Lignans from Schisandra chinensis ameliorate cognition deficits and attenuate brain oxidative damage induced by D-galactose in rats


The aim of this study was to explore the neuroprotective effects of active compounds from Schisandra chinensis (Trucz.) Baill. (Magnoliaceae) against the D-galactose (D-gal)-induced neurotoxicity in rat. The Wistar rats were subcutaneously injected with D-gal (150 mg/(kg day)) for six weeks and orally administered with water extract or 95 % ethanol extract (partitioned with petroleum ether (PE), chloroform (CF), ethyl acetate (EA) and n-Butanol (NB), respectively) of the fruits of Schisandra chinensis simultaneously. The alteration of cognitive functions was assessed by using Morris water maze and Step-down type passive avoidance test. The results demonstrated that PE fraction was the most effective fraction to ameliorate cognitive deficits. Further biochemical examination indicated that PE could attenuate the activities decreasing of superoxide dismutase (SOD), catalase (CAT), the total antioxidant (T-AOC) induced by D-gal, and maintain the normal levels of glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) in the serum, prefrontal cortex, striatum and hippocampus of the brain of related rat, selectively. Meanwhile, the compounds of PE fraction were also identified as mainly lignans, thus, these results suggest that lignans from the PE fraction of Schisandra chinensis represented a potential source of medicine for the treatment of the aging-associated neurodegenerative diseases.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. Ahn HS, Jeon TI, Lee JY, Hwang SG, Lim Y, Park DK (2002) Antioxidative activity of persimmon and grape seed extract: in vitro and in vivo. Nutr Res 22:1265–1273

    CAS  Article  Google Scholar 

  2. Anbarasi K, Vani G, Balakrishna K, Devi C.S., (2006). Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats. Life Sci 78, 1378–1384

  3. Calabrese V, Bates TE, Stella AM (2000) NO synthase and NO-dependent signalpathways in brain aging and neurodegenerative disorders: the role of oxidant/antioxidant balance. Neurochem Res 25:1315–1341

    CAS  Article  PubMed  Google Scholar 

  4. Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein JB, Pierce WM (2002) Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part I: Creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med 33:562–571

    CAS  Article  PubMed  Google Scholar 

  5. Chen, X.Q., Zhang, Y., Zu, Y.G, Fu, Y.J., Wang, W., (2011a). Composition and biological activities of the essential oil from Schisandra chinensis obtained by solvent -free microwave extraction. LWT Food Sci Technol 44, 2047–2052.

  6. Chen WW, He RR, Li YF, Li SB, Tsoi B, Kurihara H (2011b) Pharmacological studies on the anxiolytic effect of standardized Schisandra lignans extract on restraint-stressed mice. Phytomedicine 18:1144–1147

    Article  PubMed  Google Scholar 

  7. Chinese Pharmacopoeia Commission (2015) The Pharmacopoeia of the People’s Republic of China Version (2015). Press, Beijing, Chin. Med. Sci. Technol

    Google Scholar 

  8. Chiu L, Yang SH (1992) Fructus Schisandrae: possesses anti-cancer and anti- aging activities. Gansu Medical Journal 11:288

    Google Scholar 

  9. Choi YW, Takamatsu SS, Kha SI, Srinivas PV, Ferreira D, Zhao JP, Khan IA (2006) Schisandrene, a Dibenzocyclooctadiene Lignan from Schisandr chinensis: Structure-Antioxidant Activity Relationships of Dibenzocyclooctadiene Lignans. J Nat Prod 69:356–359

    CAS  Article  PubMed  Google Scholar 

  10. Cui X, Zuo P, Zhang Q, Li X, Hu Y, Long J, et al. (2006) Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice. protective effects of R-alpha-lipoic acid. J Neurosci Res 84:647–654

    CAS  Article  PubMed  Google Scholar 

  11. Freeman BA, Crapo JD (1981) Hyperoxia increases oxygen radical production in rat lungs and lung mitochondrial. J Biol Chem 256:10986–10992

    CAS  PubMed  Google Scholar 

  12. Grune, T., (2000) Oxidative stress, aging and the proteasomal system. Biogerontology1, 31–40

  13. Halliwell B (2007) Biochemistry of oxidative stress. Biochem Soc Trans 35(5):1147–1150

    CAS  Article  PubMed  Google Scholar 

  14. Harman D (1957) Aging: a theory based on free radical and radiation chemistry. J Gerontol Ser 2:298–300

    Google Scholar 

  15. Hsieh MT, Wu CR, Wang WH, Lin LW (2001) The ameliorating effect of the water layer of Fructus Schisandrae on cycloheximide-induced amnesia in rats: interaction with drugs acting at neurotransmitter receptors. Pharmacol Res 43:17–22

    CAS  Article  PubMed  Google Scholar 

  16. Huang YD, Mucke L (2012) Alzheimer Mechanisms and Therapeutic Strategies. Cell 148:1204–1222

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Hu D, Li CX, Han N, Miao LJ, Wang D, Liu ZH, Wang H, Yin J (2012) Deoxyschizandrin Isolated from the Fruits of Schisandra chinensis Ameliorates Aβ1-42-induced Memory Impairment in Mice. Planta Med 78:1332–1336

    CAS  Article  PubMed  Google Scholar 

  18. Jeong EJ, Lee HK, Lee KY, Jeon BJ, Kim DH (2013) The effects of lignan-riched extract of Shisandra chinensis on amyloid-β-induced cognitive impairment and neurotoxicity in the cortex and hippocampus of mouse. J Ethnopharmacol 146:347–354

    CAS  Article  PubMed  Google Scholar 

  19. Ko KM, Ip SP, Poon MK, Wu SS, Che CT, Ng KH, Kong YC (1995) Effect of a lignin-enriched fructus schisandrae extract on hepatic glutathione status in rats: protection against carbon tetrachloride toxicity. Planta Med 61(2):134–137

    CAS  Article  PubMed  Google Scholar 

  20. Lee TH, Jung CW, Lee DH (2012) Neuroprotective effects of Schisandrin B against transient focal cerebral ischemia in Sprague–Dawley rats. Food Chem Toxicol 50:4239–4245

    CAS  Article  PubMed  Google Scholar 

  21. Li XM, Ma YL, Liu XJ (2007) Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice. J Ethnopharmacol 111(3):504–511

    CAS  Article  PubMed  Google Scholar 

  22. Lu H, Liu GT (1991) Effect of dibenzo [a, c] cyclooctene lignans isolated from Fructus schizandrae on lipid peroxidation and antioxidative enzyme activity. Chem Biol Interact 78(1):77–84

    CAS  Article  PubMed  Google Scholar 

  23. Lu, J., Zheng, Y.L., Wu, D.M., Luo, L., Sun, D.X., Shan, Q., (2007) Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose. Biochem Pharmacol 74, 1078–1090

  24. Paradies G, Petrosillo G, Paradies V, Ruggiero FM (2011) Mitochondrial dysfunction in brain aging: role of oxidative stress and cardiolipin. Neurochem Int 58:447–457

    CAS  Article  PubMed  Google Scholar 

  25. Pratico D (2008) Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal. Trends Pharmacol Sci 29:609–615

    CAS  Article  PubMed  Google Scholar 

  26. Shan, Q., Lu, J., Zheng, Y.L., Li, J., Zhou, Z., Hu, B., Zhang, Z.F., Fan, S.H., Mao, Z., Wang, Y.J., Ma, D.F., (2009) Purple sweet potato color ameliorates cognition deficits and attenuates oxidative damage and inflammation in aging mouse brain induced by D-galactose. Journal of Biomedicine and Biotechnology, 1–9

  27. Takimoto Y, Qian HY, Yoshigai E, Okumura T, Ikeya Y, Nishizawa M (2013) Gomisin N in the herbal drug gomishi (Schisandra chinensis) suppresses inducible nitric oxide synthase gene via C/EBPβ and NF-κB in rat hepatocytes. Nitric Oxide 28:47–56

    CAS  Article  PubMed  Google Scholar 

  28. Tesseur I, Pimenova AA, Lo d AC, Ciesielska M, S.F L (2013) Chronic 5-HT4 receptor activation decreases Aβproduction and deposition in hAPP/PS1 mice. Neurobiol Aging 34:1779–1789

    CAS  Article  PubMed  Google Scholar 

  29. Tsai SJ, Chiu CP, Yang HT, Yin MC (2011) S-Allyl cysteine, s-ethyl cysteine, and s-propyl cysteine alleviate b-amyloid, glycative, and oxidative injury in brain of mice treated by D-galactose. J Agric Food Chem 59:6319–6326

    CAS  Article  PubMed  Google Scholar 

  30. Wu DM, Lu J, Zheng YL, Zhou Z, Shan Q, Ma DF (2008) Purple sweet potato color repairs D-galactose-induced spatial learning and memory impairment by regulating the expression of synaptic proteins. Neurobiol Learn Mem 90:19–27

    CAS  Article  PubMed  Google Scholar 

  31. Zhang QB, Li N, Zhou GF, Lu XL, Xu ZH, Li Z (2003) In vivo antioxidant activity of poly saccharide fraction from Porphyra haitanesis (Rhodephyta) in aging mice. Pharmacol Res 48:151–155

    CAS  Article  PubMed  Google Scholar 

  32. Zhong SZ, Ge QH, Li Q, Qu R, Ma SP (2009) Peoniflorin attenuates Aß(1-42) mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats. J Neurol Sci 280:71–78

    CAS  Article  PubMed  Google Scholar 

  33. Zhu JQ, Tuo XP, Chen HS, Lv JY, Jia LY, et al. (2007) Protective effect of Schisandrone on β-amyloid protein-inducedstress injury of hippocampal neurons. Academic Journal of Second Military Medical University 28(9):1015–1016

    CAS  Google Scholar 

Download references


This research was supported by National Natural Science Foundation of China (No. 81573580) and Natural Science Foundation of Liaoning Province of China (No. 2014020076).

Author information



Corresponding author

Correspondence to Ying Jia.

Ethics declarations

Conflict of Interest

The authors declare that there are no conflicts of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yan, T., Shang, L., Wang, M. et al. Lignans from Schisandra chinensis ameliorate cognition deficits and attenuate brain oxidative damage induced by D-galactose in rats. Metab Brain Dis 31, 653–661 (2016).

Download citation


  • Schisandra chinensis
  • Lignans
  • Cognition deficits
  • Brain oxidative damage
  • D-galactose