Download PDF
Planta Med 2014; 80(08/09): 671-675
DOI: 10.1055/s-0034-1368592
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Structure-Activity Relationship Study of Dibenzocyclooctadiene Lignans Isolated from Schisandra chinensis on Lipopolysaccharide-Induced Microglia Activation

Di Hu
1   Development and Utilization Key Laboratory of Northeast Plant Materials of Liaoning Province, Department of Pharmacognosy, Shenyang Pharmaceutical University, Shenyang, China
2   College of Pharmacy, Harbin University of Commerce, Harbin, Heilongjiang Province, China
,
Na Han
1   Development and Utilization Key Laboratory of Northeast Plant Materials of Liaoning Province, Department of Pharmacognosy, Shenyang Pharmaceutical University, Shenyang, China
,
Xuechun Yao
3   Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China
,
Zhihui Liu
1   Development and Utilization Key Laboratory of Northeast Plant Materials of Liaoning Province, Department of Pharmacognosy, Shenyang Pharmaceutical University, Shenyang, China
,
Yu Wang
4   The Chinese Peopleʼs Liberation Army 463 Hospital, Shenyang, China
,
Jingyu Yang
3   Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China
,
Jun Yin
1   Development and Utilization Key Laboratory of Northeast Plant Materials of Liaoning Province, Department of Pharmacognosy, Shenyang Pharmaceutical University, Shenyang, China
› Author Affiliations
Further Information

Publication History

received 22 January 2014
revised 07 May 2014

accepted 20 May 2014

Publication Date:
25 June 2014 (online)

    Permissions and Reprints

Abstract

To explore the relationship of the dibenzocyclooctadiene lignans from Schisandra chinensis to their anti-inflammatory activities, series of dibenzocyclooctadiene lignans were isolated and assessed by testing their inhibitory effects on nitric oxide production in lipopolysaccharide-induced BV2 mouse microglia. It was found, for the first time, that dibenzocyclooctadiene lignans which have S-biphenyl and methylenedioxy groups strongly inhibited LPS-induced microglia activation. The methoxy group on the cyclooctadiene introduced more effectiveness, but the presence of an acetyl group on the cyclooctadiene or hydroxyl group on C-7 decreased the inhibitory activity.

Key words

Schisandra chinensis - Schisandraceae - dibenzocyclooctadiene lignans - microglia - nitric oxide - structure-activity relationship

Supporting Information

 

  • References

  • 1 Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19: 312-318
    CrossrefPubMedGoogle Scholar
  • 2 Gonzalez-Scarano F, Baltuch G. Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 1999; 22: 219-240
    CrossrefPubMedGoogle Scholar
  • 3 Stoll G, Jander S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 1999; 58: 233-247
    CrossrefPubMedGoogle Scholar
  • 4 Amor S, Puentes F, Baker D, van der Valk P. Inflammation in neurodegenerative diseases. Immunology 2010; 129: 154-169
    CrossrefPubMedGoogle Scholar
  • 5 Egashira N, Kurauchi K, Iwasaki K, Mishima K, Orito K, Oishi R, Fujiwara M. Schizandrin reverses memory impairment in rats. Phytother Res 2008; 22: 49-52
    CrossrefPubMedGoogle Scholar
  • 6 Kim DH, Jung WY, Park SJ, Kim JM, Lee S, Kim YC, Ryu JH. Anti-amnesic effect of ESP-102 on Aβ 1–42-induced memory impairment in mice. Pharmacol Biochem Behav 2010; 97: 239-248
    CrossrefPubMedGoogle Scholar
  • 7 Hu D, Li CX, Han N, Miao LJ, Wang D, Liu ZH, Wang H, Yin J. Deoxyschizandrin isolated from the fruits of Schisandra chinensis ameliorates Aβ 1–42-induced memory impairment in mice. Planta Med 2012; 78: 1332-1336
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Zhang N, Hu D, Yang JY, Cai XD, Yin J, Wu CF. Studies on chemical constituents of leaf of Schisandra chinensis and inhibitory effect of schizandrin on activation of microglia induced by LPS. Chin J Med Chem 2010; 20: 110-115
    PubMedGoogle Scholar
  • 9 Chen YG, Qin GW, Xie YY. [Studies on chemical constituents of Schisandra propinqua (Wall.) Hook. f. et Thoms]. Zhongguo Zhong Yao Za Zhi 2001; 26: 694-699
    PubMedGoogle Scholar
  • 10 Smejkal K, Slapetová T, Krmenčík P, Babula P, DallʼAcqua S, Innocenti G, Vančo J, Casarin E, Carrara M, Kalvarová K, Dvorská M, Slanina J, Kramářová E, Julínek O, Urbanová M. Evaluation of cytotoxic activity of Schisandra chinensis lignans. Planta Med 2010; 76: 1672-1677
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Taguchi H, Ikeya Y. The constituents of Schizandra chinensis Baill. The structures of two new lignans, gomisins F, G, and the absolute structures of gomisins A, B, and C. Chem Pharm Bull 1977; 25: 364-366
    CrossrefPubMedGoogle Scholar
  • 12 Ikeya Y, Taguchi H, Yosioka I, Kobayashi H. The constituents of Schisandra chinensis Baill. I. Isolation and structure determination of five new lignans, gomisin A, B, C, F and G, and the absolute structure of schisandrin. Chem Pharm Bull 1979; 27: 1383-1394
    CrossrefPubMedGoogle Scholar
  • 13 Ikeya Y, Taguchi H, Sasaki H, Nakajima K, Yosioka I. The constituents of Schisandra chinensis Baill. VI. C-13 nuclear magnetic resonance spectroscopy of dibenzocyclooctadiene lignans. Chem Pharm Bull 1980; 28: 2414-2421
    CrossrefPubMedGoogle Scholar
  • 14 Ikeya Y, Taguchi H, Yosioka I. The constituents of Schizandra chinensis Baill. X. The structure of γ-schisandrin and four new lignans, (−)-gomisin L1 and L2, (±)-gomisin M1 and (+)-gomisin M2 . Chem Pharm Bull 1982; 30: 132-139
    CrossrefPubMedGoogle Scholar
  • 15 Ikeya Y, Taguchi H, Yosioka I. The constituents of Schizandra chinensis Baill. VII. The structures of three new lignans, (−)-gomisin K1 and (+)-gomisins K2 and K3 . Chem Pharm Bull 1980; 28: 2422-2427
    CrossrefPubMedGoogle Scholar
  • 16 Ikeya Y, Taguchi H, Yosioka I. The constituents of Schisandra chinensis Baill. XII. Isolation and structure of a new lignan, gomisin R, the absolute structure of wuweizisu C and isolation of schisantherin D. Chem Pharm Bull 1982; 30: 3207-3211
    CrossrefPubMedGoogle Scholar
  • 17 Ikeya Y, Taguchi H, Yosioka I. The constituents of Schizandra chinensis Baill. V. The structures of four new lignans, gomisin N and gomisin O, epigomisin O and gomisin E, and transformation of gomisin N to deangeloylgomisin B. Chem Pharm Bull 1979; 27: 2659-2709
    PubMedGoogle Scholar
  • 18 Yukinobu I, Heihachiro T, Itiro Y, Hiroshi K. The constituents of Schisandra chinensis Baill. IV. The structures of two new lignans, pre-gomisin and gomisin J. Chem Pharm Bull 1979; 27: 1583-1588
    CrossrefPubMedGoogle Scholar
  • 19 Chen YG, Qin GW, Xie YY, Cheng KF, Lin ZW, Sun HD, Kang YH, Han BH. Lignans from Kadsura angustifolia . J Asian Nat Prod Res 1998; 1: 125-131
    CrossrefPubMedGoogle Scholar
  • 20 Ren R, Ci XX, Li HZ, Li HM, Luo GJ, Li RT, Deng XM. New dibenzocyclooctadiene lignans from Schisandra sphenanthera and their proinflammatory cytokine inhibitory activities. Z Naturforsch B 2010; 65: 211-218
    PubMedGoogle Scholar
  • 21 Chun L, Huang HX, Chen JJ, Pu JX, Yang LB, Zhao Y, Liu JP, Gao XM, Xiao WL, Sun HD. Lignans from Schisandra propinqua var. propinqua . Chem Pharm Bull 2007; 55: 1281-1283
    CrossrefPubMedGoogle Scholar
  • 22 Ikeya Y, Sugama K, Okada M, Mitsuhashi H. Two lignans from Schisandra sphenanthera . Phytochemistry 1991; 30: 975-980
    CrossrefPubMedGoogle Scholar
  • 23 Wang HJ, Chen YY. [Studies of lignans from Schisandra rubriflora Rhed et Wils]. Yao Xue Xue Bao 1985; 20: 832-841
    PubMedGoogle Scholar
  • 24 Ikeya Y, Taguchi H, Yosioka I, Iitaka Y, Kobayashi H. The constituents of Schizandra chinensis Baill. II. The structure of a new lignan, gomisin D. Chem Pharm Bull 1979; 27: 1395-1401
    CrossrefPubMedGoogle Scholar
  • 25 Oh SY, Kim YH, Bae DS, Um BH, Pan CH, Kim CY, Lee HJ, Lee JK. Anti-inflammatory effects of gomisin N, gomisin J, and schisandrin C isolated from the fruit of Schisandra chinensis . Biosci Biotechnol Biochem 2010; 74: 285-291
    CrossrefPubMedGoogle Scholar
  • 26 Pan SY, Han YF, Carlier PR, Pang YP, Mak DH, Lam BY, Ko KM. Schisandrin B protects against tacrine- and bis(7)-tacrine-induced hepatotoxicity and enhances cognitive function in mice. Planta Med 2002; 68: 217-220
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Wang B, Wang XM. Schisandrin B protects rat cortical neurons against Aβ 1–42-induced neurotoxicity. Pharmazie 2009; 64: 450-454
    PubMedGoogle Scholar
  • 28 Giridharan VV, Thandavarayan RA, Sato S, Ko KM, Konishi T. Prevention of scopolamine-induced memory deficits by schisandrin B, an antioxidant lignan from Schisandra chinensis in mice. Free Radic Res 2011; 45: 950-958
    CrossrefPubMedGoogle Scholar
  • 29 Zeng KW, Zhang T, Fu H, Liu GX, Wang XM. Schisandrin B exerts anti-neuroinflammatory activity by inhibiting the Toll-like receptor 4-dependent MyD88/IKK/NF-κB signaling pathway in lipopolysaccharide-induced microglia. Eur J Pharmacol 2012; 692: 29-37
    CrossrefPubMedGoogle Scholar
  • 30 Nakajima K, Taguch H, Ikeya Y, Endo T, Yosioka I. [The constituents of Schizandra chinensis Baill. XIII. Quantitative analysis of lignans in the fruits of Schizandra chinensis Baill. by high performance liquid chromatography]. Yakugaku Zasshi 1983; 103: 743-749
    PubMedGoogle Scholar
  • 31 Ka FL, Kam MK, Ka MN. Separation and purification of schisandrin B from Fructus Schisandrae. Ind Eng Chem Res 2008; 47: 4193-4201
    CrossrefPubMedGoogle Scholar
  • 32 Song JX, Lin X, Wong RN, Sze SC, Tong Y, Shaw PC, Zhang YB. Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta-amyloid and homocysteine neurotoxicity in PC12 cells. Phytother Res 2011; 25: 435-443
    PubMedGoogle Scholar
  • 33 Chang JY, Chavis JA, Liu LZ, Drew PD. Cholesterol oxides induce programmed cell death in microglial cells. Biochem Biophys Res Commun 1998; 249: 817-821
    CrossrefPubMedGoogle Scholar
  • 34 Barger SW, Harmon AD. Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E. Nature 1997; 388: 878-881
    CrossrefPubMedGoogle Scholar