18
Chem. Pharm. Bull. 67, 18–22 (2019)
Vol. 67, No. 1
Regular Article
Three New Lignan Glycosides from the Firmiana simplex
Kyeong Wan Woo,a Jong Eel Park,a Joon Min Cha,a Lalita Subedi,b Sun Yeou Kim,b and
,a
Kang Ro Lee*
a Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University; Suwon 16419, Republic of Korea: and
b Laboratory of Pharmacognosy, College of Pharmacy, Gachon University; Incheon 21936, Republic of Korea.
Received July 13, 2018; accepted October 30, 2018
In our quest for structurally intriguing compounds from Korean medicinal plant sources, chromato-
graphic separation of the 80% MeOH extract from Firmiana simplex resulted in the isolation and identifica-
tion of three new lignan glycosides (1–3), together with six known lignan glycosides (4–9). The structures
of 1–3 were determined on the basis of spectroscopic analyses, including extensive 2D-NMR and enzyme
hydrolysis. Nitric oxide (NO) production was evaluated in the lipopolysaccharide-activated microglial cell
line, BV-2 to investigate the anti-neuroinflammatory effects of the isolated compounds (1–9). Compound 7
marginally inhibited NO levels with IC50 values of 59.83µM.
Key words Firmiana simplex; Sterculiaceae; lignan glycoside; nitric oxide; neuroinflammatory effect
at δH 4.43 (1H, t, J=8.0Hz, H-9′a), 4.05 (2H, s, H-9), and 3.67
Introduction
Neuroinflammation is a major cause underlying neurode- (1H, m, H-9′b), and one methine proton at δH 3.65 (m, H-8′).
1
generative conditions.1) Nitric oxide (NO) is a key marker of The H- and 13C-NMR spectra of 1 (Tables 1 and 2) were
neuroinflammation and is excessively produced by activated very similar to those of paulownin, which was isolated from
microglia when the inflammatory signaling is activated result- Rehmannia glutinosa.10) The major difference was the pres-
ing in the production of reactive oxygen species (ROS) and ence of an additional sugar group [δH 4.52 (1H, d, J=1.0Hz,
nitrogen species (RNS). They induce glial cell activation and H-1″), 3.65 (1H, m, H-6″a), 3.54 (1H, dd, J=12.0, 5.0Hz,
neuronal cell degeneration or death.2) Hence, the measure- H-6″b), 3.35 (1H, t, J=9.5Hz, H-5″), 3.01 (1H, dd, J=9.0,
ment of NO production is a critical screening technique for 3.0Hz, H-3″), 2.92 (1H, ddd, J=10.0, 5.0, 2.5Hz, H-5″), and
1
the evaluation of anti-neuroinflammatory and neuroprotective 2.84 (1H, d, J=3.0Hz, H-2″) in the H-NMR spectrum; δC
compounds derived from natural products.
98.4 (C-1″), 78.3 (C-5″), 75.2 (C-3″), 72.6 (C-2″), 68.1 (C-4″),
Firmiana simplex (Sterculiaceae) is a deciduous tree widely 62.7 (C-6″)] in the 13C-NMR spectrum. The identity of β-D-
distributed in Southeast Asia, Korea and China.3) The seeds mannopyranosyl sugar moiety was confirmed by comparing
of F. simplex have been used as Korean traditional medicine the coupling constant (J=1.0Hz) and 13C-NMR data with
for the treatment of diarrhea and stomach disorders.4) Several values reported in the literatures.11–13) Its position was assigned
flavonoids, lignans, and fatty acids have been isolated from as C-8′ by heteronuclear multiple bond correlation (HMBC)
F. simplex. Some compounds and extracts of F. simplex have of H-1″/C-8 (Fig. 2). The configuration of furofuran moiety
been shown to exhibit antimicrobial and hepatoprotective in 1 was to be same as that of (+)-paulownin and (+)-1-hy-
activities.4–7) A preliminary investigation of F. simplex led to droxysyringaresinol 1-glucoside based on the NMR data and
the isolation and structural elucidation of cytotoxic triterpe- optical rotation.10,14) In addition, the trans/trans configuration
noids and anti-inflammatory lignans.8,9) Further investigations of 7-H/8-OH and 7′-H/8′-H in the furofuran moiety was con-
yielded three new lignan glycosides, designated as firmiside firmed by comparison with the chemical shift differences.15)
A–C (1–3) (Fig. 1) and six known lignan glycosides (4–9) Thus, the structure of 1 was determined (Fig. 1), and named
from EtOAc and BuOH fractions of F. simplex, and evaluated firmiside A.
for their anti-inflammatory activities (1–9).
Compound 2 was obtained as a colorless gum. The mo-
lecular formula of 2 was determined as C27H32O12 based on
the molecular ion peak [M+Na]+ at m/z 571.1785 (Calcd
Results and Discussion
Compound 1 was obtained as a colorless gum with a nega- for C27H32NaO12, 571.1786) on HR-FAB-MS. The 1H- and
tive optical rotation ([α]D25 −27.0). The molecular formula of 1 13C-NMR spectra of 2 (Tables 1 and 2) were almost identical
was determined as C26H28O12 using positive-mode high-resolu- to those of 5-methoxybalanophonin, which was isolated from
tion (HR)-FAB-MS data at m/z 555.1470 [M +Na]+ (Calcd for the same plant source,9) except for the additional glucose moi-
1
C26H28NaO12, 555.1473). The H-NMR spectrum revealed two ety [δH 4.91 (1H, d, J=8.0Hz, H-1″), 3.79 (1H, m, H-6″a), 3.68
sets of 1,3,4-trisubstitued aromatic protons at [δH 6.94 (1H, (1H, m, H-6″b), 3.50 (1H, m, H-2″), 3.43 (1H, m, H-5″), 3.42
1
d, J=2.0Hz, H-2′), 6.88 (1H, dd, J=8.5, 2.0Hz, H-6′), 6.82 (1H, m, H-4″), and 3.22 (1H, m, H-3″) in the H-NMR spec-
(1H, d, J=1.5Hz, H-2), 6.80 (1H, dd, J=7.5, 1.5Hz, H-6), trum; δC 105.0 (C-1″), 78.1 (C-3″), 77.6 (C-5″), 75.8 (C-2″), 71.4
6.71 (1H, d, J=7.5Hz, H-5), 6.70 (1H, d, J=8.0Hz, H-5′)], (C-4″), and 62.4 (C-6″)] in the 13C-NMR spectrum. The cou-
two methylenedioxy protons at δH 5.83 (4H, s, –OH2O–), two pling constant (J=8.0) of the H-1″ suggested β-glucose.16) The
oxygenated methine protons at δH 4.77 (1H, d, J=4.0Hz, linkage of the glucose moiety was deduced by HMBC cross
H-7′) and 4.72 (1H, s, H-7), two oxygenated methylene protons peaks of H-1″/C-4 (Fig. 2). Enzyme hydrolysis of 2 yielded the
*To whom correspondence should be addressed. e-mail: krlee@skku.edu
© 2019 The Pharmaceutical Society of Japan