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Archiv der Pharmazie
FULL PAPER
Structure Characterization and Antibacterial, Antifungal,
and Antiquorum‐Sensing Activity of New Metabolites
From the Lipophilic Fractions of Platycodon
grandiflorum Root
Hyukbean Kwon1 | Jimin Moon1 | Jeong‐Hyeon Kim2 | Prima F. Hillman3 | Silviani Velina1,4 | Joo‐Won Nam1
Sang‐Jip Nam2 | Inho Choi4,5
| Kyung Sik Song6 | Geum Jin Kim7 | Hyukjae Choi1,4
|
1
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeong‐buk, Republic of Korea | 2Department of Chemistry and Nanoscience, Ewha Womans
University, Seoul, Republic of Korea | 3Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Andalas, Kampus Limau Manis,
Padang, Indonesia | 4Research, Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeong‐buk, Republic of Korea | 5Department of Medical
Biotechnology, Yeungnam University, Gyeongsan, Gyeong‐buk, Republic of Korea | 6Research, Institute of Pharmaceutical Sciences, College of Pharmacy,
Kyungpook National University, Daegu, Republic of Korea | 7Department of Pharmacology, School of Medicine, Dongguk University, Gyeongju, Gyeong‐buk,
Republic of Korea
Correspondence: Geum Jin Kim (geumjinkim@dongguk.ac.kr) | Hyukjae Choi (h5choi@yu.ac.kr)
Received: 22 February 2025 | Revised: 6 June 2025 | Accepted: 14 June 2025
Funding: This study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) grants funded by the Korean
government (MSIT) (Grant No. NRF‐2020R1A6A1A03044512, and NRF‐2021R1A2C1010727), [Cooperative Research Program for Agriculture Science &
Technology Development (PJ014208032023) funded by Rural Development Administration] and Yeungnam University research grant funded by Yeungnam
University.
Keywords: antimicrobial | antiquorum‐sensing | lipophilic fraction | Platycodon grandiflorum | polyacetylene
ABSTRACT
The root of Platycodon grandiflorum has long been used as a vegetable and traditional medicine. Although the antibacterial activity of
the plant's lipophilic (hexanes and dichloromethane) fractions has been reported, the specific antibacterial compounds have not been
identified. In this study, chemical analysis of the lipophilic fractions of P. grandiflorum extracts led to the discovery of five new
polyacetylenes (1–5) and nine known compounds (6–14). Their structures were elucidated and confirmed based on 1D and 2D NMR
data together with mass spectra. In particular, the relative and absolute configurations of 1 were elucidated by coupling constants,
NOESY and J‐based configurational analysis in combination with Mosher's method. Compounds 1 and 2 demonstrated strong antifungal activity against Candida albicans. Additionally, compound 1 significantly inhibited quorum sensing in Chromobacterium violaceum, a commonly used biosensor strain. Compounds 2 and 14 also exhibited mild inhibitory activity. Compounds 8 and 12–14
exhibited potent antibacterial activity against Escherichia coli, Kocuria rhizophila, and Staphylococcus aureus, as well as antifungal
activity against Candida albicans. These compounds may be responsible of the antimicrobial activity of P. grandiflorum.
1 | Introduction
Platycodon grandiflorum is an herbaceous perennial plant in the
family Campanulaceae, widely distributed in East Asia. The
root of P. grandiflorum is a common vegetable and traditional
medicine in Korea, China, and Japan. As a vegetable in Korean
cuisine, it is called Doraji and used as raw material in cooking
or for wine and tea preparation, with its characteristic flavor
Hyukbean Kwon and Jimin Moon contributed equally to this study.
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work
is properly cited, the use is non‐commercial and no modifications or adaptations are made.
© 2025 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.
Archiv der Pharmazie, 2025; 358:e70043
https://doi.org/10.1002/ardp.70043
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Escherichia coli KCTC2441 (Supporting Information S1:
Table S1). Thus, the lipophilic (hexanes and dichloromethane)
fractions of P. grandiflorum extracts were selected for chemical
investigation, leading to the isolation of five novel polyacetylenes (1–5), along with nine known compounds (6–14),
and the discovery of antimicrobial compounds among the isolates (Figure 1). Extensive inspection of 1D and 2D NMR data,
together with J‐based configuration analysis for 1, was conducted to elucidate its planar structure with relative configurations. The absolute configurations of 1 were determined using
advanced Mosher's analysis. Furthermore, the antibacterial,
antifungal, and quorum‐sensing inhibitory activities of isolates
(1–2, 5–14) were evaluated to uncover the principles of the
antimicrobial activities of P. grandiflorum.
2 | Results and Discussion
2.1 | Structural Elucidation
In our preliminary study, a 70% ethanolic extract of
P. grandiflorum and its hexanes fraction showed antibacterial
activity against Staphylococcus aureus KCTC1927 and
FIGURE 1
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Platypyran A (1) was isolated as a brown oil. Its molecular
formula, C14H18O2, was determined by a protonated ion peak at
| Structures of compounds (1–14) isolated from the roots of Platycodon grandiflorum.
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and bitter taste. Additionally, it is used in traditional medicine
(Platycodonis radix) to treat colds, coughs, sore throats, upper
respiratory infections, tonsillitis, and chest congestion in East
Asia [1]. To date, many natural products from this plant have
been reported, including triterpene saponins, polysaccharides
[2], flavonoids [3, 4], phenolic acids [5], polyacetylenes [6–8],
and sterols [9]. Triterpenoid saponins, such as platycodin D,
are the major bioactive components of Platycodonis radix,
with over 60 triterpene saponins reported [10]. Extracts from
this plant have shown antitumor [11, 12], antitussive [1],
anti‐inflammatory [13], antiobesity [14], antifibrosis [15], antioxidant [16], hepatoprotective [17], blood lipid‐lowering [18],
immune‐modulatory [19], and antibacterial [20] activities. Most
of these pharmacological activities are attributed to triterpene
saponins and polysaccharides [10]. However, the compound
responsible for the antibacterial activity of P. grandiflorum
remains unknown. Previously, lipophilic extracts were reported
to have antibacterial and antifungal activities [21].
TABLE 1
|
(δC 79.6)/C‐9 (δC 72.7). Additionally, the vicinal 1H–1H coupling at 3JH‐2,H‐3 measured at 15.9 Hz, suggested a trans configuration for the olefin. These data resulted in the planar
structure of 1 (Figure 2). The relative configuration between C‐9
and C‐10 was determined through analysis of vicinal 1H–1H
coupling constants, NOESY spectra, and J‐based configuration
analysis [22]. The two large vicinal 1H–1H couplings between
H‐10 and H‐11b (11.1 Hz) and between H‐13b and H‐14a
(11.2 Hz) indicate that these protons are all axially oriented. The
relatively small vicinal 1H–1H couplings between H‐10 an H‐11a
(2.1 Hz), between H‐13a and H‐14a (2.8 Hz), between H‐13a and
H‐14b (2.3 Hz), and between H‐13b and H‐14b (2.3 Hz) indicated that H‐11a, H‐13a, and H‐14b are in equatorial orientations. The NOESY cross‐peak between H‐11b and H‐13b further
supported their axial positioning (Figure 2 and Supporting
Information S1: Figure S7).
The 1H‐13C heteronuclear coupling constants were measured
through HETLOC experiments (Supporting Information S1:
Figure S8). The key 1H–1H vicinal coupling constant at
3
JH‐9,H‐10 was evaluated at 5.6 Hz, indicating a medium‐range
coupling consistent with the equilibrium between anti‐ and
gauche‐rotamers. Additionally, the two relatively small 3JH,C
values between H‐9 and C‐11 (1.2 Hz) as well as between C‐8
and H‐10 (2.4 Hz), along with the two medium 2JH,C values
between H‐9 and C‐10 (−1.5 Hz) as well as C‐9 and H‐10
(−2.1 Hz), suggested that C‐9/C‐10 adopt a threo form, with the
two major rotamers being A‐1 and A‐3 (Figure 3). This was
further supported by NOESY correlations: from H‐10 to
1
H NMR data at 600 MHz and 13C NMR data at 150 MHz of compounds 1 and 2 in CDCl3 (δ in ppm, J in Hz).
Compound 1
Compound 2
No.
δC
δH
δC
δH
1
19.0
1.80 dd (6.9, 1.4)
4.5
1.95 s
2
143.5
6.29 dq (15.9, 6.9)
75.2
3
109.9
5.50 dq (15.9, 1.4)
64.9
4
74.5
59.6
5
76.9
a
60.9
6
67.0
67.3
7
79.6
8
24.4
75.1
2.53 dd (17.3, 5.6)
24.1
2.62 dd (17.3, 5.6)
2.59 dd (17.4, 5.6)
9
72.7
3.58 q (5.6)
72.4
3.58 p (5.6)
10
78.7
3.36 ddd (11.1, 5.6, 2.1)
78.5
3.34 ddd (11.1, 5.6, 2.1)
11
27.8
1.44 m
27.6
1.45 m
1.57 m
b
1.56 m
12
26.0
1.53 m
25.9
1.53 mb
13
23.1
1.53 mb
22.9
1.53 mb
1.87 m
14
68.7
3.46 td (11.2, 2.8)
4.01 dt (11.2, 2.3)
9‐OH
a
b
2.50 dd (17.4, 5.6)
1.88 m
68.6
3.46 td (11.1, 2.7)
4.01 dt (11.1, 2.2)
2.60 brsb
Assigned by HMBC.
Overlapped signals.
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m/z 219.1391 [M + H]+ in the HR–FAB–MS spectrum, indicating six degrees of unsaturation (Supporting Information S1:
Figure S1). The analysis of 1H and 13C NMR, along with phase‐
edited HSQC spectra, allowed for the assignment of H–C connectivity and the protonation of each carbon. The data revealed
two olefinic methines (δC 143.5/δH 6.29; δC 109.9/δH 5.50), two
oxygenated methanetriyl group (δC 78.7/δH 3.36; δC 72.7/δH
3.58), one oxygenated methylene (δC 68.7/δH 3.46, 4.01), four
nonoxygenated methylenes (δC 27.8/δH 1.44, 1.57; δC 26.0/δH
1.53; δC 24.4/δH 2.53, 2.62; δC 23.1/δH 1.53, 1.87), a methyl group
(δC 19.0/δH 1.80), and four nonprotonated carbons (δC 79.6,
76.9, 74.5, and 67.0) (Table 1). Analysis of 1D and 2D NMR
(HSQC, COSY and HMBC) data, enabled the construction of
partial structures (Supporting Information S1: Figures S2–S6).
COSY correlations of H‐2 (δH 6.29) with H‐1 (δH 1.80), and H‐3
(δH 5.50) suggested a propene fragment, supported by HMBC
correlations from H‐1 to C‐2 (δC 143.5) and C‐3 (δC 109.9). A
series of COSY correlations from H‐8 to H‐14 via H‐9, H‐10,
H‐11, H‐12, and H‐13, along with HMBC correlations from H‐14
(δH 3.46 and 4.01) to C‐10 (δC 78.7), suggested the presence of a
1‐(tetrahydro‐2H‐pyran‐2‐yl)ethanol spin system. The two partial structures were connected via a diyne linkage based on the
long‐range HMBC correlations from H‐1 to C‐4 (δC 74.5)/C‐6
(δC 67.0)/C‐7 (δC 79.6)/C‐9 (δC 72.7), from H‐2 (δH 6.29) to C‐4
(δC 74.5)/C‐6 (δC 67.0), from H‐3 (δH 5.50) to C‐4 (δC
74.5)/C‐6 (δC 67.0)/C‐7 (δC 79.6)/C‐9 (δC 72.7), from H‐8a (δH
2.53) to C‐2 (δC 143.5)/C‐3 (δC 109.9)/C‐4 (δC 74.5)/C‐6 (δC
67.0)/C‐7 (δC 79.6)/C‐9 (δC 72.7), and from H‐8b (δH 2.62) to C‐2
(δC 143.5)/C‐3 (δC 109.9)/C‐4 (δC 74.5)/C‐6 (δC 67.0)/C‐7
H‐8a/H‐8b/H‐9 and from H‐9 to H‐11a/H‐11b for the A‐1 rotamer; from H‐8 to H‐10/H‐11b, and from H‐9 to H‐11a/H‐11b
for the A‐3 rotamer (Figure 3). Comparison of 1H NMR data
with previously reported synthetic model compounds showed
strong agreement with the threo configuration [23]. The absolute configuration of compound 1 was determined using the
advanced Mosher's method, and the ΔδS−R values indicated
the R configurations for both C‐9 and C‐10 (Figure 4) [24].
Consequently, the absolute configuration of compound 1 was
unambiguously established as 2E, 9R, and 10R.
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Platypyran B (2) was isolated as yellow oil. The molecular
formula of 2 was determined as C14H16O2 by an ion peak
of protonated molecule at m/z 217.1228 [M+H]+ in the
HR–FAB–MS spectrum, indicating 7 degrees of unsaturation in
2 (Supporting Information S1: Figure S9). The similarities in the
1
H NMR spectrum, along with mass spectrometry data, suggested a structural resemblance between compounds 2 and 1
(Table 1). The distinctive differences in the 1H and 13C NMR
spectra of 2 from those of 1 were the absence of signals from a
double bond and the presence of two additional unprotonated
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FIGURE 2 | Key 2D NMR correlations of 1. (A) Planar structure of 1 with key COSY and HMBC correlations. (B) Key NOESY correlations.
(C) 1H–1H coupling constants based on proton assignment of axial‐equatorial orientation on a pyran ring structure of 1. (D) Zoomed in 1H NMR
spectra of H‐9, H‐10, H‐14a, and H‐14b.
correlations [8]. However, similarities in the 1H and 13C NMR
spectra including chemical shifts and 1H–1H coupling constants
of isolobetyol with compounds 1 and 2 suggested the relative
configuration of 9R* and 10R* to be threo form.
FIGURE 4
| ΔδS–R values of the MTPA esters of 1 in pyridine‐d5.
carbons at δC 75.2 and δC 64.9. Extensive 1D and 2D NMR data
analysis (Supporting Information S1: Figures S10–S14) suggested that compound 2 had a triyne structure, as shown in
Figure 1. The key HMBC correlations from H‐1 (δH 1.95) to C‐2
(δC 75.2)/C‐3 (δC 64.9)/C‐4 (δC 59.6)/C‐6 (δC 67.3), and from H‐8
(δH 2.50 and 2.59) to C‐4 (δC 59.6)/C‐6 (δC 67.3)/C‐7 (δC 75.1)
strongly supported the connection between the methyl group
and partial structures via a triyne linkage. A careful comparison
of 1H NMR spectra of 2 with that of 1 revealed an addition of
exchangeable proton signal at δH 2.60, assigned to 9‐OH, and a
difference in H‐9 multiplicity (a pentet in 2 vs. a quartet in 1)
caused by additional 1H–1H coupling between H‐9 and 9‐OH in
2. The relative configuration of 2 was inferred based on the
high similarity of 1 and 2 in their 1H and 13C NMR chemical
shifts and 1H–1H coupling constants. The specific rotation of
2 was measured as [α]D30 − 3.71 (c 0.1, CH2Cl2), very similar to
that of 1 {[α]D30 − 3.17 (c 0.1, CH2Cl2)}. Thus, the absolute
configurations of 2 were assigned as 9R and 10R. Previously,
isolobetyol, a tetrahydropyran‐bearing polyacetylene from
P. grandiflorum, was reported with the erythro configuration for
its 1‐(tetrahydro‐2H‐pyran‐2‐yl)ethanol unit, based on NOESY
Pilosulinene D (3) was purified as a white powder. The
molecular formula of compound 3 was determined as
C16H18O3 by HR–ESI–MS at m/z 257.1187 [M–H]–, indicating
seven degrees of unsaturation (Supporting Information S1:
Figure S15). The 1H NMR spectrum showed signals for a
methyl proton (δH 1.77), an oxygenated methine (δH 5.36),
three aromatic protons (δH 7.24, 7.17, 6.98), a hydroxy proton
(δH 5.65), and four olefinic protons (δH 6.89, 6.09, 6.07, 5.55).
The 13C NMR spectrum displayed signals for a methyl carbon
(δC 19.0), a di‐oxygenated methine (δC 101.8), ten sp2 carbons
(δC 153.0, 141.9, 136.9, 134.0, 129.0, 121.9, 119.0, 117.2, 113.1,
110.4), and two unprotonated carbons (δC 97.1, 83.9) (Table 2
and Supporting Information S1: Figures S16 and S17). COSY
spectrum showed the correlations of H‐3 (δH 7.24) with H‐2
(δH 7.17) and H‐4 (δH 6.98), H‐7 (δH 6.89) and H‐8 (δH 6.07), as
well as H‐12 (δH 6.09) with H‐11 (δH 5.55) and H‐13 (δH 1.77)
(Supporting Information S1: Figure S18). HMBC correlations
from H‐2 (δH 7.17) to C‐6 (δC 121.9), from H‐3 (δH 7.24) to C‐1
(δC 136.9)/C‐5 (δC 153.0), from H‐4 (δH 6.98) to C‐5 (δC 153.0)/
C‐6 (δC 121.9), from H‐7 (δH 6.89) to C‐1 (δC 136.9)/C‐5 (δC
153.0)/C‐9 (δC 83.9), and from H‐13 (δH 1.77) to C‐9 (δC 83.9)/
C‐10 (δC 97.1) supported the partial structure of an alkyne‐
substituted phenol (Figure 5 and Supporting Information S1:
Figures S19 and S20). Additional HMBC correlations from
H‐14 (δH 5.36) to C‐2 (δC 119.0)/C‐6 (δC 121.9)/C‐15 (δC 53.1)/
C‐16 (δC 53.1) suggested a di‐O‐methylated acetal at the C‐1
position (Figure 5). The two vicinal coupling constants
between H‐7 and H‐8 (3JH‐7, H‐8 = 11.4 Hz), and between H‐11
and H‐12 (3JH‐11,H‐12 = 15.7 Hz) indicated the cis configuration at
H‐7/H‐8 and the trans configurations at H‐11/H‐12, respectively.
Pilosulinene C (4) was also isolated as a white powder.
The molecular formula of compound 4 was determined to be
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FIGURE 3 | Approaches for determination of relative configurations at C9–C10 of 1. Comparison data of homo‐ and hetero‐nucleus coupling
constants with J‐based configuration analysis (JBCA) models. Newman projections for C‐10/C‐9 by analysis result of JBCA.
|
1
H NMR data at 600 MHz and 13C NMR data at 150 MHz of compounds 3–6 in CDCl3 (δ in ppm, J in Hz).
Compound 3
δC
Compound 5
δH
δC
1
136.9
2
119.0
3
4
5
153.0
153.4
152.3
153.8
6
121.9
121.9
123.5
125.5
7
134.0
6.89, d (11.4)
134.0
7.07, d (16.6)
132.7
7.06, d (11.5)
132.5
7.33, d (16.4)
8
113.1
6.07, dd (11.4, 2.0)
115.7
6.26, dd (16.6, 1.9)
115.0
6.21, dd (11.5, 2.4)
117.9
6.14, dd (16.4, 1.7)
9
83.9
86.7a
93.8
86.1
10
97.1
a
96.9
92.7
11
110.4
5.55, dt (15.7, 2.0)
110.9
5.68, dt (15.7, 1.9)
110.0
5.52, dt (15.8, 1.8)
110.7
5.69, dt (15.8, 1.7)
12
141.9
6.09, dq (15.7, 6.9)
140.5
6.23, dq (15.7, 6.9)
141.9
6.10, dq (15.8, 6.9)
141.2
6.26, dq (15.8, 7.0)
13
19.0
1.77, dd (6.9, 2.0)
19.0
1.84, dd (6.9, 1.9)
18.5
1.77, dd (6.9, 1.8)
19.0
1.85, dd (7.0, 1.7)
14
101.8
5.36, s
101.6
5.38, s
192.7
10.11, s
192.1
10.15, s
15
53.1
3.30, s
53.3
3.31, s
16
53.1
3.30, s
53.3
3.31, s
137.0
δH
Compound 6
δC
135.2
135.1
129.0
7.24, t (7.9)
128.6
7.17, m
129.6
7.39, t (7.8)
129.2
7.34, d (7.7)
117.2
6.98, dd (7.9, 1.1)
116.3
6.87, dd (6.1, 3.1)
122.2
7.22, dd (7.8, 1.2)
121.3
7.13, d (7.7)
5.65, brs
123.9
δH
119.4
91.5
7.17, m
δC
7.17, dd (7.9, 1.1)
5‐OH
a
δH
Compound 4
No.
5.30, brs
7.50, dd (7.8, 1.2)
5.63, brs
123.9
7.46, d (7.7)
5.44, brs
Assigned by HMBC.
FIGURE 5
| Planar structure of 3 based on key COSY and HMBC correlations.
C16H18O3 based on the deprotonated molecular ion found in HR–
ESI–MS (m/z 257.1187 [M–H]–) as shown in Supporting Information S1: Figure S21. The 1D NMR spectra of 4 are highly
similar to those of 3 (Table 2 and Supporting Information S1:
Figures S22–S26). The notable difference in the 1H NMR spectrum of 4 was the larger 1H–1H vicinal coupling constant
between H‐7 and H‐8 (16.6 Hz in 4, 11.4 Hz in 3), indicating a
trans configuration for H‐7/H‐8 in 4.
The acetal groups in 3 and 4 may have been converted from
aldehydes through the addition of alcohols (Supporting Information S1: Figure S27). Therefore, compounds 3 and 4 could be
artifacts generated during purification. Careful inspection of the
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LR‐LC‐MS data for the parent fraction (PG‐H2) did not reveal
peaks corresponding to 3 and 4 (m/z 257 [M–H]–). However,
peaks with m/z values of 211, corresponding to the respective
aldehydes, were observed. This finding implied that extract or
fraction was relatively less changeable than purified compound.
It also supported that the potential formation of artifacts
should be considered while alcohols was used in separation of
aldehyde compounds. As a result, compound isolation was
carried out using normal‐phase chromatography under alcohol‐
free mobile phase conditions. This led to the isolation of the
original aldehyde‐containing compounds of 3 and 4, identified
as 5 and 6, respectively. Spectroscopic data comparison identified compound 6 as a known polyacetylene, pilosulinene A [25].
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TABLE 2
1
1
1
1
> 128
> 128
> 128
0.5
> 128
> 128
> 128
> 128
> 128
A. fumigatus KCTC6145
1
0.25
0.25
0.5
0.5
0.25
0.25
0.5
> 128
> 128
> 128
> 128
> 128
> 128
0.25
0.25
> 128
> 128
> 128
> 128
> 128
> 128
1
8
C. glabrata KCTC7219
64
0.25
C. albicansK KCTC 7122
8
Antifungal activity
MIC (μg/mL)
1
2
5
6
> 128
> 128
> 128
> 128
> 128
> 128
K. pneumonia KCTC2690
> 128
> 128
> 128
S. typhimurium KCTC2515
> 128
> 128
> 128
> 128
> 128
> 128
8
E. coli KCTC2441
Gram (–) bacteria
4
> 128
8
> 128
S. aureus KCTC1927
8
> 128
> 128
> 128
> 128
> 128
> 128
> 128
B. subilis KCTC 1021
Gram (+) bacteria
K. rhizophila KCTC1915
> 128
> 128
7
> 128
> 128
1
2
1
> 128
8
7
6
5
2
1
Antibacterial activity
MIC (μg/mL)
Antibacterial and antifungal activities of isolated compounds.
|
TABLE 3
An investigation into the antimicrobial and antifungal activities
were evaluated against several strains of Gram‐positive and Gram‐
negative bacteria together with fungal strains that are related to
antimicrobial susceptibility studies. The results of the investigation
for P. grandiflorum extracts and fractions revealed that the 70%
EtOH extract and its hexanes fraction inhibited both S. aureus
KCTC 1927 and E. coli KCTC 2441 (Supporting Information S1:
Table S1). Furthermore, 12 compounds (1–2, 5–14) were evaluated
for antibacterial and antifungal activities, with results expressed as
MIC (Table 3). Compounds 8, 12–14 displayed potent antibacterial
activities against Gram‐positive K. rhizophila KCTC 1915 and S.
aureus KCTC 1927, as well as Gram‐negative E. coli KCTC 2441,
and antifungal activities against C. albicans KCTC 7122, C. glabrata KCTC 7219, and A. fumigatus KCTC 6145. Compounds 1–2,
5, and 7 showed moderate antimicrobial activity against S. aureus
KCTC 1927, while compounds 1 and 2 exhibited antifungal
activity against C. albicans KCTC 7122. Additionally, anti‐quorum
sensing (QS) activity was tested with compounds 1–2, 5, 8, and
12–14 against Chromobacterium violaceum KCTC 2897, a Gram‐
negative QS reporter strain widely used in quorum sensing inhibition assays. Novel compound 1 showed the strongest anti‐QS
activity between tested compounds in the qualitative screening of
anti‐QS activity using the disc diffusion assay by inhibition of violacein production as indicator of QS inhibition (Figure 6). Compound 1 also showed the highest anti‐QS activity with a 39.6%
inhibition of violacein production at 128 μg/mL. Compounds 2 and
14 exhibited weak inhibition (Supporting Information S1: Table S2).
The antibacterial activities of 8 and 12 were previously reported
[34, 35]; however, this study is the first report about their inhibitory
effects on K. rhizophila KCTC 1915 and their antifungal activities.
The antibacterial and antifungal activities of 13 and 14 were also
revealed for the first time in this study. Collectively, compounds 1
and 2 are considered key contributors to the antimicrobial activities
in P. grandiflorum.
Pathogen fungi
Cyclohexamide
14
13
12
11
10
9
Compounds
> 128
> 128
> 128
2
> 128
> 128
> 128
> 128
> 128
> 128
> 128
> 128
> 128
> 128
> 128
> 128
> 128
4
1
1
1
> 128
> 128
> 128
> 128
0.25
0.5
0.5
0.5
> 128
> 128
> 128
0.25
0.25
0.5
0.5
> 128
1
1
> 128
> 128
1
> 128
> 128
> 128
> 128
> 128
11
9
2.2 | Antimicrobial and Antifungal Activities of
Isolated Compounds
10
Compounds
12
Compounds 6–13 were isolated from the root of P. grandiflorum for
the first time. Notably, compound 13 has primarily been reported as
a synthetic additive for diesel fuel [32] and can be synthesized from
butanal and butanol. However, butanol was never used during
extraction, hexanes fraction preparation, or purification in this
study, suggesting that compound 13 is naturally derived.
> 128
Vancomycin
Ampicillin
13
14
The structures of other known analogs (7–14) were confirmed
by careful comparison of their MS and NMR data along
with specific rotations, to literature values. They were identified
as 9Z,16E‐octadeca‐9,16‐dien‐12,14‐diynoic acid (7) [26], α‐
dimorphecolic acid (8) [27], vanillin (9) [28], E−4‐(3‐ethoxyprop‐
1‐en‐1‐yl)−2‐methoxyphenol (10) [29], butyl ferulate (11) [30],
1‐acetyl‐β‐carboline (12) [31], 1,1‐dibutoxybutane (13) [32], and
lobetyol (14) [33] (Supporting Information S1: Figures S38–S73).
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Pilosulinene B (5) was found to have the same m/z value and a
similar 1H NMR spectrum to 6. A detailed comparison of the 1H
NMR spectra of 5 and 6 (Table 2) indicated that the geometry
between H‐7 and H‐8 in 5 was cis (3JH‐7,H‐8 = 11.5 Hz), while in
6 it was trans (3JH‐7,H‐8 = 16.4 Hz) (Supporting Information S1:
Figures S28–S37).
| Anti‐QS screening results using disk diffusion assay.
3 | Conclusion
As a result, five novel polyacetylenes (1–5) were isolated from the
root of the edible plant, P. grandiflorum (Campanulaceae), along
with nine known compounds (6–14). Among the isolated known
analogs, compounds 6–13 were first observed from this plant. In
addition, the absolute configurations of platypyran A (1) were
unambiguously assigned using J‐based configuration analysis,
1
H–1H coupling constant analysis, and Mosher's esterification of
secondary alcohols. The family Campanulaceae have been reported as one of major producer of polyacetylenes [36]. All the
novel polyacetylenes in this study had a C14 skeleton, supporting
the view that P. grandiflorum is a major producer of C14 polyacetylenes. Polyacetylenes were reported with multiple pharmacological activities including antibacterial activities [36] and can be
considered as a phytoalexins produced by the response to tissue
damage or a pathogenic infection. Therefore, polyacetylenes could
be attractive molecules for further studies on characteristic structure features related to antimicrobial activities. This study identified potential antimicrobial polyacetylenes (1 and 2) through
evaluation of their antimicrobial and QS inhibitory activities and
demonstrated the new pharmacological potentials of the compounds 8, 12, 13, and 14. In conclusion, this study expanded the
chemical space of P. grandiflorum and provided insights into its
potential antimicrobial principles, furthering its medicinal use.
4 | Experimental
4.1 | Chemistry
4.1.1 | General
Specific rotations were measured by a JASCO DIP‐100 polarimeter
(JASCO Co., Tokyo, Japan). NMR spectra were obtained on an
AVANCE NEO 600 spectrometer (NFEC‐2019‐09‐257998, Bruker
8 of 11
4.1.2 | Plant Materials
The dried root of P. grandiflorum was prepared from Naemome
Dah (Ulsan, Republic of Korea). The voucher specimen was
identified and deposited by Dr. Hyukjae Choi at the Pharmacognosy Laboratory, Yeungnam University, Gyeongsan, Korea.
4.1.3 | Extraction and Isolation
The dried roots of P. grandiflorum (9.5 kg) were extracted three
times using 70% EtOH (30 L) at room temperature (RT) for
3 days. The combined extract was evaporated to yield 2.5 kg of
black gummy crude extract. The dried extract (2.0 kg) was suspended in deionized water (3.5 L) and successively extracted
three times with 5.0 L of hexanes, dichloromethane (DCM), ethyl
acetate (EtOAc), and n‐butanol (n‐BuOH), respectively, and then
concentrated to yield fractions of hexanes (PG‐H, 3.3 g), DCM
(PG‐D, 25.4 g), EtOAc (PG‐E, 31.8 g), n‐BuOH (PG‐B, 154.0 g),
and water (PG‐W, 2.3 kg). A portion of the hexanes fraction (3.0 g)
was separated into 10 subfractions (PG‐H1–PG‐H10) by normal‐
phase (NP) MPLC with following conditions; Biotage SNAP KP‐
Sil 100 g column, a linear gradient of mixtures with DCM and
MeOH from 100:0 to 0:100. PG‐H1 (13, 1018.2 mg) was further
separated via MPLC. A portion of the fraction PG‐H2 (23.1 mg)
was subjected to reversed‐phase (RP) preparative HPLC (Hector
M 5 micron C18 100 Å, 250 × 21.2 mm) under isocratic conditions
of H2O:ACN (61:39) to yield compounds 3 (0.5 mg, tR = 12.5 min)
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FIGURE 6
Switzerland AG, Fällanden, Switzerland) at the Core Research
Support Center for Natural Products and Medicinal Materials
(CRCNM) and on Bruker AVANCE DPX 400 and DMX 250
spectrometers at the College of Pharmacy, Yeungnam University,
with CDCl3 (δC 77.16, δH 7.26) at 298 K. HR–FAB–MS spectra were
recorded on a JMS‐700 mass spectrometer (JEOL, Tokyo, Japan)
with a 6890 Series GC system (Agilent Technologies, Santa Clara,
CA, USA). HR–ESI–MS was measured using a Q Exactive UHMR
Hybrid Quadrupole‐Orbitrap MS system coupled with a Vanquish
UHPLC (Thermo Fisher Scientific, Waltham, MA, USA) at the
CRCNM. GCMS was recorded on a GCMS‐QP2010 (Shimadzu,
Kyoto, Japan). LR–ESI–MS spectra were measured using an Agilent
6120 mass spectrometer (Santa Clara, CA, USA) with a reversed‐
phase (RP) Phenomenex Luna 3μ C18(2) 100 Å column
(150 × 4.6 mm). Vacuum liquid chromatography (VLC) and open‐
column chromatography were performed using 70–230 mesh silica
gel (Merck). Medium‐pressure liquid chromatography (MPLC) was
performed using a Biotage Isolera One system (Uppsala, Sweden)
with a Biotage SNAP KP‐Sil 100‐g silica column. HPLC isolation
was conducted using a combination of a Waters 1525 binary pump/
2487 dual‐wavelength detector or a Waters 1525 binary pump/996
Photodiode Array (PDA) detector with an analytical or semipreparative Hector M 5‐micron C18 column (250 × 4.6 or
250 × 10 mm). Preparative HPLC was performed using on a Gilson
321 HPLC system (a 321 pump and UV/Vis‐155 detector) with a
preparative Hector M 5‐micron C18 100 Å column (250 × 21.2 mm).
Absorbance values for the QS inhibition assay were measured using
a SpectraMax ABS Plus microplate reader (Molecular Devices, San
Jose, CA, USA). The InChI codes of the investigated compounds,
together with some biological activity data, are provided as
Supporting Information.
Platypyran A (1): Brown oil; [α]D30 − 3.17 (c 0.1, CH2Cl2); HR–
FAB–MS obsd. m/z 219.1391 [M+H]+, calcd. for C14H18O2+,
219.1380; 1H and 13C NMR, see Table 1.
Platypyran B (2): Yellow oil; [α]D30 − 3.71 (c 0.1, CH2Cl2);
HR–FAB–MS obsd. m/z 217.1228 [M+H]+, calcd. for C14H16O2+,
217.1223; 1H and 13C NMR, see Table 1.
Pilosulinene B (5): White powder; HR–ESI–MS obsd. m/z
211.0759 [M–H]–, calcd. for C14H11O2–, 211.0765; 1H and 13C
NMR, see Table 2.
4.1.4 | Advanced Mosher's Method
Two samples of compound 1 (2 mg each) were prepared. To one
vial, a catalytic amount of 4‐dimethylaminopyridine (Sigma‐
Aldrich, St. Louis, MO, USA), 20 μL of S‐(+)‐α‐methoxy‐α‐
(trifluoromethyl)phenylacetyl chloride (S‐MTPA Cl) (Sigma‐
Aldrich, St. Louis, MO, USA), and pyridine‐d5 (0.7 mL) were
added. The vial was sealed and reacted for 16 h at 40°C with
stirring. The other vial of 1 was derivatized with R‐MTPA Cl
(Sigma‐Aldrich, St. Louis, MO, USA) following the same procedure. The resulting products were dried under a N2 stream.
The evaporated materials were suspended in deionized water
(1 mL) respectively, and Mosher's ester products of 1 were
extracted with n‐hexane (1 mL × 3). The combined n‐hexane
layers were evaporated to give the S/R‐MTPA esters of 1, and
their 1H NMR spectra were measured to assign the absolute
configuration of C‐9 by calculating ΔδS–R values [24].
4.2 | Antimicrobial and Quorum‐Sensing
Inhibitory Activities
4.2.1 | Minimum Inhibitory Concentration (MIC)
Against Bacteria and Fungi
The antibacterial and antifungal activities were tested on six
bacterial strains (Bacillus subtilis KCTC1021, Escherichia coli
KCTC2441, Klebsiella pneumonia KCTC 2690, Kocuria rhizophila KCTC1915, Salmonella typhimurium KCTC 2515, and
Staphylococcus aureus KCTC1927) and three fungal strains
(Candida albicans KCTC 7122, Candida glabrata KCTC 7219,
and Aspergillus fumigatus KCTC 6145). These strains were
selected as representative Gram‐positive and Gram‐negative
bacteria and clinically relevant fungal pathogens, widely employed in antimicrobial susceptibility studies. These strains
were inoculated in Muller–Hinton Broth (BD Difco) at 37°C for
24 h and calibrated to a McFarland standard of 0.5 (equivalent
to 1.5 × 108 cfu/mL). The test samples and positive controls
were prepared in DMSO at a concentration of 10 mg/mL. The
stock solutions of compounds were then serially diluted twofold
using Muller–Hinton Broth in 96‐well plates to a concentration
range of 256–0.5 μg/mL. Then, 50 μL of bacterial cultures was
added to each well, resulting in a final sample concentration
range as 128–0.25 μg/mL. The total inoculum concentration was
5.0 × 105 cfu/mL. After the incubation of 96‐well plate at 37°C for
24 h, the MIC was evaluated by the observation of visible bacterial
growth inhibition. Ampicillin and vancomycin served as positive
controls for antibacterial activity, while cycloheximide was used as
the positive control for antifungal activity [37].
Pilosulinene D (3): White powder; HR–ESI–MS obsd. m/z
257.1187 [M–H]–, calcd. for C16H18O3–, 257.1183; 1H and 13C
NMR, see Table 2.
4.2.2 | Qualitative Screening of QS Inhibitory Activity
Pilosulinene C (4): White powder; HR–ESI–MS obsd. m/z
257.1184 [M–H]–, calcd. for C16H18O3–, 257.1183; 1H and 13C
NMR, see Table 2.
A disc diffusion assay was performed to test QS inhibitory activity
by measuring the inhibition of violacein pigment production
of the isolates, except for compounds 3, 4, 6, 7, 9, 10, and 11
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and 4 (1.0 mg, tR = 18.0 min). The remaining PG‐H2 fraction was
further separated by NP analytical HPLC (Hector M Sil 5 micron,
250 × 4.6 mm) under isocratic conditions of hexanes:EtOAc
(75:25), yielding fraction PG‐H2‐A (6.5 mg, tR = 19.5 min), 5
(3.9 mg, tR = 20.5 min), and 11 (2.6 mg, tR = 21.5 min). Fraction
PG‐H2‐A was applied further isolation by NP analytical HPLC
(Hector M Sil 5 micron, 250 × 4.6 mm) under isocratic conditions
of hexanes:EtOAc (85:15) to get 6 (2.5 mg, tR = 35.2 min). Fractions PG‐H4–H6 (282.9 mg) were combined and subjected to RP
semipreparative HPLC with Hector M 5 micron C18 100 Å column (250 × 10 mm) and step gradient elution of water and acetonitrile (50:50–0:100) to afford compounds 1 (32.4 mg) and 2
(5.3 mg). Subfraction PG‐H4H (1.6 mg) was further separated
by RP HPLC (Hector M 5 micron C18 100 Å, 250 × 4.6 mm) to
yield compound 7 (0.5 mg). PG‐H9 was chromatographed via
RP semipreparative HPLC (Hector M 5 micron C18 100 Å,
250 × 10 mm) under isocratic conditions with 65% acetonitrile in
deionized water, yielding compound 8 (2.0 mg). PG‐H3 (222.5 mg)
was fractionated by silica gel open‐column chromatography
(column size: 1.8 × 23 cm) by step gradient mixtures of hexanes
and EtOAc (100:0–0:100) to yield compound 9 (9.6 mg).
The second extraction of the dried roots of P. grandiflorum (9.5 kg)
followed the same method as the first, and the extract was evaporated in vacuo, yielding a black gummy extract (2.3 kg). The
dried extract (1.9 kg) was dissolved in water and successively extracted with hexanes, DCM, EtOAc, and n‐BuOH, and then concentrated to yield hexanes (PG2‐H, 3.6 g), DCM (PG2‐D, 20.0 g),
EtOAc (PG2‐E, 12.6 g), n‐BuOH (PG2‐B, 176.2 g), and water (PG2‐
W, 2.1 kg) fractions, respectively. A portion of the hexanes layer
(3.0 g) was fractionated into eight fractions (PG2‐H1–PG2‐H8) via
MPLC using a silica column (Biotage SNAP KP‐Sil 100 g)
following similar chromatographic methods with PG‐1 as a linear
gradient of DCM:MeOH (100:0–0:100). PG2‐H3 was chromatographed via RP semipreparative HPLC with a Hector M 5 micron
C18 column (250 × 10 mm) by a step gradient of acetonitrile and
water (45:55–100:0), yielding compounds 10 (3.2 mg) and 12
(5.0 mg). The DCM layer (11.9 g) was fractionated into nine fractions (PG‐D1–PG‐D9) via silica gel VLC using a step gradient
of hexanes and EtOAc (100:0–0:100) and EtOAc:MeOH
(75:25–0:100). Fraction PG‐D7 (600.0 mg) was separated into 12
fractions (PG‐D7A–PG‐D7L) via silica open‐column chromatography using a step gradient of DCM:MeOH (100:0–0:100). PG‐D7J
(99.9 mg) was purified by RP preparative HPLC (Hector M
5 micron C18 100 Å, 250 × 21.2 mm) under isocratic conditions
with 35% acetonitrile to elute compound 14 (35.9 mg).
Data Availability Statement
4.2.3 | Quantitative Analysis of QS Inhibitory Activity
4. A. Inada, H. Murata, M. Somekawa, and T. Nakanishi, “Phytochemical
Studies of Seeds of Medicinal Plants. II. A New Dihydroflavonol Glycoside and a New 3‐Methyl‐1‐butanol Glycoside From Seeds of Platycodon
grandiflorum A. DE CANDOLLE,” Chemical and Pharmaceutical Bulletin
40 (1992): 3081–3083, https://doi.org/10.1248/cpb.40.3081.
The 96‐well plate assay was employed to evaluate QS inhibitory activity of the isolates, except for compounds 3, 4, 6, 7, 9,
10, and 11. The assay was conducted using C. violaceum
KCTC 2897 cultured in LB broth, along with positive and
negative controls. Vanillin and quercetin were used as QS
inhibition (positive) controls [39, 40]. The protocol was
slightly modified from previously published studies [38]. Test
samples and controls were dissolved in DMSO at a stock
concentration of 10 mg/mL. The stock solutions were serially
diluted twofold in liquid LB medium to achieve a concentration range of 256 to 0.5 μg/mL in the 96‐well plate.
Subsequently, 50 μL of calibrated bacterial suspension was
added to each well, resulting in a final concentration range of
128 to 0.25 μg/mL for the test samples. The final bacterial
inoculum was adjusted to 5.0 × 10⁵ CFU/mL. Plate was
incubated at 37°C for 20 h, depending on the microbial
strains. After incubation, 100 μL from each well was transferred to microcentrifuge tubes and centrifuged at 13,000 rpm
for 10 min to precipitate violacein. The resulting pellets were
resuspended in 200 μL of 1 × PBS and subjected to sonication
for 30 s to extract violacein. The lysates were then centrifuged
again at 13,000 rpm for 10 min to remove cell debris. Subsequently, 100 μL of the violacein‐containing supernatant was
transferred to a 96‐well plate, and the absorbance was measured at 585 nm using a microplate spectrophotometer. All
experiments were conducted in three independent trials,
each performed in triplicate.
Acknowledgments
This study was supported by the Basic Science Research Program of the
National Research Foundation of Korea (NRF) grants funded by the
Ministry of Science and ICT (Grant No. RS‐2020‐NR049591, and RS‐
2021‐NR‐058513), [Cooperative Research Program for Agriculture Science & Technology Development (PJ014208032023) funded by Rural
Development Administration], the Korea Basic Science Institute
(National Research Facilities and Equipment Center) grant funded by
the Ministry of Education (Grant No. RS‐2025‐02317758) and
Yeungnam University research grant funded by Yeungnam University.
Conflicts of Interest
The authors declare no conflicts of interest.
10 of 11
The data that supports the findings of this study are available in the
supporting material of this article.
References
1. L. Zhang, X. Wang, J. Zhang, D. Liu, and G. Bai, “Ethnopharmacology, Phytochemistry, Pharmacology and Product Application of
Platycodon grandiflorum: A Review,” Chinese Herbal Medicines 16
(2024): 327–343, https://doi.org/10.1016/j.chmed.2024.01.005.
2. Y. Zhang, M. Sun, Y. He, et al., “Polysaccharides From Platycodon
grandiflorum: A Review of Their Extraction, Structures, Modifications,
and Bioactivities,” International Journal of Biological Macromolecules
271 (2024): 132617, https://doi.org/10.1016/j.ijbiomac.2024.132617.
3. T. Goto, H. Tadao Kondo, H. Tamura, K. Kawahori, and H. Hattori,
“Structure of Platyconin, a Diacylated Anthocyanin Isolated From the
Chinese Bell‐Flower Platycodon grandiflorum,” Tetrahedron Letters 24
(1983): 2181–2184, https://doi.org/10.1016/S0040‐4039(00)81877‐8.
5. J. Y. Lee, J. W. Yoon, C. T. Kim, and S. T. Lim, “Antioxidant Activity
of Phenylpropanoid Esters Isolated and Identified From Platycodon
grandiflorum A. DC,” Phytochemistry 65 (2004): 3033–3039, https://doi.
org/10.1016/j.phytochem.2004.08.030.
6. B. Chen, Z. Liu, Y. Zhang, et al., “Application of High‐Speed Counter‐
Current Chromatography and HPLC to Separate and Purify of Three
Polyacetylenes From Platycodon grandiflorum,” Journal of Separation
Science 41 (2018): 789–796, https://doi.org/10.1002/jssc.201700767.
7. J. C. Ahn, B. Hwang, H. Tada, K. Ishimaru, K. Sasaki, and
K. Shimomura, “Polyacetylenes in Hairy Roots of Platycodon grandiflorum,” Phytochemistry 42 (1996): 69–72, https://doi.org/10.1016/0031‐
9422(95)00849‐7.
8. W. Li, “Isolobetyol, a New Polyacetylene Derivative From Platycodon
grandiflorum Root,” Natural Product Research 36, no. 1 (2022): 466–469,
https://doi.org/10.1080/14786419.2020.1779269.
9. L. Zhang, Y. Wang, D. Yang, et al., “Platycodon grandiflorus —An
Ethnopharmacological, Phytochemical and Pharmacological Review,”
Journal of Ethnopharmacology 164 (2015): 147–161, https://doi.org/10.
1016/j.jep.2015.01.052.
10. L. L. Zhang, M. Y. Huang, Y. Yang, et al., “Bioactive Platycodins
From Platycodonis Radix: Phytochemistry, Pharmacological Activities,
Toxicology and Pharmacokinetics,” Food Chemistry 327 (2020): 127029,
https://doi.org/10.1016/j.foodchem.2020.127029.
11. Y. H. Choi, D. S. Yoo, M. R. Cha, et al., “Antiproliferative Effects of
Saponins From the Roots of Platycodon grandiflorumon Cultured Human
Tumor Cells,” Journal of Natural Products 73 (2010): 1863–1867, https://
doi.org/10.1021/np100496p.
12. L. Zhang, Z. H. Liu, and J. K. Tian, “Cytotoxic Triterpenoid Saponins
From the Roots of Platycodon grandiflorum,” Molecules 12 (2007):
832–841, https://doi.org/10.3390/12040832.
13. K. J. Jang, H. K. Kim, M. H. Han, et al., “Anti‐Inflammatory Effects
of Saponins Derived From the Roots of Platycodon grandiflorus
in Lipopolysaccharide‐Stimulated BV2 Microglial Cells,” International
Journal of Molecular Medicine 31 (2013): 1357–1366, https://doi.org/10.
3892/ijmm.2013.1330.
14. H. L. Kim, J. Park, H. Park, et al., “Platycodon grandiflorum A.
De Candolle Ethanolic Extract Inhibits Adipogenic Regulators in
3T3‐L1 Cells and Induces Mitochondrial Biogenesis in Primary Brown
Preadipocytes,” Journal of Agricultural and Food Chemistry 63 (2015):
7721–7730, https://doi.org/10.1021/acs.jafc.5b01908.
Archiv der Pharmazie, 2025
15214184, 2025, 7, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ardp.70043 by Ewha Womans University Library, Wiley Online Library on [07/12/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
(due to quantity limitations), with a previously described method
with a minor modification [38]. The strain, C. violaceum KCTC
2897, was used as the reporter strain to assess anti‐QS. Briefly,
5 mL of an overnight culture of the reporter strain was added to
45 mL LB medium containing 0.3% agar, and the mixture was
cooled to approximately 45°C. The suspension was then added to
the plates and left to solidify. Sterile filter paper discs (5 mm in
diameter) were evenly placed on the surface of the LB agar. The
test samples and reference compounds were dissolved in DMSO at
a concentration of 10 mg/mL, and 20 μL of each solution was
applied to the discs. The plates were incubated at 37°C for 18 h.
DMSO was used as the negative control, while kanamycin, quercetin, and vanillin served as positive controls for QS inhibition [39,
40]. The anti‐QS effect was evaluated by observing the absence of
violacein pigmentation on the discs.
16. J. Y. Lee, W. I. Hwang, and S. T. Lim, “Antioxidant and Anticancer
Activities of Organic Extracts From Platycodon grandiflorum A. De
Candolle Roots,” Journal of Ethnopharmacology 93 (2004): 409–415,
https://doi.org/10.1016/j.jep.2004.04.017.
17. T. Khanal, J. H. Choi, Y. P. Hwang, Y. C. Chung, and H. G. Jeong,
“Saponins Isolated From the Root of Platycodon grandiflorum Protect
Against Acute Ethanol‐Induced Hepatotoxicity in Mice,” Food and Chemical
Toxicology 47 (2009): 530–535, https://doi.org/10.1016/j.fct.2008.12.009.
18. K. S. Kim, O. Ezaki, S. Ikemoto, and H. Itakura, “Effects of Platycodon
grandiflorum Feeding on Serum and Liver Lipid Concentrations in Rats
With Diet‐Induced Hyperlipidemia,” Journal of Nutritional Science and
Vitaminology 41 (1995): 485–491, https://doi.org/10.3177/jnsv.41.485.
19. Y. Xie, H. Pan, H. Sun, and D. Li, “A Promising Balanced Th1 and
Th2 Directing Immunological Adjuvant, Saponins From the Root of
Platycodon grandiflorum,” Vaccine 26 (2008): 3937–3945, https://doi.
org/10.1016/j.vaccine.2008.01.061.
20. J. Kim, “Antibacterial and Anti‐Inflammatory Effects of Platycodon
grandiflorum Extracts,” Journal of Digital Convergence 12 (2014): 359–366,
https://doi.org/10.14400/JDC.2014.12.3.359.
21. I. S. Lee, M. C. Choi, and H. Y. Moon, “Effect of Platycodon
grandiflorum A. DC Extract on the Bronchus Diseases Bacteria,” Korean
Society for Biotechnology and Bioengineering Journal 15 (2000): 162–166.
22. N. Matsumori, D. Kaneno, M. Murata, H. Nakamura, and
K. Tachibana, “Stereochemical Determination of Acyclic Structures Based
on Carbon−Proton Spin‐Coupling Constants. A Method of Configuration
Analysis for Natural Products,” Journal of Organic Chemistry 64 (1999):
866–876, https://doi.org/10.1021/jo981810k.
23. Y. Ahn and T. Cohen, “A General Diastereoselective Synthesis
of Spiroacetals Related to Those in Ionophores via the Reaction of
Lactones With Cerium(III).Gamma. Cerioalkoxide. MAD Reverses the
Diastereoselectivity of the Addition of Methylmetallics to a .beta.‐Keto
Ether,” Journal of Organic Chemistry 59 (1994): 3142–3150, https://doi.
org/10.1021/jo00090a036.
24. K. Fujii, Y. Ikai, H. Oka, M. Suzuki, and K. Harada, “A Nonempirical Method Using LC/MS for Determination of the Absolute
Configuration of Constituent Amino Acids in a Peptide: Combination of
Marfey's Method With Mass Spectrometry and Its Practical Application,” Analytical Chemistry 69 (1997): 5146–5151, https://doi.org/10.
1021/ac970289b.
25. R. Y. Wang, P. J. Su, B. Li, et al., “Two New Aromatic Derivatives
From Codonopsis pilosula and Their α‐Glucosidase Inhibitory Activities,” Natural Product Research 36 (2022): 4929–4935, https://doi.org/10.
1080/14786419.2021.1912749.
26. K. Oka, F. Saito, T. Yasuhara, and A. Sugimoto, “The Allergens of
Dendropanax trifidus Makino and Fatsia Japonica Decne. et Planch. and
Evaluation of Cross‐Reactions With Other Plants of the Araliaceae
Family,” Contact Dermatitis 40 (1999): 209–213, https://doi.org/10.
1111/j.1600‐0536.1999.tb06036.x.
30. J. Chen, L. Zhang, P. Zhao, G. Ma, Q. Li, and X. Yu, “Synthesized Alkyl
Ferulates With Different Chain Lengths Inhibited the Formation of Lipid
Oxidation Products in Soybean Oil During Deep Frying,” Food Chemistry
410 (2023): 135458, https://doi.org/10.1016/j.foodchem.2023.135458.
31. H. J. Shin, H. S. Lee, and D. S. Lee, “The Synergistic Antibacterial
Activity of 1‐Acetyl‐Beta‐Carboline and Beta‐Lactams Against Methicillin‐
Resistant Staphylococcus aureus (MRSA),” Journal of Microbiology and
Biotechnology 20 (2010): 501–505, https://doi.org/10.4014/jmb.0910.10019.
32. I. I. Yoeswono and T. Falah, “1,1‐Dibutoxybutane as a Petroleum
Diesel Fuel Blending Component and Their Mixture Performance,”
Journal of Energy and Power Engineering 10 (2016): 726, https://doi.org/
10.17265/1934‐8975/2016.12.002.
33. M. Ma, M. Wu, B. Tian, et al., “Polyacetylenes With Xanthine
Oxidase Inhibitory Activity From the Medicinal and Edible Fruits of
Cyclocodon lancifolius (Roxburgh) Kurz,” Fitoterapia 170 (2023):
105631, https://doi.org/10.1016/j.fitote.2023.105631.
34. J. M. McRae, Q. Yang, R. J. Crawford, and E. A. Palombo, “Antibacterial
Compounds From Planchonia careya Leaf Extracts,” Journal of
Ethnopharmacology 116 (2008): 554–560, https://doi.org/10.1016/j.jep.2008.
01.007.
35. O. Kenny, N. P. Brunton, D. Walsh, C. M. Hewage, P. McLoughlin, and
T. J. Smyth, “Characterisation of Antimicrobial Extracts From Dandelion
Root (Taraxacum officinale) Using LC‐SPE‐NMR,” Phytotherapy Research
29 (2015): 526–532, https://doi.org/10.1002/ptr.5276.
36. Q. Xie and C. Wang, “Polyacetylenes in Herbal Medicine: A
Comprehensive Review of Its Occurrence, Pharmacology, Toxicology,
and Pharmacokinetics (2014–2021),” Phytochemistry 201 (2022): 113288,
https://doi.org/10.1016/j.phytochem.2022.113288.
37. I. Wiegand, K. Hilpert, and R. E. W. Hancock, “Agar and Broth
Dilution Methods to Determine the Minimal Inhibitory Concentration
(MIC) of Antimicrobial Substances,” Nature Protocols 3 (2008): 163–175,
https://doi.org/10.1038/nprot.2007.521.
38. N. K. Vijayan, H. Tanimu, and B. O. Sukumaran, “Comparative Study
on Quorum Modulatory Effect of Selected Medicinal Plants on Chromobacterium Violaceum ATCC 12472 (MTCC 2656),” Journal of Pure and
Applied Microbiology 18 (2024): 1848–1859, https://doi.org/10.22207/JPAM.
18.3.34.
39. M. Skogman, S. Kanerva, S. Manner, P. Vuorela, and A. Fallarero,
“Flavones as Quorum Sensing Inhibitors Identified by a Newly Optimized Screening Platform Using Chromobacterium violaceum as
Reporter Bacteria,” Molecules 21 (2016): 1211, https://doi.org/10.3390/
molecules21091211.
40. D. Deryabin and A. Tolmacheva, “Antibacterial and Anti‐Quorum
Sensing Molecular Composition Derived From Quercus Cortex (Oak
Bark) Extract,” Molecules 20 (2015): 17093–17108, https://doi.org/10.
3390/molecules200917093.
Supporting Information
Additional supporting information can be found online in the
Supporting Information section.
27. S. V. Naidu, P. Gupta, and P. Kumar, “Enantioselective Syntheses of
(−)‐Pinellic Acid, α‐ and β‐Dimorphecolic Acid,” Tetrahedron 63 (2007):
7624–7633, https://doi.org/10.1016/j.tet.2007.05.047.
28. S. Annen, T. Zweifel, F. Ricatto, and H. Grützmacher, “Catalytic
Aerobic Dehydrogenative Coupling of Primary Alcohols and Water to
Acids Promoted by a Rhodium(I) Amido N‐Heterocyclic Carbene
Complex,” ChemCatChem 2 (2010): 1286–1295, https://doi.org/10.1002/
cctc.201000100.
29. F. Wang, H. M. Hua, X. Bian, Y. H. Pei, and Y. K. Jing, “Two New
Aromatic Compounds From the Resin of Styrax tonkinensis (Pier.)
Craib,” Journal of Asian Natural Products Research 8 (2006): 137–141,
https://doi.org/10.1080/10286020500480712.
11 of 11
15214184, 2025, 7, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ardp.70043 by Ewha Womans University Library, Wiley Online Library on [07/12/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
15. M. Y. Ji, A. Bo, M. Yang, et al., “The Pharmacological Effects and
Health Benefits of Platycodon grandiflorus—A Medicine Food Homology
Species,” Foods 9 (2020): 142, https://doi.org/10.3390/foods9020142.