Indole alkaloid glycosides from Isatis tinctoria roots

Article abstract of DOI:10.1080/14786419.2019.1624960

Isatindigoside A and B (1 ? 2), two new indole alkaloid glycosides along with five known ones (3 ? 7) were obtained from the roots of I. tinctoria. Their structures were determined as isatindigoside A (1), isatindigoside B (2), isatindosulfonicacid A 3-O-β-D-glucopyranoside (3), indole-3-acetonitrile 6-O-β-D-glucopyranoside (4), isatindigobisindoloside A (5), isatindigobisindoloside B (6) isatindigobisindoloside F (7), by physicochemical properties and spectroscopic methods including 1 D, 2 D NMR, IR, HR-ESI-MS data. Nitric oxide (NO) inhibitory activities of all of the isolated compounds (1 ? 7) were also evaluated. Compounds 2 and 7 showed inhibitory effects against LPS-stimulated RAW 264.7 cells with IC₅₀ values of 27.6 μM and 18.8 μM, respectively.

Full text of DOI:10.1080/14786419.2019.1624960

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: https://www.tandfonline.com/loi/gnpl20
Indole alkaloid glycosides from Isatis tinctoria roots
Dongdong Zhang, Kang Du, Yitian Zhao, Songshan Shi, Yingchun Wu, Qi Jia,
Kaixian Chen, Yiming Li & Rui Wang
To cite this article: Dongdong Zhang, Kang Du, Yitian Zhao, Songshan Shi, Yingchun Wu, Qi Jia,
Kaixian Chen, Yiming Li & Rui Wang (2019): Indole alkaloid glycosides from Isatisꢀtinctoria roots,
Natural Product Research, DOI: 10.1080/14786419.2019.1624960
To link to this article: https://doi.org/10.1080/14786419.2019.1624960
View supplementary material
Published online: 07 Jun 2019.
Submit your article to this journal
Article views: 12
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=gnpl20

NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2019.1624960
Indole alkaloid glycosides from Isatis tinctoria roots
Dongdong Zhanga , Kang Dua, Yitian Zhaoa, Songshan Shib, Yingchun Wua,
Qi Jiaa, Kaixian Chena,c, Yiming Lia
and Rui Wanga
aSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China;
bInstitute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai,
c
China; Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, China
ABSTRACT
ARTICLE HISTORY
Received 3 February 2019
Accepted 25 May 2019
Isatindigoside A and B (1 ꢀ 2), two new indole alkaloid glycosides
along with five known ones (3 ꢀ 7) were obtained from the roots
of I. tinctoria. Their structures were determined as isatindigoside A
(1), isatindigoside B (2), isatindosulfonicacid A 3-O-b-D-glucopyra-
noside (3), indole-3-acetonitrile 6-O-b-D-glucopyranoside (4), isa-
KEYWORDS
Isatis tinctoria; indole
alkaloid glycosides;
structure determination;
anti-inflammatory activity
tindigobisindoloside
A
(5), isatindigobisindoloside
B
(6)
isatindigobisindoloside F (7), by physicochemical properties and
spectroscopic methods including 1 D, 2 D NMR, IR, HR-ESI-MS
data. Nitric oxide (NO) inhibitory activities of all of the isolated
compounds (1 ꢀ 7) were also evaluated. Compounds 2 and 7
showed inhibitory effects against LPS-stimulated RAW 264.7 cells
with IC50 values of 27.6 lM and 18.8 lM, respectively.
CONTACT Rui Wang
wr@shutcm.edu.cn; Yiming Li
ymlius@163.com
Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1624960.
ß 2019 Informa UK Limited, trading as Taylor & Francis Group

2
D. ZHANG ET AL.
1. Introduction
Isatis tinctoria L. (Chinese pharmacopeia named Isatis indigotica Fort., Cruciferae), a
biennial herbaceous plant, is widely distributed and cultivated in China (Guo et al.
2018). Its roots, named Ban Lan Gen, are usually used as traditional Chinese medicines
(TCMs) for the treatment of different kinds of diseases, especially for the treatments of
influenza, cold, fever and infections (Xi et al. 2018; Xie et al. 2011; Yang et al. 2014).
Various kinds of compounds, including alkaloids (Chen et al. 2012), lignans (Meng
et al. 2017b), organic acids, flavonoids (Wu et al. 2011) and nucleotides (Liu et al.
2018) have been isolated from the extracts. Among them, indole alkaloids are consid-
ered as the main active constituents which process anti-inflammatory, antiviral, anti-
bacterial and antitumor activities (Chen et al. 2015). As part of our research project to
explore more bioactive lead compounds from TCMs (Cui et al. 2015; Zhang et al.
2014), the chemical constituents and pharmacological investigation of I. tinctoria were
studied and seven indole alkaloid glycosides were obtained. Isatindigoside A and isa-
tindigoside B (1and 2), were deduced as two undescribed ones, whose structures
were determined by extensive spectroscopic data analysis, including 1 D, 2 D NMR, IR
and HR-ESI-MS data analysis. The known glycosides (3 ꢀ 7) were identified by compari-
son of spectroscopic and optical rotation data with those reported in the literatures as
isatindosulfonicacid A 3-O-b-D-glucopyranoside (3) (Meng et al. 2017a), indole-3-aceto-
nitrile 6-O-b-D-glucopyranoside (4) (Li et al. 2003), isatindigobisindoloside A (5) (Liu
et al. 2015), isatindigobisindoloside B (6) (Liu et al. 2015) and isatindigobisindoloside F
(7) (Liu et al. 2015). The nitric oxide (NO) inhibitory activities of all the isolated com-
pounds (1 ꢀ 7) were also evaluated. Reported herein are the isolation, structure eluci-
dation and the NO inhibitory activities of these compounds.
2. Results and discussion
Isatindigoside A (1) was obtained as a white amorphous powder with [a]2D0ꢀ11.4ꢁ (c
0.21, MeOH). Its molecular formula was assigned as C24H26N2O9, implying 13 indices of
hydrogen deficiency (IHD), by the 1 D NMR data and the HR-ESI-MS positive molecular
1
ion peak observed at m/z 487.1714 [M þ H]þ, (calcd for 487.1711 [M þ H]þ). The H
NMR spectrum of 1 showed signals of a 1, 2, 3-trisubstitute benzene ring (Chen et al.
2015) at dH 6.69 (1H, d, J ¼ 7.7 Hz, H-5’), 6.96 (1H, dd, J ¼ 7.7, 7.3 Hz, H-6’), 7.07 (1H, d,
J ¼ 7.3 Hz, H-7’); an ortho-disubstituted benzene ring (Liu et al. 2016) at dH 7.89 (1H, d,
J ¼ 8.0 Hz, H-4’’), 7.09 (1H, dd, J ¼ 8.0, 8.5 Hz, H-5’’), 7.51 (1H, dd, J ¼ 8.5, 8.5 Hz, H-6’’),
8.56 (1H, d, J ¼ 8.5 Hz, H-7’’); a trisubstituted double bond at dH 7.24 (1H, s, H-2’); a
disubstituted methylene proton at dH 4.01 (1H, d, J ¼ 16.5 Hz, H-1a) and 4.08 (1H, d,
J ¼ 16.5 Hz, H-1b) and also showed signals of an anomeric proton 5.01 (1H, d,
J ¼ 7.8 Hz, Glc-H1) and a methoxy proton at dH 3.57 (3H, s, 3’’-OMe). The 13C NMR
spectrum displayed 24 carbon signals, based on the DEPT 135ꢁ and 2 D NMR experi-
ments (Figure S17, Supplementary material), a O-glucopyranosyl unit (Liu et al. 2015)
and a 1H-indol-3-methane moiety (Liu et al. 2015) as well as a methyl 2-carbamoylben-
zoate moiety (Trachsel et al. 2009) were observed. The 1H-indol-3-methane moiety
was connected with the methyl 2-carbamoylbenzoate moiety via a C-1 ꢀ N-1’’ (C-N)
bond which was supported by the HMBC correlations of H1/C-2’’ and the downfield of

NATURAL PRODUCT RESEARCH
3
Figure 1. Structures of compounds 1–7.
C-1 at dC (37.9) compared with a C-C disubstituted bond methane at dC(20.2) (Liu
et al. 2015). The 4’-O-glucopyranosyl unit was deduced by the HMBC correlations of
Glc-H1/C-4’ and the downfield of C-4’ at dC (153.1) (Chen et al. 2012; Liu et al. 2016).
Acid hydrolysis of 1 resulted in the product of D-glucose which was confirmed by GC
analysis derivatives of the hydrolysate of 1 and the authentic sugars (tR D-glucose 41.
3 min, tR L-glucose 40.9 min). The large coupling constant of Glc-H1 (J ¼ 7.8 Hz)
revealed the b-glucopyranosyl linkage in 1 (Song et al. 2015b; Zhang et al. 2016). The
structure of isatindigoside A (1) was thus deduced as depicted (Figure 1).
Isatindigoside B (2) was isolated as a yellow amorphous power, [a]2D0ꢀ5.4ꢁ (c 0.13,
MeOH), with a molecular formula as C23H22N2O7, (14 IHD), which was deduced from
the 1 D NMR data and the HR-ESI-MS positive molecular ion peak observed at m/z
439.1507 [M þ H]þ, (calcd for 439.1500 [M þ H]þ). The 13C NMR spectrum displayed 23
carbon signals, based on the DEPT 135ꢁ and HSQC experiments, a O-glucopyranosyl
unit (107.0, 74.3, 76.8, 70.1, 77.6, 61.4) was observed by comparing its NMR data with
the literatures (Liu et al. 2016; Liu et al. 2015), the remaining 17 carbons (13 IHD),
compared with the reported literatures (Chen et al. 2012; Liu et al. 2015), represent a
1
bisindole aglycone of 2. This was deduced by H-1H COSY and HMBC data analysis
(Figure S17, Supplementary material). 1H-1H COSY correlations of H-4’/H-5’/H-6’/H-7’
along with the HMBC correlations of NH-1’/C-2’, C-3’, C-3’a and C-7’a deduced a 1H-
1
indol-2, 3-diyl moiety in 2; H-1H COSY correlations of H-4’’/H-5’’/H-6’’/H-7’’ along with
the HMBC correlations of H-2’’/C-1, C-3’’ and C-3’’a and NH-1’’/C-2’’, C-3’’ and C-7’’a
deduced a 1H-indol-3-one moiety in 2. HMBC correlations of N-1’/C-1, C-2’ and C-3’; H-
2’’/C-1, C-3’’ and N-1’’/C-2’’ and C-3’’ indicated the the two indolyl moieties were con-
jugated as bis(indol-2’/3’’-yl)methanone. HMBC correlation of Glc-H1/C-3’ indicated the
O-glucopyranosyl unit linked at C-3’ of the aglycone. The D-absolute configuration of
the glucose moiety in 2 was deduced as the same method as 1. The large coupling
constant of Glc-H1 (J ¼ 7.8 Hz) supported the b-glucopyranosyl linkage in 2 (Song
et al. 2015a). Accordingly, the structure of isatindigoside B (2) was elucidated as
depicted (Figure 1).
Indole alkaloids are one of the main types of alkaloids in I. tinctoria, which have
been reported to process potential anti-inflammatory effects (Yang et al. 2014). This
pharmacologic action, together with the traditional use for the treatment of epi-
demic hepatitis promoted us to test inhibitory effects on NO production, a main

4
D. ZHANG ET AL.
indicator to assess the inflammatory activities (Hu et al. 2018). Herein, all the glyco-
sides (1 ꢀ 7) were assessed for their abilities to inhibit NO production in LPS-stimu-
lated RAW 264.7 cells. The IC50 values (Table S2) showed that only compounds 2
and 7 exhibited inhibitory activities (27.6 lM and 18.8 lM, respectively) against
NO production.
3. Experimental
The General experimental procedures and Extraction and isolation sections see
Supplementary material.
3.1. Plant material
The I. tinctoria roots (Ban Lan Gen) were collected on July, 2017 from the Daqing city,
HeiLongJiang Province of China, and it was authenticated by one of our Co-authors
Rui Wang professor (School of Pharmacy, Shanghai University of Traditional Chinese
Medicine). A voucher specimen (herbarium No. 20170716SL) has been deposited in
the Medicinal Plants Herbarium (MPH), School of Pharmacy, Shanghai University of
Traditional Chinese Medicine, Shanghai, China.
3.2. Isatindigoside A (1), white amorphous power; [a]2D0ꢀ11.4ꢁ (c 0.21, MeOH); IR
(KBr) ꢀmax: 3363, 2924, 1703, 1667, 1611, 1514, 1443, 1310, 1260, 1073, 1026, 957,
762 cmꢀ1; HRESIMS: m/z 487.1714 [M þ H]þ, (calcd for 487.1711 [M þ H]þ); EIMS: 487
[M þ H]þ, 485 [M ꢀ H]ꢀ, 453 [M ꢀ OCH3]ꢀ, 323 [M ꢀ glc]ꢀ; 1H NMR (Methanol-d4,
600 MHz, d in ppm): 4.01 (1H, d, J ¼ 16.5 Hz, H-1a), 4.08 (1H, d, J ¼ 16.5 Hz, H-1b), 7.24
(1H, s, H-2’), 6.69 (1H, d, J ¼ 7.7 Hz, H-5’), 6.96 (1H, dd, J ¼ 7.7, 7.3 Hz, H-6’), 7.07 (1H, d,
J ¼ 7.3 Hz, H-7’), 7.89 (1H, d, J ¼ 8.0 Hz, H-4’’), 7.09 (1H, dd, J ¼ 8.0, 8.5 Hz, H-5’’), 7.51
(1H, dd, J ¼ 8.5, 8.5 Hz, H-6’’), 8.56 (1H, d, J ¼ 8.5 Hz, H-7’’), 3.57 (3H, s, OMe), 5.01 (1H,
d, J ¼ 7.8Hz, Glc-H1), 3.54 (1H, m, Glc-H2), 3.39 (1H, m, Glc-H3), 3.30 (1H, overlap, Glc-
H4), 3.44 (1H, m, Glc-H5), 3.53 (1H, dd, J ¼ 10.5, 5.9 Hz, Glc-H6a), 3.77 (1H, dd, J ¼ 10.5,
2.3 Hz, Glc-H6b); 13C NMR (Methanol-d4, 150 MHz, d in ppm): 37.9 (C-1, t), 125.7 (C-2’,
d), 108.1 (C-3’, s), 119.2 (C-3’a, s), 153.1 (C-4’, s), 104.4 (C-5’, d), 123.7 (C-6’, d), 107.3 (C-
7’, d), 140.6 (C-7’a, s), 175.7 (C-2’’, s), 168.9 (C-3’’, s), 118.2 (C-3’’a, s), 131.9 (C-4’’, d),
124.2 (C-5’’, d), 134.9 (C-6’’, d), 122.0 (C-7’’, d), 141.4 (C-7’’a, s), 52.6 (OMe, q), 101.9
(Glc-C1, d), 75.1 (Glc-C2, d), 78.2 (Glc-C3, d), 71.7 (Glc-C4, d), 78.0 (Glc-C5, d), 62.8 (Glc-
C6, t), or see Table S1 (Supplementary material).
3.3 Isatindigoside B (2), yellow amorphous power; [a]2D0ꢀ5.4ꢁ (c 0.13, MeOH); IR
(KBr) ꢀmax: 3420, 2925, 1728, 1647, 1617, 1518, 1464, 1396, 1250, 1071, 1030, 888,
759 cmꢀ1; HRESIMS: m/z 439.1507 [M þ H]þ, (calcd for 439.1500 [M þ H]þ), EIMS: 439
1
[M þ H]þ, 437 [M ꢀ H]ꢀ, 275 [M ꢀ glc]ꢀ; H NMR (DMSO-d6, 600 MHz, d in ppm): 12.55
(1H, brs, H-1’), 7.94 (1H, d, J ¼ 8.1 Hz, H-4’), 7.05 (1H, td, J ¼ 8.1, 7.3 Hz, H-5’), 7.22 (1H,
td, J ¼ 7.7, 7.3 Hz, H-6’), 6.91 (1H, d, J ¼ 7.7 Hz, H-7’), 11.01 (1H, brs, H-1’’), 8.12 (1H, s,
H-2’’), 7.71 (1H, d, J ¼ 7.4 Hz, H-4’’), 7.03 (1H, td, J ¼ 7.7, 7.4 Hz, H-5’’), 7.28 (1H, td,
J ¼ 8.3, 7.7 Hz, H-6’’), 7.51 (1H, d, J ¼ 8.3 Hz, H-7’’), 4.64 (1H, d, J ¼ 7.8 Hz, Glc-H1), 3.46
(1H, overlap, Glc-H2), 3.27 (1H, overlap, Glc-H3), 3.28 (1H, overlap, Glc-H4), 3.21 (1H, m,
Glc-H5), 3.53 (1H, dd, J ¼ 11.8, 5.7 Hz, Glc-H6a), 3.77 (1H, dd, J ¼ 11.8, 2.4 Hz, Glc-H6b);

NATURAL PRODUCT RESEARCH
5
13C NMR (DMSO-d6, 150 MHz, d in ppm): 169.6 (C-1, s), 121.0 (C-2’, s), 143.2 (C-3’, s),
125.3 (C-3’a, s), 120.7 (C-4’, d), 120.3 (C-5’, d), 128.5 (C-6’, d), 110.2 (C-7’, d), 135.2 (C-
7’a, s), 122.2 (C-2’’, d), 106.9 (C-3’’, s), 120.1 (C-3’’a, s), 119.9 (C-4’’, d), 121.9 (C-5’’, d),
126.4 (C-6’’, d), 112.8 (C-7’’, d), 140.3 (C-7’’a, s), 107.0 (Glc-C1, d), 74.3 (Glc-C2, d), 76.8
(Glc-C3, d), 70.1 (Glc-C4, d), 77.6 (Glc-C5, d), 61.4 (Glc-C6, t), or see Table S1
(Supplementary material).
3.4. Absolute configuration determination of sugar
Solutions of 1 and 2 (1.8 mg each) in 2 M hydrochloric acid (4 mL) was hydrolyzed at
80 ꢁC for 2 h. After cooling, each solution was concentrated under vacuum, dissolved
with water, and extracted twice with dichloromethane (CH2Cl2). The aqueous parts
were treated via a similar method described previously (Cui et al. 2015). The D config-
urations of the glucose moiety in 1 and 2 were confirmed through comparison their
retention times (tR) with those of authentic sugar samples (tR D-glucose 41.3 min, tR
L-glucose 40.9 min).
3.5. Inhibitory assay of NO production
Cytotoxicity was examined using the Cell Counting Kit-8 (CCK-8). The absorbance at
450 nm was measured using a microplate reader (Thermo Fisher Scientific). Viability
was defined as the ratio (expressed as a percentage) of absorbance values of treated
cells to untreated cells.
Compounds 1–7 were dissolved in dimethyl sulfoxidediluted (DMSO) with complete
medium to 6 degrees of concentration (0.1 lmol ꢂ Lꢀ1, 1 lmol ꢂ Lꢀ1, 10 lmol ꢂ Lꢀ1
,
25 lmol ꢂ Lꢀ1, 50 lmol ꢂ Lꢀ1, 100 lmol ꢂ Lꢀ1) for inhibition rate determination. RAW
264.7 cells were maintained in Dulbecco’s modified Eagle’s medium (high-glucose con-
dition) supplemented with 10% fetal calf serum, 100 U/ml penicillin, and 100 lg/mL
streptomycin at 37 ꢁC in 5% CO2. RAW 264.7 cells were pre-treated with each tested
compound for 30 min, and then stimulated with lipopolysaccharide (LPS) (100 ng/mL)
for 24 h. Aminoguanidine hydrochloride (100 lM) was used as a positive control. The
NO production was measured using the Griess reagent. Briefly, cell culture supernatant
was reacted with equal volumes of Griess reagent in a 96-well plate for 10 min, and
then the absorbance at 540 nm was measured by a plate reader. All experiments were
performed in triplicate. All of the tested compounds were prepared as stock solutions
with a concentration of 10 mM in DMSO. The IC50 values of compounds 1 – 7 were
calculated (see Table S2, Supplementary material).
4. Conclusions
Seven indole alkaloid glycosides were obtained from the roots of I. tinctoria, among
them, compounds 2 and 7 exhibited inhibitory activities against NO production with
IC50 values of 27.6 lM and 18.8 lM. This study enriched the chemical and pharmaco-
logical diversity of I. tinctoria.

6
D. ZHANG ET AL.
Disclosure statement
The authors declare no competing financial interest.
Acknowledgement
This work was supported by National Natural Science Foundation of China (81573571,
81673570), Excellent Academic Leaders Program of Shanghai (16XD1403500), the programs of
High level University Innovation Team and Shanghai E-Research Institute of Bioactive
Constituents in Traditional Chinese Medicine.
ORCID
Dongdong Zhang
http://orcid.org/0000-0003-0956-1261
Yiming Li
Rui Wang
http://orcid.org/0000-0003-3416-1331
http://orcid.org/0000-0002-6204-5015
References
Chen M, Gan L, Lin S, Wang X, Li L, Li Y, Zhu C, Wang Y, Jiang B, Jiang J, et al. 2012. Alkaloids
from the root of Isatis indigotica. J Nat Prod. 75(6):1167–1176.
Chen M, Sheng L, Li L, Zhu C, Wang X, Wang Y, Jiang B, Wang S, Li Y, Jiang J, Shi J. 2015.
Enantiomers of an indole alkaloid containing unusual dihydrothiopyran and 1,2,4-thiadiazole
rings from the root of Isatis indigotica. Orgnic Lett. 45:1523–7052.
Cui B, Wang X, Yang Y, Yang Y, Shi S, Guo F, Li Y. 2015. Sixteen novel C-21 steroidal glycosides
from the roots of Cynanchum mooreanum. Steroids. 104:1878–5867.
Guo Q, Xu C, Chen M, Lin S, Li Y, Zhu C, Jiang J, Yang Y, Shi J. 2018. Sulfur-enriched alkaloids
from the root of Isatis indigotica. Acta Pharmaceutica Sinica B. 8(6):933–943.
Hu HJ, Zhou Y, Han ZZ, Shi YH, Zhang SS, Wang ZT, Yang L. 2018. Abietane diterpenoids from
the roots of clerodendrum trichotomum and their nitric oxide inhibitory activities. J Nat Prod.
81(7):1508–1516.
Li B, Chen W-S, Zhang H-M, Zhang W-D, Yang G-J, Qiao C-Z. 2003. Two new alkaloids isolated
from tetraloidy BANLANGEN. Yao Xue Xue Bao. 38(6):430.
Liu SF, Zhang YY, Zhou L, Lin B, Huang XX, Wang XB, Song SJ. 2018. Alkaloids with neuroprotec-
tive effects from the leaves of Isatis indigotica collected in the Anhui Province, China.
Phytochemistry. 149:132–139.
Liu YF, Chen MH, Lin S, Li YH, Zhang D, Jiang JD, Shi JG. 2016. Indole alkaloid glucosides from
the roots of Isatis indigotica. J Asian Nat Prod Res. 18(1):1–12.
Liu YF, Ming Hua C, Qing Lan G, Sheng L, Cheng Bo X, Yue Ping J, Yu Huan L, Jian Dong J, Jian
Gong S. 2015. Antiviral glycosidic bisindole alkaloids from the roots of Isatis indigotica. J
Asian Nat Prod Res. 17(7):689–704.
Meng L, Guo Q, Liu Y, Chen M, Li Y, Jiang J, Shi J. 2017. Indole alkaloid sulfonic acids from an
aqueous extract of Isatis indigotica roots and their antiviral activity. Acta Pharmaceutica Sinica
B. 7(3):334–341.
Meng L, Guo Q, Liu Y, Shi J. 2017. 8,40-Oxyneolignane glucosides from an aqueous extract of
“ban lan gen”(Isatis indigotica root)and their absolute configurations. Acta Pharmaceutica
Sinica B. 7(6):638–646.
Song X, Li Y, Zhang D, Jiang Y, Wang W, Song B, Tang Z, Cui J, Yue Z. 2015. Two new spirosta-
nol saponins from the the roots and rhizomes of Tupistra chinensis. Phytochem Lett. 13:6–10.
Song X, Zhang D, He H, Li Y, Yang X, Deng C, Tang Z, Cui J, Yue Z. 2015. Steroidal glycosides
from Reineckia carnea. Fitoterapia. 105:240–245.

NATURAL PRODUCT RESEARCH
7
Trachsel A, de Saint Laumer J-Y, Haefliger OP, Herrmann ANDREAS. 2009. Parameters influencing
the release of tertiary alcohols from the surface of "spherical" dendrimers and "linear" stylom-
ers by neighbouring-group-assisted hydrolysis of 2-carbamoylbenzoates. Chem Eur J. 15(12):
2846–2860.
Wu Y, Zhang Z, Hu H, Li D, Qiu G, Hu X, He X. 2011. Novel indole C-glycosides from Isatis indi-
gotica and their potential cytotoxic activity. Fitoterapia. 82(2):288–292.
Xi YF, Zhou L, Bai M, Wang J, Lin B, Wang XB, Huang XX, Song SJ. 2018. N -acylanthranilic acid
derivatives with anti-A b 1–42 aggregation activity from the leaves of Isatis indigotica fortune.
Fitoterapia. 128:169.
Xie Z, Shi Y, Wang Z, Wang R, Li Y. 2011. Biotransformation of glucosinolates epiprogoitrin and
progoitrin to (R)- and (S)-Goitrin in Radix isatidis. J Agric Food Chem. 59(23):12467–12472.
Yang L, Wang G, Wang M, Jiang H, Chen L, Zhao F, Qiu F. 2014. Indole alkaloids from the roots
of Isatis indigotica and their inhibitory effects on nitric oxide production. Fitoterapia. 95:
175–181.
Zhang D, Wang W, Li Y, Li Z, Jiang Y, Tang Z, Song X, Yue Z. 2016. Two new pregnane
glycosides from Reineckia carnea. Phytochemistry Lett. 15:142–146.
Zhang L, Zhu T, Qian F, Xu J, Dorje G, Zhao Z, Guo F, Li Y. 2014. Iridoid glycosides isolated from
Scrophularia dentata Royle ex Benth. and their anti-inflammatory activity. Fitoterapia. 98:
84–90.