Regulation of Chaihu Shugan Powder on kynurenine in raphe nucleus of depressive rats induced by reserpine

Abstract

Objective To investigate the antidepressant effects of Chaihu Shugan Powder(CSP) on depressive rats induced by reserpine and its influences on the kynurenine (KYN), indoleamine 2, 3-dioxygenase(IDO), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α). Methods Forty rats with similar behavior results were divide into 4 groups randomly, including Control group(Con), Model group(Res), Fluoxetine group(Res+ Flu) and Chaihu Shugan Powder group(CSP). The depressive rat model was established by intraperitoneal injection reserpine.The rats in Res+ Flu group were administered with fluoxetine by intraperitoneal and rats in Res+ CSP group were administered with CSP by intraperitoneal. After 14 days, the behavior of rats was measured and then the rats were executed and sampled. The content of tryptophan and kynurenine in raphe nuclei tissue were detected. The mRNA expression level of IDO, IL-6, TNF-α in raphe nuclei tissue were detected. Results (1) Compared with Con group((81.81±36.13)s, (83.51±5.34)%), the swimming immobility time((150.50±31.45)s) in Res group increased(t=68.7, P<0.05) and the sucrose perference (59.73±11.30)%) in Res group decreased(t=23.8, P<0.05). Compared with Res group, the swimming immobility time in Res+ Flu group((114.90±14.29)s) and Res+ CSP group((111.7±11.34)s) decreased(t=35.6, 35.8, both P<0.05). Compared with Res group, the sucrose preference in Res+ Flu group((78.21±10.07)%) increased(t=18.3, P<0.05). (2)Compared with Con group(KYN/TRP: (0.023±0.016), IDO mRNA: (1.00±0.05), IL-6 mRNA: (1.00±0.58), TNF-α mRNA: (1.00±0.32)), the activity of IDO(KYN/TRP(0.039±0.003)) and the mRNA levels of IDO mRNA(3.63±0.31), IL-6 mRNA(2.36±0.23), TNF-α mRNA(3.56±0.14)of Raphe Nuclei tissue in Res group were significantly increased (t=21.2, 12.9, 38.3, 19.7, all P<0.05). Compared with Res group, the activity of IDO(KYN/TRP(0.030±0.013)), the mRNA expression levels of IDO mRNA(1.56±0.36), IL-6 mRNA(1.62±0.16), TNF-α mRNA(2.64±0.20)of Raphe Nuclei tissue in Res+ Flu group were significantly decreased(t=38.8, 15.8, 12.8, 26.4, all P<0.05). And compared with Res group, the activity of IDO(KYN/TRP(0.028±0.021)) , the mRNA expression level of IDO mRNA(1.33±0.29), IL-6 mRNA(1.36±0.34), TNF-α mRNA(1.93±0.21)of raphe nuclei tissue in Res+ CSP group were also significantly decreased(t=23.21, 17.3, 19.8, 29.8, all P<0.05). Compared with Res+ Flu group, the level of IDO mRNA and inflammatory factors' mRNA in Res+ CSP group were significantly decreased(t=18.3, 20.8, 31.5, all P<0.05). Conclusion Chaihu Shugan Powder has antidepressant effect, and the mechanism is related with decreasing the inflammatory factors, inhibiting IDO activation and decreasing the IDO mRNA. Key words: Chaihu Shugan Powder(CSP); Reserpine; Depression; Indoleamine 2, 3-dioxygenase; Kynurenine; Rat