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Forsythoneosides A−D, Neuroprotective Phenethanoid and Flavone
Glycoside Heterodimers from the Fruits of Forsythia suspensa
Fan Zhang,† Ya-Nan Yang,† Xiu-Yun Song, Si-Yuan Shao, Zi-Ming Feng, Jian-Shuang Jiang, Li Li,
Nai-Hong Chen, and Pei-Cheng Zhang*
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of
Medical Sciences and Peking Union Medical College, Beijing 100050, People’s Republic of China
S
* Supporting Information
ABSTRACT: Forsythoneosides A−D (1−4), four unusual adducts of a flavonoid unit fused to a phenylethanoid glycoside
through a pyran ring or carbon−carbon bond, and four new phenylethanoid glycosides (5−8) were isolated from the fruits of
Forsythia suspensa, together with nine known compounds. The structures of 1−8, including their absolute configurations, were
elucidated by spectroscopic data as well as experimental and calculated electronic circular dichroism analysis. Compounds 2 and
4 inhibited PC12 cell damage induced by rotenone, and increased cell viability from 53.9 7.1% to 70.1 4.0% and 67.9 5.2%
at 0.1 μM, respectively.
Forsythia suspensa (Thunb.) Vahl grows in northern mainland
China, and its fruits, known as Fructus Forsythiae, are used
widely as a traditional Chinese medicine to treat inflammation,
pyrexia, ulcers, gonorrhea, and erysipela.1,2 Over the past few
decades, a series of phenylethanoid glycosides, lignans,
flavonoids, alkaloids, and triterpenoids have been reported
from species of this genus, and a few have been found to exhibit
antioxidant, neuroprotective, cytotoxic, anti-inflammatory,
antibacterial, and antiviral effects.3−10
Of particular interest for this study was the n-BuOH-soluble
portion of the fruits of F. suspensa obtained from a 75% EtOH
extract, which exhibited neuroprotective effects and could
inhibit rotenone-induced damage of pheochromocytoma
(PC12) cells, increasing the cell viability from 54.2 2.8% to
RESULTS AND DISCUSSION
■
Compound 1 was obtained as a yellow, amorphous powder.
The molecular formula, C56H62O31, was established by the
protonated molecular ion peak at m/z 1231.3354 [M + H]+
(calcd for C56H63O31, 1231.3353) in the HRESIMS, indicating
26 degrees of unsaturation. The IR spectrum showed
absorption bands attributed to hydroxy groups (3371 cm−1),
carbonyl groups (1693 cm−1), and aromatic rings (1601 and
1519 cm−1). Analysis of the 1H NMR spectrum (Table 1) of 1
revealed the presence of two sets of ABX system aromatic
protons at δH 7.92 (1H, d, J = 2.5 Hz), 7.10 (1H, d, J = 8.5 Hz),
and 7.95 (1H, dd, J = 8.5, 2.5 Hz) and δH 7.15 (1H, d, J = 2.5
Hz), 6.85 (1H, d, J = 8.5 Hz), and 7.02 (1H, dd, J = 8.5, 2.5
Hz), three singlet aromatic protons at δH 7.12 (1H, s), 6.70
(1H, s), and 6.52 (1H, s), and two olefinic protons at δH 7.64
(1H, d, J = 16.0 Hz) and 6.33 (1H, d, J = 16.0 Hz). In addition,
there were many aliphatic proton signals between δH 5.10 and
1.20, including a methylene signal at δH 3.98 (1H, dd, J = 10.5,
7.5 Hz) and 3.87 (1H, m), a methine signal at δH 4.64 (1H, dd,
J = 7.5, 4.0 Hz), and four anomeric protons at δH 5.10 (1H, d, J
= 7.5 Hz), 4.48 (1H, d, J = 8.0 Hz), 4.74 (1H, br s), and 4.70
78.5
5.0% at a concentration of 10 μg/mL (Table S1,
Supporting Information). Through bioactivity-guided isolation,
four heterodimers of phenylethanoid glycoside and flavonoid
units, i.e., forsythoneosides A−D (1−4), and four new
phenylethanoid glycosides (5−8) were isolated from the fruits
of F. suspensa, together with nine known compounds. Reported
herein are the isolation and structure elucidation of compounds
1−8 and the evaluation of compounds 1−4 as potential
neuroprotective agents in inhibiting cell damage in PC12 cells.
Received: April 29, 2015
© XXXX American Chemical Society and
American Society of Pharmacognosy
A
DOI: 10.1021/acs.jnatprod.5b00372
J. Nat. Prod. XXXX, XXX, XXX−XXX