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

Yu-Fei Xi; Li-Li Lou; Zhi-Yong Xu; Zi-Lin Hou; Xiao-Bo Wang; Xiao-Xiao Huang; Shao-Jiang Song

doi:10.1055/a-1023-8940

Planta Medica, Table of Contents

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

Authors

Yu-Fei Xi

¹School 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

¹School 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

¹School 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

¹School 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

²Chinese Peopleʼs Liberation Army Logistics Support Force No. 967 Hospital, Dalian, Peopleʼs Republic of China
Xiao-Xiao Huang

¹School 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

²Chinese Peopleʼs Liberation Army Logistics Support Force No. 967 Hospital, Dalian, Peopleʼs Republic of China
Shao-Jiang Song

¹School 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

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

Full Text

References

References
1 Jiangsu New Medical College. Dictionary of traditional Chinese medicine. Shanghai: Shanghai Science and Technology Publishing House; 1985: 1250-1252
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
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
4 Wu XY, Liu YH, Sheng WY, Sun J, Qin GW. Chemical constituents of Isatis indigotica . Planta Med 1997; 63: 55-57
5 Wu XY, Qin GW, Cheung KK, Cheng KF. New alkaloids from Isatis indigotica . Tetrahedron 1997; 53: 13323-13328
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
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
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
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
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
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
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
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
14 Ho YL, Chang YS. Studies on the antinociceptive, anti-inflammatory and anti pyretic effects of Isatis indigotica root. Phytomedicine 2002; 9: 419-424
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
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
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
18 Finefield JM, Sherman DH, Kreitman M, Williams RM. Enantiomeric natural products: occurrence and biogenesis. Angew Chem Int Ed Engl 2012; 51: 4802-4836
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
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
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
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
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
24 Chen BC, Zhou P, Davis FA, Ciganek E. α-Hydroxylation of Enolates and Silyl Enol Ethers. Org React 2003; 62: 1-356
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
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
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
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

Supplementary Material

Supporting Information (PDF)