities (P<0.001). There was significant decrease in liver TRP (P<0.01), serum TRP (P<0.05), brain TRP (P<0.001), 5-HT (P<0.001) and 5-HIAA (P<0.001) concentrations with reduction in immobility time during swim test when compared with saline injected FS group. SJW injected group but when compared with untreated controls showed significant increase in total and apo enzyme activities (P<0.001) while holo enzyme activity was decreased (P<0.001), serum TRP, brain TRP and 5-HIAA levels were significantly decreased (P<0.001). Changes in 5-HT concentrations were not significant. It is concluded that SJW treatment alter stress induced augmented 5-HT levels by decreasing precursor availability to the brain and that serotonergic system is involve in the mechanism of action of the drug.
本研究显示了圣约翰草提取物(SJW,20毫克/千克)对游泳应激诱导的大鼠色氨酸(TRP)代谢和分布变化的影响。结果表明,强迫游泳试验(FST)后,肝脏色氨酸吡咯酶(全酶和总酶)活性显著降低(P<0.001)。肝脏TRP增加(P<0.001),而血清TRP降低(P<0.01)。脑TRP、5-羟色胺(5-HT,血清素)和5-羟吲哚乙酸(5-HIAA)浓度增加(P<0.001),同样,游泳试验期间的不动时间也增加。SJW预处理的FST组大鼠全酶活性降低(P<0.001),而总酶和脱辅基酶活性增加(P<0.001)。与注射生理盐水的FST组相比,肝脏TRP(P<0.01)、血清TRP(P<0.05)、脑TRP(P<0.001)、5-HT(P<0.001)和5-HIAA(P<0.001)浓度显著降低,游泳试验期间的不动时间减少。与未处理的对照组相比,注射SJW的组总酶和脱辅基酶活性显著增加(P<0.001),而全酶活性降低(P<0.001),血清TRP、脑TRP和5-HIAA水平显著降低(P<0.001)。5-HT浓度变化不显著。结论是,SJW治疗通过减少大脑中前体的可用性来改变应激诱导的5-HT水平升高,并且血清素能系统参与了该药物的作用机制。