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Bioactive Flavonoid Derivatives from Scutellaria luzonica

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Meng Bai at Hainan Normal University
Meng Bai
Cai-Juan Zheng at Hainan Normal University
Cai-Juan Zheng
Li-Jun Wu
Li-Jun Wu
Li-Jun Wu
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Shou-Yuan Wu
Shou-Yuan Wu
Shou-Yuan Wu
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350 0009-3130/18/5402-0350 2018 Springer Science+Business Media, LLC
Chemistry of Natural Compounds, Vol. 54, No. 2, March, 2018
BIOACTIVE FLAVONOID DERIVATIVES FROM Scutellaria luzonica
Meng Bai, Cai-Juan Zheng, Li-Jun Wu,
Shou-Yuan Wu, Yue Cai, Guang-Ying Chen,
Chang-Ri Han,* and Xiao-Ping Song*
Scutellaria is one of the most widely used traditional Chinese herbal medicines, and the other name is “HuangQin” in
Chinese [1]. Its root is the traditional medicinal part and has been listed in the Chinese Pharmacopoeia for a long time [2].
The aerial parts of Scutellaria also have diverse and strong therapeutic functions and potentially beneficial effects, such as
cardiovascular [3], neuroprotective [4], antitubercular [5], memory improving [6], antitumor [7], and antibacterial activity [8].
There have been previous investigations on the chemical constituents of the roots of Scutellaria luzonica Rolfe, and 18 flavonoids,
including 13 flavones, two flavanones, one chalcone, and one flavone glycoside, were isolated from this plant [9]. However,
Scutellaria luzonica is a variant of Scutellaria luzonica, and the chemical constituents and bioactivities of S. luzonica have not
been reported. In order to search for the bioactive chemical constituents of S. luzonica, 14 flavonoid derivatives were isolated
from the EtOAc extract of S. luzonica. The isolated compounds were identified as 5-hydroxy-7-methoxyflavanone (1) [10],
6-methoxynaringenin (2) [11], 5,6,7,4c-tetrahydroxyflavanone (3) [12], 5,7,2c-trihydroxyflavone (4) [13], 5,7-dihydroxyflavone
(5) [14], hispidulin (6) [15], 5,7,8-trihydroxyl-6-methoxyflavone (7) [16], wogonin (8) [17], 5,6-dihydroxy-7-methoxyflavone
(9) [18], 5,7,3c,4c-tetrahydroxyflavone (10) [19], baicalein (11) [20], oroxylin A (12) [21], 5,8-dihydroxy-7-methoxyflavone
(13) [22], and 5,7,2c-trihydroxy-8-methoxyflavone (14) [23], on the basis of their spectroscopic data and by comparison with
those previously reported in the literature. All compounds were isolated from S. luzonica for the first time.
The biological activity of all the isolated compounds was evaluated against seven pathogenic bacteria, including
Candida albicans, Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Escherichia coli, Vibrio parahaemolyticus and
V. alginolyticus; Antimosquito larva activity was also tested. Compounds 8 and 11 showed significant antibacterial activity
against C. albicans with the same MIC values of 4.17 Pg/mL. Compounds 8, 10, and 11 showed strong antibacterial activity
against V. parahaemolyticus with the same MIC values of 3.12 Pg/mL. Compounds 8, 11, and 12 showed significant antibacterial
activity against V. alginolyticus with the same MIC values of 6.25 Pg/mL. The other compounds showed weak or no antibacterial
activity with MIC values greater than 10 Pg/mL (Table 1). Compounds 5, 12 and 14 showed Antimosquito larva activity with
LC50 values of 50, 30, and 100 Pg/mL, respectively.
General. 1D (1H, 13C, DEPT) and 2D (1H–1H COSY, NOESY, HMQC, HMBC) NMR spectra were recorded on a
Bruker AV 400 NMR spectrometer. ESI-MS spectra were recorded on an Agilent 1200 series HPLC interfaced to a Bruker
Esquire 6000 Ion Trap mass spectrometer equipped with an electrospray ionization source. HPLC separation was performed
on an Agilent-HPLC column (Eclipse XDB-C18, 10 u 250 mm, 5 Pm). Silica gel and GF254 were obtained from the Qingdao
Marine Chemical Factory. Sephadex LH-20 was manufactured by Pharmacia Co. Ltd.
Plant Material. The dried whole plants of Scutellaria luzonica Rolfe were collected in Ledong County, Hainan
Province, China, in September 2014 and were identified by Dr. Rongtao Li, Hainan Branch of the Institute of Medicinal Plant
Development, Chinese Academy of Medical Sciences and Peking Union Medical College. A voucher specimen has been
deposited in the Key Laboratory of Tropical Medicinal Plant Chemistry of the Ministry of Education, Hainan Normal University.
Extraction and Isolation. The dried whole plants of Scutellaria luzonica (2 kg) were powdered and refluxed with
85% EtOH three times. Evaporation of the solvent under reduced pressure gave the ethanolic extract (55 g), which
was dissolved in water and then extracted with petroleum ether and ethyl acetate successively at room temperature.
Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, College of Chemistry and Chemical
Engineering, Hainan Normal University, 571158, Haikou, Hainan, P. R. China, fax: (86) 89865889422, e-mail: sxp628@126.com.
Published in Khimiya Prirodnykh Soedinenii, No. 2, March–April, 2018, pp. 295–297. Original article submitted
June 8, 2016.
DOI 10.1007/s10600-018-2342-y
351
The ethyl acetate extract (10 g) was subjected to silica gel column chromatography (CC) (petroleum ether–EtOAc, gradient
100:0–0:100) to yield seven fractions (Frs. 1–7). Fraction 2 was isolated by CC on silica gel eluted with petroleum ether–EtOAc
(3:1) and then subjected to Sephadex LH-20 CC eluting with mixtures of CHCl3–MeOH (1:1) to obtain 1 (15.0 mg), 3 (5.0 mg),
and 9 (6.0 mg). Fraction 3 was isolated by CC on silica gel eluted with petroleum ether–EtOAc (5:3) and then subjected to
Sephadex LH-20 CC eluting with mixtures of CHCl3–MeOH (1:1) to obtain 2 (7.0 mg), 6 (5.0 mg), and 7 (3.0 mg). Fraction
4 was subjected to repeated Sephadex LH-20 CC (CHCl3–MeOH, 1:1) and further purified by HPLC on an ODS semipreparative
column (Kromasil C18, 10 u 250 mm, 5 Pm, 2 mL/min) eluted with 50% MeOH–H2O to obtain 4 (4.0 mg) and 5 (6.0 mg).
Fraction 5 was subjected to repeated Sephadex LH-20 CC (MeOH) and further purified on HPLC (40% MeOH–H2O) to
afford 8 (3.8 mg), 10 (4.2 mg), and 12 (3.2 mg). Fraction 6 was subjected to repeated Sephadex LH-20 CC (MeOH) and further
purified by HPLC (30% MeOH–H2O) to afford 11 (2.8 mg), 13 (2.2 mg) and 14 (2.5 mg).
Assessment of Bioactivity. Antibacterial activity against seven bacterial strains, C. albicans (60193), S. aureus
(ATCC 27154), B. cereus (ACCC 11077), B. subtilis (ACCC 11060), E. coli (ATCC 25922), Vibrio parahaemolyticus
(ATCC 17802), and V. alginolyticus (17749) was determined by a serial dilution technique using 96-well microtiter plates
[24]. The compounds were dissolved in DMSO to give a stock solution. Bacterial species were cultured overnight at 37qC in
LB broth and diluted to 106 cfu/mL when used. LB broth was used as a blank control, and DMSO was used as a negative
control, while ciprofloxacin was used as a positive control.
Bioassay against Mosquito larvae. The compounds were diluted in 6-well microtiter plates with 8 mL dechlorinated
water for larvicidal activity test. Third instar larvae of Culex quinquefasciatus and Aedes albopictus were exposed to serial
dilutions of the compounds. Ten Mosquito larvae were introduced into each 6-well microtiter plate with a pipette, and the
mortality was recorded after 48 h. All the bioassays were conducted at 26qC with 60–70% relative humidity and a photoperiod
of 14 h light and 10 h dark. Six-well microtiter plates with only 8 mL dechlorinated water was used as a blank control, and
DMSO was used as a negative control [25].
5-Hydroxy-7-methoxyflavanone (1). 1H NMR (400 MHz, CDCl3, G, ppm, J/Hz): 7.44 (2H, dd, J = 7.8, 1.8, H-2c, 6c),
7.42 (3H, m, H-3c, 4c, 5c), 6.55 (1H, d, J = 1.8, H-6), 6.14 (1H, d, J = 1.8, H-8), 5.40 (1H, dd, J = 13.0, 3.0, H-2), 3.95 (3H, s,
11-OCH3), 3.06 (1H, dd, J = 16.6, 13.0, H-3a), 2.85 (1H, dd, J = 16.6, 3.0, H-3b). 13C NMR (100 MHz, CDCl3, G, ppm): 196.8
(C, C-4), 158.7 (C, C-7), 157.7 (C, C-5), 154.5 (C, C-9), 138.1 (C, C-1c), 129.1 (CH, C-3c, 5c), 128.5 (CH, C-8), 126.3 (CH,
C-2c, 6c), 103.2 (C, C-10), 94.8 (CH, C-6), 94.8 (CH, C-4c), 79.4 (CH, C-2), 61.1 (CH3, C-11), 43.5 (CH2, C-3). ESI-MS m/z
271.3 [M + H]+.
6-Methoxynaringenin (2). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 7.30 (2H, d, J = 8.6, H-2c, 6c), 6.78 (2H,
d, J = 8.6, H-3c, 5), 5.90 (1H, s, H-8), 5.40 (1H, dd, J = 13.0, 3.0, H-2), 3.64 (3H, s, 6-OCH3), 3.23 (1H, dd, J = 16.8, 13.0, H-3a),
2.64 (1H, dd, J = 16.8, 3.0, H-3b). 13C NMR (100 MHz, DMSO-d6, G, ppm): 197.1 (C, C-4), 159.5 (C, C-9), 158.0 (C, C-7),
157.7 (C, C-4c), 155.1 (C, C-5), 129 (C, C-6), 128.9 (C, C-1c), 128.3 (CH, C-2c, 6c), 115.1 (CH, C-3c, 5c), 101.8 (C, C-10), 95.0
(CH, C-8), 78.5 (CH, C-2), 60.0 (CH3, C-11), 42.0 (CH2, C-3). ESI-MS m/z 303.3 [M + H]+.
5,6,7,4cc
cc
c-Tetrahydroxyflavanone (3). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 7.30 (2H, d, J = 8.6, H-2c, 6c),
6.78 (2H, d, J = 8.6, H-3c, 5c), 5.92 (1H, s, H-8), 5.37 (1H, dd, J = 12.6, 3.0, H-2), 3.21 (1H, dd, J = 17.2, 12.6, H-3a), 2.65 (1H,
dd, J = 17.2, 3.0, H-3b). 13C NMR (100 MHz, DMSO-d6, G, ppm): 196.9 (C, C-4), 157.7 (C, C-4c), 155.8 (C, C-7), 155.0
(C, C-5), 150.2 (C, C-9), 129.1 (C, C-1c), 128.9 (CH, C-2c, 6c), 128.2 (C, C-6), 115.1 (CH, C-3c, 5c), 95.2 (C, C-10), 95.0 (CH,
C-8), 78.4 (CH, C-2), 42.0 (CH2, C-3). ESI-MS m/z 289.3 [M + H]+.
TABLE 1. Antibacterial Activity of Compounds 2, 8, and 10–12 (MIC, Pg/mL)
Compound C. albicans V. alginolyticus V. parahaemolyticus
2 12.5 25 6.25
8 4.17 6.25 3.12
10 12.5 25 3.12
11 4.17 6.25 3.12
12 12.5 6.25 25
Ciprofloxacina 3.12 3.12 3.12
______
aCiprofloxacin was used as a positive control.
352
5,7,2cc
cc
c-Trihydroxyflavone (4). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 7.85 (1H, dd, J = 8.0, 1.8, H-6c), 7.36
(1H, m, H-4c), 7.11 (1H, s, H-3), 7.03 (1H d, J = 8.0, 1.8, H-3c), 6.94 (1H, m, H-5c), 6.43 (1H, d, J = 1.8, H-8), 6.16 (1H, d,
J = 1.8, H-6). 13C NMR (100 MHz, DMSO-d6, G, ppm): 182.3 (C, C-4), 166.1 (C, C-7), 161.9 (C, C-2), 161.8 (C, C-5), 158.3 (C,
C-9), 158.1 (C, C-2c), 133.2 (CH, C-4c), 128.9 (CH, C-6c), 119.3 (CH, C-5c), 117.9 (C, C-1c), 117.7 (CH, C-3c), 109.2 (CH, C-3),
103.8 (C, C-10), 99.5 (CH, C-6), 94.5 (CH, C-8). ESI-MS m/z 271.2 [M + H]+.
5,7-Dihydroxyflavone (5). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 8.02 (2H, dd, J = 7.8, 2.0, H-2c, 6c), 7.54
(3H, m, H-3c, 4c, 5c), 6.90 (1H, s, H-3), 6.49 (1H, d, J = 2.0, H-8), 6.21 (1H, d, J = 2.0, H-6). 13C NMR (100 MHz, DMSO-d6, G,
ppm): 181.8 (C, C-4), 164.5 (C, C-7), 163.1 (C, C-2), 161.5 (C, C-5), 157.4 (C, C-9), 132 (CH, C-4c), 130.7 (C, C-1c), 129.1
(CH, C-3c, 5c), 126.4 (CH, C-2c, 6c), 105.2 (CH, C-3), 103.9 (C, C-10), 99 (CH, C-6), 94.1 (CH, C-8). ESI-MS m/z 255.2
[M + H]+.
Hispidulin (6). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 7.90 (2H, d, J = 8.8, H-2c, 6c), 6.92 (2H, d, J = 8.8,
H-3c, 5c), 6.74 (1H, s, H-3), 6.57 (1H, s, H-8), 3.74 (3H, s, 11-OCH3). 13C NMR (100 MHz, DMSO-d6, G, ppm): 182 (C, C-4),
163.7 (C, C-2), 161.3 (C, C-4c), 158.3 (C, C-7), 152.7 (C, C-5), 152.5 (C, C-9), 131.6 (C, C-6), 128.4 (CH, C-2c, 6c), 121.2 (C,
C-1c), 115.9 (CH, C-3c, 5c), 103.7 (C, C-10), 102.3 (CH, C-3), 94.4 (CH, C-8), 59.9 (CH3, C-11). ESI-MS m/z 301.3 [M + H]+.
5,7,8-Trihydroxy-6-methoxyflavone (7). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 8.03 (2H, dd, J = 7.8, 2.0,
H-2c, 6c), 7.55 (3H, m, H-3c, 4c, 5c), 6.72 (1H, s, H-3), 3.83 (3H , s, 11-OCH3). 13C NMR (100 MHz, DMSO-d6, G, ppm): 180
(C, C-4), 160.5 (C, C-2), 154.2 (C, C-7), 139.4 (C, C-8), 138.6 (C, C-6), 135.1 (C, C-9), 131.3 (C, C-5), 131.2 (C, C-1c), 129.8
(CH, C-4c), 129 (CH, C-3c, 5c), 125.7 (CH, C-2c, 6c), 105.6 (CH, C-3), 99.4 (C, C-10), 59.7 (CH3, C-11). ESI-MS m/z 301.3 [M + H]+.
Wogonin (8). 13C NMR (100 MHz, CDCl3, G, ppm): 182.6 (C, C-4), 163.8 (C, C-2), 157.7 (C, C-7), 155.4 (C, C-5),
149.0 (C, C-9), 132.0 (CH, C-4c), 131.3 (C, C-1c), 129.2 (CH, C-3c, 5c), 127.0 (C, C-8), 126.2 (CH, C-2c, 6c), 106.0 (CH, C-3),
105.3 (C, C-10), 98.9 (CH, C-6), 62.1 (CH3, C-11). ESI-MS m/z 285.3 [M + H]+.
5,6-Dihydroxy-7-methoxyflavone (9). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 8.06 (2H, dd, J = 8.0, 1.6,
H-2c, 6c), 7.55 (3H, m, H-3c, 4c, 5c), 6.95 (1H, s, H-3), 6.61 (1H, s, H-8), 3.76 (3H, s, 11-OCH3). 13C NMR (100 MHz, DMSO-d6,
G, ppm): 182.1 (C, C-4), 163.1 (C, C-2), 158.4 (C, C-5), 157.9 (CH, C-8), 152.7 (C, C-9), 131.9 (CH, C-4c), 131.7 (C, C-1c),
130.8 (C, C-7), 129.1 (CH, C-3c, 5c), 126.4 (CH, C-2c, 6c), 104.6 (C, C-10), 104 (CH, C-3), 94.5 (C, C-6), 61.1 (CH3, C-11).
ESI-MS m/z 285.3 [M + H]+.
5,7,3cc
cc
c,4cc
cc
c-Tetrahydroxyflavone (10). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 7.42 (1H, dd, J = 8.2, 2.0, H-6c),
7.40 (1H, d, J = 2.0, H-2c), 6.89 (1H, d, J = 8.2, H-5c), 6.67 (1H, s, H-3), 6.44 (1H, d, J = 2.0, H-8), 6.19 (1H, d, J = 2.0, H-6).
13C NMR (100 MHz, DMSO-d6, G, ppm): 181.7 (C, C-4), 164.1 (C, C-2), 163.9 (C, C-7), 161.5 (C, C-9), 157.3 (C, C-5), 149.7
(C, C-4c), 145.7 (C, C-3c), 121 (C, C-1c), 119 (CH, C-6c), 116 (CH, C-5c), 113.4 (CH, C-2c), 103.7 (C, C-10), 102.9 (CH, C-3),
98.8 (CH, C-6), 93.8 (CH, C-8). ESI-MS m/z 287.2 [M + H]+.
Baicalein (11). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 7.97 (2H, dd, J = 8.6, 1.8, H-2c, 6c), 7.56 (3H, m,
H-3c, 4c, 5c), 6.71 (1H, s, H-8), 6.61 (1H, s, H-3).13C NMR (100 MHz, DMSO-d6, G, ppm): 184.2 (C, C-4), 165.6 (C, C-2),
154.9 (C, C-7), 152.2 (C, C-5), 132.9 (C, C-6), 132.8 (C, C-1c), 147.9 (C, C-9), 130.8 (CH, C-4c), 130.2 (CH, C-3c, 5c), 127.4
(CH, C-2c, 6c), 105.8 (C, C-10), 105.4 (CH, C-3), 95.0 (CH, C-8). ESI-MS m/z 271.2 [M + H]+.
Oroxylin A (12). 13C NMR (100 MHz, CDCl3, G, ppm): 183.1 (C, C-4), 164.1 (C, C-2), 155.2 (C, C-7), 153.3 (C, C-5),
152.1 (C, C-9), 131.9 (C, C-6), 131.3 (CH, C-4c), 130.4 (C, C-1c), 129.1 (CH, C-3c, 5c), 126.3 (CH, C-2c, 6c), 105.9 (CH, C-3),
105.3 (C, C-10), 93.5 (CH, C-8), 60.9 (CH3, C-11). ESI-MS m/z 285.3 [M + H]+.
5,8-Dihydroxy-7-methoxyflavone (13). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 7.99 (2H, dd, J = 8.8, 2.0,
H-2c, 6c), 7.56 (3H, m, H-3c, 4c, 5c), 6.74 (1H, s, H-6), 6.59 (1H s, H-3), 3.89 (3H, s, 11-OCH3). 13C NMR (100 MHz, DMSO-d6,
G, ppm): 184.0 (C, C-4), 165.7 (C, C-2), 159.8 (C, C-5), 154.9 (C, C-8), 154.0 (C, C-9), 133.0 (C, C-4c), 132.5 (C, C-1c), 130.2
(C, C-7), 127.4 (CH, C-3c, 5c), 126.4 (CH, C-2c, 6c), 105.7 (C, C-10), 105.5 (CH, C-3), 95.6 (CH, C-6), 60.9 (CH3, C-11).
ESI-MS m/z 285.3 [M + H]+.
5,7,2cc
cc
c-Trihydroxy-8-methoxyflavone (14). 1H NMR (400 MHz, DMSO-d6, G, ppm, J/Hz): 7.85 (1H, dd, J = 8.0,
1.8, H-6c), 7.36 (1H, m, H-4c), 7.09 (1H, s, H-3), 7.03 (1H, d, J = 8.0, 1.8, H-3c), 6.94 (1H, m, H-5c), 6.06 (1H, s, H-6), 3.78
(3H, s, 11-OCH3). 13C NMR (100 MHz, DMSO-d6, G, ppm): 181.7 (C, C-4), 166.2 (C, C-7), 161.2 (C, C-2), 161.8 (C, C-5),
156.3 (C, C-9), 149.7 (C, C-2c), 132.7 (CH, C-4c), 128.2 (CH, C-6c), 119.1 (CH, C-5c), 117.4 (C, C-1c), 117.7 (CH, C-3c), 108.7
(CH, C-3), 102.8 (C, C-10), 99.3 (CH, C-6), 94.4 (C, C-8), 60.4 (CH3, C-11). ESI-MS m/z 301.3 [M + H]+.
353
ACKNOWLEDGMENT
We acknowledge funding from the International S&T cooperation Program of China (ISTCP) (2014DFA40850),
Hainan province Natural Science Foundation of innovative research team project (2016CXTD007), Hainan special project for
TCM modernization (2015ZY19), and the National Natural Science Foundation of China (21362009 and 81360478).
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... This is the first time that A. integrifolia (Jacq) Moldenke has been analyzed phytochemically and compared to the literature (Goswami et al., 2015;Barakat and Al Majid 2017;Bai et al., 2018;Soares et al., 2018;Hou et al., 2019;Loesche et al., 2019;Fernandes et al., 2019). Only one phytochemical study with this genus was previously carried out with the species A. sellowiana (Camargos et al., 1996). ...
... After analyzing by MS, IR and 1 H NMR spectra and comparing with the literature data, the isolated compound 2 was suggested to be the flavonoid pectolinarigenin (Lu et al., 2014;Zheng et al., 2018). An additional 13 C NMR spectrum experiment was performed in order to confirm the structure of compound 2. It was possible to identify the signals, confirming the connectivity at 163.7 (C-2), 103.4 (C-3), 182.5 (C-4), 153.1 (C-5; 6), 60.3 (C-6; -OCH 3 ), 157.7 (C-7; -OH), 94.7 (C-8), 152.8 (C-9) and 104.5 (C-10) A and C. The signals 123.3 (C-1 ′ ), 128.6 (C-2 ′ and C-6 ′ ), 114.9 (C-3 ′ and C-5 ′ ), 162.6 55.9 (C-4 ′ , -OCH 3 ), associated with the carbons of the B ring, confirmed the pectolinarigenin structure (Fig. 1). ...
... In the 1 H NMR it was possible to observe a signal at δH 13.26 (OH-5; 1H, s) assigned to the carbonyl chelated hydroxyl hydrogen, and signals at δH 9.26 (1H, s) and 9.21 (1H, s), referring to the hydroxyl hydrogens OH-7 and OH-4 ′ , respectively. Two doublets were observed at δH 7.95 (2H, d) and 7.04 (2H, d) corresponding to the hydrogen pairs H-2 ′ and 6 ′ and H-3 ′ and 5 ′ , respectively, as well as a signal at δH 3.87 (-OCH 3; 3H, s), which was characteristic of a methoxy at position 6 (Zhang et al., 2015;Wang et al., 2016;Bai et al., 2018). ...
Phytochemical composition, antisnake venom and antibacterial activities of ethanolic extract of Aegiphila integrifolia (Jacq) Moldenke leaves
Article
  • May 2021
  • TOXICON
Snakebites are considered a major neglected tropical disease, resulting in around 100,000 deaths per year. The recommended treatment by the WHO is serotherapy, which has limited effectiveness against the toxins involved in local tissue damage. In some countries, patients use plants from folk medicines as antivenoms. Aegiphila species are common plants from the Brazilian Amazon and are used to treat snakebites. In this study, leaves from Aegiphila integrifolia (Jacq) Moldenke were collected from Roraima state, Brazil and its ethanolic extract was evaluated through in vitro and in vivo experiments to verify their antiophidic activity against Bothrops atrox crude venom. The isolated compounds from A. integrifolia were analyzed and the chemical structures were elucidated on the basis of infrared, ultraviolet, mass, ¹H and ¹³C NMR spectrometry data. Among the described compounds, lupeol (7), betulinic acid (1), β-sitosterol (6), stigmasterol (5), mannitol (4), and the flavonoids, pectolinarigenin (2) and hispidulin (3), were identified. The ethanolic extract and flavonoids (2 and 3) partially inhibited the proteolytic, phospholipase A2 and hyaluronidase activities of B. atrox venom, and the skin hemorrhage induced by this venom in mice. Antimicrobial activity against different bacteria was evaluated and the extract partially inhibited bacterial growth. Thus, taken together, A. integrifolia ethanolic extract has promising use as an antiophidic and antimicrobial.
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Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation
Article
Full-text available
  • Apr 2024
Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb–compound–biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)–saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)–lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)–glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA’s downstream regulators [interleukin (IL)-1β and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG’s effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.
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Detection and characterization of immunomarkers in apple by matrix-free laser desorption ionization and LC-ESI-MS
Thesis
  • Dec 2020
Erwinia amylovora is one of the major pathogens of apple. In order to prevent infections by this bacterium, various chemical products are commonly used in industrial agriculture. This, however, poses a heavy burden on the environment, so alternative methods of crop protection are being widely explored. In this regard, the induced formation of natural defense compounds (including phytoalexins) represents a promising alternative to conventional methods of plant protection. Phytoalexins are small antimicrobial secondary metabolites, synthesized "de novo" inplants in response to an infection or abiotic stress. The present work evaluates the impact of Bion® 50 WG, a plant resistance inducer (PRI) on the metabolomic profile of apple seedlings infected with E. amylovora. The chemical profile of samples were studied by two different methods : Laser desorptionionization mass spectrometry (LDI-MS) and liquid chromatography coupled to masss pectrometry, using electro spray ionization (LC-ESI-MS). While both methods revealed different chemical profiles, identical group separation by statistical analysis was observed for all analyzed samples. Moreover, marker signals, responsible for the statistical separation of differently treated plant groups, were identified. Based on database research, high-resolution (HR) MS as well as MS fragmentation patterns, specific immune markers responsible for acquired resistance against E. amylovora are proposed.
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Screening and detection of antimicrobials from Dai pharmaceuticals against clinical diseases by methicillin‐resistant Staphylococcus aureus
Article
  • Oct 2021
Oroxylum indicum is one of valuable Dai pharmaceutical, the dry seeds and bark of O. indicum were used to treat acute cough, sore throat and so on. Of the seven compounds from O. indicum were determined and obtained using bioassay‐guided method. Among them, compound 7 was obtained from the plant for the first time. Eight bacterial strains and one yeast fungi were exposed to the compounds. Minimum inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) or minimum fungicidal concentrations (MFCs) were determined according to the standard broth microdilution method. Baicalein (2) exhibited relative strong antibacterial activities with MIC of 8 μg.ml‐1 and MBC of 16 μg.ml‐1 against three MRSA strains of Staphylococcus aureus of SCCmec III type. While flavonoids 3, 5 and 7 showed some degree of activities against methicillin‐susceptible Staphylococcus aureus (MSSA, ATCC25923). The findings may offer new evidences that why O. indicum was used widely in Dai peoples’ life.
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Chemical characterization of constituents from Polygonatum cyrtonema Hua and their cytotoxic and antioxidant evaluation View supplementary material Chemical characterization of constituents from Polygonatum cyrtonema Hua and their cytotoxic and antioxidant evaluation
Article
  • Dec 2018
Twenty-four compounds were isolated from the roots of Polygonatum cyrtonema Hua, including a new octopamine dimer, named trans-bis(N-feruloyl)octopamine (1). The structure was established on the basis of spectroscopic and chemical methods. All the extracts and compounds were evaluated for cytotoxic and antioxidant activities by using MTT and chemiluminescence assay. The extracts showed activity against MCF-7 and HepG-2 cell lines from IC 50 0.30 to 1.01 mg mL À1. Compound 3 exhibited activity against HepG-2 cell lines with IC 50 8.99 lM. Compound 7 exhibited activity against Hela cell lines with IC 50 2.53 lM and BGC-823 cell lines with IC 50 7.77 lM. Moreover, compound 7 showed anti-oxidant with IC 50 12 mM compared to the positive control with IC 50 77 mM. Compound 16 exhibited activity against HepG-2 cell lines with IC 50 1.05 lM and MCF-7 cell lines with IC 50 1.89 lM. These results indicated that this plant might be potential in natural medicine and healthy food. ARTICLE HISTORY
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New Flavonoid Glucuronides from the Aerial Part of Scutellaria intermedia
Article
Full-text available
  • Jul 2017
The aerial part of the plant Scutellaria intermedia Popov yielded five glucuronides, three of which were identified as chrysin 7-O-β-D-glucuronide, wogonin 7-O-β-D-glucuronide, and baicalein 7-O-β-Dglucuronide (baicalin). IR, UV, PMR, and 13C NMR spectral data and acid hydrolysis of the two new glucuronides established their structures as 5,7,2′-trihydroxyflavone 2′-O-β-D-glucuronopyranoside (4) and scutevulin 2′-O-β-D-glucuronopyranoside (5).
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In vitro Antitumor Mechanisms of Various Scutellaria Extracts and Constituent Flavonoids
Article
Full-text available
  • Dec 2008
Scutellaria is a traditional herbal remedy with potential anti-cancer activity. The purpose of this study was to evaluate anticancer mechanisms of thirteen Scutellaria species and analyze their leaf, stem and root extracts for levels of common biologically active flavonoids: apigenin, baicalein, baicalin, chrysin, scutellarein, and wogonin. Malignant glioma, breast carcinoma and prostate cancer cells were used to determine tumor-specific effects of Scutellaria on cell proliferation, apoptosis and cell cycle progression, via the MTT assay and flow cytometry-based apoptosis and cell cycle analysis. The extracts and individual flavonoids inhibited the proliferation of malignant glioma and breast carcinoma cells without affecting primary or non-malignant cells. The flavonoids exhibited different mechanisms of anti-tumor activity as well as positive interactions. The antitumor mechanisms involved induction of apoptosis and cell cycle arrest at G1/G2. Of the extracts tested, leaf extracts of S. angulosa, S. integrifolia, S. ocmulgee and S. scandens were found to have strong anticancer activity. This study provides basis for further mechanistic and translational studies into adjuvant therapy of malignant tumors using Scutellaria leaf tissues.
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Flavonoids from the Roots of Scutellaria Luzonica Rolfe
Article
  • Dec 1991
  • J CHIN CHEM SOC-TAIP
Seventeen flavonoids were isolated from the roots of Scutellaria luzonica Rolfe. These compounds in elude thirteen flavones (1–13), two flavanones (14–15), a chalcone (16) and a flavone glucoside (17).
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Phenolic Compounds of Plants of the Scutellaria L. Genus. Distribution, Structure, and Properties
Article
  • Jul 2002
Information on flavones, flavanones, flavanonols, flavonols, chalcones, isoflavones, biflavonoids, lignoflavonoids, and lignane glycosides and stilbenes isolated from plants of the Scutellaria L. genus was systematized and reviewed. A list of 208 phenolic compounds was given according to flavonoid type with an indication of the plant sources, structures, and physicochemical properties and citations of the original articles.
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Dihydrochalcones and phenanthrene derivatives from Fissistigma bracteolatum
Article
  • Aug 2010
Three dihydrochalcones derivatives 1-3, flavone 4 and phenanthrene derivative 5 were isolated, together with 9 known compounds, from the air-dried root bark of Fissistigma bracteolatum Chatterjee. Their structures were determined by spectroscopic (NMR, MS) and chemical methodologies.
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Characterization of a new highly mosquitocidal isolate of Bacillus thuringiensis - An alternative to Bti?
Article
  • Nov 2011
  • J INVERTEBR PATHOL
The mosquito is a very important vector involved in the worldwide transmission of disease-causing viruses and parasites. Controlling the mosquito population remains one of the best means for preventing the serious infectious diseases of malaria, yellow fever, dengue, filariasis and so on and there has been an increasing interest in developing biopesticides as a useful substitute to chemical insecticides. As a result, Bacillus thuringiensis subsp. israelensis (Bti) has been extensively used due to its specificity and high toxicity to a variety of mosquito larvae. However it is prudent to seek alternatives to Bti with alternative spectra of mosquitocidal activity or that are able to overcome any resistance that might develop against Bti. The Bt S2160-1 strain was isolated from soil samples collected from Southern China and found to have a comparable mosquitocidal activity to Bti. However there were significant differences in terms of their plasmid profiles, crystal proteins produced and cry gene complement. A PCR-restriction fragment length polymorphism identification system was developed and used in order to identify novel cry-type genes and four such genes (cry30Ea, cry30Ga, cry50Ba and cry54Ba) were identified in Bt S2160-1. In conclusion, Bt S2160-1 has been identified as a potential alternative to Bti, which could be used for the control of mosquito populations in order to reduce the incidence of mosquito-borne diseases.
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Identification of flavonoids in the stems and leaves of Scutellaria baicalensis Georgi
Article
  • Mar 2011
Scutellaria baicalensis Georgi (S. baicalensis), a perennial herb of the Labiatae family, is a well-known traditional Chinese medicine. In the present study, a comprehensive qualitative analysis of flavonoids in the stems and leaves of S. baicalensis was performed. Under the optimized experimental conditions, 21 flavonoids were clearly detected. 17 of them were successfully identified based on the on-line UV and MS(n) data and were sequentially confirmed by the literature search. The rest 4 flavonones, which were not on-line identified, were successfully isolated and were identified by 1D and 2D NMR. One of them, 5,6,7,3',4'-pentahydroxy flavanone-7-O-glucuronide (2) is a new compound.
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Prevention of oxidative injury by flavonoids from stems and leaves of Scutellaria Baicalensis Georgi in PC12 cells
Article
  • Jan 2006
Reactive oxygen species (ROS) are important mediators in a number of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The neuroprotective effects of flavonoids from the stems and leaves of Scutellaria baicalensis Georgi (SSF) against hydrogen peroxide (H2O2)-induced rat pheochromocytoma line PC12 injury were evaluated by cell lesion, free radicals and ATPase disorders. Following a 30 min exposure of the cells to H2O2 (100 microm), a marked decrease in cell survival and activity of superoxide dismutase (SOD) and Na+-K+-ATPase as well as an increase of malondialdehyde (MDA) production and lactate dehydrogenase (LDH) release were observed. Pretreatment of the cells with SSF (18-76 microg/mL) prior to H2O2 exposure notably elevated the cell survival and activity of SOD and Na+-K+-ATPase, and lowered the MDA level and LDH release. Neuroprotection by SSF was also observed in animal models. The present results indicated that SSF exerts neuroprotective effects against H2O2 toxicity, which might be of importance and might contribute to its clinical efficacy for the treatment of neurodegenerative disease.
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Effects of Amelioration of Total Flavonoids from Stems and Leaves of Scutellaria baicalensis Georgi on Cognitive Deficits, Neuronal Damage and Free Radicals Disorder Induced by Cerebral Ischemia in Rats
Article
  • May 2006
Previous studies reported that the total flavonoids from the stems and leaves of Scutellaria baicalensis Georgi (TFSS) could enhance and improve learning and memory abilities in experimental animals, and reduce the neuronal pathologic alterations induced by some reagents in mice. The present study examined whether TFSS can improve memory dysfunction, neuronal damage, and abnormal free radicals induced by permanent cerebral ischemia in rats. The permanent cerebral ischemic model in rats was produced by bilateral ligation of the common carotid arteries. The influence of permanent cerebral ischemia on learning and memory was determined in the Morris water maze. The neuronal damage in the hippocampus and cerebral cortex was assessed by the neuronal morphologic observations. The contents of malondialdehyde (MDA) and nitric oxide (NO), and the activities of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and cerebral cortex were measured using thiobarbituric acid, nitrate reductase, xanthine-xanthine oxidase, and ammonium molybdate spectrophotometric methods, respectively. In learning and memory performance tests, cerebral ischemic rats always required a longer latency time to find the hidden platform and spent a shorter time in the target quadrant in the Morris water maze. TFSS 17.5-70 mg.kg(-1) daily orally administered to ischemic rats for 20 d, from day 16-35 after operation differently reduced the prolonged latency and increased swimming time spent in the target quadrant. In neuronal morphologic observations, daily oral TFSS 17.5-70 mg.kg(-1) for 21 d, from day 16-36 after operation markedly inhibited the ischemia-induced neuronal damage. In addition, the increased contents of MDA and NO, and SOD activity, and the decreased activity of CAT in the hippocampus and cerebral cortex induced by cerebral ischemia were differently reversed. The reference drug piracetam (140 mg.kg(-1) per day for 20-21 d) similarly improved impaired memory and neuronal damage but had no significant effects on free radicals in ligated rats. TFSS can improve memory deficits and neuronal damage in rats after permanent cerebral ischemia, which may be beneficial in the treatment of cerebrovascular dementia.
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Isolation and Identification of Ten Metabolites of Breviscapine in Rat Urine
Article
  • Jul 2007
Breviscapine, is the total flavonoid components (the content of scutellarin > or =85%) extracted from the dried whole plant of Erigeron breviscapus (VANT.) HAND.-MAZZ, and its preparations are generally used in the clinic for the treatment of cerebral and cardio-vascular diseases in China. In this paper, the metabolites of breviscapine in the urine of rats after oral administration were investigated. The ten metabolites were isolated by open-column chromatography and preparative high-performance liquid chromatography, and their structures were elucidated by MS, NMR spectroscopy including (1)H-NMR, (13)C-NMR, and NOESY (nuclear Overhauser enhancement spectroscopy), enzymatic hydrolysis and chemical evidence. The ten metabolites were identified as scutellarein-6,7-di-O-beta-D-glucuronide (M-1), scutellarein (M-2), 6-O-methyl-scutellarin (M-3), 6-O-methyl-scutellarein (M-4), scutellarein-6-O-beta-D-glucuronide (M-5), scutellarein-5-O-beta-D-glucuronide (M-6), scutellarin (M-7), scutellarein-7-O-sulfate (M-8), apigenin-5-O-beta-D-glucuronide (M-9), and apigenin-4'-O-beta-D-glucuronide (M-10) respectively. The results of this study indicated that the metabolites of brevisvapine were excreted in rats urine as glucuronidated, sulfated or methylated forms, as well as the aglycone of scutellarin-scutellarein after oral administration, and the metabolic pathways were also proposed.
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