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Planta Med 2019; 85(17): 1374-1382
DOI: 10.1055/a-1023-8940
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Alkaloid Enantiomers from Isatis tinctoria with Neuroprotective Effects against H2O2-Induced SH-SY5Y Cell Injury

Yu-Fei Xi
1   School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
,
Li-Li Lou
1   School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
,
Zhi-Yong Xu
1   School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
,
Zi-Lin Hou
1   School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
,
Xiao-Bo Wang
2   Chinese Peopleʼs Liberation Army Logistics Support Force No. 967 Hospital, Dalian, Peopleʼs Republic of China
,
Xiao-Xiao Huang
1   School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
2   Chinese Peopleʼs Liberation Army Logistics Support Force No. 967 Hospital, Dalian, Peopleʼs Republic of China
,
Shao-Jiang Song
1   School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Peopleʼs Republic of China
› Author AffiliationsSupported by: National Natural Science Foundation of China 81973462
Supported by: China Postdoctoral Science Foundation 2016M593031
Supported by: China Postdoctoral Science Foundation 2018T111135
Supported by: Natural Science Foundation of Liaoning Province of China 2019-MS-303
Supported by: Career Development Support Plan for Young, Middle-aged Teachers in Shenyang Pharmaceutical University ZQN2018006
Further Information

Publication History

received 29 August 2019
revised 28 September 2019

accepted 06 October 2019

Publication Date:
04 November 2019 (online)

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Abstract

Six pairs of alkaloid enantiomers including 11 new alkaloids (1a/1b–5a/5b, 6a) were isolated from the leaves of Isatis tinctoria. Their structures were established by extensive spectroscopic analyses. Enantiomers were separated successfully by chiral chromatographic column and the absolute configurations of all isolates were determined by comparison of experimental and calculated electronic circular dichroism spectra. The isolated alkaloids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that 5a/5b and 6a/6b exhibited potent neuroprotective activities at 50 µM compared with the H2O2-treated group.

Key words

Isatis tinctoria - Brassicaceae - alkaloids - enantiomers - neuroprotective effects

Supporting Information

    NMR, HRESIMS, UV, ECD spectrum, chiral HPLC chromatograms, and further detailed experimental information are available as Supporting Information.

  • Supporting Information
 

  • References

  • 1 Jiangsu New Medical College. Dictionary of traditional Chinese medicine. Shanghai: Shanghai Science and Technology Publishing House; 1985: 1250-1252
    Google Scholar
  • 2 Chang HN, Huang ST, Yeh YC, Wang HS, Wang TH, Wu YH, Pang JHS. Indigo naturalis and its component tryptanthrin exert anti-angiogenic effect by arresting cell cycle and inhibiting Akt and FAK signaling in human vascular endothelial cells. J Ethnopharmacol 2015; 174: 474-481
    CrossrefPubMedGoogle Scholar
  • 3 Chen MH, Gan LS, Lin S, Wang XL, Li L, Li YH, Zhu CG, Wang YN, Jiang BY, Jiang JD, Yang YC, Shi JG. Alkaloids from the root of Isatis indigotica . J Nat Prod 2012; 75: 1167-1176
    CrossrefPubMedGoogle Scholar
  • 4 Wu XY, Liu YH, Sheng WY, Sun J, Qin GW. Chemical constituents of Isatis indigotica . Planta Med 1997; 63: 55-57
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Wu XY, Qin GW, Cheung KK, Cheng KF. New alkaloids from Isatis indigotica . Tetrahedron 1997; 53: 13323-13328
    CrossrefPubMedGoogle Scholar
  • 6 Wu YX, Zhang ZX, Hu H, Li DM, Qiu GF, Hu XM, He XJ. Novel indole-glycosides from Isatis indigotica and their potential cytotoxic activity. Fitoterapia 2011; 82: 288-292
    CrossrefPubMedGoogle Scholar
  • 7 He LW, Li X, Chen JW, Sun DD, Ju WZ, Wang KC. Chemical constituents from water extract of Radix isatidis . Acta Pharm Sin 2006; 41: 1193-1196
    PubMedGoogle Scholar
  • 8 Zuo L, Li JB, Xu J, Yang JZ, Zhang DM, Tong YL. Studies on chemical constituents in root of Isatis indigotica . China J Chin Mater Med 2007; 32: 688-691
    PubMedGoogle Scholar
  • 9 Liu JF, Zhang XM, Xue DQ, Jiang ZY, Qiong GU, Chen JJ. Studies on chemical constituents from leaves of Isatis indigotica . China J Chin Mater Med 2006; 31: 1961-1965
    PubMedGoogle Scholar
  • 10 Sun DD, Dong WW. Isolation, structural determination and cytotoxic activity of two new ceramides from the root of Isatis indigotica . Sci China Chem 2009; 52: 621-625
    CrossrefPubMedGoogle Scholar
  • 11 Li B, Chen WS, Yang GJ, Zhang WD, Qiao CZ. Organic acids of tetraploid Isatis indigotica . Acad J Second Mil Med Univ 2000; 21: 207-208
    PubMedGoogle Scholar
  • 12 Liu HL, Wu LJ, Li H, Wang J. Study on the chemical constituents of Isatis indigotica Fort. J Shenyang Pharm Univ 2002; 19: 93-95
    PubMedGoogle Scholar
  • 13 Hsuan SL, Chang SC, Wang SY, Liao TL, Jong TT, Chien MS, Lee WC, Chen SS, Liao JW. The cytotoxicity to leukemia cells and antiviral effects of Isatis indigotica extracts on pseudorabies virus. J Ethnopharmacol 2009; 123: 61-67
    CrossrefPubMedGoogle Scholar
  • 14 Ho YL, Chang YS. Studies on the antinociceptive, anti-inflammatory and anti pyretic effects of Isatis indigotica root. Phytomedicine 2002; 9: 419-424
    CrossrefPubMedGoogle Scholar
  • 15 Liu SF, Zhang YY, Zhou L, Lin B, Huang XX, Wang XB, Song SJ. Alkaloids with neuroprotective effects from the leaves of Isatis indigotica collected in the Anhui Province, China. Phytochemistry 2018; 149: 132-139
    CrossrefPubMedGoogle Scholar
  • 16 Huang S, Meng N, Liu ZM, Guo L, Dong LS, Li B, Ye Q. Neuroprotective Effects of Taraxacum officinale Wigg. Extract on Glutamate-Induced Oxidative Stress in HT22 Cells via HO-1/Nrf2 Pathways. Nutrients 2018; 10: 926-937
    CrossrefPubMedGoogle Scholar
  • 17 Sherer TB, Betarbet R, Stout AK, Lund S, Baptista M, Panov AV, Cookson MR, Greenamyre JT. An in vitro model of Parkinsonʼs disease: linking mitochondrial impairment to altered α-synuclein metabolism and oxidative damage. J Neurosci 2002; 22: 7006-7015
    CrossrefPubMedGoogle Scholar
  • 18 Finefield JM, Sherman DH, Kreitman M, Williams RM. Enantiomeric natural products: occurrence and biogenesis. Angew Chem Int Ed Engl 2012; 51: 4802-4836
    CrossrefPubMedGoogle Scholar
  • 19 Liu HJ, Xia YL, Cai WD, Zhang YN, Zhang XQ, Du ST. Enantioselective oxidative stress and oxidative damage caused by Rac- and S-metolachlor to Scenedesmus obliquus . Chemosphere 2017; 173: 22-30
    CrossrefPubMedGoogle Scholar
  • 20 Zhang WJ, Cheng C, Chen L, Di SS, Liu CX, Diao JL, Zhou ZQ. Enantioselective toxic effects of cyproconazole enantiomers against Chlorella pyrenoidosa . Chemosphere 2016; 159: 50-57
    CrossrefPubMedGoogle Scholar
  • 21 Liu SF, Lin B, Xi YF, Zhou L, Lou LL, Huang XX, Wang XB, Song SJ. Bioactive spiropyrrolizidine oxindole alkaloid enantiomers from Isatis indigotica Fortune. Org Biomol Chem 2018; 16: 9430-9439
    CrossrefPubMedGoogle Scholar
  • 22 Xi YF, Zhou L, Bai M, Wang J, Lin B, Wang XB, Huang XX, Song SJ. N-acylanthranilic acid derivatives with anti-Aβ 1–42 aggregation activity from the leaves of Isatis indigotica Fortune. Fitoterapia 2018; 128: 169-174
    CrossrefPubMedGoogle Scholar
  • 23 Xi YF, Liu SF, Hong W, Song XY, Lou LL, Zhou L, Yao GD, Lin B, Wang XB, Huang XX, Song SJ. Discovery of cycloneolignan enantiomers from Isatis indigotica Fortune with neuroprotective effects against MPP+-induced SH-SY5Y cell injury. Bioorg Chem 2019; 88: 102926-102931
    CrossrefPubMedGoogle Scholar
  • 24 Chen BC, Zhou P, Davis FA, Ciganek E. α-Hydroxylation of Enolates and Silyl Enol Ethers. Org React 2003; 62: 1-356
    PubMedGoogle Scholar
  • 25 Kafka S, Proisl K, Kašpárková V, Urankar D, Kimmel R, Košmrlj J. Oxidative ring opening of 3-hydroxyquinoline-2, 4(1H,3H)-diones into N-(α-ketoacyl)anthranilic acids. Tetrahedron 2013; 69: 10826-10835
    CrossrefPubMedGoogle Scholar
  • 26 Stadlbauer W, Lutschounig H, Schindler G, Witoszynskyj T, Kappe T. Synthesis of 3-nitro- and 3-aminoquinoline-2, 4-diones. An unexpected route to 3-hydroxyquinoline-2, 4-diones. J Heterocycl Chem 1992; 29: 1535-1540
    CrossrefPubMedGoogle Scholar
  • 27 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich A, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery jr JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ. Gaussian 09, A.01 ed. Wallingford: Gaussian, Inc.; 2016
    Google Scholar
  • 28 Bruhn T, Schaumlöffel A, Hemberger Y, Bringmann G. SpecDis: quantifying the comparison of calculated and experimental electronic circular dichroism spectra. Chirality 2013; 25: 243-249
    CrossrefPubMedGoogle Scholar