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Citation: Ben Hsouna, A.; Michalak,
M.; Kukula-Koch, W.; Ben Saad, R.;
ben Romdhane, W.; Zeljkovi´c, S. ´
C.;
Mnif, W. Evaluation of Halophyte
Biopotential as an Unused Natural
Resource: The Case of Lobularia
maritima.Biomolecules 2022,12, 1583.
https://doi.org/10.3390/
biom12111583
Academic Editor: Jen-Tsung Chen
Received: 6 October 2022
Accepted: 26 October 2022
Published: 28 October 2022
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4.0/).
biomolecules
Review
Evaluation of Halophyte Biopotential as an Unused Natural
Resource: The Case of Lobularia maritima
Anis Ben Hsouna 1,2 , Monika Michalak 3, Wirginia Kukula-Koch 4, Rania Ben Saad 1,
Walid ben Romdhane 5, Sanja ´
Cavar Zeljkovi´c 6,7 and Wissem Mnif 8,9,*
1Laboratory of Biotechnology and Plant Improvement, Centre of Biotechnology of Sfax, University of Sfax,
Sfax 3018, Tunisia
2
Department of Environmental Sciences and Nutrition, Higher Institute of Applied Sciences and Technology of
Mahdia, University of Monastir-Tunisia, Monastir 5000, Tunisia
3Collegium Medicum, Jan Kochanowski University, IX WiekówKielc 19, 35-317 Kielce, Poland
4Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Lublin, 1 Chodzki Str.,
20-093 Lublin, Poland
5Plant Production, College of Food and Agriculture Sciences, King Saud University,
Riyadh 11451, Saudi Arabia
6
Centre of the Region Hanáfor Biotechnological and Agricultural Research, Department of Genetic Resources
for Vegetables, Medicinal and Special Plants, Crop Research Institute, Šlechtitel˚u 29,
78371 Olomouc, Czech Republic
7Centre of Region Hanáfor Biotechnological and Agricultural Research, Czech Advanced Technology and
Research Institute, Palacky University, Šlechtitel˚u 27, 78371 Olomouc, Czech Republic
8Department of Chemistry, Faculty of Sciences and Arts in Balgarn, University of Bisha,
Bisha 61922, Saudi Arabia
9ISBST, BVBGR-LR11ES31, Biotechpole Sidi Thabet, University of Manouba, Ariana 2020, Tunisia
*Correspondence: wmoneef@ub.edu.sa or w_mnif@yahoo.fr; Tel.: +216-98-94-73-71
Abstract:
Halophytes are plant species widely distributed in saline habitats, such as beaches, postin-
dustrial wastelands, irrigated lands, salt flats, and others. Excessive salt level, known to limit plant
growth, is not harmful to halophytes, which have developed a variety of defense mechanisms allow-
ing them to colonize harsh environments. Plants under stress are known to respond with several
morpho-anatomical adaptations, but also to enhance the production of secondary metabolites to bet-
ter cope with difficult conditions. Owing to these adaptations, halophytes are an interesting group of
undemanding plants with a high potential for application in the food and pharmaceutical industries.
Therefore, this review aims to present the characteristics of halophytes, describe changes in their
gene expression, and discuss their synthesized metabolites of pharmacognostic and pharmacological
significance. Lobularia maritima is characterized as a widely spread halophyte that has been shown
to exhibit various pharmacological properties
in vitro
and
in vivo
. It is concluded that halophytes
may become important sources of natural products for the treatment of various ailments and for
supplementing the human diet with necessary non-nutrients and minerals. However, extensive
studies are needed to deepen the knowledge of their biological potential
in vivo
, so that they can be
introduced to the pharmaceutical and food industries.
Keywords:
halophyte; Lobularia maritima; phytochemicals; stress genes; molecular mechanisms; biopotential
1. Introduction
Halophytes are flowering plants that have adapted to soils with high salt concentra-
tions and benefit from a salt-rich environment [
1
]. Plants with high salt tolerance represent
just 2% of the world’s flora [
2
]. Salinization of the soil, which is undoubtedly one of the
most important factors limiting plant growth [
3
], is a common occurrence, already affecting
about 20% of the world’s agricultural land [
4
]. Interestingly, the total area of saline soils is
increasing every year due to the formation of vast new areas of irrigated and cultivated
Biomolecules 2022,12, 1583. https://doi.org/10.3390/biom12111583 https://www.mdpi.com/journal/biomolecules
Biomolecules 2022,12, 1583 2 of 21
lands, postindustrial wastelands, swamps, and lands in the vicinity of salty waters. In light
of these trends, the studies on halophytes and their application in foods, medicine, and
industry are gaining importance, as their ability to thrive on poor-quality water and soil
makes them economically beneficial [3] (Figure 1, Table 1).
Biomolecules 2022, 12, x FOR PEER REVIEW 2 of 22
already affecting about 20% of the world’s agricultural land [4]. Interestingly, the total
area of saline soils is increasing every year due to the formation of vast new areas of ir-
rigated and cultivated lands, postindustrial wastelands, swamps, and lands in the vicin-
ity of salty waters. In light of these trends, the studies on halophytes and their application
in foods, medicine, and industry are gaining importance, as their ability to thrive on
poor-quality water and soil makes them economically beneficial [3] (Figure 1, Table 1).
Figure 1. Potential use of halophytes (based [3,4]).
It is worth noting that plants under stress are known to develop a variety of defense
mechanisms and to increase the biosynthesis of secondary metabolites enabling them to
survive in a difficult environment. These substances can be of great importance to hu-
mans and can exhibit important biological functions [5] (Figure 1).
Therefore, this review aims to shed light on halophytes—species capable of surviv-
ing harsh environmental conditions—and to describe the Mediterranean plant Lobularia
maritima, an example of a perennial, diploid (2 = 24) herbaceous halophyte of the family
Brassicaceae, commonly known as sweet alyssum, in terms of its composition and
pharmacological potential [6–9].
Table 1. Examples of use of selected species of halophytes [3,4].
Use
Species
Crops
- Lobularia maritima
- Aeluropus littoralis
- Populus euphratica
- Karelinia caspica
Figure 1. Potential use of halophytes (based [3,4]).
It is worth noting that plants under stress are known to develop a variety of defense
mechanisms and to increase the biosynthesis of secondary metabolites enabling them to
survive in a difficult environment. These substances can be of great importance to humans
and can exhibit important biological functions [5] (Figure 1).
Therefore, this review aims to shed light on halophytes—species capable of surviving
harsh environmental conditions—and to describe the Mediterranean plant Lobularia mar-
itima, an example of a perennial, diploid (2 = 24) herbaceous halophyte of the family
Brassicaceae, commonly known as sweet alyssum, in terms of its composition and pharma-
cological potential [6–9].
Biomolecules 2022,12, 1583 3 of 21
Table 1. Examples of use of selected species of halophytes [3,4].
Use Species
Crops
- Lobularia maritima
- Aeluropus littoralis
- Populus euphratica
- Karelinia caspica
- Suaeda salsa
- Kalidium foliatum
- Puccinellia tenuiflora
Food
- Lobularia maritima
- Suaeda fruticosa
- Arthrocnemum macrostachyum
- Halopyrum mucronatum
- Cressa cretica
- Haloxylon stocksii
- Alhaji maurorum
Medicine
- Lobularia maritima
- Enicostema verticillatum
- Haloxylon stocksii
- Parkinsonia aculeata
Fodder/forage
- Aeluropus logopoides
- Atriplex stocksii
- Chenopodium album
- Panicum turgidum
- Desmostachya bipinnata
- Salvadora persica
- Sporobolus helvolus
- Tamarix indica
- Urochondra setulosa
Biofuel
- Desmostachya bipinnata
- Phragmites karka
- Halopyrum mucronatum
- Panicum turgidum
- Typha domingensis
2. Salt Tolerance in Halophytes
Halophytes (salt-tolerant plants), unlike glycophytes (salt-sensitive plants), include
plants that have adapted to complete their life cycle in the presence of high salt concen-
trations (
≥
0.2 M NaCl) [
1
,
4
]. Halophytes and glycophytes have similar salt response
mechanisms, but the processes are differentially regulated [
1
]. Environmental stress toler-
ance mechanisms, including the modulation of photosynthesis, gas exchange, cell death,
cell wall composition, cellular ion homeostasis, the transcription of stress-related genes,
stress-protein synthesis, the generation of reactive oxygen species, the accumulation of sec-
ondary metabolites, antioxidant activity, and hormonal balance, involve several molecules
and proteins encoded by stress-related genes [
10
–
12
]. Numerous genes of this kind have
been isolated and functionally characterized among the representatives of halophytes, in-
cluding Salicornia brachiata [
13
,
14
], Aeluropus littoralis [
15
–
18
], Thellungiella halophila
[19–21]
,
Puccinellia tenuiflora [
22
–
24
], Phragmites australis [
25
–
27
], and Suaeda salsa [
28
,
29
]. The
above-mentioned genes encode transcription factors, signaling molecules, transmembrane
proteins, osmoprotectants, Na
+
/H
+
antiporters, potassium transporters, and antioxida-
tive enzymes [
30
]. The molecular diversity and stress responses of halophytes are poorly
studied; therefore, elucidating their tolerance mechanisms is important for application in
other crops. Despite the complex nature of environmental stress tolerance mechanisms,
master genes from halophytes have the biotechnological potential for crop improvement.
These new crop varieties will help to meet the goal of a sustainable increase in global food
production, minimize yield losses due to various environmental stresses, add value to food
crops by fortification with vitamins, iron, carotenoids, anthocyanins, enhance the shelf life
Biomolecules 2022,12, 1583 4 of 21
of fruits and vegetables, and stabilize food prices by ensuring a fluctuation-free assured
food supply.
This section of the review article highlights the Lobularia maritima as a sample widespread
halophyte, whose genes can have the potential for improving environmental stress tolerance
in other plants or crops.
2.1. Lobularia Maritima Genes as Tools for Conferring Environmental Stress Tolerance to Crops
Halophytes are ideal models for elucidating the physiological, biochemical, and ge-
netic mechanisms involved in alleviating cellular ionic imbalance and conferring salt
tolerance [
31
]. Recently, several reviews have examined various aspects of halophyte physi-
ology and discussed their potential applications in saline agriculture [
30
–
34
]; this has led
to a renewed research interest in this area. To improve environmental stress tolerance in
crop plants, it is necessary to identify candidate genes from halophytes to transfer them to
salt-sensitive crops [
35
,
36
]. However, owing to the limited gene-sequencing information
and challenges in identifying stress-related genes and their products, most halophytes are
yet unsuitable for such studies. By contrast, the genomes of typical model glycophytes
such as Arabidopsis sp. and rice, which have low stress tolerance, have been completely
sequenced and their environmental stress response mechanisms extensively studied [
37
,
38
].
These sequencing data could facilitate deciphering stress tolerance mechanisms in closely
related halophytes by comparative genomics. Lobularia maritima is an ideal halophyte
model that meets these criteria [
6
–
8
]. Besides tolerating dry, poor, and polluted soils, L. mar-
itima is a nickel hyperaccumulator that can remove different heavy metals from the soil [
8
].
Lobularia maritima is a facultative halophyte closely linked to Arabidopsis thaliana [
39
]; thus,
it could be a suitable model for deciphering the molecular pathways underlying environ-
mental stress tolerance in plants. Transcripts from L. maritima share 90% identity on average
with homologous genes in Arabidopsis [40].
Many studies on L. maritima have focused on its maintenance, rapid
in vitro
multi-
plication, and methods of culture [
8
]. Despite the salt tolerance of L. maritima, it does not
possess any salt-adapted morphological specializations (e.g., bladder cells or salt glands).
Instead, its tolerance is attributed to adjustments in ionic and osmotic homeostasis [
41
].
Ben Hsouna et al. [
42
] demonstrated that L. maritima was a salt-tolerant halophyte that
transported and accumulated Na
+
in its shoots. Under salt stress, L. maritima successfully
translocated Na
+
from its roots while maintaining root K
+
contents at levels similar to those
in control plants [
42
]. Following this observed accumulation of ions, L. maritima exhibited a
differential regulation of several Na
+
and K
+
transporter genes that are involved in main-
taining ionic balance to survive high salt concentrations [
39
]. These findings confirm that
L. maritima adapts to a high salinity and manages oxidative stress by rapidly developing
efficient physiological and antioxidant mechanisms [42].
Recent studies have shown that L. maritima genome is ~197.70 Mb in size, with 88.31%
(174.59 Mb) of the sequences assigned to 12 pseudochromosomes [
9
]. The L. maritima
genome is smaller than that of other Brassicaceae species; it contains 25,813 genes and
large numbers of repetitive elements [
9
]. The adaptive divergence of a species from closely
related species is frequently linked to gene families with significantly enlarged or contracted
copy numbers [
43
]. The identification and isolation of novel salt-responsive genes and
promoters from L. maritima should be explored for the potential genetic engineering of
crop plants to enhance their abiotic stress tolerance using a transgenic approach. A better
understanding of the salt response of L. maritima is necessary to exploit its potential as a
source of stress-related genes. Several interesting genes with a demonstrated influence on
salt tolerance have recently been isolated from this species. A total of 319 stress-related
genes belonging to twenty-five gene families were found to be significantly enriched in
L. maritima genome, which might have facilitated its adaptation to harsh environments [
9
].
These genes are primarily involved in the responses of L. maritima to (i) molecules of
bacterial and fungal origin, (ii) insects, (iii) wounding stress, and (iv) heavy metals and
abiotic stresses [
9
] (Figure 2). For example, the expanded KTI (Kunitz trypsin inhibitor) gene
Biomolecules 2022,12, 1583 5 of 21
family comprises versatile protease inhibitors that are involved in the defense against insect
attacks [
44
]. The HIPP (heavy-metal-associated isoprenylated plant protein) gene family is
involved in responses to heavy metal stress [
45
], and EIF4A3 (eukaryotic initiation factor)
is important for abiotic stress adaptation and can partially regulate plant resistance to such
stress by regulating the expression of acetoacetyl-CoA thiolase [
46
]. The SGT1B (suppressor
of the G2 allele of skp1) gene is involved in the innate immunity and resistance of plants
mediated by multiple R genes [
47
,
48
], wherasYchF1 (an unconventional G protein) has been
implicated in salinity stress tolerance and disease resistance against bacterial pathogens [
49
].
Dabbous et al. [
50
] described the complete isolation of LmVHA-E1 gene (vacuolar H+ -
ATPase subunit E1) from L. maritima.LmVHA-E1 overexpression in A. thaliana led to
improved tolerance to salinity and osmotic stress in transgenic plants, which was mainly
associated with a reduced relative water loss and oxidative damages, and increased levels of
sodium, possibly due to higher H+ -ATPase activity than that in the wild-type plants (WT).
A recent study has revealed that the gene that encodes the h-type Trx protein—LmTrxh2—in
L. maritima is more strongly induced in response to salt stress than to osmotic or oxidative
stress, especially in the roots [
51
]. However, LmTrxh2 overexpression in transgenic tobacco
has been shown to enhance the overall tolerance of these plants to salt and osmotic stresses,
possibly via the regulation of redox homeostasis [51].
Biomolecules 2022, 12, x FOR PEER REVIEW 5 of 22
(iv) heavy metals and abiotic stresses [9] (Figure 2). For example, the expanded KTI (Ku-
nitz trypsin inhibitor) gene family comprises versatile protease inhibitors that are in-
volved in the defense against insect attacks [44]. The HIPP (heavy-metal-associated iso-
prenylated plant protein) gene family is involved in responses to heavy metal stress [45],
and EIF4A3 (eukaryotic initiation factor) is important for abiotic stress adaptation and
can partially regulate plant resistance to such stress by regulating the expression of
acetoacetyl-CoA thiolase [46]. The SGT1B (suppressor of the G2 allele of skp1) gene is
involved in the innate immunity and resistance of plants mediated by multiple R genes
[47,48], wherasYchF1 (an unconventional G protein) has been implicated in salinity stress
tolerance and disease resistance against bacterial pathogens [49]. Dabbous et al. [50] de-
scribed the complete isolation of LmVHA-E1 gene (vacuolar H+ -ATPase subunit E1) from
L. maritima. LmVHA-E1 overexpression in A. thaliana led to improved tolerance to salinity
and osmotic stress in transgenic plants, which was mainly associated with a reduced
relative water loss and oxidative damages, and increased levels of sodium, possibly due
to higher H+ -ATPase activity than that in the wild-type plants (WT). A recent study has
revealed that the gene that encodes the h-type Trx protein—LmTrxh2—in L. maritima is
more strongly induced in response to salt stress than to osmotic or oxidative stress, es-
pecially in the roots [51]. However, LmTrxh2 overexpression in transgenic tobacco has
been shown to enhance the overall tolerance of these plants to salt and osmotic stresses,
possibly via the regulation of redox homeostasis [51].
Summarily, species-specific genes and expanded gene families may have promoted
the adaptation of L. maritima to harsh environments, which is consistent with previous
findings in numerous plants [52,53] (Figure 2). These genomic traits may explain why L.
maritima hyperaccumulates nickel [8] and exhibits a high tolerance to salt stress [39].
Figure 2. Environmental stress factors and main genes involved in adaptation and response in
Lobularia maritima. Abbreviations: LmSAP: stress-associated protein; LmVHA-E1: vacuolar H+
-ATPase subunit E1; LmTrxh2: h-type Trx protein; ABI: ABA insensitive; EFR: EF-TU receptor; EIF:
eukaryotic initiation factor; ERD: early responsive to dehydration stress; ERF: ethylene-responsive
factor; HIPP: heavy-metal-associated isoprenylated plant protein; KTI: Kunitz trypsin inhibitor;
MYB: myeloblastosis oncogene; PME: pectin methyl esterase; ROSY: interactor of synaptotagmin;
RPP: resistance to P. pachyrhizi; RTM: restricted tobacco etches virus movement; TIL: tempera-
ture-induced lipocalin; DSC2: desmocollin-2.
Figure 2.
Environmental stress factors and main genes involved in adaptation and response in Lobu-
laria maritima. Abbreviations: LmSAP: stress-associated protein; LmVHA-E1: vacuolar
H+ -ATPase
subunit E1; LmTrxh2: h-type Trx protein; ABI: ABA insensitive; EFR: EF-TU receptor; EIF: eukaryotic
initiation factor; ERD: early responsive to dehydration stress; ERF: ethylene-responsive factor; HIPP:
heavy-metal-associated isoprenylated plant protein; KTI: Kunitz trypsin inhibitor; MYB: myeloblasto-
sis oncogene; PME: pectin methyl esterase; ROSY: interactor of synaptotagmin; RPP: resistance to
P. pachyrhizi;RTM: restricted tobacco etches virus movement; TIL: temperature-induced lipocalin;
DSC2: desmocollin-2.
Summarily, species-specific genes and expanded gene families may have promoted
the adaptation of L. maritima to harsh environments, which is consistent with previous
findings in numerous plants [
52
,
53
] (Figure 2). These genomic traits may explain why
L. maritima hyperaccumulates nickel [8] and exhibits a high tolerance to salt stress [39].
Biomolecules 2022,12, 1583 6 of 21
2.2. Halophyte SAP Genes for Abiotic and Biotic Stress Response: A Well-Known Success Story
Over the last 15 years, interest in the A20/AN1 domain stress-associated protein (SAP)
family (a class of zinc-finger proteins) has increased. These proteins exhibit structural and
functional conservation among plant species [
54
,
55
]. In plants, SAP genes are induced
by one or multiple abiotic stresses and function in a stress- and/or tissue-specific man-
ner
[54,56–59]
. Recent studies suggest that SAPs act as ubiquitin ligases, redox sensors,
and/or gene expression regulators under stress conditions [
55
,
60
–
66
]. Interestingly, the
majority of the studies attempting to constitutively express SAPs in model plants (such as
tobacco, Arabidopsis, and rice) report enhanced tolerance to multiple abiotic stress factors,
including drought, salinity, cold, heat, oxidative stresses, and heavy metals [62,67–70].
Halophytes serve as a valuable source of adaptive genes. The A20/AN1 SAP gene,
AlSAP, was first isolated from the halophyte grass A. littoralis [
71
]. The overexpression
of this gene in transgenic tobacco [
56
], durum wheat [
72
], and japonica rice cv. Nippon-
bare [
73
] enhanced the plants’ tolerance to cold, drought, salinity, and oxidative stresses.
Notably, AlSAP rice lines grown under drought stress during the reproductive stage ex-
hibited higher yields than that obtained from the wild-type control, without incurring
any yield penalty under irrigated field conditions [
74
]. Furthermore, the transcriptomic
analysis performed by employing RNA-Seq technology using two AlSAP-expressor rice
lines revealed a large number of deregulated stress-related genes [
75
]. This suggests that
AlSAP transcript accumulation primes the expression of stress-related genes involved in
transcription, signaling, protein degradation, and hormone homeostasis in rice plants [
75
].
Additionally, the upregulation of several negative pathogen defense regulators in AlSAP
rice lines was associated with a low resistance to Magnaporthe oryzae.
The second SAP-encoding gene isolated from the halotolerant plant L. maritima was
designated LmSAP [
57
]. Its expression in L. maritima is induced by salt and ionic stresses,
and its overexpression in transgenic tobacco plants enhances its tolerance to abiotic and
heavy metal stress [
65
]. Ben Saad et al. [
66
] showed that LmSAP was involved in main-
taining gibberellic acid (GA) homeostasis under abiotic stress conditions by regulating
the expression of GA metabolism-related genes in transgenic tobacco, mainly via its A20
domain (Figure 3). Plants overexpressing LmSAP—full-length or truncated forms—that
contained the A20 domain exhibited increased tolerance to salt and osmotic stresses, pre-
sumably via the positive modulation of the antioxidant genes expression involved in ROS
scavenging and by reducing oxidative damage [
76
]. Additionally, LmSAP protects plant
cells against oxidative stress by promoting ROS scavenging and by decreasing the intra-
cellular concentration of free heavy metals (through its effect on metal-binding proteins
in the cytosol) (Figure 3). Therefore, the LmSAP gene may be a potential candidate for
introgression to crop plants to impart stress tolerance and phytoremediation.
Mishra and Tanna [
30
] argued that promoters from halophytes were promising candi-
dates for genetic engineering since many stress-responsive genes are expressed in response
to high stress. Thus, various cis-regulatory motifs of stress-responsive genes from halo-
phytes have been examined in the last two decades [
77
–
81
]. The putative promoter region
(1147-bp upstream of ATG) of the LmSAP gene (PrLmSAP) was also isolated from L. maritima,
and its analysis revealed an active and organ-specific promoter induced by environmental
stresses and wounding in transgenic rice [
82
]. Similar characteristics are exhibited by the
promoter of the AlSAP gene, which shows an age-dependent activation, and its response
to abiotic stress is induced in a tissue-specific manner [
83
,
84
]. To sum up, halophyte SAP
genes represent a potential tool for engineering stress tolerance in crop species.
Biomolecules 2022,12, 1583 7 of 21
Biomolecules 2022, 12, x FOR PEER REVIEW 7 of 22
Figure 3. Hypothetical model for LmSAP-mediated abiotic stress tolerance via ROS modulation,
GA homoeostasis, and heavy metals accumulation.
3. Phytochemical Composition of Halophytes
The results of studies on halophytes show that soil salinity affects not only the
physiology of the plants, causing disturbances in their metabolism, development, and
growth, but also the quality of plant material. Literature data indicate that salinity re-
duces the plant’s capacity for photosynthesis, which may decrease the total content of
carbohydrates, fatty acids, and proteins [85]. On the other hand, in the conditions of sa-
linity, plants have been observed to accumulate nitrogen-containing compounds such as
amino acids (especially proline, but also alanine, arginine, glycine, serine, leucine, and
valine), amides (such as glutamine and asparagine), polyamines, or specific classes of
proteins (osmotin, dehydrins, and defensive proteins, i.e., late embryogenesis abundant
(LEA) proteins) [86]. The concentrations of various secondary plant metabolites are
strongly dependent both on the species and on the plant’s growing conditions, especially
environmental conditions. The type of substances produced is species-specific [85,86]. In
the scientific literature, there are contradictory reports on the changes in the phenolic
compounds, chlorophylls, carotenoids, essential oils, and alkaloids content induced by
salt stress [85,87]. Studies on various plant species show that the concentrations of phe-
nolic compounds such as flavonoids, e.g., quercetin, apigenin [88], and anthocyanins [87],
as well as phenolic acids, e.g., protocatechuic, chlorogenic, caffeic and trans-cinnamic
acids [89], increase with soil salinity in plants. In the case of the essential oil constituents
of various plants, the content of anethole [90], carvacrol [91], and eugenol [92] has been
shown to decrease under saline conditions, while that of chamazulene, α-bisabolol,
trans-β-farnesene [93], γ-terpinene [94] and linalool [92] increases. There is strong evi-
dence that the content of photosynthetic enzymes, chlorophyll a, chlorophyll b, and total
carotenoids decreases significantly as salinity increases [95].
3.1. Nitrogen-Containing Compounds and the Salt Tolerance of Halophytes
In general, halophytes adapt to increased salt levels via ionic compartmentalization,
the production of osmolytes and compatible solutes, enzymatic changes, as well as the
absorption of selective ions. The majority of these processes include the accumulation of
Figure 3.
Hypothetical model for LmSAP-mediated abiotic stress tolerance via ROS modulation, GA
homoeostasis, and heavy metals accumulation.
3. Phytochemical Composition of Halophytes
The results of studies on halophytes show that soil salinity affects not only the physi-
ology of the plants, causing disturbances in their metabolism, development, and growth,
but also the quality of plant material. Literature data indicate that salinity reduces the
plant’s capacity for photosynthesis, which may decrease the total content of carbohydrates,
fatty acids, and proteins [
85
]. On the other hand, in the conditions of salinity, plants
have been observed to accumulate nitrogen-containing compounds such as amino acids
(especially proline, but also alanine, arginine, glycine, serine, leucine, and valine), amides
(such as glutamine and asparagine), polyamines, or specific classes of proteins (osmotin,
dehydrins, and defensive proteins, i.e., late embryogenesis abundant (LEA) proteins) [
86
].
The concentrations of various secondary plant metabolites are strongly dependent both
on the species and on the plant’s growing conditions, especially environmental conditions.
The type of substances produced is species-specific [
85
,
86
]. In the scientific literature,
there are contradictory reports on the changes in the phenolic compounds, chlorophylls,
carotenoids, essential oils, and alkaloids content induced by salt stress [
85
,
87
]. Studies
on various plant species show that the concentrations of phenolic compounds such as
flavonoids, e.g., quercetin, apigenin [
88
], and anthocyanins [
87
], as well as phenolic acids,
e.g., protocatechuic, chlorogenic, caffeic and trans-cinnamic acids [
89
], increase with soil
salinity in plants. In the case of the essential oil constituents of various plants, the content
of anethole [90], carvacrol [91], and eugenol [92] has been shown to decrease under saline
conditions, while that of chamazulene,
α
-bisabolol, trans-
β
-farnesene [
93
],
γ
-terpinene [
94
]
and linalool [
92
] increases. There is strong evidence that the content of photosynthetic
enzymes, chlorophyll a, chlorophyll b, and total carotenoids decreases significantly as
salinity increases [95].
Biomolecules 2022,12, 1583 8 of 21
3.1. Nitrogen-Containing Compounds and the Salt Tolerance of Halophytes
In general, halophytes adapt to increased salt levels via ionic compartmentalization,
the production of osmolytes and compatible solutes, enzymatic changes, as well as the
absorption of selective ions. The majority of these processes include the accumulation of
nitrogen-containing compounds as a response to salt stress [
96
–
98
]. These compounds are
mainly amino acids and polyamines, which are involved in various functions at cellular
levels, such as salt excretion, maintaining the ion balance, the mitigation of oxidative
stress, growth stimulation, favoring osmoregulation, etc. [
99
–
103
]. As stated by several au-
thors
[97,104,105]
, the content of nitrogen-containing compounds is mainly species-related,
but still, the levels of the particular amino acids and polyamines increase significantly when
plants are subjected to higher levels of salt. Kumari et al. [
106
] concluded that among amino
acids, mainly proline, tyrosine, arginine, glycine, glutamine, and asparagine, together with
the nonprotein amino acids, such as
γ
-aminobutyric acid, citrulline, and ornithine, are
accumulated in halophytes under conditions of high salinity. In addition, polyamines,
mainly putrescine, spermidine, spermine, and cadaverine, play a critical role in plants’
salt tolerance [
106
,
107
]. Polyamine biosynthesis starts from two amino acids, arginine
and ornithine, which are decarboxylated to putrescine, a substrate for the synthesis of
spermidine and spermine [
96
]. Moreover, spermidine and spermine serve as regulators of
both nitrogen and carbon metabolism, causing the accumulation of other nitrogen forms
such as amino acids glutamate, glutamine, and aspartate [108,109].
Since the understanding of the regulatory mechanisms acting on plant metabolic
pathways is of great help to identify the potential candidates of plant metabolism under
different environmental conditions, the evaluation and comparison of metabolite profiling
data derived from the salt-sensitive (such as Sujala and MTU 7029 rice varieties) and salt-
tolerant plant genotypes (such as Bhutnath, and Nonabokra rice varieties) can lead to the
discovery of novel metabolites responsible for salinity tolerance in halophytes [
110
]. These
authors suggest polyamines as the most promising compounds for acquiring resistance
against salinity of their contribution not only to the protection of membranes, proteins, leaf
water status, and cellular homeostasis but also to efficient biomass production under salinity
conditions. Moreover, according to the available literature, it can be concluded that the
manipulation of nitrogen metabolism is crucial for the understanding of plant salt tolerance.
On the other hand, due to its complexity, the manipulation of plant metabolism is a difficult
task. For example, the rate of amino acid and protein biosynthesis decreases in stressed
plant cells, whereas protein degradation along with the accumulation of certain amino acids
(e.g., proline) is highly induced [
106
,
111
]. Therefore, the manipulation of the amino acid
and protein metabolism is not favorable because the homeostasis of these two processes is
critical both under normal and stress conditions. As stated above, plants rich in polyamines
usually show a strong salt tolerance [
112
]. Among them, spermidine and spermine seem
to be the most important indicators [
113
–
115
]. However, Hernándiz et al. [
116
] recently
showed that Arabidopsis thaliana seed priming with both putrescine and 1,3-diaminopropane
showed an efficient level of salt tolerance for this salt-sensitive species. They found that
the two polyamines induced glutamate metabolism, which was related to the synthesis
of the polyamines. Moreover, the authors primed the seeds with ornithine to increase
their tolerance to salt stress, but without any success. The reason for that might be in the
activation of a ubiquitous strategy to better deal with stress or in the induction of negative
stress (distress) in the plant. Therefore, the manipulation of polyamine biosynthesis seems
to have the potential for the improvement of crop performance under salt stress. It is worth
noting that due to the fluctuations in polyamine biosynthesis and their conversions, the
timing and localization of the biosynthesis and conversion processes are crucial factors for
this research [110].
Halophyte plants seem to be perfect models for studying polyamine metabolism, but
still, there are just a few studies published on this topic that has been recently reviewed
by Bueno and Cordovilla [
98
]. To the best of our knowledge, there is no literature review
on polyamine profiles and/or contents of another halophyte: Lobularia maritima. However,
Biomolecules 2022,12, 1583 9 of 21
Ben Hsouna et al. [
42
] found that proline content increased significantly when a plant
was suffering salt stress, which is one of the plant strategies for its survival. Although
this species was investigated thoroughly for its ability to survive severe abiotic stress
conditions, there is still a lack of knowledge about its metabolome, especially nitrogen-
containing compounds that might be responsible for managing salt stress. This is of high
importance, especially for crops, whether they are halophytes or glycophytes. ´
Cavar
Zeljkovi´c et al. [
117
] recently showed that the quality of basil and mint crops, defined
by chemical composition and plant biomass, significantly changed when plants were
grown in hydroponic solutions containing salt. Moreover, they found that stressed plants
accumulated a polyamine—histamine. This fact significantly reduces plant quality, since
histamine is an allergen to humans characterized by a low amine oxidase activity.
3.2. Active Components of Lobularia Maritima and Its Biological Properties
This section of the review highlights the chemical composition (Table 2) of L. maritima
concerning its biological activity (in vitro studies).
Table 2. Important bioactive compounds in Lobularia maritima [118–126].
Compound Key Biological Properties
Phenolic compounds
TP (mg GAE/g):
-flowers 60.845
- leaves 147.451
- stems 307.873
- roots 368.150
- classified as primary antioxidants
- eliminate radicals through direct reactions, scavenging, or
reduction of free radicals (e.g., hydroxyl, superoxide,
peroxide, and alcoxyl radicals) to less reactive compounds
- chelate transition metal cations (e.g., Cu2+and Fe2+)
- inhibit the activity of many enzymes involved in
free-radical generation (e.g., xanthine oxidase, protein
kinase and lipoxygenase)
- exhibit anti-inflammatory, antibacterial, antifungal,
antiviral, antiallergic, anticancer, anticoagulant, and
astringent properties
TF (mg CE/g):
- leaves 0.432
- roots 0.346
- flowers 0.088
- stems 0.021
TC (mg CE/g):
- stems 0.310
- flowers 0.303
- leaves0.195
- roots 0.109
Fatty acids e.g., capric, lauric, palmitic,
myristic, stearic acid
- important cell membrane components
- precursors of eicosanoids (PG, PGI, TX, LT), tissue
hormones with a broad spectrum of activity
- exhibit anti-inflammatory and antiallergic effects
- activate metabolic processes and cell division
Phytosterols e.g., β-sitosterol
- play structural roles in cell membranes
- reduce cholesterol and LDL-C plasma levels
- exert antiatherogenic effects
Terpenoids e.g., neophytadiene, betulin
aldehyde, β-amyrin
- exhibit effective activity against various bacterial, fungal,
and yeast strains
- exhibit anti-inflammatory activity
- exert anticancer effects
Essential oil compounds e.g., linalool, benzyl alcohol,
1-phenyl butanone, 1-terpineol
- exhibit antiseptic, antimicrobial, antifungal,
anti-inflammatory, immunostimulatory, neuroprotective,
and antioxidant properties
Macromolecules e.g., proteins, polysaccharides
- important organic components of the body
- exhibit antioxidant properties through a variety of
mechanisms, including free-radicals scavenging, electron or
hydrogen transfer reduction, transition-metal-chelating
activity, ferric reducing power, and prevention of LPO
TP, total phenols; TF, total flavonoids; CT, condensed tannins; GAE, gallic acid equivalent; CE, catechin equivalent;
PG, prostaglandins; PGI, prostacyclin; TX, thromboxanes; LT, leukotrienes; LDL-C, low-density lipoprotein
cholesterol; LPO, lipid peroxidation.
Biomolecules 2022,12, 1583 10 of 21
Phytochemical screening indicates that L. maritima contains substances with high ther-
apeutic value, such as fatty acids (capric, 9-oxononanoic, lauric, 14-methylpentadecanoic,
palmitic, myristic, stearic, 16-methyloctadecanoic acid), terpenoids (dihydroactinidiolide,
neophytadiene, betulinaldehyde,
β
-amyrin acetate, (+)-2-bornanone, and nootkaton-11,12-
epoxide), and phytosterols (
β
-sitosterol, 24-methylenecycloartanol, and tremulone)
[118–120]
.
In addition, many compounds accumulated by L. maritima function as antioxidants, eliminat-
ing reactive oxygen species, but are also responsible for the antibacterial, anti-inflammatory,
anticancer, antiobesity, and hepatoprotective properties of the raw plants [
86
,
118
,
119
]. This
group includes flavonoids, anthocyanins, phenolic acids, and tannins, as well as essential
oil compounds and macromolecules such as proteins and polysaccharides [119–122].
An investigation of the phytochemical composition of L. maritima detected such phe-
nolic compounds as 2,4-di-tert-butylphenol, vanillic acid, kaempferol, and quercetin deriva-
tives [
119
]. Moreover, six acylated pelargonidin 3-O-sambubioside-5-O-glucosides have
been found in the red-purple flowers of L. maritima [
121
]. GC/MS analysis showed that
yellow essential oil obtained from the aerial parts of L. maritima contains 40 constituents,
including oxygenated monoterpenes (74.40%) and monoterpene hydrocarbons (16.15%).
The dominant components of the volatile oil are linalool (22.43%), benzyl alcohol (8.65%),
1-phenyl butanone (7.33%),
γ
-terpinene (6.15%), 1-terpineol (5.6%),
α
-cadinol (4.91%), glob-
ulol (4.32%), terpinen-4-ol (4.31%), a-terpineol (3.9%), ledol (3.59%),
α
-pinene (3.51%), and
pulegone (3.33%) [
122
]. Heteropolysaccharides, composed of glucose, galactose, and xy-
lose, with a molecular weight of 130.62 kDa, are interesting recently listed components of
L. maritima [118].
3.2.1. Antioxidant Activity
Scientific studies on halophytes often describe the role and the number of antioxidants
that are capable of scavenging ROS in saline conditions [
123
]. Some reports show that
plants with high levels of antioxidants, such as polyphenols, flavonoids, and vitamins, are
much more resistant to salt stress [
34
,
123
]. Previous studies have shown that salt treatment
(200 mM NaCl) significantly increased the phenolic and flavonoid content in the leaves of
L. maritima, while a higher salinity (400 mM NaCl) caused a significant reduction in the
content of these compounds. These results correlate with an antioxidant activity. The leaf
extract of L. maritima displayed higher DPPH free-radical-quenching activity at 200 mM
NaCl compared to the treatment with 400 mM NaCl [
42
]. In another study, the methanolic
extract from the leaves of L. maritima was used for a compositional analysis and bioactivity
studies [
124
]. The HPLC-DAD analysis revealed that the major constituents of the extract
were gallic, salicylic, ellagic, ferulic acids, catechin, and quercetin, with salicylic acid as the
leading molecule (120 mg/100 g DW). Thanks to the plentitude of phenolic components
(total phenolic content: 175
±
2.66 mg GAE/g DW, total flavonoids 35
±
2.88 mg QE/g
DW) the extract was found to be an active radical scavenger in
in vitro
tests (DPPH, lipid
peroxidation inhibition test) [118].
The antioxidant activity of different parts of L. maritima from various geographic
locations was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) colorimetric assay.
DPPH scavenging potency was estimated at IC
50
5.16 to 9.33 mg/mL for the methanolic
extract and 14.87 to 74.17 mg/mL for the aqueous extract of L. maritima aerial parts [
125
].
Another study showed that among various parts of the L. maritima plant, the root ex-
tract showed the highest capacity to scavenge DPPH free radicals, expressed as EC
50
(0.08 mg/mL), which was comparable to the BHA standard (0.051 mg/mL). A lower anti-
radical activity was shown for extracts from the stem (3.9 mg/mL), flower (about 4 mg/mL),
and leaf (4.2 mg/mL) [
120
]. Extracts from the aerial parts of L. maritima have also been
shown to have good antioxidant properties in the
β
-carotene bleaching method, in which
lipid substrates were used to determine biological activity [119].
Among plant secondary metabolites, essential oils and their constituents have also
been shown to have antioxidant properties. These organic compounds (including terpene
hydrocarbons and their oxygen derivatives, alcohols, aldehydes, and ketones) play an im-
Biomolecules 2022,12, 1583 11 of 21
portant role in scavenging free radicals and reducing oxidative stress due to the conjugated
carbon double bonds and hydroxyl groups present in their structure, which can donate
hydrogen [
126
]. The evaluation of the antioxidant properties of L. maritima essential oil has
shown that monoterpene hydrocarbons, oxygenated monoterpenes, and/or sesquiterpenes
may act as primary antioxidants. Research results showed that L. maritima essential oil
exhibited strong radical scavenging activity compared to the standard ascorbic acid. In
addition, the essential oil was shown to exert inhibitory effects on lipid peroxidation in the
β
-carotene bleaching method. Both the DPPH test and the
β
-carotene/linoleic acid bleach-
ing test revealed that antioxidant activity increased in a dose-dependent manner [122].
An important group of plant-derived bioactive compounds that can regulate the redox
state is polysaccharides. These high-molecular-weight polymers, composed of at least
10 monosaccharide molecules connected by glycosidic bonds, exert numerous beneficial
biological effects, including antioxidant properties. Plant polysaccharides can be explored
as a novel potential antioxidant, as they increase antioxidant enzyme activity, scavenge
free radicals, and inhibit lipid peroxidation [
126
]. Studies concerning the antioxidant
potential of crude polysaccharides from L. maritima showed that DPPH scavenging activity
was proportional to the extract concentration. At high concentrations (300
µ
g/mL) the
antioxidant properties of these macromolecules were higher than those of catechin at the
same dose. Moreover, L. maritima polysaccharides presented the significant potential to
inhibit C18:2 peroxidation, as well as moderate the reducing power, proportional to the
polysaccharide concentration [118].
3.2.2. Anti-Inflammatory Activity
Inflammation is a natural aspect of the immune system’s response to any type of
damage. Irrespective of the route of activation and the factor inducing inflammation
(including bacteria, viruses, parasites, or carcinogens), many proinflammatory mediators
are released. These include numerous cytokines, such as interleukin 1
β
(IL-1
β
), interleukin
6 (IL-6), tumor necrosis factor
α
(TNF-
α
), and interferon
γ
(IFN-
γ
), which stimulate white
blood cells, mainly macrophages, to produce large amounts of NO through the long-term
activation of the enzyme nitric oxide synthase (iNOS). Another crucial enzyme for the
inflammatory response, involved in the conversion of arachidonic acid to prostaglandins,
is cyclooxygenase (COX). Similar to inducible NOS (iNOS), the most proinflammatory
NOS isoform, COX-2 is recognized as the most active of the three known COX isoforms
(COX-1, COX-2, and COX-3) during inflammatory processes [
127
,
128
]. Inflammation
accompanies the development of many disorders and diseases, such as obesity, diabetes,
cancer, atherosclerosis, and cardiovascular diseases. For this reason, researchers have been
searching for new active substances with anti-inflammatory activity, including substances
of natural origin [
127
,
128
]. In recent years, numerous articles have been published on the
anti-inflammatory activity of plants and their secondary metabolites, e.g., polyphenols
such as kaempferol, quercetin, rutin, luteolin, daidzein, genistein, and hesperidin, as well
as alkaloids and terpenes [
127
,
129
]. Plants and their metabolites act by modulating induced
iNOS and cells involved with inflammation, inhibiting the production of proinflammatory
cytokines and modulating the activity of arachidic acid pathways, such as cyclooxygenase
(COX), lipoxygenase (LOX), and phospholipase A2 [127,129].
In vitro
studies have shown the inhibitory potential of L. maritima extract on NO
production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages [
119
]. Studies
on the effects of L. maritima essential oil on inflammatory mediators in LPS-stimulated
macrophages have shown that these bioactive compounds can regulate the expression
of inflammatory cytokines. It was demonstrated that essential oil could modulate the
inflammatory mode of macrophages by reducing levels of enzymes iNOS and COX-2 as
well as proinflammatory cytokines IL-1β, IL-6, and TNF-α[122].
Biomolecules 2022,12, 1583 12 of 21
3.2.3. Antiobesity
Obesity is associated with the development of many diseases, including diabetes,
hypertension, osteoarthritis, cardiovascular diseases, and inflammation-based patholo-
gies [
130
,
131
]. This is because adipose tissue is not only involved in energy storage but
also functions as an endocrine organ secreting numerous bioactive substances known
as adipokines. Most of them are proinflammatory, modulating the immune response
agents that promote the development of metabolic diseases. Adipose tissue also produces
pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β[131].
Literature data indicate that natural products can play a significant role as antiobesity
drug candidates. Therefore, the search for new plant resources exhibiting potential health
benefits is extremely important in the treatment of obesity. In the search for effective drugs,
the role of polyphenolic compounds (such as quercetin, rutin, isorhamnetin, myricetin,
hesperidin, and genistein) cannot be skipped, nor can the studies on their molecular mech-
anisms of action preventing and/or treating obesity [
131
]. The effects of polyphenolic
compounds may rely on reducing the number of lipids absorbed from food products by
inhibiting the activity of lipases. Therefore, one of the most commonly tested mechanisms
for evaluating the potential efficacy of natural products as antiobesity agents is the in-
hibition of pancreatic lipase, a key enzyme for the absorption of dietary fats [
119
,
130
].
Inhibitory properties against pancreatic lipase have been confirmed for terpenes, saponins,
and polyphenolic compounds, including flavonoids. Many plants have been screened for
their potential to inhibit pancreatic lipase, including Juniperus communis,Panax japonicus,
Spilanthes acmella,Salvia officinalis,Glycyrrhiza uralensis,Vitis vinifera, and others [
130
]. Mar-
relli et al. [
119
] conducted an
in vitro
study using a colorimetric method based on the use
of 4-nitrophenyl caprylate as a substrate to confirm the potential antiobesity properties of
L. maritima. The ethyl acetate polar fraction of L. maritima showed an inhibitory activity
against pancreatic lipase, with an IC50 value of 1.33 ±0.03 mg/mL [119].
3.2.4. Antimicrobial Activity
Many studies have demonstrated the antimicrobial effects of plant extracts on various
groups of pathogenic organisms. The antimicrobial properties of plants may be associated
with their content of secondary metabolites such as flavonoids and tannins, as well as
essential oils and their active components [
120
,
132
]. Phenolic compounds have been shown
to exhibit a significant antimicrobial activity owing to the presence of the hydroxyl group.
This group probably interacts with the cell membrane, disrupting its integrity and causing
excessive leakage of metabolites and enzymes from the cell and a change in the lipid profile.
This causes structural changes in the outer cell envelope and ultimately leads to a loss of
viability [
120
]. Other known antimicrobial biomolecules include tannins, polyphenolic
compounds containing hydroxyls, and other groups, such as carboxyls, which form strong
complexes with various macromolecules [133].
Mechanisms explaining the antimicrobial activity of tannins include the inhibition
of extracellular microbial enzymes, the deprivation of substrates required for microbial
growth, or a direct action on the metabolism of microorganisms [
120
,
133
]. As in the case
of phenolic compounds, terpenes act on the cell membrane, increasing its permeability.
Terpenoids are known to affect the antibacterial properties of certain plants, possibly by
influencing the nonmevalonate pathway. This pathway is very important in microorgan-
isms (including Gram-negative bacteria and fungi) for the synthesis of cell membrane
components and as a secondary carbon source [
132
]. Future investigations of plant material
should focus on detailed phytochemical analysis and identifying correlations between
secondary metabolites and antimicrobial activity.
Previous research has shown that L. maritima leaf, root, and flower extracts exhibit
an antimicrobial activity against Gram-positive and Gram-negative bacteria (including
Staphylococcus aureus,Enterococcus faecalis,Pseudomonas aeruginosa, and Escherichia coli)
and fungi (Aspergillus ochraceus and Aspergillus carbonarius). The effective antimicrobial
activity of L. maritima may be linked to the presence of tannins and flavonoids in dif-
Biomolecules 2022,12, 1583 13 of 21
ferent plant organs. The antimicrobial potential of different parts of L. maritima is also
associated with compounds such as terpenoids, e.g., betulinaldehyde, neophytadiene,
nootkaton-11,12-epoxide, menthol, (1S, 2S, 5R)-1
0
-(butyn-3-one-1-yl), and (+)-2-bornanone
(camphor), as well as (E,E)-2,4-heptadienal, (Z)-9-octadecenamide, tributylacetylcitrate,
and others. Most of the terpenes, including betulinaldehyde and menthol, responsible for
the antibacterial and antifungal properties of L. maritima, were found to be present in the
flower extracts. In addition, benzyl benzoate and 6-(methylsulfinyl) hexyl isothiocyanate
were identified in the roots, while (E,E)-2,4-heptadienal, and 6-hydroxy-4,4,7a-trimethyl-
5,6,7,7a-tetrahydrobenzofuran-2(4H)-one, also known as loliolide, was detected in leaf
extracts [120].
Based on the literature and available research, it can be concluded that L. maritima,
due to its content of bioactive compounds, could be a promising phytotherapeutic agent.
4. Pharmacological Properties of Halophytes with a Focus on Lobularia maritima
(In Vivo Studies)
Halophytes are represented by a wide group of plant species that were proved to
exhibit various pharmacological functions. Some of them are listed in the Table 3.
Table 3. Selected biological properties of halophytes.
Species Botanical Family Properties Reference
Rubia tinctorum Rubiaceae Diuretic action; treatment of type II diabetes mellitus [134,135]
Tamarix gllica Tamarixaceae Astringent, antibacterial, anti-inflammatory, wound-healing,
and diuretic properties [136]
Limoniastrum
monopetalum Plumbaginaceae Cardioprotective, antidysenteric, antioxidant,
antidiarrheal properties [137,138]
Verbena officinalis Vebenaceae Analgesic, anti-inflammatory, anticancer, neuroprotective,
and anticonvulsant activity [139]
Plantago lanceolata,
P. major, P. ovata Plantaginaceae Anticancer, anti-infectious, anti-inflammatory action in
hepatitis; treatment of cold, cough, and digestive disorders [140,141]
Teucrium genus Labiatae Antispasmodic, hypoglycemic, anti-inflammatory,
analgesic properties [142]
Caesalpinia crista Leguminosae Treatment of headaches, cough, asthma, neurodegenerative
diseases, and upset stomach [143,144]
Terminalia catappa Combretaceae Preventing hepatoma, hepatitis, fever, and diarrhea [145–147]
Cakile maritima Brassicaceae Diuretic, antiscorbutic, anti-inflammatory, purgative and
digestive properties [148,149]
Salsola kali Amaranthaceae Hypotensive, hypoglycemic, anticancer, procognitive,
antiviral, antimicrobial, hepatoprotective properties [150]
Inula viscosa Asteraceae Antiseptic, antiscabies, antipyretic, anticancer,
anti-inflammatory agent [151,152]
This section however focuses on a detailed analysis of the pharmacological profile of
Lobularia maritima. This plant has been traditionally used in the Mediterranean region as a
diuretic, antiscorbutic, antioxidant, and anti-inflammatory agent [
153
]. Vast applications of
the plant in traditional medicine were certainly influenced by the presence of polyphenols
and polysaccharides in the extract. The major indication for its use were urinary problems,
including bladder and kidney infections, lithiasis, or prostate inflammation [
153
]. A 30-
day-long therapy based on one cap of a whole plant infusion was recommended, e.g., in
Algeria, and was found to show a detoxifying, diuretic, and antispasmodic action [153].
According to Ben Hsouna and coauthors [
118
], heteropolysaccharide isolated from
L. maritima was found to exhibit protective properties toward the liver in the CCl
4
-induced
hepatotoxicity model in Wistar albino rats. The molecule was characterized by a molecu-
lar weight of 130.62 kDa and when hydrolyzed, it was found to contain glucose, xylose,
fructose, rhamnose, mannose, and galactose moieties. The administered compound signifi-
cantly decreased the secretion of liver enzymes (AST, ALT, ALP, and LDH) whose levels
in the control group were elevated due to the intoxication process. Moreover, a marked
Biomolecules 2022,12, 1583 14 of 21
antioxidant potential of the polysaccharide was noted in several assays. The authors
reported that the tested compound protected the liver against oxidative stress damage.
In addition, the tested molecule induced the secretion of IL-10 in the rat serum, which
explained its anti-inflammatory potential and the ability to reverse the toxic effects of CCl
4
(observed downregulation of TGF-
β
1 and TNF-
α
). Furthermore, upon the administration
of the polysaccharide, the liver (analyzed postmortem) did not show any signs of fibrosis.
Moreover, when tested on Wistar male rats in a similar assay as reported previously [
118
],
500 mg/kg b.w. of the tested sample showed a statistically insignificant 21% decrease in the
levels of liver enzymes (AST/GOT) and (ALT/GPT) in comparison with the CCl
4
-exposed
group. However, a marked elevation of the catalase (CAT), superoxide dismutase (SOD),
and glutathione peroxidase (GPx) levels was described in the alyssum-treated group in com-
parison to the intoxicated animals. Furthermore, a moderate correction of the CCl
4
-induced
damage to the liver was visualized in histological analysis in the group supplemented with
L. maritima. The applied dose was not toxic to the animals.
The flowers of sweet alyssum are rich sources of volatile components that can exhibit
different functions. The major components of the essential oil investigated for its
in vivo
effects were described as linalool benzyl alcohol 1-phenyl butanone
γ
-terpinene
α
-cadinol
and others [
122
]. The above-described oil was found to exhibit similar protective properties
as previously described polysaccharides isolated from the plant or methanolic extract from
the leaves of L. maritima. The essential oil induced the production of antioxidant enzymes in
CCl
4
-treated rats, at a dose of 250 mg/kg b.w., modulated the response of the immunologic
system by reducing iNOS and COX-2 enzymes together with IL-1
β
, IL-6, TNF
α
, and reduce
the expression of cytokines responsible for the liver inflammation (Table 4).
Table 4. Pharmacological properties of Lobularia maritima in the light of in vivo studies.
Compound Organism Administration Dose Duration Action Mode Reference
Heterpolysaccharide Male Wistar
albino rats i.p. 250 mg/kg b.w. 15 days
Anti-inflammatory,
detoxifying
↓ALT
↓AST
↓ALP
↓LDH
↑SOD
↑CAT
↑GPx
↑IL-10
↓TGF-β1
↓TNF-α
[118]
Methanolic extract
from the leaves
Male Wistar
albino rats p.o. 100–500 mg/
kg b.w. 30 days
Anti-inflammatory
and detoxifying
↓(AST/GOT)
↓(ALT/GPT) ↑
SOD
↑CAT
↑GPx
[124]
Whole plant infusion Traditional
medicine p.o. One cup on an
empty stomach 30 days
Treatment of
urinary problems
Antiradical,
anti-inflammatory,
diuretic properties
[153]
Biomolecules 2022,12, 1583 15 of 21
Table 4. Cont.
Compound Organism Administration Dose Duration Action Mode Reference
Essential oil Male albino
Wistar rats i.p. 250 mg/kg b.w. 15 days
Anti-inflammatory
properties,
antioxidant
properties
↓IL-1β
↓IL-6
↓TNF-α
↓iNOS
↓COX-2
↓Inflammatory
cytokines
[122]
i.p., intraperitoneal administration; p.o., oral administration; b.w., body weight.
The essential oil obtained from the flowering parts of the plant is commonly used as
a repellent to protect crops from deterioration. In their study, Renkema and Smith [
154
]
described a reduction in the number of attracted Drosophila suzukii flies to raspberries—most
probably thanks to the presence of acetophenone and benzaldehyde among the volatiles
of the plant. The repellent and insecticidal properties of the essential oil from L. maritima
were also described by Wang and colleagues [
155
] in an assay with three-grain pests:
Sitophilus oryzae,Tribolium castaneum,and Callosobruchus maculatus. Thanks to the presence
of trans-3-pentenenitrile, a strong fumigant effect of the oil was observed especially against
C. maculatus. A 100% repellency was noted for the concentrations of 0.05 and 0.1 nL/cm
2
against C. maculatus and S. orizae, respectively, and 93% against T. castanum (0.2 nL/cm2).
The above examples of its application confirm the anti-inflammatory, antioxidant,
antispasmodic, detoxifying, and repellent properties of the plant and its constituents.
However, more studies related to the
in vivo
application of L. maritima should be performed
soon to complete its activity profile in animal tests as the plant is abundantly studied in
in vitro
models. These tasks are very important, concerning the fact that L. maritima is
regarded as an edible and safe plant.
5. Conclusions
Based on the review it can be concluded that halophytes are important sources of
primary and secondary metabolites of different kinds. They were proven to contain chloro-
phylls, polyphenols, terpenes, saponins, fatty acids, and other groups of natural products.
The extracts obtained from halophytes (e.g., from Lobularia maritima) exhibited important
biological properties, e.g., antimicrobial, anticancer, anti-inflammatory, detoxifying, and
weight-reducing action. Having in mind the cited references, the majority of studies were
however performed in
in vitro
tests and the anti-inflammatory action was the only one
proved in
in vivo
test on animals. Therefore, it is important to pursue more detailed studies
on living organisms to add novel results to the existing research.
Author Contributions:
Conceptualization, A.B.H. and W.M.; writing—review and editing, A.B.H.,
M.M., W.K.-K., R.B.S., W.b.R., S. ´
C.Z. and W.M. All authors have read and agreed to the published
version of the manuscript.
Funding:
This work was funded by project no. RO0418 (Sustainable systems and technologies, improv-
ing crop production for higher quality of production of food, feed, and raw materials, under conditions
of changing climate) funded by the Ministry of Agriculture, Czechia, and by the project “Plants as a
tool for sustainable global development” (registration number CZ.02.1.01/0.0/0.0/16_019/0000827)
within the program Research, Development, and Education (OP RDE) and by Research project
No.SUPB.RN.22.049, Jan Kochanowski University, Kielce, Poland.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Biomolecules 2022,12, 1583 16 of 21
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
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