| Chaihu-Shu-Gan-San (CSGS), a classical traditional Chinese herbal formula consisting of seven herbal medicines has been applied to relieve stagnancy in liver and promote blood circulation to alleviate pain in China. It has been widely used in clinical treatment of various diseases in digestive system, neural system, cadiovascular system, gynaecology and et al. Pharmacological researches confirmed that CSGS provided with antidepressive effect. Nowadays, people have to face all kinds of tremendous mental stresses, which lead to the possible result that depression had been attested to be the second disease threatened the health of Chinese people. In order to clarify the possible mechanism and material basis of CSGS antidepressive efficacy, we carried out the studies on antioxidant activity of CSGS to understand the relationship between its antioxidant properties and antidepressive effect and pharmacokinetics of antidepressive ingredient Naringin (NA) in CSGS to compare the differences of metabolism in rats between NA in CSGS and NA monomer.The antioxidant activity in vitro was evaluated by employing six antioxidant assays. CSGS showed a ferric reducing antioxidant power that was equivalent to 0.24 mmol FeSO4 per gram CSGS aqueous extract and certain scavenging activities on free radicals. The IC50 values of CSGS in scavenging DPPH radicals, ABTS cation radicals, O2'-(superoxide anion) and·OH (hydroxyl free radicals) were 0.83 mg·mL-1,1.03 mg·mL-1,10.31 mg·mL-1 and 7.79 mg·mL-1, respectively. The ORAC value of oxygen radical absorbance capacity was 1.50±0.19μmol Trolox/mg. The in vivo study was carried out to investigate the effect of CSGS on mice in restraint stress model by determining glutathione (GSH) contents in blood and malondialdehyde (MDA) values, superoxide dismutase (SOD) and catalase (CAT) activities in liver. Under restraint stress, CSGS could significantly improve activities of SOD and CAT, increase content of GSH to enhance antioxidant capacity of the organism, as well as inhibit lipid peroxidation to decrease content of MDA.NA is one of the active and aitidepressive ingredients in the prescription. A specific LC-MS/MS method was built up for fast quantitative analysis of NA using intenal standard substance. Double peaks phenomenon was observed in both serum concentration-time profiles of rats after orally administered CSGS aqueous extract (2.5 g·kg-1) and the same amount of pure NA (5.075 mg·kg-1) as in CSGS, which manifested that metabolism of NA may experience enterohepatic circulation. Pharmacokinetics was analyzed using the non-compartmental model of the software-WinNonlin. Terminal elimination half-life of CSGS and NA were 171.8932 min and 255.7001 min respectively, which indicated that NA in CSGS was better than NA monomer with fast elimination, short time accumulation and small toxic and side-effect. AUCall of CSGS and NA were 840.2175 min*mg/L and 114.0243 min*mg/L respectively. The data showed that there was more NA in the prescription absorbed into blood circulation, so CSGS had higher bioavailability. And the mean residence time of the two were 523.3516 min and 274.8070 min, which manifested that the prescription had long term efficacy.CSGS exhibited the ability of eliminating free radicals, inhibiting lipid peroxidation, relieving oxidative injury and regulating antioxidant capacity of organisms, which may make contributions to its antidepressive effect. Differences of pharmacokinetic study in rats between NA in CSGS and NA monomer showed that NA in the prescription had long term efficacy, high bioavailability and low toxic side-effect which the monomer could not come up to and confirmed that herbal combination in CSGS was rational.
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