Chemical Composition, Market Survey, and Safety Assessment of Blue Lotus (Nymphaea caerulea Savigny) Extracts

Abstract

Blue lotus, also known as Nymphaea caerulea (Nymphaeaceae), is a water lily found globally in lakes and rivers. With its long history of use in Egyptian culture, blue lotus has been associated with spiritual rituals and health benefits. Nowadays, blue lotus is still consumed as a tea or tincture to induce relaxation and heightened spiritual awareness. In this study, six authentic N. caerulea extracts from trusted sources and eleven commercial products were analyzed using gas chromatography−mass spectrometry (GC-MS). Authentic blue lotus extracts were produced in industrial settings. Overall, the extracts were a mixture of aliphatic hydrocarbons, aromatic alcohols, fatty acids, phenyl derivatives, diterpenoids, phytosterols, and stigmastanes. Apomorphine and nuciferine, which are responsible for psychoactive effects of the blue lotus flower, were virtually absent from the authentic blue lotus extract. Although blue lotus has a long history of use, the safety data on the plant and its extracts is limited; however, together with the analytical data, the available information does not indicate major safety concerns for the topical application of authentic blue lotus flower concrete or absolute when diluted as a fragrance ingredient.

Full text

Citation: Dosoky, N.S.; Shah, S.A.;
Dawson, J.T.; Banjara, S.S.; Poudel, A.;
Bascoul, C.; Satyal, P. Chemical
Composition, Market Survey, and
Safety Assessment of Blue Lotus
(Nymphaea caerulea Savigny) Extracts.
Molecules 2023,28, 7014. https://
doi.org/10.3390/molecules28207014
Academic Editors: Lucia Panzella
and Zhi Na
Received: 7 August 2023
Revised: 6 September 2023
Accepted: 29 September 2023
Published: 10 October 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
molecules
Article
Chemical Composition, Market Survey, and Safety Assessment
of Blue Lotus (Nymphaea caerulea Savigny) Extracts
Noura S. Dosoky 1, Sara A. Shah 2, Joseph T. Dawson 2, Sushant Sharma Banjara 1, Ambika Poudel 1,
Cécile Bascoul 2and Prabodh Satyal 1, *
1Essential Oil Science, d¯
oTERRA International, Pleasant Grove, UT 84062, USA;
ndosoky@doterra.com (N.S.D.); ssharmabanja@doterra.com (S.S.B.); apoudel@doterra.com (A.P.)
2Product Safety, d ¯
oTERRA International, Pleasant Grove, UT 84062, USA; sshah@doterra.com (S.A.S.);
jdawson@doterra.com (J.T.D.); cbascoul@doterra.com (C.B.)
*Correspondence: psatyal@doterra.com; Tel.: +1-2566526062
Abstract:
Blue lotus, also known as Nymphaea caerulea (Nymphaeaceae), is a water lily found globally
in lakes and rivers. With its long history of use in Egyptian culture, blue lotus has been associ-
ated with spiritual rituals and health benefits. Nowadays, blue lotus is still consumed as a tea
or tincture to induce relaxation and heightened spiritual awareness. In this study, six authentic
N. caerulea
extracts from trusted sources and eleven commercial products were analyzed using gas
chromatography
−
mass spectrometry (GC-MS). Authentic blue lotus extracts were produced in in-
dustrial settings. Overall, the extracts were a mixture of aliphatic hydrocarbons, aromatic alcohols,
fatty acids, phenyl derivatives, diterpenoids, phytosterols, and stigmastanes. Apomorphine and
nuciferine, which are responsible for psychoactive effects of the blue lotus flower, were virtually
absent from the authentic blue lotus extract. Although blue lotus has a long history of use, the safety
data on the plant and its extracts is limited; however, together with the analytical data, the available
information does not indicate major safety concerns for the topical application of authentic blue lotus
flower concrete or absolute when diluted as a fragrance ingredient.
Keywords: blue lotus; water lily; Nymphaea caerulea; aquatic plants
1. Introduction
Blue lotus, water lily, and Egyptian lotus are common names of Nymphaea caerulea
Savigny (Nymphaeaceae). It is an aquatic perennial plant that grows globally along rivers
and lakes at altitudes ranging from sea level to 2700 m asl [
1
]. N. caerulea is a recognized
synonym of N. nouchali var. caerulea (Sav.) Verdc. [
2
]. The plant is characterized by its
floating round or oval flat leaves (up to 40 cm in diameter) that arise from a perennial
spongy rhizome submerged in the mud of pond habitats. The leaves stay afloat because
of their top surface, which is covered with a smooth, waxy cuticle and slightly rolled-up
margins [
1
]. The flowers of N. caerulea are its characteristic feature. Blooming in September
until February, the flowers are presented in a star-like pattern when fully open, measuring
about 15–20 cm in diameter. The flowers close in the afternoon after opening in mid-
morning and can be found in a range of colors, such as blue, white, and pink, with blue
being the most common.
Blue lotus has long-standing historical and cultural significance. Drawings and paint-
ings of the blue lotus flower were reported on Egyptian papyri and tombs from the 14th
century B.C., indicating its use in shamanistic rituals and health-related practices [
3
,
4
].
Nymphaea species were revered as the epitome of holiness and beauty in ancient Greece
and Rome. Based on its regional distribution, the plant is classified into tropical and
hardy water lilies [
5
]. Blue lotus is a popular ornamental plant used in landscaping and
is used in water purification. The flowers, stems, and roots are used for health-related
purposes [
6
,
7
]. In traditional medicine, N. caerulea is reputed to have calming and soothing
Molecules 2023,28, 7014. https://doi.org/10.3390/molecules28207014 https://www.mdpi.com/journal/molecules

Molecules 2023,28, 7014 2 of 13
effects. In Ayurvedic medicine, it is used for a variety of health-related issues [
8
]. The
family Nymphaeaceae has been studied extensively in the field of pharmacognosy due to
their ability to produce aminogenic secondary metabolites. These metabolites have been
found to have a range of pharmacological activities including analgesic, anti-inflammatory,
and antimicrobial properties. N. caerulea is a rich source of different secondary metabo-
lites such as anthocyanins, anthraquinones, fatty acids, flavonoids, leuecoanthocyanins,
phenols, coumarins, tannins, and triterpenoids [
9
–
12
]. The leaf and flower extracts are
excellent sources of phytoconstituents when compared with the rhizome and root [
11
].
The flavonoid composition has been reported to determine the flower color. Cultivars
with amaranth flowers contain delphinidin 3-galactoside, blue flowers contain delphinidin
3-O-galactoside, red flowers contain derivatives of delphinidin and cyanidin, while white
and yellow flowers lack anthocyanins [
13
]. Because of its high content of polyphenols,
blue lotus is recognized as a natural source of antioxidants that can delay food spoilage,
slow down the aging process, support healthy cell growth, and promote cardiovascular
health [
12
,
14
]. Kaempferol, quercetin, quercitin, chalcone, and gallic acid have been identi-
fied from the plant [
12
,
15
,
16
]. According to Agnihotri et al. [
7
], the ethyl acetate fraction
of N. caerulea flowers and nine isolated compounds can be used as a natural solution for
oxidative stress. The blue lotus flower has been chiefly utilized in relation to relaxation
and sleep in modern times. At high doses, some users might experience hallucinations and
euphoria [
4
]. In a case series, five active-duty patients presented to the emergency depart-
ment with altered mental status following the use of blue lotus products, four after vaping
and one after making an infused beverage [
4
]. Although the case series did not include
confirmatory analytical data, the effects were attributed to two compounds, apomorphine
and nuciferine, which were previously found to be present in these types of products [
17
].
Interestingly, these two compounds have been studied and used as therapeutic agents
using oral doses in the range of 15–150 mg/day [
18
,
19
]. Little is known about industrially
produced blue lotus extracts. Currently, various blue lotus products are accessible online
including dried leaves, teas, plant resins, flower extracts, oils, concentrated alkaloids, and
electronic cigarette liquids [
17
]. These products are labeled as natural, but mostly have
not been approved by the Federal Drug Administration (FDA) for human consumption.
Therefore, we aimed to investigate the chemical composition of industrially produced floral
extracts of N. caerulea and compare the composition to the commercial products available
in the U.S. market. Moreover, we assessed the safety of N. caerulea extracts.
2. Results and Discussion
2.1. Authentic Blue Lotus Extracts
Authentic blue lotus extracts were produced in industrial settings. The average yields
were 0.18% and 0.09% for the concrete and absolute, respectively. The aroma of N. caerulea
extracts can be described as floral, fruity, sweet, fig-like, leathery, and slightly herbaceous.
The volatile fraction ranged from 38.7–65.1% of the total extract. Table 1summarizes
the chemical compositions of authentic N. caerulea extracts. Overall, the extracts were
a mixture of aliphatic hydrocarbons, aromatic alcohols, fatty acids, phenyl derivatives,
diterpenoids, phytosterols, and stigmastanes. The chemical makeup of the flower is
quite complex. Fossen and coworkers identified seven flavonoids and five anthocyanins,
including three acylated anthocyanins from the methanolic extract of the flower [
20
,
21
].
Agnihotri and colleagues isolated and identified several compounds from the flower
ethanolic extract with a considerable antioxidant activity [
7
]. In a study using headspace
solid-phase microextraction (HS-SPME) followed by GC-MS analysis, the vapor phase of
a trapped N. caerulea live flower contained benzyl acetate (10.4%), pentadecane (15.5%),
6,9-heptadecadiene (40.1%), and 8-heptadecene (15.3%) as the main components [
22
]. When
the stamens, pistils, and petals were compared, it was reported that the majority of volatiles
were produced by the stamens, with alkanes, alkenes, aldehydes, and ketones being the
most abundant [23].

Molecules 2023,28, 7014 3 of 13
Table 1. Chemical composition of authentic blue lotus extracts.
RIexp aRT Compound Name Concrete (Area %) Absolute (Area %)
1 2 3 Avg SD 1 2 3 Avg SD
1038
13.253
Benzyl alcohol 7.94 8.20 6.61 7.58 0.85
12.09
9.74 9.53
10.46
1.42
1166
19.126
Benzyl acetate 0.21 0.10 0.17 0.16 0.05 0.28 0.20 0.13 0.20 0.07
1284
24.686
p-Anisyl alcohol 0.59 0.41 0.15 0.38 0.23 1.15 0.79 0.80 0.91 0.20
1435
31.304
(E)-α-Bergamotene 0.28 0.28 0.36 0.30 0.05 0.27 0.37 0.38 0.34 0.06
1454
32.119
(E)-β-Farnesene 1.43 1.27 1.48 1.39 0.11 1.44 1.59 1.87 1.63 0.22
1500
34.135
Pentadecane 4.24 4.16 5.53 4.64 0.77 3.41 4.40 5.01 4.27 0.81
1504
34.275
(E,E)-α-Farnesene 0.73 0.63 0.78 0.71 0.08 0.73 0.86 1.04 0.88 0.16
1525
35.084
β-Sesquiphellandrene 0.64 0.63 0.83 0.70 0.11 0.59 0.80 0.82 0.74 0.13
1670
40.752
6,9-Heptadecadiene
11.10 10.89 13.85 11.95
1.65 9.80
11.96 12.75 11.50
1.53
1674
40.901
(Z,Z,Z)-1,8,11,14-Heptadecatetraene 0.48 0.46 0.61 0.52 0.08 0.45 0.55 0.62 0.54 0.08
1678
41.058
Tetradecanol 5.51 5.46 7.01 5.99 0.88 4.56 5.37 6.04 5.32 0.74
1697
41.823
2-Pentadecanone 0.21 0.15 0.21 0.19 0.03 0.31 0.31 0.31 0.31 0.00
1700
41.932
Heptadecane 0.50 0.87 1.15 0.84 0.33 0.71 0.78 0.84 0.78 0.07
1837
46.789
Neophytadiene 0.52 0.42 0.48 0.47 0.05 0.23 0.25 0.26 0.25 0.01
1900
48.999
Nonadecane 4.78 4.45 4.72 4.65 0.18 4.51 3.10 2.90 3.50 0.88
1908
49.234
(E,E)-7,11,15-Trimethyl-3-methylene-
hexadeca-1,6,10,14-tetraene 0.34 0.26 0.28 0.29 0.04 0.38 0.32 0.33 0.34 0.03
1959
50.907
Palmitic acid 2.22 1.81 1.91 1.98 0.22 3.11 2.57 2.28 2.65 0.42
1993
52.041
Ethyl Palmitate 0.44 0.69 0.52 0.55 0.13 1.31 1.16 1.33 1.27 0.09
2008
52.512
Hexadecyl acetate 0.87 0.94 1.27 1.03 0.21 0.83 1.39 1.03 1.08 0.28
2101
55.438
Heneicosane 4.52 4.47 5.55 4.85 0.61 1.88 2.20 2.57 2.22 0.35
2104
55.544
2-Nonadecanone 1.50 1.63 1.78 1.64 0.14 0.17 0.10 0.20 0.16 0.05
2108
55.649
Phytol 1.92 1.46 1.23 1.53 0.35 2.74 2.09 2.21 2.35 0.35
2129
56.277
Linoleic acid 3.26 2.61 2.57 2.81 0.38 4.77 3.50 3.52 3.93 0.73
2135
56.454
Oleic Acid 4.29 4.26 4.10 4.22 0.10 6.12 4.42 4.38 4.97 1.00
2159
57.189
Ethyl Stearate 1.16 1.42 1.01 1.20 0.21 2.75 1.09 1.45 1.76 0.87
2165
57.363
Ethyl linoleate 0.85 1.15 0.85 0.95 0.17 2.34 2.14 1.51 2.00 0.43
2180
57.832
Tetrapenol 3.12 3.12 2.69 2.98 0.25 4.42 3.30 3.32 3.68 0.64
2287
60.929
(E,E,E)-2,6,10,14-Hexadecatetraen-1-ol
3,7,11,15-tetramethyl acetate 0.49 0.47 0.41 0.46 0.04 0.56 0.48 0.54 0.53 0.04
2301 61.34 n-Tricosane 7.84 8.06 8.19 8.03 0.18 1.39 2.27 2.62 2.09 0.63
2400
64.105
n-Tetracosane 0.23 0.24 0.22 0.23 0.01
2501 66.78 n-Pentacosane 3.04 3.19 2.91 3.05 0.14 0.23 0.56 0.58 0.46 0.19
2577
68.726
Benzyl hexadecanoate 0.81 0.73 0.81 0.78 0.04 1.06 1.49 1.59 1.38 0.28
2600
69.344
n-Hexacosane 0.12 0.14 0.19 0.15 0.04
2683
71.394
n- Heptacosane 1.54 1.69 1.51 1.58 0.10 0.51 0.71 0.48 0.57 0.12
2749
73.056
Benzyl linoleate 1.36 1.23 1.22 1.27 0.08 1.73 2.27 2.00 0.38
2757
73.256
Benzyl linolenate 0.83 0.71 0.82 0.79 0.06 1.17 1.58 1.73 1.49 0.29
2779
73.833
Benzyl stearate 0.20 0.13 0.18 0.17 0.04 0.22 0.24 0.28 0.25 0.03
2790
74.114
Octacosane 0.12 0.09 0.14 0.12 0.03
2803
74.447
(E)-Squalene 3.67 4.09 3.78 3.85 0.22 2.30 2.23 2.16 2.23 0.07
2880
76.512
3-((8Z,11Z)-Heptadeca-8,11-dien-1-
yl)-5-methoxyphenol 2.53 2.97 1.09 2.20 0.98 2.79 2.48 2.60 2.62 0.16
3023
80.457
β-Sitosterol acetate 0.25 0.35 0.14 0.25 0.10 0.20 0.13 0.17 0.05
3055
81.361
Vitamin E 0.22 0.21 0.21 0.21 0.00 0.26 1.02 1.12 0.80 0.47
3123
83.327
Methyl cholesterol
1.047
1.11 0.99 1.05 0.06 1.18 1.29 1.28 1.25 0.06
3142
83.885
Stigmasterol 0.97 1.12 1.11 1.07 0.08 1.20 1.28 1.28 1.25 0.05
3184
85.156
γ-Sitosterol 2.83 2.13 2.14 2.37 0.40 3.34 3.90 3.87 3.70 0.32
Total identified %
91.73 90.85 93.76 89.47 87.28 87.52
RI
exp
= experimental retention index, RT = retention time,
a
retention index determined with respect to a
homologous series of n-alkanes on a ZB-5ms column.
2.2. Alkaloids
Alkaloids are mainly found in lotus leaves [
24
,
25
]. Nuciferine is insoluble in water and
soluble in acidic aqueous solutions and organic solvents such as chloroform, ethanol, and
methanol [
24
]. While acid-ethanol extraction was traditionally used to extract nuciferine,

Molecules 2023,28, 7014 4 of 13
ultrasound-assisted acid-ethanol extraction seemed to improve the results [
24
]. In the
current study, blue lotus concretes and absolutes were free of apomorphine and contained
negligible traces of nuciferine (10–72 ppb). This finding indicates that the extraction
conditions to produce concrete and absolute using hexane followed by ethanol were not
optimal for their extraction.
2.3. Commercial Products
Eleven commercially available blue lotus products were purchased online. Inter-
estingly, the aroma varied greatly between the commercial products and none of these
products resembled the original aroma. More than 150 compounds were identified from
the obtained products (Table 2). All of the tested samples contained synthetic fragrance
components. Unlike the authentic samples, terpenes were among the identified compounds.
C1, C2, and C7 showed signs of a Citrus oil, Lavandula oil, and Geranium oil addition, re-
spectively. It was hard to recognize which oil was added to C8-C11. Furthermore, there is
evidence that herculyn D was used as a fragrance fixative in C4, C8, and C9, as indicated
by the presence of abietic acid derivatives.
Table 2. Chemical composition of commercial (C) samples.
RI Compounds C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11
778 Isobutyl acetate 0.12
931 α-Pinene 0.06 0.09 0.04 0.04 tr 0.07 0.07
948 Camphene 0.01 0.03 0.01
962 Benzaldehyde 0.02 0.17 0.01
967 Glycerin
58.33
971 Sabinene 0.06 0.01 0.02 0.03
978 β-Pinene 0.37 0.18 0.14 0.03 0.36 0.38
983 3-Octanone 0.05
988 Myrcene 0.05 0.05 0.04 0.05
991 2,6-Dimethyl-2-heptanol 0.05 0.01 0.01 0.04 0.05
997 Diethyl diglycol 0.24 0.84 0.78 0.42 0.33
1010 Hexyl acetate 0.04
1013 1,4-Cineole 0.06 0.04 0.04
1019 p-Methyl anisole 0.15
1023 p-Cymene 0.09 6.92 3.00 2.17
1024 Dipropylene glycol 1 0.69 2.61
1026 Dipropylene glycol 2 6.03 0.90 6.04
1027 Limonene 3.08 0.80 3.48 0.03 0.29 0.04 0.06 3.75 4.21
1031 1,8-Cineole 0.05 0.21 0.07 0.28 0.28 0.09
1033 (Z)-β-Ocimene 0.17 0.37
1034 Benzyl alcohol 0.01
1043 Dipropylene glycol 3 0.64 1.91 4.66
1044 (E)-β-Ocimene 0.01
1045 (E)-βOcimene 0.01
1046 Dipropylene glycol 4 4.67 6.04 1.11
1049 Dipropylene glycol 5 1.06 0.73
1056 Dipropylene glycol 6 4.66
1057 γ-Terpinene 0.22 0.11 0.23 0.38 0.55
1069 (Z)-Linalool oxide (furanoid) 0.29 0.01
1069 Dihydro myrcenol 3.22 3.40 3.62 3.42
1080 Dipropylene glycol 7 0.66
1085 Terpinolene 0.05 0.02 0.02 0.10
1086 (E)-Linalool oxide (furanoid) 0.27 0.01
1090 3-(Z)-Hexenyl methyl carbonate 0.04 0.03 0.04
1094 Methyl benzoate 0.31
1098 Linalool 6.85
12.38 12.33
4.73 2.22 2.64 2.64
12.75 11.69
1114 Phenyl ethyl alcohol 0.31 1.87 7.01 7.74 4.11 3.79
1118 3-Octanol acetate 0.37

Molecules 2023,28, 7014 5 of 13
Table 2. Cont.
RI Compounds C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11
1127
allo-Ocimene 0.01
1127
(E)-Rose oxide 0.02
1134
Dihydro linalool 0.07 0.08 0.04 0.02
1149
Camphor 2.47 0.02 0.29 0.29
1151
Citronellal 0.04
1157
Menthone 0.30
1161
Benzyl acetate 0.55 1.23 2.26 2.07 1.16 1.23
1164
Borneol
1166
Isomenthone 0.15
1170
Isononyl acetate 0.19 0.19 0.18
1174
2-Phenyl ethyl formate 0.07
1178
(Z)-Pinocamphone 0.02
1181
Terpinen-4-ol 0.18 0.07 0.37 0.12 0.12
1192
Methyl salicylate 0.31
1194
Dihydro citronellol 0.01
1195
α-Terpineol 0.08 0.09 0.16 0.01 0.15 0.15 0.08 0.08
1198
Florosa 0.44 0.32 0.77 0.48 0.41
1215
(E)-Rozanol 1.52 1.29 3.93 2.20 2.03
1225
Citronellol 0.69 1.39 3.12 8.55
11.77
4.68 4.18
1225
Nerol 0.81 1.71
1226
Sabinene hydrate acetate 0.02
1239
Neral 0.02
1247
Linalyl acetate 7.78 2.92 5.14 1.70 3.53 2.43 2.36 5.19 5.10
1248
Geraniol 0.40 1.72 3.23 2.15 1.37
1267
Dihydro linalyl acetate 0.10 0.05 0.03 0.07 0.07
1267
Geranial 0.03 0.03
1269
1-Isoprpyl-3-tert-butylbenzene 0.04 0.04
1272
Citronellyl formate 0.79
1275
Neryl formate 0.04
1279
Lavandulyl acetate 0.14
1286
Hydroxy citronellal 7.43 0.19 2.01 3.59 4.07 2.39 2.38 0.18 0.20
1288
(Z)-2-tert-butyl cyclohexanol acetate 1.01
1292
Indole 0.07 0.09 0.09 0.08 0.09
1297
Geranyl formate 0.16
1330
2-Propanol,
1,1’-[(1-methyl-1,2-ethanediyl)bis 2.51
1345
α-Terpinyl acetate 0.06 0.03 0.03 0.03
1347
Citronellyl acetate 0.22
1354
Neryl acetate 0.16 0.21 0.05 0.20 0.07 0.06 0.02
1374
Geranyl acetate 0.29 0.52 0.34 0.11 0.12 0.21 0.16 0.15 0.34 0.36
1377
α-Copaene 0.2
1380
α-α-α-2-Trimethyl benzeneacetic 0.02 0.03
1388
(E)-α-Damascone 0.17 0.03 0.02 0.03
1395
Vanillin 0.63
1408
β-Maaliene 0.17
1410
Calone 0.15 0.27 0.27 0.32
1421
β-Caryophyllene 1.10 0.08 0.42 0.01 0.11 0.11
1423
Allyl cyclohexyl propanoate 0.06 0.05 0.07
1438
Coumarin 0.22
1442
Dihydro curcumene 0.23 1.47
1443
(E)-Cinnamyl acetate 0.29
1446
(E)-Isoeugenol 0.21
1447
1-(4-tert-Butylphenyl)propan-2-one 0.16 0.05 0.24 0.28 0.10 0.10
1449
(E)-β-farnesene 0.25
1458
α-humulene 0.09
1460
Cyclamanal 0.76 1.86 1.73 0.94 0.94
1465
γ-Decalactone 0.55 0.93

Molecules 2023,28, 7014 6 of 13
Table 2. Cont.
RI Compounds C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11
1472
Isomethyl-α-(Z)-ionone 1.15
1478
(E)-β-Ionone 0.29 0.27 0.31
1480
Sandal mysore core 1.81
1501
Butylated hydroxy toluene 0.22 0.21 0.26
1502
α-Bulnesene 0.08
1513
6-Methyl α-ionone 0.34
1527
(Z)-Nerolidol 0.08
1529
Lilial 5.65
13.68
9.34
16.93 15.43
9.69
10.13 13.79 14.04
1538
(E)-α-Bisabolene 0.07
1549
Raspberry ketone 0.19
1553
Geranyl butyrate 0.01
1560
(E)-Nerolidol 0.15 0.31 0.29 0.28 0.30
1565
Tropional 0.88
1569
Methyl-β-ionone 0.13
1570
γ-Undecalactone 0.18 0.19 0.19
1585
Caryophyllene oxide 0.28
1625
γ-Eudesmol 0.07
1626
Cedryl methyl ether 0.25 0.25 0.31
1649
(Z)-Methyl dihydro jasmonate 2.29
10.26 21.79
6.75
12.73 12.02
7.34 7.30
21.37 20.66
1656
(7-α-Isopropenyl-4,5-dimethyl
octahydroinden-4-yl)methanol 2.54
1659
Lyral 1.71 9.70 6.67 9.29 9.38 5.46 5.41
1669
3-(Z)-Hexenyl salicylate 0.47 5.83
1669
Iso-(E)-γ-Super 2.17 2.20 0.58
1675
(E)-Methyl dihydro jasmonate 0.27 1.41 2.34 0.80 2.16 0.05 0.86 0.84 2.49 2.65
1678
Salicylic acid hexyl ester 1.94 9.74
1693
Iso-(E)-α-Super 0.44 0.53
1696
2-(Z)-6-(Z)-Farnesol 0.35
1729
2-Methoxy ethoxy cyclododecane 0.86 1.73 1.74 0.97 0.98
1746
2-Hexyl-(E)-cinnamaldehyde 11.84 2.56 4.34 8.29 0.47 4.86 4.85 2.62 2.95
1756
Cosmone isomer II 0.04 0.07 0.04
1768
Ambroxide 0.26 0.21 0.18 0.18
1768
Benzyl benzoate 0.56
1769
Methyl cedryl ketone 2.41
1770
2-Hexyl-(Z)-cinnamaldehyde 0.16 0.45 0.34 0.32 0.11 0.16
1802
(Z, E)-Farnesyl acetate 0.08
1827
(E,E)-Farnesyl acetate
1844
Acetyl methyl tetralin 10.15 5.03 4.72 5.96
1870
Galaxolide 1 0.24 0.16 0.15 0.21
1871
Benzyl salicylate 0.39
1875
Galaxolide 2 0.18 0.14 0.13 0.19
1892
Galaxolide 3 0.31 0.2 0.18 0.25
1903
Galaxolide 4 0.31 0.19 0.18 0.23
2011
Ethylene brassylate 1.10 1.89 1.83 2.02
2057
Ricenalidic acid lactone 8.40
2098
Benzyl cinnamate 0.03
2234
Methyl Pimarate 0.09 0.13 0.11
2249
Methyl pimar-8(14)-en-18-oate 1.72 2.02 6.08
2290
Methyl pimaran-18-oate 2.24 2.89 2.96
2300
Methyl-8-piramen-18-oate isomer I 2.64
2311
trans-3-Phenylpropyl cinnamate 0.54
2315
Methyl 13-abieten-18-oate 2.98 3.03 2.99
2324
Methyl-8-piramen-18-oate isomer II
23.82
5.84
2330
Methyl 7-isopimaren-18-oate 0.29 0.20 0.20
2338
Methyl dehydroabietate 6.47 6.17
2360
Methyl abiet-7-en-18-oate 0.56 0.58 0.62
2387
Methyl abietate 1.82 1.87 2.07

Molecules 2023,28, 7014 7 of 13
Table 2. Cont.
RI Compounds C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C11
2420
Cinnamyl cinnamate 0.95
2435
Methyl neoabietate 0.18 0.23 0.25
2695
Verdantiol isomer II 0.07 0.05 0.05 0.09
2927
Tricaprylin Triglyceride 1.68
3084
β-Sitosterol acetate 7.54
3116
Caprin Biscaprylin Triglyceride 3.19
3301
Caprylin Biscaprin Triglyceride 1.82
3325
β-Amyrone 0.17
3376
Lupenone 2.85
3486
Tricaprin Triglyceride 0.40
Total 66.81
70.84 97.76 97.06 74.27 91.82 91.99 77.66 68.39 97.83 97.59
Unidentified 33.2 28.8 2.19 2.75 25.69 8.18 7.88 22.24 31.59 2.13 2.38
2.4. Safety Assessment
N. caerulea is not GRAS classified, and no published safety data were found on the
plant or the extracts as a whole. However, the plant has a long history of use. The safety
data for all constituents present at 1% and above are presented in Table 3. The three main
constituents detected in the concrete were 6,9-heptadecadiene (11.95
±
1.65%), n-tricosane
(8.03
±
0.18%), and benzyl alcohol (7.58
±
0.85%). The three main constituents identified in
the absolute were 6,9-heptadecadiene (11.05
±
1.53%), benzyl alcohol (10.46
±
1.42%), and
tetradecanol (5.32
±
0.74%). Tsai et al. [
22
] studied the volatile compounds of N. caerulea
(water lily) flowers using GC-MS and reported four main compounds: 6,9-heptadecadiene
(40.1%), pentadecane (15.5%), 8-heptadecene (15.3%), and benzyl acetate (10.4%). This is
different from our GC-FID results, except that the main compound, 6,9-heptadecadiene, was
identified as the most abundant compound, although at a substantially lesser concentration
in the flower extracts.
As these are absolute and concrete materials, they may contain an unknown and
significant portion of nonvolatile compounds. As such, quantification through GC-FID may
not be accurate and compounds present in the absolute and concrete may not be detected
and therefore not evaluated as part of this assessment. Since the safety of unidentified
compounds cannot be guaranteed, this presents an unknown safety risk.
Of the 28 compounds investigated (making up 85.43% of the concrete and 80.52% of
the absolute), safety information was not found for 10 compounds (making up 27.29%
of the concrete and 25.11% of the absolute) including 6.9-heptadecadiene, n-pentacosane,
tetrapenol, 3-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-5-methoxyphenol, 2-nonadecanone, hep-
tacosane, benzyl linoleate, methyl cholesterol, benzyl linolenate, and benzyl hexadecanoate.
We were able to gather safety information for the remaining 18 compounds (making up
58.69% of the concrete and 56.68% of the absolute) including n-tricosane, benzyl alcohol,
tetradecanol, heneicasane, nonadecane, pentadecane, oleic acid, E-squalene, linoleic acid,
γ
-sitosterol, palmitic acid, phytol, E-
β
-farnesene, ethyl stearate, stigmasterol, hexadecyl
acetate, ethyl linoleate, and ethyl palmitate. According to the data available from CIR, all
of the assessed compounds, except two, were found to be at concentrations considered
safe in accordance with current usage practices, as indicated in Table 3. Benzyl alcohol and
tetradecanol are slightly above the maximum concentrations; however, when blue lotus
extracts are used as part of a formulation, the concentration of these compounds will be
reduced. For compounds with data on genotoxicity, there was no indication of genotoxicity
risks. Very limited information was available on acute or chronic toxicity and phototoxicity
or photoallergenicity. However, the data are not indicative of major safety risks.

Molecules 2023,28, 7014 8 of 13
Table 3. Toxicological reference values from CIR, RIFM, and ECHA for compounds ≥1% identified in authentic blue lotus extracts.
Compound Name CAS
Number
Average
Concentration (%)
CIR RIFM ECHA
Ref.
Max Use
Concentra-
tion
Genotoxicity Phototoxicity
NOAEL (mg/kg/day)
NESIL
(ug/cm2)
LD50 Repeated Dose ±
Concrete Absolute Repeated
Dose
Developmental
& Repro-
ductive
Oral
(mg/kg)
Dermal
(mg/kg)
Inhalation
(mg/L)
Oral NOAEL
(mg/kg/d)
Inhalation
NOAEC
(mg/m3)
6,9-Heptadecadiene - 11.95% 11.50% - - - - - - - - - - - N.A.
n-Tricosane 638-67-5 8.03% 2.09% - NIG - - - - - - - - - [26]
Benzyl alcohol 100-51-6 7.58% 10.46% ≤10% NG NPT/A 100 †500 5900 1620 >2000 >4.2 400 * 1072 ‡[27–29]
Tetradecanol 112-72-1 5.99% 5.32% <5% NIG - - - - >2000 8000 >1.5 3548 ‡1000 †[30–32]
Heneicosane 629-94-7 4.85% 2.22% - NIG - - - - - - - - - [33]
Nonadecane 629-92-5 4.65% 3.50% - NIG - - - - - - - - - [34]
Pentadecane 629-62-9 4.64% 4.27% - NIG - - - - >5000 #>2000 #>6.0 #≥500 #,† ≥6000 #, † [35,36]
Oleic acid 112-80-1 4.22% 4.97% ≤20.9% NIG - - - - - - - - - [37,38]
(E)-Squalene 111-02-4 3.85% 2.23% ≤10% - - - - - >5000 - 13,800 >600 ‡- [39,40]
n-Pentacosane 629-99-2 3.05% 0.46% - - - - - - - - - - - N.A.
Tetrapenol 24034-73-9 2.98% 3.68% - - - - - - - - - - - N.A.
Linoleic acid 60-33-3 2.81% 3.93% ≤21.8% NIG - - - - - - - - - [37,41]
γ-Sitosterol 83-47-6 2.37% 3.70% ≤10% - - - - - - - - - - [42]
3-((8Z,11Z)-
Heptadeca-8,11-
dien-1-yl)-5-
methoxyphenol
- 2.20% 2.62% - - - - - - - - - - - N.A.
Palmitic acid 57-10-3 1.98% 2.65% ≤21% NG NPT/A - - - >5000 >2000 #>0.15 #1000–5000 #,† - [37,43,44]
2-Nonadecanone 629-66-3 1.64% 0.16% - - - - - - - - - - - N.A.
Heptacosane 593-49-7 1.58% 0.57% - - - - - - - - - - - N.A.
Phytol 150-86-7 1.53% 2.35% - NG #NPT/A 333 #,† -2700 #>10,000 >4000 - 100 - [45]
(E)-β-Farnesene 18794-84-8 1.39% 1.63% - NG #NPT/A #- - 3700 #>5000 >5000 >2.06 ≥1000 †- [46,47]
Benzyl linoleate 47557-83-5 1.27% 2.00% - - - - - - - - - - - N.A.
Ethyl Stearate 111-61-5 1.20% 1.76% - NIG - - - - - - - - - [48]
Stigmasterol 83-48-7 1.07% 1.25% ≤10% - - - - - - - - - - [42]
Methyl cholesterol 4651-51-8 1.05% 1.25% - - - - - - - - - - - N.A.
Hexadecyl acetate 629-70-9 1.03% 1.08% ≤12.6% - - - - - >40 mL/kg >5000 - - - [49,50]
Ethyl linoleate 544-35-4 0.95% 2.00% - NIG - - - - >2000 #>2000 #- - - [51,52]
Benzyl linolenate 77509-02-5 0.79% 1.49% - - - - - - - - - - - N.A.
Benzyl
hexadecanoate 41755-60-6 0.78% 1.38% - - - - - - - - - - - N.A.
Ethyl Palmitate 628-97-7 0.55% 1.27% - NIG - - - - >2000 #>2000 #-1000 #- [53,54]
CIR = Cosmetic Ingredient Review, RIFM = Research Institute for Fragrance Materials, Inc., ECHA = European Chemical Agency, CAS = Chemical Abstracts Service, NOAEL = No
Observed Adverse Effect Level, LD50 = Lethal Dose 50, NESIL = No Expected Sensitization Induction Level, Ref. = References, N.A. = Not Available, NG = Not Genotoxic, NIG = No
Indication of Genotoxicity, NPT/A = not phototoxic/photoallergenic, # = read-across,
†
= sub-acute study,
‡
= sub-chronic study, * = chronic study, - = not available,
±
= No ECHA
Dermal Repeated Dose NOAEL was available for the compounds listed.

Molecules 2023,28, 7014 9 of 13
3. Materials and Methods
3.1. Plant Material and Extraction
Authentic blue lotus absolutes and concrete samples were prepared using industrial
extraction methods. Cultivated blue lotus plants were collected from Hainan and Guang-
dong, China (Figure 1). The plant prefers high temperatures, humidity, and sunlight. Fresh
flowers were shredded with a flower-cutting machine. About 1000 Kg of the shredded
material was extracted twice with hexane (1: 2, w/v) in an enamel extraction tank with
continuous stirring for 12 h. After soaking, the hexane was discharged and filtered with
120 mesh stainless steel mesh. The collected extracts were allowed to settle for 4 h, then
filtered. The solvent was then recovered by heating with jacketed steam. The extract was
concentrated under atmospheric pressure with a spherical concentrator until all of the
hexane was evaporated. The concentrated extract is called concrete. To prepare the absolute,
the blue lotus concrete was dewaxed with 95% ethanol (1:5, w/v) in a stainless-steel barrel,
stirred carefully, and placed in the freezer for more than 12 h. The resulting extract was
filtered and the floral was separated. The filtrate was concentrated under low pressure in a
spherical concentrator until all of the solvent was evaporated. Samples of both the concrete
and absolute were tested for solvent residue. Eleven commercially available blue lotus oil
products were purchased online (Amazon and Etsy). The product labels of these samples
contained the information listed in Table 4.
Molecules 2023, 28, x FOR PEER REVIEW 11 of 15
3. Materials and Methods
3.1. Plant Material and Extraction
Authentic blue lotus absolutes and concrete samples were prepared using industrial
extraction methods. Cultivated blue lotus plants were collected from Hainan and Guang-
dong, China (Figure 1). The plant prefers high temperatures, humidity, and sunlight.
Fresh owers were shredded with a ower-cuing machine. About 1000 Kg of the shred-
ded material was extracted twice with hexane (1: 2, w/v) in an enamel extraction tank with
continuous stirring for 12 h. After soaking, the hexane was discharged and ltered with
120 mesh stainless steel mesh. The collected extracts were allowed to sele for 4 h, then
ltered. The solvent was then recovered by heating with jacketed steam. The extract was
concentrated under atmospheric pressure with a spherical concentrator until all of the
hexane was evaporated. The concentrated extract is called concrete. To prepare the abso-
lute, the blue lotus concrete was dewaxed with 95% ethanol (1:5, w/v) in a stainless-steel
barrel, stirred carefully, and placed in the freezer for more than 12 h. The resulting extract
was ltered and the oral was separated. The ltrate was concentrated under low pressure
in a spherical concentrator until all of the solvent was evaporated. Samples of both the
concrete and absolute were tested for solvent residue. Eleven commercially available blue
lotus oil products were purchased online (Amazon and Etsy). The product labels of these
samples contained the information listed in Table 4.
Figure 1. Fresh Nymphaea caerulea owers harvested from the eld.
Table 4. Available information on commercial blue lotus products.
Sample
Oil Name
Description
Botanical Name
C1
Egyptian Sahasrana 100%
Blue Lotus Oil Euphoria
100% Blue Lotus Oil Euphoria
NA
C2
Blue Lotus Oil
Therapeutic grade
NA
C3
Lotus Blue Oil
Pure essential oil, steam distilled
Nymphaea caerulea
C4
Blue Lotus Extra Strength
Euphoric mood + dream tonic and liquid tincture, glyc-
erin, alcohol, filtered water
Nymphaea c. 200:1
C5
Blue Lotus Absolute
100% pure, natural, and undiluted EO
Nymphaea caerulea
C6
Blue Lotus EO
100% natural ingredients
NA
C7
Blue Lotus Oil
100% pure EO
NA
C8
Blue Lotus EO
NA
NA
C9
Blue Lotus absolute Oil
Organic • 100% PURE • Absolute
NA
C10
Blue Lotus essential Oil
NA
NA
C11
Blue Lotus essential Oil
NA
NA
NA = not applicable.
Figure 1. Fresh Nymphaea caerulea flowers harvested from the field.
Table 4. Available information on commercial blue lotus products.
Sample Oil Name Description Botanical Name
C1 Egyptian Sahasrana 100%
Blue Lotus Oil Euphoria 100% Blue Lotus Oil Euphoria NA
C2 Blue Lotus Oil Therapeutic grade NA
C3 Lotus Blue Oil Pure essential oil, steam distilled Nymphaea caerulea
C4 Blue Lotus Extra Strength
Euphoric mood + dream tonic
and liquid tincture, glycerin,
alcohol, filtered water
Nymphaea c. 200:1
C5 Blue Lotus Absolute
100% pure, natural, and undiluted
EO Nymphaea caerulea
C6 Blue Lotus EO 100% natural ingredients NA
C7 Blue Lotus Oil 100% pure EO NA
C8 Blue Lotus EO NA NA
C9 Blue Lotus absolute Oil Organic •100% PURE •Absolute NA
C10 Blue Lotus essential Oil NA NA
C11 Blue Lotus essential Oil NA NA
NA = not applicable.

Molecules 2023,28, 7014 10 of 13
3.2. Gas Chromatography−Mass Spectrometry (GC–MS) Analysis
Authentic and commercial samples were analyzed using a gas chromatograph cou-
pled to a mass spectrometer QP2010 Ultra (Shimadzu Scientific Instruments, Columbia,
MD, USA) with electron impact (EI) mode with 70 eV, as previously described [
55
]. The
components were identified by comparing the mass spectral fragmentation patterns (over
80% similarity match) and retention indices (RI) based on a series of homologous C8-C20
n-alkanes with those reported in databases (NIST database, and our in-house library) using
the Lab Solutions GCMS post-run analysis software version 4.45 (Shimadzu Scientific
Instruments, Columbia, MD, USA).
3.3. Gas Chromatography–Flame Ionization Detection (GC–FID) Analysis
Analysis of E. purpurea essential oil was carried out using a Shimadzu GC 2010
equipped with a flame ionization detector (Shimadzu Scientific Instruments, Columbia,
MD, USA), as previously described [
56
], with a ZB-5 capillary column (Phenomenex,
Torrance, CA, USA).
3.4. Detection and Quantification of Nuciferine and Apomorphine
LCMS-grade methanol, LCMS-grade water, and HPLC-formic acid were purchased
from Sigma-Aldrich (St. Louis, MO, USA). Nuciferine and apomorphine were purchased
from Cayman Chemical (Ann Arbor, MI, USA). Stock solutions of each standard at a
concentration of 10 ppm were prepared by diluting the powder in methanol. Nuciferine
and apomorphine were quantified using a NEXERA UPLC system (Shimadzu Corp., Kyoto,
Japan) equipped with a mass spectrometer (Triple quadrupole, LCMS8060, Shimadzu,
Kyoto, Japan) as previously described [
18
,
25
]. The detection was completed in multiple
reaction monitoring mode (MRM) (Table 5). Samples were run in triplicate with external
standards in between and the injection volume was 1
µ
L. The acquired chromatographic
results were processed in LabSolutions Insight software version 3.2 (Shimadzu). For each
compound, calibration curves (0.005–0.1 ppm) were created by linking the peak area and
the concentration.
Table 5. Multiple reaction monitoring mode parameters (MRM).
Name CAS # Precursor
(m/z)
Product 1
(m/z)
Product 2
(m/z)
Product 3
(m/z)
RT
(min) r2
Apomorphine
58117-94-5 309.05 268.20 237.15 191.1 1.47 0.9995
Nuciferine
475-83-2 296.00 265.10 250.10 235.15 2.87 0.9995
r2, equation and coefficient of determination.
3.5. Safety Assessment
The safety assessment of blue lotus extracts was conducted by applying standard toxi-
cology and risk assessment methods using the analytical results (Table 2), published safety
data on the raw material as a whole plant, plant extract, and the constituents identified in
the extracts. The information considered for the safety assessment included the historical
use of the plant and extracts, safety and toxicology data on the plant and extracts, and safety
and toxicology data of all constituents present at 1% and above. This safety assessment is
based solely on the available literature. The documents collected and reviewed included
scientific articles from books and scientific journals on botany and the safety of natural
complex substances, fragrances, and flavors. Studies using different degrees of evidence
from
in vitro
methods, pre-clinical models, clinical trials, and case reports were used as
evidence of the safety or toxicity of the raw material as a whole. The sources of information
used to evaluate the safety of individual constituents included the RIFM (Research Institute
for Fragrance Materials, Inc.) Fragrance and Flavor Database, CIR (Cosmetic Ingredient
Review) assessments, and ECHA (European Chemical Agency) REACH (Registration, Eval-
uation, Authorization, and Restriction of Chemicals) registrations. The main endpoints of
interest included genotoxicity, developmental and reproductive toxicity, skin irritation and

Molecules 2023,28, 7014 11 of 13
sensitization, photoirritation and photoallergenicity, as well as acute and chronic toxicity
for oral, dermal, and inhalation routes of exposure.
4. Conclusions
In this study, we analyzed the chemical composition of six authentic blue lotus ex-
tracts and eleven commercial products. The extracts were a mixture of aliphatic hydrocar-
bons, aromatic alcohols, fatty acids, phenyl derivatives, diterpenoids, phytosterols, and
stigmastanes. The main constituents in the authentic concrete were 6,9-heptadecadiene
(
11.95 ±1.65%
), n-tricosane (8.03
±
0.18%), and benzyl alcohol (7.58
±
0.85%), while the
main constituents of the authentic absolute were 6,9-heptadecadiene (11.05
±
1.53%), ben-
zyl alcohol (
10.46 ±1.42%),
and tetradecanol (5.32
±
0.74%). Surprisingly, none of the
investigated commercial products resembled authentic extracts in aroma or composition.
Nuciferine and apomorphine were found in traces or were absent, respectively, from the
studied authentic extracts, suggesting that the risk of psychoactive effects associated with
these compounds would be virtually absent for a small dose of either of these extracts
applied topically. Other than the psychoactive effects associated with nuciferine and apo-
morphine, the available safety data from the literature are limited and do not show major
safety concerns for the authentic extracts. Surprisingly, none of the investigated commercial
products resembled authentic extracts in aroma or composition.
Author Contributions:
Conceptualization, N.S.D., C.B. and P.S.; methodology, N.S.D., S.S.B., A.P.
and C.B.; validation, N.S.D.; formal analysis, N.S.D., P.S. and A.P.; safety investigation, S.A.S., J.T.D.
and C.B.; data curation, N.S.D., P.S. and A.P.; writing—original draft preparation, N.S.D. and S.A.S.;
writing—review and editing, N.S.D., S.A.S., J.T.D., P.S., C.B. and A.P.; supervision, P.S. and C.B. All
authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Data Availability Statement: Data are contained within the article.
Acknowledgments:
We would like to thank Tim Valentiner, Simon Zhou, and Emilie Bell for kindly
providing the authentic samples and photos. Special thanks to Megan Bean for purchasing the
commercial blue lotus products.
Conflicts of Interest: The authors declare no conflict of interest.
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