Correlation between Antistress and Hepatoprotective Effects of Schisandra Lignans Was Related with Its Antioxidative Actions in Liver Cells

Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2012, Article ID 161062, 7 pages doi:10.1155/2012/161062 Research Article Correlation between Antistress and Hepatoprotective Effects of Schisandra Lignans Was Related with Its Antioxidative Actions in Liver Cells Hao-Jie Pu,1 Yun-Feng Cao,2, 3 Rong-Rong He,3 Zhi-Long Zhao,4 Jin-Hui Song,4 Bin Jiang,4 Ting Huang,2 Shu-Hong Tang,5 Jian-Min Lu,4 and Hiroshi Kurihara3 1 Nursing Department, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China 2 National Population and Family Planning Key Laboratory of Contraceptives Drugs & Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China 3 Pharmacy College, Jinan University, Guangzhou 510632, China 4 Department of Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian 116021, China 5 Department of Oncology, The Fifth Hospital of Dalian, Dalian 116021, China Correspondence should be addressed to Rong-Rong He, and Jian-Min Lu, Received 12 March 2012; Revised 26 April 2012; Accepted 26 April 2012 Academic Editor: José Luis Rı́os Copyright © 2012 Hao-Jie Pu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The present study was conducted to investigate the relationship between the anti-stress and hepato-protective effects of Schisandra Lignans Extract (SLE) on stress-induced liver damage. Seven weeks old male mice were fixed in a restraint tube for 18 h to induce liver damage. SLE was orally administered to animals for 5 days at dosages of 100 and 200 mg/kg/day before exposed to restraint stress. Oral administration of SLE significantly reduced restraint-induced liver damage in experimental animal. SLE was further found to significantly alleviate the provocation of corticosterone in stressed mice. SLE also significantly decreased oxidative damage and increased anti-oxidative capability of liver cells by preventing the over production and accumulation of free radicals. In conclusion, the protective effects of SLE on stress-induced liver damage were confirmed, and the correlation between hepatoprotective and anti-stress effects of schisandra lignans was possible related to its alleviation on the malignant effects of stressors for bio-homeostasis, such as balance of oxidation and reduction in cells. 1. Introduction Fructus schisandrae (F. schisandrae) is the dried mature fruits of Schisandra chinensis (Turcz.) Baill. It is regarded as a medical herb in both Traditional Chinese Medicine (TCM) and Western Herbal Medicine (WHM) [1]. In TCM, F. schisandrae is used to treat irritability by calming and holding the Qi [2]. Recent pharmacological studies demonstrated that its pharmacological effects in TCM were related with its antistress effects [3]. In WHM, the main application of F. schisandrae is in hepatoprotection treatment, used in acute or chronic liver disease and poor liver function [4]. Since the 1970s, the crude herb has been developed as an alternative medicine for the treatment of various liver injuries [5–7]. Chemical investigations indicated the major active compounds were schisandra lignans, including schizandrol A, schizandrol B, and schisantherin A, deoxyschizandrin, schizandrin B, schisandrin C [8], with multiple pharmacological actions [9–12]. However, there are no reports indicated the correlations between the antistress and liver protective effects of F. schisandrae. A serial of studies on the pharmacological actions of schisandra lignans extract (SLE) were conducted recently in our research group. We found that oral administration of SLE significantly reduced stress-evoked anxiety and hepatic metastases in restraint mice [3, 13]. Restraint or immobilization is a common animal model for inducing psychological stress, which results into many nonspecific physiological 2 Evidence-Based Complementary and Alternative Medicine 20 ∗∗ SLE 100 mg/kg ∗∗ ## Model control 15 ## Normal control 0 40 80 ALT (IU/L) 120 160 Figure 1: Effects of SLE on ALT levels in plasma obtained from mice loaded with restraint stress. Seven-week-old male ICR mice were fixed in a restraint tube for 18 h before ALT activities assays. The results represent the mean ± S.D of values obtained from 10 animals in each group. The significance of differences from the normal control at ## P < 0.01 and model control mice at ∗∗ P < 0.01. MDA (nmol/mgprot) Restraint stress SLE 200 mg/kg 10 ∗∗ ∗∗ 5 0 Restraint stress Normal control ∗∗ SLE 200 mg/kg Model control SLE 100 mg/kg SLE 200 mg/kg Restraint stress ∗∗ SLE 100 mg/kg (a) 80000 ## Model control Normal control 60 120 180 Corticosterone (ng/mL) 240 Figure 2: Effects of SLE on corticosterone levels in plasma obtained from mice loaded with restraint stress. The results represent the mean ± S.D of values obtained from 10 animals in each group. The significance of differences from the normal control at ## P < 0.01 and model control mice at ∗∗ P < 0.01. disorders in autonomic nervous system, endocrine system, and immune system and leads to organ dysfunctions [14, 15]. Our previous studies showed that restraint for 18 h could induce liver damage [16, 17]. Based on these previous studies, the present study was designed to investigate the liver protection effects of SLE on stress-evoked liver damage in mice and explore the possible correlations between the antistress and hepatoprotective effects of SLE. 2. Materials and Methods 2.1. Preparation of Schisandra Lignans Extract. F. schisandrae was supplied by Liaoning Ludan Ltd. (Liaoning, China). A voucher specimen (2009WWZ0006) was deposited in Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou, China. SLE was extracted and analyzed by HPLC-MS as previously reported [13]. The compounds of lignans in SLE were identified as schizandrol A, schizandrol B, schisantherin A, deoxyschizandrin, schizandrin B and schisandrin C. Total lignans were quantitated by measuring against schizandrol A standard calibration curve. Each gram of SLE contained 826.3 mg of lignans expressed as Schizandrol A [3]. 60000 ORAC (U/mL) 0 ∗∗ ∗∗ 40000 ## 20000 0 Normal control Model control SLE 100 mg/kg SLE 200 mg/kg Restraint stress (b) Figure 3: Effects of SLE on MDA (a) and ORAC (b) levels in liver obtained from mice loaded with restraint stress. The results represent the mean ± S.D of values obtained from 10 animals in each group. The significance of differences from the normal control at ## P < 0.01 and model control mice at ∗∗ P < 0.01. 2.2. Animals and Treatments. Seven-week-old male ICR mice were purchased from the Center of Laboratory Animal Science Research of Southern Medical University, Guangzhou, China. All mice were kept in a specific pathogen-free animal room under the controlled condition of (...truncated)