International Journal of Analytical Chemistry
Volume 2020 (2020), Article ID 4575030, 19 pages
https://doi.org/10.1155/2020/4575030

Research Article

Chemical Constituents and Anti-Inflammatory Effect of Incense Smoke from Agarwood Determined by GC-MS

De-Qian Peng,1,2 Zhang-Xin Yu,¹ Can-Hong Wang,¹ Bao Gong,¹ Yang-Yang Liu,¹ and Jian-He Wei1,3

¹Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization, Hainan Branch of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haikou 570311, China
²School of Pharmacy, Hainan Medical University, Haikou 571199, China
³National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

Correspondence should be addressed to Jian-He Wei; wjianh@263.net

De-Qian Peng and Zhang-Xin Yu contributed equally to this work.

Received 7 February 2020; Revised 29 June 2020; Accepted 30 June 2020; Published 1 August 2020

Academic Editor: Kevin Honeychurch

Copyright © 2020 De-Qian Peng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Agarwood is generally used to make incense sticks in China and Southeast Asia. It emits smoke with a pleasant odor when burned. There are few reports on the chemical components of smoke generated by burning or heating agarwood. The agarwoods were produced by the whole-tree agarwood-inducing technique (AWIT), agarwood induced by axe wounds (AAW), burning-chisel-drilling agarwood (BCDA), wood of Aquilaria sinensis trees (AS), respectively. Herein, we used GC-MS to analyze the chemical constituents of incense smoke generated from AWIT, AAW, BCDA, AS, and the extracts of sticks from agarwood produced by the whole-tree agarwood-inducing technique (EAWIT), and 484 compounds were identified. A total of 61 chemical constituents were shared among AWIT, AAW, and BCDA. The experimental data showed that aromatic compounds were the main chemical constituents in agarwood smoke and that some chromone derivatives could be cracked into low-molecular-weight aromatic compounds (LACs) at high temperature. Furthermore, agarwood incense smoke showed anti-inflammatory activities by inhibiting lipopolysaccharide- (LPS-) induced TNF-α and IL-1α release in RAW264.7 cells.

1. Introduction

Agarwood, called chen‐xiang in China, is a valuable resinous wood from Aquilaria spp. or Gyrinops spp. trees [1–3]. It has been applied in medicine and shown obvious medicinal effects, such as sedative, carminative, and antiemetic effects [4, 5]. Agarwood does not form until a tree has been affected by factors such as lightning strike, animal grazing, insect attack, and fungi [6, 7]. Moreover, it takes a long time (years or even decades) to form in the wild. Natural agarwood is considered to be the finest source of incense and has been applied in cultural, religious, and medicinal uses for centuries. The market demand for agarwood is increasing daily. As a result, the supply of wild agarwood is not enough to meet the market demand. Many Aquilaria plantations have been established in some Southeast Asian countries, such as Indonesia, Cambodia, Laos, Thailand, Vietnam, and Malaysia. Aquilaria trees have been planted in South China, for example, in Hainan, Guangdong, and Yunnan provinces [8]. Some artificial technologies designed to rapidly induce agarwood formation have been demonstrated to make A. sinensis (AS) trees produce agarwood [7, 9–11]. In 2009, Blanchette and Heuveling developed cultivated agarwood kits (CA-Kits) [12]. In 2013, Liu et al. developed a whole-tree agarwood-inducing technique (Agar-Wit) [11]. Recently, Peng et al. also developed a similar technology to induce agarwood formation [13]. The above methods induce agarwood formation simply and effectively.

Presently, agarwood and its volatile components are seen as important and efficient natural substances that can be used to produce valuable products such as perfumes and incense because of their fragrance characteristics. Many teams have researched the chemical constituents of agarwood [1, 14–16]. The chemical constituents of agarwood essential oil or solvent extracts have been studied by column chromatography, spectroscopic techniques, gas chromatography (GC), and multidimensional GC analysis. Many studies have reported the use of GC-MS to analyze the volatile components in agarwood smoke obtained by heating. For example, in 1993, Ishihara et al. analyzed the volatile constituents in agarwood smoke and identified 53 chemical compounds from Vietnamese agarwood [17]. Nurlaila et al. identified 8 significant compounds from agarwood smoke by Z-score analysis [18]. Recently, Zhou et al. used glass fiber pads to absorb volatile constituents of agarwood smoke from different kinds of agarwood from different countries and extracted the samples with dichloromethane (CH₂Cl₂) for GC-MS analysis [19, 20]. Kao et al. analyzed agarwood smoke from Kynam agarwood by headspace (HS) preheating with gas chromatography-mass spectrometry (HS GC-MS) and identified 40 compounds [21]. However, there are no reports on agarwood smoke produced by Agar-Wit. Herein, we analyzed the chemical constituents of agarwood smoke produced by Agar-Wit and identified 484 compounds.

2. Experimental Setup

2.1. Chemicals and Reagents

All chemicals were purchased from J&K Scientific (Beijing, China), unless otherwise indicated.

The agarwood samples were identified by Prof. Jianhe Wei (Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, China). Incense sticks of AWIT, AAW, BCDA, and AS were made by Bao Gong (Hainan Branch Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, China).

2.2. Sample Preparation

Each stick was placed in a gas washing bottle (250 mL) fitted with an air inlet/outlet tube. The smoke components were collected by bubbling through a 30 mL amount dichloromethane during the 10 min burn time. In addition, sticks made from AWIT (3.0 g) were pulverized and extracted with CH₂Cl₂ (30 mL).

2.3. Sample Analysis

Chromatographic separation of the resulting mixture (1.0 μL) was undertaken on an Agilent 7890 A GC coupled to a 5975C quadrupole mass spectrometer and an automated 7683B sample injector system (Agilent Technologies, Santa Clara, California, USA). Chromatography was performed on a HP-5MS capillary column (30 m × 250 μm ID, 0.25 μm film thickness, 5% diphenyl methyl siloxane (Agilent Technologies, USA). Helium was used as carrier gas at a constant flow rate of 1.0 mL/min. The injections (1.0 μL) were performed in splitless injection mode (10 : 1) at 240°C. The operating parameters included the following temperature program: 40°C for 3 min, increase from 40°C to 140°C at a rate of 2.5°C/min, hold at 140°C for 5 min, increase from 140°C to 170°C at a rate of 1.5°C/min, hold at 170°C for 5 min, and increase to 280°C at a rate of 4°C/min. The total run time was 100.5 min as shown in Figure 1. The mass selective detector was operated with electron energy of 70 eV in electron ionization mode. The ion source and quadrupole temperatures were 230°C and 150°C, respectively. The scan range was 40–500 amu in full scan mode. Peak identification was completed by comparing mass spectra with those stored in the NIST 11 database and MSD ChemStation, or by comparing fragmentation patterns with those published by the Dai group [22]. Table 1 shows the representative data.

Figure 1: Gas chromatograph mass spectrometry (GC-MS) chromatograms of incense smoke (AWIT: whole-tree agarwood-inducing technique, AAW: agarwood produced by axe wounds, BCDA: burning-chisel-drilling agarwood, EAWIT: extract of stick from agarwood produced by whole-tree agarwood-inducing technique, AS: A. sinensis).

Table 1: Chemical constituents and relative amounts of AAW, BCDA, AWIT, AS, and EAWIT.

No.
Name
RT (min)
Relative content (%)

AAW
BCDA
AWIT
AS
EAWIT

1
Ethylbenzene
6.774
6.215 (B)
3.296 (B)
6.384 (B)
1.313 (B)
—

2
Furfuryl alcohol
6.872
—
—
—
2.212
—

3
1,4-Xylene
7.080
3.709 (B)
—
—
1.765 (B)
—

4
1,3-Xylene
7.086
—
—
2.354 (B)
—
—

5
1,2-Xylene
7.098
—
1.326 (B)
—
0.778 (B)
—

6
Phenylacetylene
7.392
1.387 (B)
0.698 (B)
1.612 (B)
1.013 (B)
—

7
Phenyl carbamate
7.646
—
—
—
0.308 (B)
—

8
Phenylethylene
7.901
8.596 (B)
3.413 (B)
7.973 (B)
5.132 (B)
—

9
2-Methyl-2-cyclopenten-1-one
8.680
—
—
—
0.400
—

10
4,4-Dimethyl-2-cyclopenten-1-one
8.952
—
—
—
0.302
—

11
2,5-Dimethyl-2,4-hexadiene
9.056
—
—
—
0.408
—

12
Anisole
9.096
0.239 (B)
—
0.21 (B)
—
—

13
2(5H)-Furanone
9.200
0.202
0.132
0.299
0.981
—

14
3,4-Dihydro-H-pyran
9.356
0.202
0.202
—
0.381
—

15
Methyl-2-oxo-1-pyrrolidineacetate
9.605
—
0.222
—
—
—

16
Tetrahydro-22-desoxy-tomatillidine
9.610
—
—
—
0.211
—

17
1-Methylene-2-vinylcyclopentane
10.962
—
—
—
0.113
—

18
Benzaldehyde
11.118
0.671 (B)
0.28 (B)
1.008 (B)
1.146 (B)
—

19
5-Methyl-furfural
11.407
—
—
—
0.508
—

20
2,3-Dihydroxystearic acid
11.875
—
—
—
0.209
—

21
2-Chloro-2,2-difluoro-acetonitrile
11.950
—
—
—
0.157
—

22
2-Methyl-2-pentenal
12.192
—
—
—
0.104
—

23
Benzonitrile
12.308
—
—
—
0.359 (B)
—

24
2,2,4,6,6-Pentamethylheptane
12.510
0.902
0.753
1.152
—
0.126

25
Benzofuran
12.793
—
—
—
0.541 (B)
—

26
Phenol
12.839
1.225 (B)
0.558 (B)
0.592 (B)
0.852 (B)
—

27
2,2-Diethyl-3-methyl-oxazolidine
13.105
0.751
0.785
0.808
—
—

28
(2S, 3S)-2,3-Dimethoxy-N¹,N¹,N¹,N⁴-tetramethyl-1,4-butanediamine
13.111
—
—
—
0.846
—

29
5-Norbornene-2-carboxaldehyde
13.654
0.169
—
0.189
—
—

30
4-Methylanisole
14.185
0.305 (B)
0.102 (B)
0.135 (B)
0.159 (B)
—

31
2-Azido-2,4,4,6,6-pentamethylheptane
14.445
0.255
0.187
0.220
—
—

32
2,3-Dioxabicyclo[2.2.2]oct-5-ene
14.671
0.424
0.189
0.175
—
—

33
3-Methyl-1,2-cyclopentanedione
14.717
—
—
—
0.369
—

34
2-Methyl-3-furanthiol
15.918
0.106
0.201
—
—
—

35
3-Methyl-phenol
16.635
0.219 (B)
0.176 (B)
0.12 (B)
—
—

36
2-Methyl-phenol
16.669
—
—
—
0.226 (B)
—

37
3-Methyl-bicyclo[3.3.0]oct-2-en-8-one
16.918
—
—
—
0.129
—

38
2,2,2-Bicyclo-2-octene
16.935
0.496
0.183 (B)
0.453 (B)
—
—

39
p-Cresol
17.801
0.73 (B)
0.473 (B)
0.321 (B)
0.205 (B)
—

40
Guaiacol
17.998
0.877 (B)
0.51 (B)
0.608 (B)
1.362 (B)
—

41
2-t-Butylamino-acrylonitrile
18.165
0.421
0.224
0.240
—
—

42
3,5-Dimethyl-4H-pyran-4-one
18.182
—
—
—
0.107
—

43
3-Hydroxy-2-methyl-4-pyrone
19.338
—
0.169
—
0.147
—

44
2,5-Dimethylphenol
21.677
0.223 (B)
0.129 (B)
—
0.165 (B)
—

45
2,3-Dihydroxybenzaldehyde
22.064
—
—
—
0.148 (B)
—

46
5-Ethyl-3-(3-methyl-5-phenylpyrazol-1-yl)-1,2,4-triazol-4-amine
22.215
0.152 (B)
—
—
—
—

47
Ethyl disulfide
22.220
—
—
0.094
—
—

48
1-Methylene-1H-indene,
22.740
0.166 (B)
—
—
—
—

49
2-Ethylphenol
22.913
0.129 (B)
—
—
—
—

50
Trehalose
22.914
—
0.324
—
—
—

51
2-Isopropyl-5-methyl-1-heptanol
23.197
—
—
0.059
—
—

52
3-Methyl-2-butene-1-thiol
23.208
0.120
—
—
—
—

53
2-Methylbutyl pentanoic acid ester
23.225
—
0.251
—
—
—

54
4-Methoxy-1,3-benzenediamine
23.300
—
—
—
0.216 (B)
—

55
2-Methoxy-3-methyl-phenol
23.306
0.236 (B)
—
—
—
—

56
2-Methoxy-4-methylphenol
23.676
0.444 (B)
0.283 (B)
0.271 (B)
0.309 (B)
—

57
2-Methoxy-5-methylphenol
23.688
—
0.327 (B)
—
—
—

58
3,6-Dimethyl-2,6-octadiene-4,5-diol
24.144
—
—
—
0.129
—

59
1,4 : 3,6-Dianhydro-α-d-glucopyranose
24.600
0.148
0.158
0.172
0.120
—

60
trans-Cinnamaldehyde
24.866
—
—
—
0.821 (B)
—

61
(1α, 2β, 5β, 6α)-Tricyclo[4.2.1.1(2,5)]deca-3,7-diene-9,10-dione
24.883
0.446
0.325
—
—
—

62
α-Methylene-benzeneacetaldehyde
24.895
—
—
0.247 (B)
—
—

63
2,4-Cyclopentadiene-1-ethanamine
25.045
0.128
—
0.230
—
—

64
1,11-Dibromo-undecane
25.062
—
0.101
—
—
—

65
Pyrocatechol
25.357
0.125 (B)
0.287
—
0.93 (B)
—

66
2,3-Anhydro-d-galactosan
25.357
—
—
0.204 (B)
—
—

67
2,3-Dihydrobenzofuran
25.727
0.369 (B)
0.382 (B)
0.299 (B)
0.255 (B)
—

68
1-Methyl-1H-pyrrole-2(5H)-one
26.131
—
—
0.203
—
—

69
2-Isopropoxyphenol
26.183
—
—
—
0.226 (B)
—

70
3-Methoxyphenol
26.206
0.263 (B)
—
—
—
—

71
5-Hydroxymethylfurfural
26.229
—
0.252
—
0.389
—

72
4-Phenyl-2-butanone
26.339
0.77 (B)
1.13 (B)
1.06 (B)
—
0.177 (B)

73
1-Methyl-4-amino-4,5(1H)-dihydro-1,2,4-triazole-5-one
26.847
—
—
—
0.259
—

74
Anisic aldehyde
26.905
0.306 (B)
0.301 (B)
0.389 (B)
—
—

75
2-Oxohexamethylenimine
27.032
—
0.185
—
—
—

76
3-Methoxy-2-benzenediol
27.454
0.401 (B)
0.365 (B)
0.251 (B)
0.582 (B)
—

77
3-Methoxybenzenethiol
27.731
0.131 (B)
—
—
—
—

78
1-Indanone
28.043
0.279 (B)
—
—
0.148 (B)
—

80
2-Isopropyl-3-methoxypyrazine
28.291
—
—
—
0.177
—

79
4-Ethyl-2-methoxyphenol
28.291
0.292 (B)
0.104 (B)
0.071 (B)
—
—

81
3-(4-Methylphenyl)-2-propenal
28.441
—
—
—
0.206 (B)
—

82
2,3-Dihydro-2-methyl-1H-inden-1-one
28.447
0.223
—
0.056 (B)
—
—

83
α-Methylcinnamaldehyde
28.557
—
—
—
0.127 (B)
—

84
2-Methylnaphthalene
28.621
0.285 (B)
—
—
—
—

85
1-Azabicyclo[2.2.2]octane-4-methanol
29.527
—
0.158
—
—
—

86
(E)-2,4,4,7-Tetramethyl-5,7-octadien-3-ol
29.666
—
—
—
0.179
—

87
4-Hydroxy-3-methoxystyrene
30.099
2.343 (B)
1.799 (B)
1.512 (B)
2.254 (B)
—

88
o-tert-Butyl phenol
30.417
—
—
—
0.131 (B)
—

89
3-Hydroxybenzaldehyde
30.844
—
—
—
0.252 (B)
—

90
2-Methoxybenzyl alcohol
31.081
—
—
—
0.106 (B)
—

91
trans-3-Hexenedioic acid-bis(trimethylsilyl) ester
31.411
0.127
—
—
—
—

92
2-exo-Chlorobicyclo[2.2.1]heptane-1-carbonyl chloride
31.942
0.282
—
0.285
—
—

93
2-Ethyl-1H-pyrrolo[2,3-b]pyridine
32.000
—
—
—
0.157
—

94
2,6-Dimethoxyphenol
32.115
3.013 (B)
2.939 (B)
2.178 (B)
—
—

95
cis-4,5-Diethyl-1,2-dimethyl-cyclohexene
32.190
—
—
—
4.085
—

96
Eugenol
32.358
0.517 (B)
0.303 (B)
0.262 (B)
—
—

97
3-Allyl-6-methoxyphenol
32.375
—
—
—
0.413 (B)
—

98
3,4-Dimethoxyphenol
32.566
—
0.112 (B)
—
0.219 (B)
—

99
3-Ethenyl-4-methyl-1H-pyrrole-2,5-dione
32.849
0.205
—
—
0.149
—

100
3-Cyclohexene-1-acetaldehyde
33.247
0.191
—
0.136
—
—

101
11-Methylene-tricyclo[4.3.1.1(2,5)]undecane
33.247
—
—
—
—
—

102
2-Propyl-phenol
33.848
—
—
—
0.1 (B)
—

103
4-Hydroxybenzaldehyde
33.975
—
—
—
0.225 (B)
—

104
Dichlorophenylsilane
34.010
—
—
0.321 (B)
—
—

105
Phenylboronic acid
34.016
0.406 (B)
0.143 (B)
—
—
—

106
Vanillin
34.408
0.8 (B)
0.83 (B)
0.708 (B)
1.842 (B)
—

107
4-(Methylthio)-benzaldehyde
34.593
0.254 (B)
—
—
—
—

108
(E)-isoeugenol
34.899
0.341 (B)
0.18 (B)
0.133 (B)
0.31 (B)
—

109
o-Methoxy-benzenethiol
35.084
0.125 (B)
—
—
0.197 (B)
—

110
2-Methoxy-1,4-benzenediol
35.217
—
—
—
0.209 (B)
—

111
2-Benzylidenemalonaldehyde
35.217
0.204 (B)
—
—
—
—

112
2-Vinylnaphthalene
35.442
0.115 (B)
—
—
—
—

113
3-Hydroxy-2-methyl-5-(1-methylethyl)-2,5-cyclohexadiene-1,4-dione
36.083
—
—
—
0.237
—

114
Biphenylene
36.234
0.105 (B)
—
—
—
—

115
2-Methoxy-4-(1-propen-1-yl)-phenol
36.892
2.962 (B)
2.126 (B)
2.379 (B)
3.254 (B)
—

116
4-Hydroxy-2-methoxybenzaldehyde
37.227
0.243
0.142
—
0.135 (B)
—

117
2-Methoxy-4-propyl-phenol
37.429
0.268 (B)
0.242 (B)
0.257 (B)
0.454 (B)
—

118
1,7-Dimethylpentacyclo[5.5.0(4,11).0(5,9).0(8,12)]dodecane-2,6-dione
37.689
—
—
0.126 (B)
—
—

119
2-Methoxy-6-[(4H-1,2,4-triazol-4-ylamino)methyl]-phenol
37.689
0.107
—
—
—
—

120
4-Hydroxybenzylidene acetone
37.707
—
0.101
—
—
—

121
N-Phenylthioformamide
37.712
—
—
—
0.126 (B)
—

122
7-Ethylbenzo[b]thiophene
38.053
—
—
—
0.153
—

123
5,6-Dimethyl-2-benzimidazolinone
38.382
—
—
—
0.164 (B)
—

124
Cyclohexylmethylbenzene
38.440
0.145 (B)
—
0.161 (B)
—
—

125
3,4-Dimethoxy-benzaldehyde
38.573
—
—
—
0.712 (B)
—

126
4′-(Methylthio)acetophenone
38.660
0.370
0.298 (B)
0.256 (B)
—
—

127
4-(4-Methoxyphenyl)-2-butanone
39.232
1.067 (B)
1.161 (B)
1.124 (B)
0.137
—

128
Pentadecane
39.434
—
—
0.168
—
—

129
Dibenzofuran
39.451
0.186 (B)
0.145 (B)
—
—
—

130
2′,6′-Dihydroxyacetophenone, bis(trimethylsilyl) ether
39.850
0.207 (B)
—
—
—
—

131
1-Methyl-1-phenylmethoxy-1-silacyclohexane
39.873
—
0.104 (B)
0.111 (B)
—
—

132
1,3,3-Trimethyl-2-(1-methylbut-1-en-3-on-1-yl)-1-cyclohexene
40.173
0.273
—
—
—
—

133
1,2-Dimethoxy-4-(methoxymethyl)benzene
40.196
—
0.178 (B)
—
—
—

134
2,4-Di-tert-butylphenol
40.202
—
—
—
0.287 (B)
—

135
2-(2-Hydroxyhex-1-enyl)-3-methyl-5,6-dihydropyrazine
40.260
0.138
—
—
—
—

136
5-(1,1-Dimethylethyl)-1,2,3-benzenetriol
40.653
0.578 (B)
0.34 (B)
0.212 (B)
0.684 (B)
—

137
Homovanillyl alcohol
40.780
0.594 (B)
0.507 (B)
0.417 (B)
1.119 (B)
—

138
[4-(1,1-Dimethylethyl)phenoxy]-acetate-methanol
41.912
—
—
—
—
0.159 (B)

139
(S)-4,5,6,7,8,8a-Hexahydro-8aα-methylazulen-2(1H)-one
42.137
0.109
—
—
—
—

140
Acetic acid-2-propylphenyl ester
42.160
—
0.114 (B)
—
—
—

141
3-Nitrobenzaldehyde-(O-methyl oxime)
42.420
—
—
—
—
—

142
2,3,5,6-Tetrafluoroanisole
42.443
4.532 (B)
3.741 (B)
4.13 (B)
—
—

143
3-tert-Butyl-4-hydroxyanisole
42.547
—
—
—
5.641 (B)
—

144
2,5-Dihydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one
42.819
—
—
—
0.329
—

145
α-Santalol
42.848
—
—
—
—
0.511 (S)

146
2,3-Dihydro-2,2-dimethyl-3,7-benzofurandiol
42.888
0.359 (B)
0.39 (B)
0.394 (B)
—
—

147
7-(1,1-Dimethylethyl)-3,4-dihydro-1(2H)-naphthalenone
43.119
—
—
—
—
0.105 (B)

148
3-Ethoxy-4-methoxybenzaldehyde
43.183
0.324 (B)
—
0.221 (B)
—
—

149
3-Hydroxy-4-methoxybenzoic acid-methyl ester
43.200
—
0.318 (B)
—
—
—

150
Ethyl vanillate
43.211
—
—
—
0.279 (B)
—

151
α-Amino-3′-hydroxy-4′-methoxyacetophenone
43.443
0.126 (B)
0.143 (B)
—
—
—

152
(3S, 4R, 5R, 6R)-4,5-Bis(hydroxymethyl)-3,6-dimethylcyclohexene
43.610
—
—
0.202
—
—

153
Carbonic acid-2,3-dimethylphenyl methyl ester
43.628
0.41 (B)
—
—
—
—

154
3-(4-Methoxyphenyl)propionic Acid
43.656
—
0.431 (B)
—
—
—

155
Hexadecane
44.078
0.329
0.351
0.321
0.127
—

156
2,6-Dimethoxy-4-(2-propen-1-yl)-phenol
44.274
0.785 (B)
0.619 (B)
0.521 (B)
1.029 (B)
—

157
2,6-Dimethyl-4-nitrophenol
44.586
0.256 (B)
—
—
—
—

158
[1S-(1α, 4α, 7α)]-1,2,3,4,5,6,7,8-Octahydro-1,4,9,9-tetramethyl-4,7-methanoazulene
44.592
—
—
—
—
0.406 (S)

159
2-Ethyl-4-methyl-4,6-bis(1-methylethyl)-4H-1,3,2-dioxaborin
44.592
—
—
—
0.139
—

160
8-Epi-γ-eudesmol
44.633
—
0.261 (S)
0.219 (S)
—
—

161
Methyl-2,6,6-trimethyl-3-oxo-1-cyclohexene-1-acrylate
44.737
—
—
0.155
—
—

162
2′,6′-Dimethylacetanilide
44.771
—
0.187
—
—
—

163
[1S-(1α, 4aβ, 8aα)]-1,2,4a,5,8,8a-Hexahydro-4,7-dimethyl-1-(1-methylethyl)-naphthalene
45.152
—
—
—
—
0.141 (S)

164
[1R-(1α, 3aα, 7aα)]-1,2,3,6,7,7a-Hexahydro-2,2,4,7a-tetramethyl-1,3a-ethano-3aH-indene
45.326
—
0.241 (B)
—
—
0.149 (S)

165
Agarospirol
45.551
—
0.238 (S)
0.195 (S)
—
0.413 (S)

166
Methyl 3-(bicyclo[2.2.1]hept-1-yl)-propenoate
45.586
—
—
—
0.116
—

167
Hinesol
45.719
0.126
—
—
—
0.251 (S)

168
(1α, 6α, 7α)-1,5,5-Trimethyl-2-methylene-bicyclo[4.1.0]heptane-7-methanol
45.736
0.121 (S)
—
—
—
—

169
(1R, 3aR, 4R, 7R)-1,2,3,3a,4,5,6,7-Octahydro-1,4-dimethyl-7-(1-methylethenyl)-azulene
45.748
—
—
0.191 (S)
—
—

170
[1S-(1α, 4α, 7α)]-1,2,3,4,5,6,7,8-Octahydro-1,4-dimethyl-7-(1-methylethenyl)-azule
45.776
—
0.222 (B)
—
—
—

171
Longifolene
45.990
—
—
—
—
0.565 (S)

172
10S,11S-Himachala-3(12),4-diene
46.007
0.155 (S)
—
—
—
—

173
Neoisolongifolene
46.042
—
0.262 (S)
0.248 (S)
—
—

174
Ledol
46.279
—
—
0.219 (S)
—
0.519 (S)

175
β-Eudesmol
46.325
0.150
0.343 (S)
—
—
—

176
Guaiol
46.498
—
—
0.939 (S)
—
—

177
γ-Selinene
46.504
0.589 (S)
1.164 (S)
—
—
1.868 (S)

178
1-Bromooctadecane
46.712
—
—
—
—
—

179
7,9-Dimethyl-hexadecane
46.729
0.169
—
0.219
—
—

180
(4-Methoxyphenyl)glycolic acid
46.752
—
—
—
0.212
—

181
3-(4-Hydroxy-3-methoxyphenyl)-2-propenoic acid
46.880
0.629 (B)
0.509 (B)
0.517 (B)
0.814 (B)
—

182
Dehydroaromadendrene
47.301
—
—
—
—
0.442 (S)

183
3,5-Dimethoxy-4-hydroxybenzaldehyde
47.353
1.599 (B)
1.78 (B)
1.891 (B)
2.92 (B)
—

184
2,4,6-Trimethyl-pyridine
47.428
—
—
—
—
0.383

185
Camphene
47.561
—
—
—
—
0.600

186
Ethyl (3-pyridyl)carbamate N-oxide
47.608
—
0.753
—
—
—

187
Hexamethyl-benzene
47.654
0.503
—
0.646 (B)
—
—

188
1-(1,3a,4,5,6,7-Hexahydro-4-hydroxy-3,8-dimethyl-5-azulenyl)-ethanone
47.896
—
—
—
—
0.142 (S)

189
2-Allyl-1,4-dimethoxy-3-methyl-benzene
48.029
0.249 (B)
—
0.33 (B)
—
—

190
2,5-Dibutyl-furan
48.150
—
—
—
1.392
—

191
Vanillylacetone
48.208
1.036 (B)
0.967 (B)
0.425 (B)
—
—

192
[1S-(1α, 7α, 8aβ)]-1,2,3,5,6,7,8,8a-Octahydro-1,4-dimethyl-7-(1-methylethenyl)-azulene
48.480
—
—
—
—
0.55 (S)

193
Dehydro-cyclolongifolene oxide
48.509
—
0.717 (S)
0.473 (B)
—
—

194
4-Methoxymethyl-6-methyl-1H-pyrazolo[3,4-b]pyridin-3-ylamine
48.572
—
—
—
0.283
—

195
1-Cyclohexyl-2-methoxy-benzene
48.601
—
—
0.384 (B)
—
0.72 (B)

196
N,N-Diethyl-2-benzoxazolamine
48.613
0.781 (B)
—
—
—
—

197
Octahydro-2-(1-methylethylidene)-4,7-methano-1H-indene
49.161
—
—
—
—
0.361 (B)

198
4,6,6-Trimethyl-2-(3-methylbuta-1,3-dienyl)-3-oxatricyclo[5.1.0.0(2,4)]octane
49.167
—
—
0.172
—
—

199
4-Methylene-1-methyl-2-(2-methyl-1-propen-1-yl)-1-vinyl-4-methylene-1-methyl-2-(2-methyl-1-propen-1-yl)-1-vinyl-cycloheptane
49.219
0.121
0.181
—
—
—

200
3-Phenoxy-phenol
49.467
0.325
0.154 (B)
0.134 (B)
0.248 (B)
—

201
(Z)-3,7-Dimethyl-1,3,6-octatriene
49.537
—
—
—
—
0.406

202
1,7-Dimethyl-7-(4-methyl-3-pentenyl)-tricyclo[2.2.1.0(2,6)]heptane
49.612
—
0.2 (S)
0.192 (S)
—
—

203
2-Acetate-1,3-dimethoxy-5-(1-propenyl)-benzene
50.057
3.206 (B)
2.309 (B)
—
—
—

204
2,5-Dimethoxyterephthalic acid
50.178
—
—
2.516 (B)
3.780
—

205
2-(2-Furanylmethylene)-6-methyl-cyclohexanone
50.270
—
—
—
—
0.255

206
4-Propylbiphenyl
50.380
0.704 (B)
0.711 (B)
—
—
—

207
1-Ethyl-3-(phenylmethyl)-benzene
50.386
—
—
0.745 (B)
—
—

208
N,N,S-Trimethyl-3-aminothiophenol
50.415
—
—
—
0.684 (B)
—

209
Neocurdione
50.438
—
—
—
—
0.161 (S)

210
endo-Borneol
51.056
—
—
—
—
0.611

211
9-Fluorenone
51.073
0.205 (B)
—
—
—
—

212
[1S-(1α, 3aβ, 4α, 8aβ, 9R∗)]-Decahydro-4,8,8-trimethyl-1,4-methanoazulene-9-methanol
51.108
—
0.488 (S)
0.295 (S)
—
—

213
Methyl α-hydroxy-4-methoxy-benzeneacetate
51.605
—
—
—
0.101 (B)
—

214
2,2′-Methylenebis[5-methyl-furan
51.743
—
—
—
—
0.136

215
4-Hydroxy-2-methoxycinnamaldehyde
51.882
0.937 (B)
0.897 (B)
0.78 (B)
—
—

216
3-(4-Hydroxy-3-methoxyphenyl)-2-propenal
52.072
—
—
—
2.664 (B)
—

217
Acetosyringone
52.096
0.967 (B)
0.829 (B)
0.88 (B)
1.499 (B)
—

218
syn-3,3,5,6,8,8-Hexamethyl-tricyclo[5.1.0.0(2,4)]oct-5-ene,
52.333
1.530
1.979
1.762
—
0.624

219
2-Phenylethyl-1,1,2,2-d4-amine
52.541
—
—
1.184 (B)
—
—

220
2-Methyl-5-(1-methylethyl)-phenol
52.552
—
—
—
—
1.377 (B)

221
2′-Hydroxy-3,3-dimethyl-3-phenylpropanal
52.558
0.762 (B)
—
—
—
—

222
2-[3-Methoxyphenyl]-propionic acid
52.581
—
1.048 (B)
—
—
—

223
3-(2-Pentenyl)-1,2,4-cyclopentanetrione
52.679
—
—
—
6.688 (B)
—

224
7-(1,3-Dimethylbuta-1,3-dienyl)-1,6,6-trimethyl-3,8-dioxatricyclo[5.1.0.0(2,4)]octane
52.951
0.340
0.621
0.732
—
0.491

225
o-Mentha-1(7),8-dien-3-ol
53.262
—
—
—
—
0.206

226
1,10b(2H)-Dihydropyrano[3,4,5-jk]fluorene
53.488
0.153 (B)
—
—
—
—

227
Anthracene
53.499
—
—
—
0.124 (B)
—

228
(1S, 6R, 9S)-5,5,9,10-Tetramethyltricyclo[7.3.0.0(1,6)]dodec-10(11)-ene
53.609
0.121
0.457
0.414
—
—

229
(Z)-3-Methyl-2-(2,4-pentadienyl)-2-cyclopenten-1-one
53.632
—
—
—
—
0.559

230
1-Methoxy-4-methyl-2-(1-methylethyl)-benzene
54.019
—
—
—
—
0.565 (B)

231
(1Z, 3aα, 7aβ)-1H-1-Ethylideneoctahydro-7a-methyl-indene
54.089
0.466 (B)
0.773 (B)
0.531 (B)
—
—

232
3-(Phenylmethoxy)-1-propanol
54.233
—
—
—
—
0.238 (B)

233
trans-1,10-Dimethyl-2-methylene-decalin
54.510
—
—
—
—
0.113

234
3,5-Dimethoxy-4-hydroxyphenylacetic acid
54.649
1.383 (B)
1.359 (B)
1.391 (B)
2.15 (B)
—

235
(1aR, 4S, 4aR, 7S, 7aR, 7bS)-Decahydro-1,1,4,7-tetramethyl-1H-cycloprop[e]azulene
54.672
—
—
—
—
0.177 (S)

236
2,7-Dimethyl-5-(1-methylethenyl)-1,8-nonadiene
55.036
—
—
—
—
0.126

237
Longifolenaldehyde
55.261
—
0.12 (S)
—
—
—

238
(2R-cis)-1,2,3,4,4a,5,6,7-Octahydro-α,α,4a,8-tetramethyl-2-naphthalenemethanol
55.377
—
—
—
—
0.409 (B)

239
(4aR, 5S)-4,4a,5,6,7,8-Hexahydro-4a,5-dimethyl-3-(1-methylethylidene)-2(3H)-naphthalenone
55.850
0.459 (S)
0.535 (S)
0.609 (S)
—
0.611 (S)

240
1,2,4-Triethyl-benzene
56.130
—
—
—
—
0.301 (B)

241
Isoaromadendrene epoxide
56.145
0.114 (S)
—
0.143 (S)
—
—

242
2,3,4,5-Tetramethyl-tricyclo[3.2.1.02,7]oct-3-ene
56.405
—
—
—
—
0.659

243
Globulol
56.584
—
—
—
—
0.344 (S)

244
Octadecane
56.624
0.285
0.331
0.393
0.179
—

245
2,3-Dihydro-2,2-dimethyl-7-benzofuranol
56.803
—
—
—
—
0.258 (B)

246
1β, 2α-Dimethyl-3α, 5β-bis(1-methylethenyl)cyclohexane
56.844
—
—
0.285
—
—

247
4,6-Dimethoxy-1-naphthaldehyde
56.896
0.214 (B)
—
—
—
—

248
2-Bromo-1,3-dimethoxy-benzene
56.919
—
0.305 (B)
—
—
—

249
1,3,5-Triethyl-benzene
57.040
—
—
—
—
0.252 (B)

250
7-Methyl-pentadecane
57.144
—
—
0.189
—
—

251
2-Methyl-dodecane
57.150
0.154
—
—
—
—

252
Corymbolone
57.225
—
—
—
—
0.164 (S)

253
2,6,10,14-tetramethyl-Hexadecane
57.225
0.130
0.285
0.151
0.298
—

254
1-(2-Thienyl)-1-heptanone
57.520
—
—
0.500
—
—

255
1-(2-Thienyl)-1-hexanone
57.543
0.391
—
—
—
—

256
2,4-Dimethylcyclopentane-1,3-dione
57.601
—
0.475
—
—
—

257
1-(2-Thienyl)-ethanone
57.612
—
—
—
—
1.207

258
1-(2,6-Dihydroxy-4-methoxyphenyl)-ethanone
57.716
—
—
—
0.162 (B)
—

259
5-(2-Thienyl)-4-pyrimidinamine
57.832
1.086
1.513
2.402
—
—

260
1,3-Benzenedicarboxylic acid-4-methyl-1,3-dimethyl ester
57.941
—
—
—
—
5.197 (B)

261
3,4-Dimethoxy-benzaldehyde oxime
58.051
—
—
0.196 (B)
—
—

262
1,2-Dimethoxy-4-(1,2-dimethoxyethyl)benzene
58.063
0.295 (B)
0.233 (B)
—
—
—

263
5-Methoxy-[1,2,4]triazolo[4,3-a]pyridine-3-thiol
58.149
—
—
—
0.335
—

264
Methyl-3-amino-4-methoxybenzoate
58.248
0.192 (B)
0.304 (B)
0.29 (B)
—
—

265
Isomaltol
58.271
—
—
—
—
0.623

266
9-Methyl-9-azabicyclo[4.2.1]nona-2,4-diene
58.721
0.103
—
—
—
0.970

267
Chlordimeform
58.791
—
0.309 (B)
—
—
—

268
Nootkatone
59.229
—
—
—
—
0.118 (S)

269
4-(3-Methyl-2-butenyl)-phenol
59.541
—
—
—
—
0.772 (B)

270
[2R-(2α, 4aα, 8aβ)]-1,2,3,4,4a,5,6,8a-Octahydro-4a,8-dimethyl-2-(1-methylethenyl)-naphthalene
59.663
—
0.125 (S)
—
—
—

271
[1R-(1R∗, 4Z, 9S∗)]-4,11,11-trimethyl-8-methylene-bicyclo[7.2.0]undec-4-ene
59.952
—
—
—
—
0.193 (S)

272
2,3,4,5,6-Pentamethyl-benzoic acid
60.200
0.221 (B)
0.151 (B)
—
—
—

273
[1aR-(1aα, 7α, 7aα, 7bα)]-1a,2,3,5,6,7,7a,7b-Octahydro-1,1,7,7a-tetramethyl-1H-cyclopropa[a]naphthalene
60.206
—
—
—
—
0.167 (S)

274
4,5-Dihydro-6-(4-fluorophenyl)-pyridazin-3(2H)-one
60.235
—
—
—
—
—

275
N(1)-[(3-Methoxyphenyl)methyl]-1H-1,2,3,4-tetrazole-1,5-diamine
60.367
—
—
0.17 (B)
—
—

276
1-Ethenyl-1-methyl-2-(1-methylethenyl)-4-(1-methylethylidene)-cyclohexane
60.396
—
—
—
—
0.601 (S)

277
(E,E)-1,5-Dimethyl-8-(1-methylethylidene)-1,5-cyclodecadiene
60.443
—
0.165 (S)
—
—
—

278
6,7-Dimethyl-8-(1-methylethyl)-2,4(1H,3H)-pteridinedione
60.708
—
0.105
—
—
—

279
trans-Z-α-Bisabolene epoxide
60.737
—
—
—
—
0.42 (S)

280
Aromadendrene oxide-(1)
61.066
—
—
0.814 (S)
—
—

281
Cedrol
61.072
0.376 (S)
—
—
—
—

282
1-Hydroxy-6-(3-isopropenyl-cycloprop-1-enyl)-6-methyl-heptan-2-one
61.153
—
1.008
—
—
—

283
(1R, 7R, 8aS)-1,2,3,5,6,7,8,8a-Octahydro-1,8a-dimethyl-7-(1-methylethenyl)-naphthalene
61.170
—
—
—
—
2.925 (S)

284
α-Farnesene
61.546
—
—
—
—
0.429

285
2-Methylene-6,8,8-trimethyl-tricyclo[5.2.2.0(1,6)]undecan-3-ol
61.592
—
0.156
—
—
—

286
Thiocyanic acid-4-(dimethylamino)phenyl ester
61.702
—
—
—
—
0.354

287
[4aR-(4aα, 7α, 8aβ)]-Decahydro-4a-methyl-1-methylene-7-(1-methylethenyl)-naphthalene
61.892
—
—
—
—
0.198 (S)

288
Decahydro-2,2,4,8-tetramethyl-4,8-methanoazulen-9-ol stereoisomer
62.060
—
—
—
—
0.306 (S)

289
Diphenylmethane
62.551
—
—
—
0.27 (B)
—

290
[1aR-(1aα, 4β, 4aβ, 7α, 7aβ, 7bα)]-Decahydro-1,1,4,7-tetramethyl-1H-cycloprop[e]azulen-4-ol
62.568
—
—
—
—
0.205 (S)

291
Spiro(tricyclo[6.2.1.0(2,7)]undeca-2,4,6,9-tetraene-11,1′-cyclopropane
62.568
0.198 (B)
—
—
—
—

292
4-Methyl-1-[2,6,6-trimethyl-2-cyclohexen-1-yl]-1-penten-3-one,
62.603
—
0.149
—
—
—

293
[1S-(1α, 7α, 8aα)]-1,2,3,5,6,7,8,8a-Octahydro-1,8a-dimethyl-7-(1-methylethenyl)-naphthalene
62.788
—
—
—
—
0.248 (S)

294
Caryophyllene
63.007
—
—
—
—
0.172 (S)

295
Nonadecane
63.059
0.129
0.134
0.125
0.145
—

296
7-Methoxy-3,4-dihydro-2[1H]-quinoxalinone
63.233
0.241 (B)
0.27 (B)
0.367 (B)
—
—

297
2-Allyl-1,4-dimethoxybenzene
63.296
—
—
—
—
1.347 (B)

298
Dehydroxy-isocalamendiol
63.493
—
—
0.241 (S)
—
—

299
3,4,5,6-Tetramethyl-2,5-octadiene
63.504
0.133 (S)
—
—
—
—

300
Megastigmatrienone
63.539
—
—
—
—
0.914

301
6-(1-Hydroxymethylvinyl)-4,8a-dimethyl-3,5,6,7,8,8a-hexahydro-1H-naphthalen-2-one
63.573
—
0.286 (B)
—
—
—

302
α-Ethyl-benzeneacetamide
63.729
—
—
—
—
0.442 (B)

303
8-Ethenyl-3,4,4a,5,6,7,8,8a-octahydro-5-methylene-2-naphthalenecarboxylic acid
63.747
—
0.175 (B)
—
—
—

304
[1S-(1α, 2β, 4β)]-1-Ethenyl-1-methyl-2,4-bis(1-methylethenyl)-cyclohexane
63.989
—
—
—
—
0.666 (S)

305
1-Methylphenazine 5-oxide
63.989
—
—
—
0.945 (B)
—

306
3-Phenylbicyclo(3.2.2)nona-3,6-dien-2-one
63.995
—
—
0.217 (B)
—
—

307
1-(1-Hydroxybutyl)-2,5-dimethoxybenzene
64.035
0.423 (B)
0.49 (B)
—
—
—

308
Methyleugenol
64.538
0.123 (B)
0.315 (B)
0.23 (B)
—
—

309
2-Ethyl-3,4-dihydro-2H-1-benzothiopyran
64.630
—
—
—
—
1.177 (B)

310
Acetic acid-cyano-hydroxyimino-methyl ester
65.006
—
—
—
—
0.484

311
N-Dimethylaminomethylene-anthranilic acid
65.012
0.252 (S)
0.26 (S)
0.165 (S)
—
—

312
2-Methyl-9-(prop-1-en-3-ol-2-yl)-bicyclo[4.4.0]dec-2-ene-4-ol
65.243
—
—
1.25 (S)
—
—

313
(1aR, 4aR, 7R, 7aR, 7bS)-Decahydro-1,1,7-trimethyl-4-methylene-1H-cycloprop[e]azulene
65.254
0.514 (B)
1.064 (B)
—
—
—

314
[4aR-(4aα, 5α, 8aα)]-4a,5,6,7,8,8a-Hexahydro-3,4a,5-trimethyl-naphtho[2,3-b]furan-9(4H)-one
65.381
—
—
—
—
4.963 (S)

315
7,7,8,8-Tetracyanoquinodimethane
65.716
0.137 (B)
—
—
—
—

316
4-(1,3,3-Trimethyl-bicyclo[4.1.0]hept-2-yl)-but-3-en-2-one
65.780
—
0.233
—
—
—

317
Alloaromadendrene oxide
65.820
—
—
—
—
0.543 (S)

318
γ-Elemene
66.207
—
—
—
—
0.835 (S)

319
1-(2,4,6-Trimethylphenyl)-3-(2-propynyl)-thiourea
66.698
0.68 (B)
1.52 (B)
1.68 (B)
—
5.466 (B)

320
3,4-Dimethylphenyl trifluoro-acetate
66.883
—
—
0.209 (B)
—
—

321
12-Azabicyclo[9.2.2]pentadeca-1(13),11,14-trien-13-ylamine
66.901
0.205
0.276
—
—
1.177

322
1-Butyl-1H-pyrrole
67.062
0.213
0.288
0.174
—
—

323
(3aα, 8β, 8aα)-5,6-1,2,3,3a,8,8a-Hexahydro-2,2,8-trimethyl-azulenedimethanol
67.259
—
—
—
—
0.631 (S)

324
(2R, 5S, 10R)-6,10-Dimethyl-2-(1-methylethenyl)-spiro[4.5]dec-6-en-8-one
67.386
0.326 (S)
—
—
—
—

325
N-Salicylidene-N′-salicyloylhydrazine
67.496
—
0.597 (B)
—
—
—

326
3,5-Dimethyl-benzenamine
67.507
—
—
—
—
0.633 (B)

327
2-Allyl-3-ethoxy-4-methoxyphenol
67.709
—
—
1.709 (B)
—
—

328
1,2-Dimethoxy-4-(3-methoxy-1-propenyl)benzene
67.732
1.572 (B)
—
—
—
—

329
Levomenol
67.778
—
—
—
—
0.305 (S)

330
n-Hexadecanoic acid
67.807
—
—
—
1.701
—

331
2,2,8,8-Tetramethyl-3,6-nonadien-5-one
67.958
—
—
—
—
0.428

332
3,5-Dimethoxy-4-hydroxycinnamaldehyde
68.119
0.123 (B)
1.723 (B)
—
3.472 (B)
—

333
1-Hydroxy-6-methylphenazine
68.529
1.19 (B)
1.897 (B)
1.555 (B)
—
—

334
Desaspidinol
68.847
—
—
—
3.559 (B)
—

335
2-Chloro-4-cyclohexyl-phenol
68.882
0.177 (B)
—
0.302 (B)
—
—

336
5-Ethyl-1,2,3,4-tetrahydro-naphthalene
68.899
—
—
—
—
0.779 (B)

337
Heptadecane
69.361
—
—
—
0.195
—

338
Humulane-1,6-dien-3-ol
69.384
—
—
—
—
0.784 (S)

339
8,8-Dimethyl-9-methylene-1,5-cycloundecadiene
69.777
—
—
—
—
0.465 (S)

340
2,4-Dichloro-1-nitrobenzene
70.083
—
—
—
—
0.429 (B)

341
1-(2-Benzyloxyethyl)cyclohexene
70.453
—
—
0.369 (B)
—
—

342
Caryophyllene oxide
70.476
—
—
—
—
2.082 (S)

343
Aromadendrene oxide-(2)
70.476
0.272 (S)
—
—
—
—

344
Diepicedrene-1-oxide
70.545
—
0.368 (S)
—
—
—

345
3,4-Dihydro-3,3,6,8-tetramethylnaphthalen-1(2H)-one
70.580
—
—
—
0.115 (B)
—

346
1-Methyl-2,4-bis(1-methylethenyl)-cyclohexane
71.031
—
—
—
—
0.248 (S)

347
[1aR-(1aα, 4aα, 7β, 7aβ, 7bα)]-Decahydro-1,1,7-trimethyl-4-methylene-1H-cycloprop[e]azulen-7-ol
71.140
—
—
—
—
0.512 (S)

348
3-Hydroxy-2-methyl-4-[4-t-butyl]-butanal
72.481
0.242
—
—
—
—

349
1-(1-Hydroxy-3-methoxy-2-naphthyl)ethanone
72.498
—
—
—
—
1.586 (B)

350
2-(Butenyl)-5-(1,1-dimethylethyl)-1,3-dimethyl-benzene
72.544
—
0.346 (B)
—
—
—

351
(1R, 2R, 6S, 7S, 8S) -1-Methyl-8-(1-methylethyl)-tricyclo[4.4.0.02,7]dec-3-ene-3-methanol
72.885
—
—
0.359 (S)
—
—

352
4-Hydroxy-4a,5-dimethyl-3-methylene-3a,4,4a,5,6,7,9,9a-octahydro-3H-naphtho[2,3-b]furan-2-one
72.896
0.194 (B)
—
—
—
—

353
1,2,3,4-Tetrahydro-6-nitronaphthalene
72.931
—
—
—
—
0.888 (B)

354
1-(3,3-Dimethyl-1-yl)-2,2-dimethylcyclopropane-3-carboxylic acid
72.960
—
0.324
—
—
—

355
N-(p-Methoxy-trans-styryl)-formamide
73.272
—
—
—
—
0.546 (B)

356
8,9-Dehydro-9-formyl-cycloisolongifolene
73.705
0.548 (S)
—
0.691 (S)
—
—

357
2-tert-Butyl-quinoxaline 4-oxide
73.745
—
—
—
—
1.237 (B)

358
β-Vatirenene
73.763
—
0.803 (S)
—
—
—

359
Octadecanal
73.919
—
—
—
0.144
—

360
[1S-(1α, 3aβ, 4α, 7aβ)]-Octahydro-1,7a-dimethyl-4-(1-methylethenyl)-1,4-methano-1H-indene
74.872
—
—
—
—
0.368 (S)

361
1-(1-Hydroxyethyl)-1-(diethylphosphonyl)-2-methylene-cyclopropane
74.878
—
0.109
—
—
—

362
1-Nonadecene
75.265
—
—
—
0.149
—

363
(E,E)-3,7-Dimethyl-10-(1-methylethylidene)-3,7-cyclodecadien-1-one
75.692
—
—
—
—
0.232 (S)

364
Alloaromadendrene
76.195
—
—
—
—
0.488 (S)

365
Heneicosane
76.235
—
0.148
0.177
0.127
—

366
2,3-Dihydro-7-hydroxy-2,2-dimethyl-4H-1-benzopyran-4-one
76.859
—
—
—
—
0.277 (B)

367
2-Butyl-5-hexyloctahydro-1H-indene
77.344
—
—
—
—
0.253

368
2,2' : 5′,2″-Terthiophene
77.777
—
—
—
—
0.228

369
1-Methyl-4-(2-methyloxiranyl)-7-oxabicyclo[4.1.0]heptane
78.355
—
—
—
—
0.248 (B)

370
4,4-Dimethyl-1-phenyl-1-penten-3-one
78.563
—
—
—
—
0.199 (B)

371
1,5-Diphenyl-1-penten-3-one
78.603
0.16 (B)
0.354 (B)
0.139 (B)
—
—

372
(1-Methylbutyl)-benzene
79.424
—
—
—
—
0.266 (B)

373
Stearic acid
79.504
—
—
—
0.198
—

374
[1S-(1α, 2α, 3aβ, 4α, 8aβ, 9R∗)]-Decahydro-1,5,5,8a-tetramethyl-1,2,4-methenoazulene
79.666
—
—
—
—
0.186 (S)

375
Z-8-Methyl-9-tetradecenoic acid
79.799
—
0.105
—
—
—

376
1,2,3,4-Tetrahydro-1,5,7-trimethylnaphthalene
79.903
—
—
—
—
0.426 (B)

377
N-Phenyl-2-naphthylamine
80.746
0.121 (B)
—
0.186 (B)
—
—

378
Z-5-Nonadecene
81.024
0.196
—
0.181
0.230
—

379
Cyclopentadecane
81.047
—
0.188
—
—
—

380
Diaveridine
81.105
—
—
—
—
0.108 (B)

381
(Z)-3-Tridecen-1-yne
81.428
—
—
—
—
0.322

382
Ambrosin
82.277
—
—
—
—
0.102 (S)

383
2-Decanone O-methyl oxime
82.329
0.104
0.115
0.092
—
—

384
N,N-Dimethyldecanamide
82.352
—
—
—
0.140
—

385
[1aR-(1aα, 4aβ, 8aS∗)]-1,1a,5,6,7,8-Hexahydro-4a,8,8-trimethyl-cyclopropa[d]naphthalen-2(4aH)-one
82.710
—
—
—
—
0.124 (S)

386
Murolan-3,9(11)-diene-10-peroxy
83.248
—
—
—
—
0.267 (S)

387
Chromone derivative
85.396
0.109 (C)
—
0.08 (C)
—
—

388
Chromone derivative
85.818
0.132 (C)
0.217 (C)
0.151 (C)
—
—

389
Chromone derivative
86.783
2.245 (C)
1.812 (C)
1.697 (C)
3.633 (C)
—

390
Chromone derivative
87.187
0.104
—
—
0.112
—

391
Chromone derivative
87.539
—
—
—
—
0.331 (C)

392
Chromone derivative
88.724
0.159
—
—
—
—

393
Chromone derivative
88.880
0.118
—
0.123
—
—

394
Chromone derivative
88.891
—
—
—
—
—

395
Chromone derivative
88.897
—
0.152 (C)
—
0.175
—

396
Chromone derivative
89.209
0.14 (C)
0.662 (C)
0.345 (C)
—
0.334 (C)

397
Chromone derivative
89.515
—
—
0.064 (C)
0.14 (C)
—

398
Chromone derivative
89.769
—
—
0.221 (C)
—
—

399
Chromone derivative
89.787
—
0.125 (B)
—
—
—

400
Chromone derivative
89.844
0.286
—
—
—
—

401
Chromone derivative
89.867
—
0.108 (B)
—
—
—

402
Chromone derivative
90.595
—
—
3.447 (C)
—
—

403
Chromone derivative
90.601
1.127 (C)
—
—
—
—

404
Chromone derivative
90.630
—
—
—
0.179 (C)
—

405
Chromone derivative
90.641
—
3.239 (C)
—
—
—

406
Chromone derivative
90.676
—
—
—
—
7.398 (C)

407
Chromone derivative
91.000
—
—
0.197 (C)
—
—

408
Chromone derivative
91.000
0.121 (C)
—
—
—
—

409
Chromone derivative
91.017
—
0.148 (C)
—
—
—

410
Chromone derivative
91.485
—
—
3.502 (C)
—
—

411
Chromone derivative
91.485
1.32 (C)
—
—
—
—

412
Chromone derivative
91.571
—
—
—
—
0.542 (C)

413
Chromone derivative
91.571
—
4.593 (C)
—
—
—

414
Chromone derivative
91.629
—
—
—
0.105 (C)
—

415
Chromone derivative
91.710
—
—
0.649 (C)
—
—

416
Chromone derivative
91.716
0.132 (C)
—
—
—
—

417
Chromone derivative
91.727
—
—
—
—
1.405 (C)

418
Chromone derivative
91.745
—
0.561 (C)
—
—
—

419
Chromone derivative
91.803
—
—
0.592 (C)
—
—

420
Chromone derivative
91.808
0.481 (C)
—
—
—
—

421
Chromone derivative
91.837
—
—
—
0.411
—

423
Chromone derivative
91.837
—
0.539 (C)
—
—
—

422
Chromone derivative
91.953
—
—
0.88 (C)
—
—

424
Chromone derivative
91.953
0.434 (C)
—
—
—
—

425
Chromone derivative
91.987
—
0.796 (C)
—
—
—

426
Chromone derivative
92.571
—
—
—
—
0.143 (C)

427
Chromone derivative
92.894
—
0.254 (B)
—
—
—

428
Chromone derivative
92.935
—
—
—
—
1.293 (C)

429
Chromone derivative
92.958
—
—
0.221 (C)
—
—

430
Chromone derivative
92.969
—
0.485 (B)
—
—
—

431
Chromone derivative
93.339
—
—
—
—
0.388 (C)

432
Chromone derivative
93.784
—
—
—
—
0.6 (C)

433
Chromone derivative
94.136
—
—
—
—
0.14 (C)

434
Chromone derivative
94.356
—
—
0.731
—
—

435
Chromone derivative
94.361
—
—
—
—
0.125 (C)

436
Chromone derivative
94.361
0.596 (C)
—
—
—
—

437
Chromone derivative
94.390
—
0.832 (C)
—
—
—

438
Chromone derivative
94.795
—
—
0.323 (C)
—
—

439
Chromone derivative
94.800
0.187 (C)
—
—
—
—

440
Chromone derivative
94.812
—
0.371 (C)
—
—
—

441
Chromone derivative
95.228
—
—
—
—
1.254 (C)

442
Chromone derivative
95.228
—
—
0.596 (C)
—
—

443
Chromone derivative
95.257
—
0.614 (C)
—
—
—

444
Chromone derivative
95.268
0.165 (C)
—
—
—
—

445
Chromone derivative
95.609
—
—
—
—
0.217 (C)

446
Chromone derivative
95.748
0.243 (C)
—
—
—
—

447
Chromone derivative
95.754
—
—
0.237 (C)
—
—

448
Chromone derivative
95.765
—
—
—
0.478 (B)
—

449
Chromone derivative
95.771
—
0.206 (C)
—
—
—

450
Chromone derivative
95.834
—
—
—
—
0.414 (C)

451
Chromone derivative
95.904
0.291 (C)
—
—
—
—

452
Chromone derivative
95.921
—
—
—
0.678 (B)
—

453
Chromone derivative
95.967
0.713 (C)
—
—
—
—

454
Chromone derivative
95.973
—
—
3.243 (C)
—
—

455
Chromone derivative
96.019
—
2.703 (C)
—
—
—

456
Chromone derivative
96.088
—
—
—
—
7.2 (C)

457
Chromone derivative
96.308
—
—
0.178 (C)
—
—

458
Chromone derivative
96.308
0.192 (C)
—
—
—
—

459
Chromone derivative
96.319
—
—
—
0.177 (B)
—

460
Chromone derivative
96.343
—
0.281 (C)
—
—
—

461
Chromone derivative
96.372
—
—
—
—
0.498 (C)

462
Chromone derivative
96.395
—
—
0.267 (C)
—
—

463
Chromone derivative
96.400
0.313 (C)
—
—
—
—

464
Chromone derivative
96.412
—
—
—
0.381
—

465
Chromone derivative
96.418
—
0.43 (B)
—
—
—

466
Chromone derivative
96.556
—
0.138 (B)
—
—
—

467
Chromone derivative
96.632
—
—
0.058 (C)
—
—

468
Chromone derivative
96.637
0.312 (C)
—
—
—
—

469
Chromone derivative
96.649
—
—
—
0.236 (B)
—

470
Chromone derivative
96.655
—
0.16 (B)
—
—
—

471
Chromone derivative
96.718
—
—
—
—
0.332 (C)

472
Chromone derivative
96.753
—
0.206
—
—
—

473
Chromone derivative
97.088
—
—
—
—
0.464 (C)

474
Chromone derivative
97.319
—
—
—
—
0.176 (C)

475
Chromone derivative
97.469
—
—
—
—
0.171 (C)

476
Chromone derivative
97.700
—
—
—
—
0.469 (C)

477
Chromone derivative
98.341
—
—
—
—
0.863 (C)

478
Chromone derivative
98.399
—
0.103
—
—
—

479
Chromone derivative
98.982
—
—
—
—
0.104 (C)

480
Chromone derivative
99.242
—
—
—
—
0.374 (C)

481
Chromone derivative
99.566
—
—
—
—
0.264 (C)

482
Chromone derivative
99.751
—
—
—
—
0.192 (C)

483
Chromone derivative
100.034
—
—
—
—
0.281 (C)

484
Chromone derivative
100.346
—
—
—
—
0.577 (C)

Total
97.620
97.164
99.859
97.040
96.079

B: aromatic compound; C: chromone derivative; S: sesquiterpenes; —: not detected.

2.4. LPS-Stimulated TNF-α and IL-1α Release in RAW264.7 Cells

2.4.1. Isolation and Culture of RAW264.7 Cells

RAW264.7 cells in logarithmic growth phase were washed twice with phosphate-buffered saline (PBS) and inoculated in 96-well plates at a density of 1 × 10⁴ cells per well, and 100 μL of cell suspension was added to each well. Three compound wells were set in each group and cultured at 37°C in 5% CO₂ for 24 h.

2.4.2. Measurement of TNF-α and IL-1α Production

The cells were incubated with 1 ng/mL LPS in the presence of indomethacin, AAW, BCDA, and AWIT (20, 40 and 80 μg/mL) and cultured at 37°C and 5% CO₂ for 24 h. Then, the levels of TNF-α and IL-1α in the cell-free culture supernatant were determined by ELISA kits. Briefly, 10 μL of supernatant was mixed with an equal volume of reagents A and B [1 : 1 (v/v)] in a 96-well flat-bottom plate. The absorbance at 540 nm was measured after 10 min using an ELISA reader. The amounts of TNF-α and IL-1α were calculated from a standard curve created using known concentrations of standards.

3. Results and Discussion

3.1. GC-MS Analysis

n-Hexane, methanol, DMSO, and CH₂Cl₂ were used to collect the chemical constituents of incense smoke from agarwood. The GC-MS peaks of incense smoke samples collected using CH₂Cl₂ were the most intense among the peaks obtained using the above solvents. Therefore, CH₂Cl₂ was selected to dissolve the chemical constituents of smoke samples (agarwood and AS). Finally, 484 compounds in total (Table 1 and Figure 1) were identified from the incense smoke samples (AAW, BCDA, AWIT, and AS) and the samples obtained by CH₂Cl₂ extraction of sticks from AWIT. The numbers of compounds identified in incense smoke from AAW, BCDA, AWIT, AS, and EAWIT were 167, 158, 141, 127, and 131, respectively. Aromatics and chromone derivatives were the main chemical constituents in AAW, BCDA, and AWIT; among all chemical constituents, aromatics represented 69.617, 55.038, and 60.483%, and chromone derivatives represented 9.252, 17.725, and 16.946%, respectively.

The chemical constituents of incense smoke may be quantifiable. Therefore, the chemical constituents of incense smoke from agarwood produced by AWIT were compared with the corresponding constituents from agarwood produced by AAW and BCDA. A total of 61 compounds in the AWIT sample, representing 54.837%, were also found in the AAW and BCDA samples. The major compounds (relative content >1%) were phenylethylene (7.973%); ethylbenzene (6.384%); 2,3,5,6-tetrafluoroanisole (4.130%); 5-(2-thienyl)-4-pyrimidinamine (2.402%); 2-methoxy-4-(1-propen-1-yl)-phenol (2.379%); 2,6-dimethoxyphenol (2.178%); syn-3,3,5,6,8,8-hexamethyl-tricyclo[5.1.0.0(2,4)]oct-5-ene (1.762%); 1-(2,4,6-trimethylphenyl)-3-(2-propynyl)-thiourea (1.680%); phenylacetylene (1.612%); 1-hydroxy-6-methylphenazine (1.555%); 4-hydroxy-3-methoxystyrene(1.512%) 3,5-dimethoxy-4-hydroxyphenylacetic acid (1.391%); 2,2,4,6,6-pentamethylheptane (1.152%); 4-(4-methoxyphenyl)-2-butanone (1.124%); 4-phenyl-2-butanone (1.060%); and benzaldehyde (1.008%). Moreover, chromone derivatives and sesquiterpenes are the main components responsible for pharmacodynamic effects [23–25]. In this experiment, 21 compounds, representing 16.946%, were identified as chromone derivatives according to the peaks at m/z 91, 121, 137, 107, 160, 176, 190, 220, 250, 266, 280, 282, 296, 310, 312, 326, 328, and 342 [22], and 16 compounds were identified as sesquiterpenes, representing 6.768%. In short, aromatic compounds were the main chemical constituents of incense smoke from agarwood, including AWIT, AAW, and BCDA samples.

To identify whether agarwood (AAW, AWIT, and BCDA) contained chemical constituents of AS, incense smoke produced from AS was tested by the same method. No sesquiterpenes were detected among the chemical constituents of the smoke, and chromones only represented 4.569%, which was less than the contents in AWIT (16.946%), AAW (9.252%), and BCDA (17.725%). Finally, 29 compounds, representing 32.627%, were also found in AWIT, AAW, and BCDA. The main compounds (relative amount >1%) were phenylethylene (5.132%); 2-methoxy-4-(1-propen-1-yl)-phenol (3.254%); 3,5-dimethoxy-4-hydroxybenzaldehyde (2.920%); 4-hydroxy-3-methoxystyrene (2.254%); 3,5-dimethoxy-4-hydroxyphenylacetic acid (2.150%); vanillin (1.842%); acetosyringone (1.499%); guaiacol (1.362%); ethylbenzene (1.313%); benzaldehyde (1.146%); homovanillyl alcohol (1.119%); 2,6-dimethoxy-4-(2-propen-1-yl)-phenol (1.029%); and phenylacetylene (1.013%). These components may be from the residue of A. sinensis, a sticky powder, making agarwood powder bind, used in the preparation of sticks of AS (making sticks from pure AS alone is difficult, so the addition of a sticky powder is necessary) or agarwood in A. sinensis (AS can form agarwood in the process of storage).

The data for incense smoke from agarwood (AAW, AWIT, and BCDA) showed that low-molecular-weight aromatic compounds (LACs) represented more than 55% of the total constituents. Michiho Ito et al. reported that chromone derivatives could be converted and produce the pleasant smell of agarwood through the generation of LACs in the process of heating [26,27] (Scheme 1). Chromone derivatives are among the main chemical constituents of agarwood. They can generate unique and different LACs at high temperature (when burned). As a result, many LACs were detected in the agarwood smoke. To verify the results, an extraction experiment of sticks from AWIT was carried out at room temperature (to avoid high temperature). The results showed that chromone derivatives, sesquiterpenes, and aromatics were the main chemical constituents, representing 26.547, 26.767, and 26.941% of the total constituents, respectively. Few chemical constituents of EAWIT were observed before 40 min (tR), as shown in Figure 1, while there was far higher number of peaks after 58 min (tR), which is indicative of chromone derivatives and sesquiterpenes. Interestingly, the chemical constituents of incense smoke showed the opposite trend in Figure 1. The results indicated that high-molecular-weight compounds might be cracked into low-molecular-weight compounds at high temperature. In other words, some chromone derivatives and sesquiterpenes might be converted into low-molecular-weight compounds, which is consistent with the reported literature [26, 27]. Therefore, low-molecular-weight compounds accounted for a high percentage of the incense smoke obtained from agarwood during burning. Moreover, some studies suggested that the inhalation of some LACs had a sedative or hypnotic effect on mice and that benzylacetone in particular reduces mouse locomotor activity [28–30]. Hence, inhalation of the pleasant aroma generated by agarwood during heating could lead to pharmacological effects.

Scheme 1: LACs generated from agaroterol on heating.

3.2. Effect of Chemical Constituents on TNF-α and IL-1α Release in LPS-Stimulated RAW264.7 Cells

As shown in Tables 2 and 3, normal inactivated RAW264.7 cells produced low amounts of TNF-α and IL-1α after 24 h of incubation at 37°C, and exposure to LPS induced higher amounts of TNF-α and IL-1α. In contrast, under indomethacin treatment, AAW, BCDA, and AWIT produced a concentration-dependent decrease at concentrations of 20, 40, and 80 μg/mL. The TNF-α and IL-1α levels of model group were significantly higher than those of the normal group ( or ). The incense components of AAW, BCDA, AWIT, and indomethacin significantly reduced TNF-α and IL-1α levels (, , or ), showing better anti-inflammatory effects. These results showed that the anti-inflammatory activities of AAW, AWIT, and indomethacin were comparable and superior to that of BCDA.

Table 2: LPS-induced release of TNF-α in RAW264.7 cells.

Drug/dose

80 μg/mL
40 μg/mL
20 μg/mL

Normal
189.09 ± 15.25

Model
236.09 ± 18.79

Indomethacin

152.39 ± 16.67###
169.14 ± 18.23###
200.19 ± 19.42#

AAW

157.69 ± 15.98###
181.79 ± 19.45##
209.19 ± 21.03#

BCDA

165.09 ± 16.12###
194.84 ± 17.67##
213.04 ± 22.43#

AWIT

154.89 ± 17.13###
187.84 ± 18.37##
212.84 ± 19.35#

Note. This result is the average of three parallel experiments. vs normal; , , vs model.

Table 3: LPS-induced release of IL-1α in RAW264.7 cells.

Durg/dose

80 μg/mL
40 μg/mL
20 μg/mL

Normal
15.00 ± 1.78

Model
20.43 ± 2.32

Indomethacin

10.38 ± 2.12##
12.52 ± 2.65##
17.87 ± 1.85#

AAW

10.78 ± 2.56##
15.72 ± 2.57#
19.10 ± 2.58

BCDA

15.05 ± 1.74#
18.99 ± 2.97
22.19 ± 2.94

AWIT

10.88 ± 1.97##
12.15 ± 2.72##
22.52 ± 2.93

Note. This result is the average of three parallel experiments. vs normal; , vs model.

4. Conclusions

The chemical constituents of incense smoke from AAW, BCDA, AWIT, AS, and EAWIT were analyzed by GC-MS, and 484 compounds were identified. Aromatic compounds were the main chemical constituents of incense smoke from AAW, BCDA, and AWIT. A total of 61 aromatic compounds from AWIT, representing 54.837%, were also found in AAW and BCDA. All experimental data suggested that aromatic compounds were the main chemical constituents in agarwood smoke and that some chromone derivatives could be cracked into LACs at high temperature. Furthermore, agarwood incense smoke showed anti-inflammatory activities by inhibiting lipopolysaccharide- (LPS-) induced TNF-α and IL-1α release in RAW264.7 cells.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no conflicts of interest in any form.

Authors’ Contributions

De-Qian Peng, Zhang-Xin Yu contributed equally to this work.

Acknowledgments

This research work was financially supported by the Natural Science  Foundation of Hainan Province (no. 217291), the Science and Technology  Programs from Hainan Province of China  (no. ZDKJ2016004), and the  Major  Science  and Technology  Innovation  Project  of  the  Chinese  Academy of  Medical  Sciences  (no. 2016-I2M-2-003). The authors are grateful to Hai-Yan Wang (an English teacher) of Qiqihar University and Ass. Prof. Lu-Jia Mao of Hainan Medical University for revising the manuscript.

References

S. Wang, Z. Yu, C. Wang, C. Wu, P. Guo, and J. Wei, “Chemical constituents and pharmacological activity of agarwood and Aquilaria plants,” Molecules, vol. 23, no. 2, p. 342, 2018.

T. Miyoshi, M. Ito, T. Kitayama, S. Isomori, and F. Yamashita, “Sedative effects of inhaled benzylacetone and structural features contributing to its activity,” Biological and Pharmaceutical Bulletin, vol. 36, no. 9, pp. 1474–1481, 2013.

H. Tian, H. Wang, L. Yang et al., “Two new sesquiterpenoids from agarwood originated from Aquilaria sp.,” Journal of Asian Natural Products Research, vol. 22, no. 7, pp. 626–631, 2019.

Y. Z. H.-Y. Hashim, P. G. Kerr, P. Abbas, and H. Mohd Salleh, “Aquilaria spp. (agarwood) as source of health beneficial compounds: a review of traditional use, phytochemistry and pharmacology,” Journal of Ethnopharmacology, vol. 189, pp. 331–360, 2016.

Y.-Y. Liu, J.-H. Wei, Z. H. Gao, Z. Zhang, and J.-C. Lyu, “A review of quality assessment and grading for agarwood,” Chinese Herbal Medicines, vol. 9, no. 1, pp. 22–30, 2017.

S. L. Wang, Y. C. Tsai, S. L. Fu, M. J. Cheng, M. I. Chung, and J. J. Chen, “2-(2-Phenylethyl)-4H-chromen-4-one derivatives from the resinous wood of Aquilaria sinensis with anti-inflammatory effects in LPS-induced macrophages,” Molecules, vol. 23, no. 2, p. 2969, 2018.

H. Chhipa, K. Chowdhary, and N. Kaushik, “Artificial production of agarwood oil in Aquilaria sp. by fungi: a review,” Phytochemistry Reviews, vol. 16, no. 5, pp. 835–860, 2017.

Z. Gao, W. Zhao, P. Sun, and J. Wei, “Species and conservation status of the endangered agarwood-producing genus Aquilaria,” Modern Chinese Medicine, vol. 19, p. 1057, 2017.

X. Chen, Y. Liu, Y. Yang et al., “Trunk surface agarwood-inducing technique with Rigidoporus vinctus: An efficient novel method for agarwood production,” PLoS One, vol. 13, no. 6, 2018.

X. Gao, M. Xie, S. Liu et al., “Chromatographic fingerprint analysis of metabolites in natural and artificial agarwood using gas chromatography-mass spectrometry combined with chemometric methods,” Journal of Chromatography B, vol. 967, pp. 264–273, 2014.

Y. Liu, H. Chen, Y. Yang et al., “Whole-tree agarwood-inducing technique: an efficient novel technique for producing high-quality agarwood in cultivated Aquilaria sinensis trees,” Molecules, vol. 18, no. 3, pp. 3086–3106, 2013.

R. Blanchette, and V. B. H. Heuveling, US7638145B2, (2009).

C. S. Peng, M. F. Osman, N. Bahari, R. Zakaria, and K. A. Rahim, “Agarwood inducement technology: a method for producing oil grade agarwood in cultivated Aquilaria malaccensis Lamk,” Journal of Agrobiotechnology, vol. 6, p. 1, 2015.

H. Chen, J. Wei, J. Yang et al., “Chemical constituents of agarwood originating from the endemic genus Aquilaria plants,” Chemistry & Biodiversity, vol. 9, no. 2, pp. 236–250, 2012.

J. Sperry, Z. E. Wilson, D. C. K. Rathwell, and M. A. Brimble, “Isolation, biological activity and synthesis of benzannulated spiroketal natural products,” Natural Product Reports, vol. 27, no. 8, p. 1117, 2010.

R. Kalra and N. Kaushik, “A review of chemistry, quality and analysis of infected agarwood tree (Aquilaria sp.),” Phytochemistry Reviews, vol. 16, no. 5, pp. 1045–1079, 2017.

M. Ishihara, T. Tsuneya, and K. Uneyama, “Components of the agarwood smoke on heating,” Journal of Essential Oil Research, vol. 5, no. 4, pp. 419–423, 1993.

I. Nurlaila, H. F. R. Mohd, N. T. Mohd, I. Mastura, Z. Seema, and N. T. Saiful, IEEE International Colloquium on Signal Processing & Its Applications, p. 203, 2015.

R. Zhou, B. Yang, and Y. H. Wang, “Higher cytotoxicity and genotoxicity of cultivated versus natural agarwood incense smoke,” Environmental Chemistry Letters, vol. 14, no. 4, pp. 501–506, 2016.

R. Zhou, Q. An, X. W. Pan, B. Yang, J. Hu, and Y. H. Wang, “Higher cytotoxicity and genotoxicity of burning incense than cigarette,” Environmental Chemistry Letters, vol. 13, no. 4, pp. 465–471, 2015.

W. Y. Kao, C. Y. Hsiang, S. C. Ho, T. Y. Ho, and K. T. Lee, “Chemical profiles of incense smoke ingredients from agarwood by headspace gas chromatography-tandem mass spectrometry,” Molecules, vol. 23, no. 11, p. 2969, 2018.

W. Mei, D. Yang, H. Wang et al., “Characterization and determination of 2-(2-phenylethyl)chromones in agarwood by GC-MS,” Molecules, vol. 18, no. 10, pp. 12324–12345, 2013.

H. Huo, Z. Zhu, Y. Song et al., “Anti-inflammatory dimeric 2-(2-phenylethyl)chromones from the resinous wood of Aquilaria sinensis,” Journal of Natural Products, vol. 81, no. 3, pp. 543–553, 2018.

M. Gao, X. Han, Y. Sun et al., “Overview of sesquiterpenes and chromones of agarwood originating from four main species of the genus Aquilaria,” RSC Advances, vol. 9, no. 8, pp. 4113–4130, 2019.

D. Chen, Z. Xu, X. Chai et al., “Nine 2-(2-Phenylethyl)chromone derivatives from the resinous wood of Aquilaria sinensis and their inhibition of LPS-induced NO production in RAW 264.7 Cells,” European Journal of Organic Chemistry, vol. 2012, no. 27, pp. 5389–5397, 2012.

S. Takamatsu and M. Ito, “Agarotetrol: a source compound for low molecular weight aromatic compounds from agarwood heating,” Journal of Natural Medicines, vol. 72, no. 2, pp. 537–541, 2018.

K. Hashimoto, S. Nakahara, T. Inoue, Y. Sumida, M. Takahashi, and Y. Masada, “A new chromone from agarwood and pyrolysis products of chromone derivatives,” Chemical & Pharmaceutical Bulletin, vol. 33, no. 11, pp. 5088–5091, 1985.

K. Ito and M. Ito, “Sedative effects of vapor inhalation of the essential oil of Microtoena patchoulii and its related compounds,” Journal of Natural Medicines, vol. 65, no. 2, pp. 336–343, 2011.

H. Takemoto, M. Ito, T. Shiraki, T. Yagura, and G. Honda, “Sedative effects of vapor inhalation of agarwood oil and spikenard extract and identification of their active components,” Journal of Natural Medicines, vol. 62, no. 1, pp. 41–46, 2008.

S. Wang, C. Wang, D. Peng et al., “Agarwood essential oil displays sedative-hypnotic effects through the GABAergic system,” Molecules, vol. 22, no. 12, p. 2190, 2017.