Salicornia europaea L. and Suaeda maritima (L.) Dumort: bioactive compounds and future perspectives

Abstract

Halophyte plants have a phytochemical composition that results from the harsh conditions characteristic of their specific habitats. These plants have been used since ancient times because of the various biological activities which they possess. The aim of this review is to evaluate the main bioactive compounds and to outline the future therapeutic applications of two halophyte plants in Bulgaria. Studies on the phytochemical composition and biological activities of Salicornia europaea L. and Suaeda maritima (L.) Dumort are included. These halophyte plants are found along the Black Sea coast around salt lakes and marshes in Bulgaria. The data obtained indicate that these plants exhibit hepatoprotective, antineoplastic, antioxidant, anti-inflammatory, antidepressant, antimicrobial and antiviral biological activities, and their extracts have promising potential for inclusion in functional foods, dietary supplements and novel herbal pharmaceuticals.

Keywords:

• Salicornia europaea L
• Suaeda maritima
• salt-tolerant plants
• halophyte
• bioactive compounds
• phytochemicals
• biological activity

Introduction

Halophytes include plant species that belong to various botanical families. They are associated with salt tolerance and grow in a salt concentration of at least 200 mmol/L NaCl [1]. Unlike most plants, they are able to grow in areas characterised by severe conditions, including not only salinity but also high concentrations of heavy metals, flooding or drought and temperature variations [2,3].

There are two main types of halophyte plants – obligate and facultative. Obligate halophytes require high salt concentrations to complete their life cycle, while facultative halophytes do not require salinity [4,5]. Halophytes live in shore shallows and estuaries, mangrove forests, coastal salt marshes, salt lakes and saline desserts [2].

To grow and reproduce in such stressful environments, halophyte plants have developed different mechanisms of salt tolerance, including membrane ion transporters, metabolic changes, synthesis of specific enzymes, genetic adaptations, etc. [2]. Because saline soils are unfavourable, only 2% of the worldwide flora are halophyte plants [6].

The amount of land with high soil salinity is steadily increasing due to global urbanisation and an increasing amount of irrigated and cultivated land [6]. Therefore, the investigation of the salt resistance mechanism of halophytes and the subsequent creation and cultivation of hybrid plants, which can successfully grow on saline soil, can solve the problem of the growing need for food, due to the rapidly increasing global population and the increase in the areas with high soil salinity [7,8]. Furthermore, the consumption of these plants can provide essential nutrients and antioxidants, and another advantage is that they taste like conventional salad crops [9–11].

The phytochemical composition of halophytes includes minerals, vitamins, phenolic compounds, fatty acids, fibres, flavonoids, alkaloids, coumarins, saponins, terpenoids and sterols [1]. The synthesis of these bioactive compounds determines the valuable medicinal application of halophytes as a future perspective [1]. During the last decade, the biological effects of halophytes have been studied in detail; as a result it was shown that they have anti-inflammatory, antibacterial, antiviral, antioxidant, cytoprotective, anticancer and hepatoprotective properties [6]. Growth under such harsh conditions induces the production and accumulation of reactive oxygen species (ROS) by these plants. Reactive oxygen species are free oxygen radicals that can cause cellular and tissue damage, metabolic disorders and premature ageing [12]. To protect themselves from these harmful effects of ROS, halophytes synthesise antioxidants and secondary metabolites (for example phenolics, saponins and alkaloids) [12]. With the biosynthesis of these compounds, the useful pharmacological properties of halophyte plants can be explained [12]. Particularly relevant are studies related to the antitumoral activity of halophytes because of the lack of serious side effects in contrast to conventional anticancer drugs. Studies have shown that these plants exhibit activities associated with inhibition of tumour cells, lowering the levels of intracellular ROS and apoptosis induction, which makes halophytes a promising source of active substances with potential use in the treatment of cancer [12–14].

Another beneficial application of halophyte plants is their possible use as alternatives to salt, and the introduction of halophytes into diets could provide food with a healthy level of sodium [11,15–17]. According to the WHO, this will undoubtedly lower the risk of hypertension and cardiovascular diseases and consequently the risk of premature mortality [15,16].

Another application with potential future success is the production of biofuel from halophyte plant species [18,19]. Halophyte-based biofuel is a prospective solution to global environmental and economic issues [18,19].

The aim of this review is to outline and evaluate the information about the nutrients, bioactive compounds and potential medicinal applications of the two most common halophyte plants distributed in Bulgaria, Salicornia europaea L. and Suaeda maritima L. The review is focused on these two species as S. europaea L. and S. maritima L. are associated with a rich phytochemical composition, and have also been used since ancient times to treat a variety of symptoms and diseases and have promising potential to be incorporated into novel products with applications in cosmetics, medicine and agriculture.

Materials and methods

The search strategy was to look for studies referring to the isolation of bioactive compounds from Salicornia europaea L. and Suaeda maritima L. and their biological activities. This was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, which is presented in Figure 1. This search was performed using the following databases: Science Direct, PubMed and Web of Science.

Figure 1. PRISMA 2020 flow diagram [20].

The keywords included in the search were: ‘halophytes’, ‘Salicornia europaea L.’, ‘Suaeda maritima L.’, ‘bioactive compounds’, ‘phytochemicals’, ‘animal studies’, ‘human studies’ and ‘cell culture studies’. The selected articles were read and identified in the final step. Overall, 76 studies were selected and included in the present review.

Results and discussion

Salicornia europaea L

General characteristics, history, morphology and distribution

Salicornia europaea L. is a succulent, halophyte plant that belongs to the Chenopodiaceae family [21]. S. europaea is relatively popular under the names ‘saltwort’ and ‘marsh samphire’ and is also known as S. herbacea [21]. The name Salicornia comes from the Latin word meaning’ salt’, because species from the genus Salicornia, including S. europaea L., are the most salt-resistant plants in the world [22]. S. europaea L. requires salt to gain biomass and is a typical example of an obligate halophyte [5]. Studies have shown that the optimum salinity for the genus Salicornia is between 200 and 400 mmol/L NaCl [5]. However, studies suggest that this plant could tolerate soil salinity levels at or above approximately 1000 mmol/L NaCl [22]. These unique characteristics have led to heightened interest in this halophyte plant species [22].

S. europaea naturally grows on the coasts of Europe, the United States of America, South Africa, Southwest and Central Asia, and the Mediterranean basin [23–25]. In Bulgaria, the plant can be found along the coasts of the Black Sea, south of the Bulgarian city of Sozopol [25]. The halophyte has a limited distribution, and its period of blooming in Bulgaria is during the months of August and September [25]. S. europaea is not included in European Pharmacopoeia.

Morphologically, S. europaea has leafless stems with many opposite branches, with heights up to 35 cm [22,25]. The plant has a dark green colour, which turns green-yellow, and then pink or red, when the plant completes its life cycle [22]. Furthermore, the dark green stems could become yellow or red during the autumn, when the plant is saturated with more salt than during the other periods of the year [22].

S. europaea is well known in European and Korean folk medicine [26,27]. Because of the high nutritional value of this halophyte, it is an edible vegetable in countries, such as Italy, France and Spain [26]. Moreover, this halophyte plant is used for vinegar production in some countries in Europe [26]. It is also used as a source of oilseed and is associated with beneficial biological effects [26]. The aerial parts of this plant are basically used as a food and as a medicinal plant in the folk medicine of different nations [26].

Chemical study and biological activities

S. europaea is a source of compounds with antioxidant properties, whose function is to protect its cells from the influence of harsh conditions, which characterize its unfavourable habitat [8,26,28]. Examples of substances with antioxidant activity produced from S. europaea, are phenolic compounds with a total phenolic content of 43.1 and 40.3 mg GAE/g dw for leaves and roots, respectively [8,17,26,29]. Moreover, this plant is rich in minerals such as magnesium, calcium, potassium and iron [16,30]. The content of such substances explains the use of this plant in traditional medicine for the management of diseases and disorders such as diabetes, obesity, cancer, constipation or diarrhoea, nephropathy and hepatitis [26].

The main bioactive compounds detected in S. europaea are oleanane triterpenoid saponins, caffeoylquinic acid derivatives, flavonoids, chromones, lignans, sterols, organic acids and aliphatic compounds [28]. Table 1 presents the bioactive compounds isolated from the herb of S. europaea. The rich phytochemical composition of this halophyte defines its future application for the prevention and treatment of many diseases. Therefore, this plant has the potential to be included in pharmaceuticals, dietary supplements or herbal drugs, and cosmetic products.

Table 1. Phytochemical composition of S. europaea L.

Biologically active compound	Plant part	References
Macroelements
Sodium	Leaves, Stems and Roots	[30]
Calcium	Leaves, Stems and Roots	[16,30]
Potassium	Leaves, Stems and Roots	[16,30]
Magnesium	Leaves and Stems	[16,30]
Phosphorus	Leaves and Stems	[30]
Microelements
Iron	Leaves and Stems	[16,30]
Copper	Leaves and Stems	[30]
Zinc	Leaves and Stems	[30]
Manganese	Leaves and Stems	[30]
Nickel	Leaves and Stems	[30]
Silicon	Leaves and Stems	[30]
Vitamins
Vitamin A	Leaves and Stems	[30]
Vitamin C	Leaves and Stems	[30]
Vitamin B1	Leaves and Stems	[30]
Vitamin B2	Leaves and Stems	[30]
Vitamin B3	Leaves and Stems	[30]
Vitamin B6	Leaves and Stems	[30]
Pigments
β-carotene	Leaves and Stems	[30]
Oleanane triterpenoid saponins
3b-Hydroxy-23-oxo-30-noroleana- 12,20(29)-diene-28-oic acid	Leaves and Stems	[28]
3-O-β-D-Glucuronopyranosyl-28-O-β-D-glucopyranoside	Leaves and Stems	[28]
30-Norhederagenin 3-O-b-D-glucuronopyranosyl-28-O-b-D-glucopyranoside	Leaves and Stems	[28]
30-Norhederagenin 3-O-b-D-glucuronopyranosyl-28-O-b-D-glucopyranoside	Leaves and Stems	[28]
Gypsogenin	Leaves and Stems	[31]
Gypsogenin 3-O-b-D-glucuronopyranoside	Leaves and Stems	[28,31]
Gypsogenin 3-O-b-D-glucuronopyranosyl-28-O-b-D-glucopyranoside	Leaves and Stems	[28]
3b,29-Dihydroxyolean-12-en-28-oic acid 28-O-b-D-glucopyranosyl ester	Leaves and Stems	[28]
Oleanolic acid 28-O-b-D-glucopyranoside	Leaves and Stems	[28]
Chikusetsusaponin IVa	Leaves and Stems	[31,32]
Chikusetsusaponin IVa methyl ester	Leaves and Stems	[28,32]
Calenduloside E	Leaves and Stems	[28,31]
Calenduloside E 60-methyl ester	Leaves and Stems	[28]
Caffeoylquinic acid derivatives
Tungtungmadic acid (3-caffeoyl-4-dihydrocaffeoyl quinic acid	Leaves and Stems	[28]
5-dicaffeoylquinic acid	Leaves and Stems	[28]
Methyl 3,5-dicaffeoylquinate	Leaves and Stems	[28]
3,4-Dicaffeoylquinic acid	Leaves and Stems	[28]
Methyl 4-caffeoyl-3-dihydrocaffeoylquinate	Leaves and Stems	[28]
4-Dihydrocaffeoyl quinic acid	Leaves and Stems	[33]
Flavonoids and flavanones
20-Hydroxy-67-methylenedioxyisoflavone	Leaves and Stems	[28]
(-)-(2S)-20-Hydroxy-6,7-methylenedioxyflavanone	Leaves and Stems	[28]
20,7-Dihydroxy-6-methoxyisoflavone	Leaves and Stems	[28]
5,7,2-Trihydroxy-6-methoxyisoflavone (Irilin B)	Leaves and Stems	[34]
Quercetin 3-O-(6″-O-malonyl)-β-D-glucoside	Leaves and Stems	[28]
Quercetin	Leaves and Stems	[26, 28,32]
Quercetin 3-O-β-D-glucopyranoside	Leaves and Stems	[26,28,31,35]
Quercetin-3′,4′-di-O-β-D-glucopyranoside	Leaves and Stems	[33]
Rutin	Leaves and Stems	[26,28,29,32]
Isorhamnetin 3-O-β-D-glucopyranoside	Leaves and Stems	[28,35]
Quercetin 3-O-(6”-O-malonyl)-b-D-glucoside	Leaves and Stems	[28]
Isoquercitrin 6”-O-methyloxalate	Leaves and Stems	[28]
2S-20,7-Dihydroxy-6-methoxyflavanone	Leaves and Stems	[28]
2S-20-Hydroxy-6,7-dimethoxy-flavanone	Leaves and Stems	[28]
2S-5,20-Dihydroxy-6,7-methylenedioxyflavanone	Leaves and Stems	[28]
Luteolin	Leaves and Stems	[26,28,31,32]
Acacetin	Leaves and Stems	[31]
Kaempferol	Leaves and Stems	[28,32]
Kaempferol-3-O-b-D-glucoside	Leaves and Stems	[28,31,32]
Hesperidin	Leaves and Stems	[26,31]
Hesperetin	Leaves and Stems	[31]
Rhamnetin	Leaves and Stems	[26]
Isorhamnetin	Leaves and Stems	[31]
Isorhamnetin-3-O-b-Dglucopyranoside	Leaves and Stems	[31]
Chromones
6,7-Methylenedioxychromone	Leaves and Stems	[28]
6,7-Dimethoxychromone	Leaves and Stems	[28]
7-Hydroxy-6-methoxychromone	Leaves and Stems	[28]
7-O-b-D-Glucopyranosyl-6-methoxychromone	Leaves and Stems	[28]
7-Hydroxy-6,8-dimethoxychromone	Leaves and Stems	[28]
Sterols
Stigmasterol	Leaves and Stems	[28,32]
Ergosterol	Leaves and Stems	[28]
β-Daucosterol	Leaves and Stems	[28,32]
Cerevisterol	Leaves and Stems	[28]
β-Sitosterol	Leaves and Stems	[28,32]
Lignans
Syringaresinol 4-O-b-D-glucopyranoside	Leaves and Stems	[28]
Erythro-1-(4-O-b-D-glucopyranosyl-3,5-dimethoxyphenyl)-2-syringaresinoxyl-propane-1,3-diol	Leaves and Stems	[28]
Ongifloroside B	Leaves and Stems	[28]
(-)-Syringaresinol	Leaves and Stems	[28,32]
Episyringaresinol-40′′-O-b-D-glucopyranoside	Leaves and Stems	[28]
Tortoside A	Leaves and Stems	[28]
Acanthoside B	Leaves and Stems	[17,28]
Fatty acids
Stearic acid	Leaves and Stems	[28,36,37]
γ-Linolenic acid	Leaves and Stems	[28,36,37]
Linoleic acid	Leaves and Stems	[28,36,37]
Palmitic acid	Leaves and Stems	[28,36,37]
Oleinic acid	Leaves and Stems	[36,37]
Myristic acid	Leaves and Stems	[37]
Phenolic acids
Vanillic aldehyde	Leaves and Stems	[26,28]
Catechol benzoic acid	Leaves and Stems	[28]
Tannic acid	Leaves and Stems	[26]
Quinic acid	Leaves and Stems	[26]
Hydroxycinnamic acids
Protocatechuic acid	Leaves and Stems	[28]
Ferulic acid	Leaves and Stems	[16,28,38]
Caffeic acid	Leaves and Stems	[28]
p-Coumaric acid	Leaves and Stems	[16,26,35]
Rosmarinic acid	Leaves and Stems	[26]
Chlorogenic acid	Leaves and Stems	[26,29]
Others
Uracil	Leaves and Stems	[28]
Icariside B2	Leaves and Stems	[28]
Phytol	Leaves and Stems	[28,31,32]
Dioctyl phthalate	Leaves and Stems	[28]
Dibutyl phthalate	Leaves and Stems	[28]
Pheophorbide A	Leaves and Stems	[28]
(13^2S)-Hydroxy-pheophorbide A	Leaves and Stems	[28]
Malic acid	Leaves and Stems	[26]
5-(Hydroxymethyl)furfural	Leaves and Stems	[16]
1-Octadecanol	Leaves and Stems	[28]
1-Octacosanol	Leaves and Stems	[28]

According to data obtained from animal and human studies, S. europaea has promising potential to be used for the treatment of inflammation, depression, memory and cognitive deficits, cardiovascular diseases, bacterial and fungal infections, obesity and cancer. Table 2 summarises the main benefitial biological activities of S. europaea.

Table 2. Biological activities of S. europaea L.

Study objectives	Study design	Study duration	Main results	Ref.
Evaluation of the effects on memory of S. europaea L.	Fifty-three participants: 26 participants received 600 mg of S. europaea L.extract daily, 27 were in the placebo group.	12 weeks	Improvement of the cognitive function in the patients with mild cognitive impairment.	[39]
Assessment of the influence of S. europaea L. on progression of Alzheimer’s disease	Forty male mice divided into five groups: control group - intraperitoneal injection with 0.9% saline; 2^nd group − 2 mg/kg scopolamine intraperitoneally; 3rd group − 50 mg/kg S. europaea L. extract orally and 2 mg/kg scopolamine intraperitoneally; 4^th group − 100 mg/kg S. europaea L. extract orally and 2 mg/kg scopolamine intraperitoneally; 5^th group − 10 mg/kg tacrine orally and 2 mg/kg scopolamine intraperitoneally.	1 week	Antiamnesic effects, improved behavioural and cognitive deficits. Anti-cholinesterase, antioxidative and anti-neuroinflammatory activity.	[40]
Evaluation of the effects of S. europaea L. on vascular dysfunction and hypertension, caused by excessive salt intake.	Male rats randomly divided into six groups: Two control groups, Group 3 consumed high quantity of salt, Group 4 and 5 had intake of 1400 mg/kg S. europaea L. extract daily.	6 weeks	S. europaea L. did not cause dysfunction of the coronary artery even though it had a high salt content. Improved prevention of the occurrence of hypertension and vascular dysfunction.	[16]
Examination of the effects of S. europaea L. on prevention of atherosclerosis and postangioplasty restenosis.	Twenty-eight male mice divided into four groups: the 1^st, 2^nd and 3^rd group received orally desalted S. europaea L. extract 1.5, 15 and 150 mg/kg daily, respectively; the control group received orally an equivalent volume of 1% gum Arabic solution.	2 weeks	Suppressed vascular smooth muscle cells migration and proliferation.	[35]
Assessment of the influence of S. europaea L. on microglial inflammation.	Thirty-six male mice divided into 4 groups: the 1st group received orally 0.9% isotonic solution, the 2^nd (negative control) received orally neurotoxin. Groups 3 and 4 had also oral intake of S. europaea L. extract and the neurotoxin.	7 days	Anti-neuroinflammatory and antioxidant activity.	[34]
Evaluation of antidepressant effects of S. europaea L.	Sixty male mice divided into six groups: The 1^st and the 2^nd group had intake of distilled water. The 3^rd group received venlafaxine in a dose of 9.38 mg/kg. Groups 4, 5 and 6 received S. europaea L. extract in a dose of 1.8, 1.35 and 0.9 g/kg, respectively.	3 weeks	S. europaea L. extract demonstrated antidepressant effect.	[41]
Evaluation of the efficacy of S. europaea L. on obesity.	Fifty male rats divided equally into 5 groups: 1^st received saline, 2^nd received high-fat diet, 3^th group - high-fat diet and 250 mg/kg daily orally desalted S. europaea L. powder, 4^th group - high-fat diet and 500 mg/kg daily orally desalted S. europaea L. powder, 5^th group - high-fat diet and 200 mg/kg daily Garcinia cambogia.	12 weeks	Antiobesity activity.	[42]
Evaluation of the antimicrobial and antifungal effects of S. europaea L.	In vitro study: Escherichia coli, Klebsiella pneumonia, Bacillus subtilis and Staphylococcus aureus and two fungal strains including Candida albicans and Candida parapsilosis were used. For controls were used ampicillin for bacteria and fluconazole for fungal strains.	–	Antimicrobial and antifungal activity.	[43]
Assessment of the protective effect of S. europaea L. on skin epithelium.	Twenty-nine healthy women (age 30-55). Cream containing S. europaea L. extract was topically applied on the one side of the face of the participants. The test zones of the face were exposed to sun for 3 h daily from September to November.	12 weeks	Improved skin surface texture in the sun-exposed areas. No adverse effects were observed.	[44]
Evaluation of the influence of S. europaea L. on PGE2, NO production and ROS levels	In vitro cell culture study. Model cells: RAW 264.7 macrophages.	–	Suppression of PGE2 production. Inhibition of NO release. Inhibition of intracellular ROS activity.	[33]

It was suggested that the enhancement of the cognitive function is due to the bioactive lignan acanthoside B found in S. europaea [17,39]. The extract of this plant has anti-amnesic effects, which lead to improved memory [17,39]. Consequently, the extract of this plant has the potential to be used in the treatment of Alzheimer’s disease, which affects millions of people worldwide and is characterized by cognitive and memory dysfunction [17,39,45].

Studies have also shown that S. europaea extract contains polyphenolic compounds, including flavonoids, tannins and lignans, which are known for their wide range of biological effects [33,46]. These compounds are considered to contribute to antioxidant and anti-inflammatory effects of the halophyte with mechanisms, including decreasing the prostaglandin E2 and nitric oxide levels [33]. In addition to providing antioxidant and anti-inflammatory activity, the polyphenols in S. europaea L. have been investigated for cytotoxic activity [6,12]. Studies have suggested that decreased ROS levels are a possible reason for the antineoplastic effect of the extract [12,33]. The halophyte also has enzymatic antioxidant systems, protecting it from the stressful environment, which can cause tumour destruction [12,47]. Oxidative stress and inflammatory manifestations are very common features of many diseases and could be successfully treated with S. europaea in the future.

Studies have indicated that S. europaea L. contains irilin B, which can be applied to treat neuroinflammation [34]. Irilin B, which belongs to the isoflavone class, also has antioxidative effects [34].

The obtained data also suggest the future application of S. europaea in the prevention and treatment of high blood pressure, cardiovascular diseases, atherosclerosis and vascular restenosis [16,35]. Despite the presence of a high concentration of sodium, the extract of S. europaea does not lead to vascular dysfunction [16]. trans-Ferulic acid might be associated with vasoprotective properties [16,38,48,49]. This bioactive phenolic acid may also contribute to antioxidant, anti-inflammatory and antineoplastic activities [48,49].

The extract of S. europaea has no known side effects. The safety of the extract is another advantage to consider. However, since there are few clinical studies evaluating the benefits and adverse effects of this extract, it is recommended for more in vivo studies and multicentre randomized double-blind studies to be performed in the future.

Suaeda maritima (L.) dumort

General characteristics, history, morphology and distribution

Suaeda maritima (L.) Dumort is a typical example of an obligatory halophyte that grows on soils characterised by high sodium concentration, such as salt marshes and coastal belts [50]. The halophyte belongs to the Chenopodiaceae family [50]. The plant is known by the name ‘suwaid’, which means ‘black’ in Arabic, because the halophyte has a black colour at the end of its life cycle [51]. In England, S. maritima is known by the common name ‘seepweed’ and ‘annual sea blite’ [51,52].

S. maritima is a cosmopolitan plant. It can be found in inland saline areas and over the coasts of India, the Canary Islands, Europe, Asia, Australia, North America and Argentina [25,51,53–55]. Additionally, this plant grows along the coast of the Mediterranean and Arabian seas [51]. In Bulgaria, it can be found along the coast of the Black Sea; in the northeastern parts, especially in the Village Razdelna, which is near the city of Varna; and over the hilly plain of the Tundzha River, especially in the villages of Radnevo, Topoclovo and Straldzha [25]. The halophyte has a blooming period in Bulgaria during July and August [25]. S. maritima is not included in European Pharmacopoeia.

S. maritima is a succulent plant with small green leaves, and the stem can be branched or not [25,53]. The plant grows to approximately 10-50 cm [25] and has a green colour, which turns grey when the halophyte dries up [25,53].

S. maritima is well known in Indian traditional medicine; the whole plant is used for the treatment of hepatitis [52,56–59]. It is also widely used in other countries in Asia [31]. In Thailand, the roots of this plant are traditionally used in the treatment of different skin problems and allergies [33]. In folk medicine, this halophyte is also used for the treatment of viral and bacterial infections [57]. In the past, S. maritima was associated with cytotoxic activity [60]. Its leaves are edible and popular as vegetables in some countries, especially in Asia [31,52,61].

S. maritima could be promising source for the production of novel eco-friendly insecticides because the extract from this plant has larvicidal, ovicidal and pupicidal properties [57]. Furthermore, S. maritima could protect plants not only from insects but also from pathogens due to its proven antibacterial activity [57,62,63]. The use of plant-based insecticides could reduce the harmful effects on human health and the environment and lower the level of resistance among microorganisms [57].

Chemical study and biological activities

The phytochemical composition of the extract of S. maritima includes carbohydrates, phenolic compounds (anthroquinone glycosides, flavonoids and tannins), sterols, cardiac glycosides, saponins and alkaloids [31,64,65]. Its main biologically active compounds are summarized in Table 3.

Table 3. Phytochemical composition of S. maritima L.

Biological compound	Plant part	References
Macroelements
Sodium	Leaves and Stems	[11]
Calcium	Leaves and Stems	[11]
Potassium	Leaves and Stems	[11,64]
Magnesium	Leaves and Stems	[11,59]
Phosphorus	Leaves and Stems	[64]
Microelements
Iron	Leaves and Stems	[11,59]
Chromium	Leaves and Stems	[11,59]
Copper	Leaves and Stems	[11,59]
Manganese	Leaves and Stems	[11,59]
Zinc	Leaves and Stems	[11,59]
Nickel	Leaves and Stems	[11]
Pigments
Lutein	Leaves and Stems	[11]
β-Carotene	Leaves and Stems	[11,31]
Vitamins
Vitamin A	Leaves, Stems and Roots	[11,31]
Vitamin E	Leaves, Stems and Roots	[11,31]
Vitamin C	Leaves and Stems	[11,31,64]
Vitamin B1	Leaves and Stems	[64]
Vitamin B2	Leaves and Stems	[64]
Vitamin B6	Leaves and Stems	[11]
Phenolic acids
3,4-Dihydroxybenzoic acid	Leaves and Stems	[11]
p-Hydroxybenzoic acid	Leaves and Stems	[11]
3-Hydroxybenzoic acid	Leaves and Stems	[11]
Vanillic acid	Leaves and Stems	[11]
Syringic acid	Leaves and Stems	[11]
Salicylic acid	Leaves and Stems	[11]
Ellagic acid	Leaves and Stems	[11]
Hydroxycinnamic acids
Neochlorogenic acid	Leaves and Stems	[11]
Chlorogenic acid	Leaves and Stems	[11,31,66]
Caffeic acid	Leaves and Stems	[11,31,66]
Coumaric acid	Leaves and Stems	[11]
Ferulic acid	Leaves and Stems	[11,66]
Methyl trans-ferulate	Leaves and Stems	[31]
Methyl cis-ferulate	Leaves and Stems	[31]
Sinapic acid	Leaves and Stems	[31,66]
Rosmarinic acid	Leaves and Stems	[11]
Cinnamic acid	Leaves and Stems	[11]
n-Tetradecanyl dihydrocaffeate	Leaves and Stems	[66]
n-Hexadecanyl dihydrocaffeate	Leaves and Stems	[66]
Flavonoids
Catechin hydrate	Leaves and Stems	[11]
Epigallocatechin gallate	Leaves and Stems	[11]
Epicatechin	Leaves and Stems	[11,63]
Ouratea-catechin	Leaves and Stems	[11]
Quercetin	Leaves and Stems	[11,31,66]
Kaempferol	Leaves, Stems and Roots	[31,56,63,66]
Taxifolin	Leaves and Stems	[11]
Naringenin-7-glucoside	Leaves and Stems	[11]
Luteolin-7-o-glucoside	Leaves and Stems	[11]
Rutin	Leaves and Stems	[11]
Tannins
Ellagitannin	Leaves	[63]
Fatty acids
Myristic acid	Leaves	[65]
Palmitic acid	Leaves	[61,65]
Methyl palmitate	Leaves	[65]
Stearic acid	Leaves	[61]
Oleic acid	Leaves	[61]
Linoleic acid	Leaves	[61]
Linolenic acid	Leaves	[61]
6,11-Eicosadienoic acid methyl ester	Leaves	[65]
9,12-Octadecadienoic acid	Leaves	[65]
Steroids
Campesterol	Leaves	[65]
Essential oils
Cirtonellyl propionate	Leaves	[65]
Cirtonellyl acetate	Leaves	[65]
2-hexyl-1-octanol	Leaves	[65]
Citronellal	Leaves	[65]
Aciphyllene	Leaves	[65]

S. maritima contains minerals, such as sodium, calcium, potassium, magnesium, iron, chromium, copper, manganese, zinc and nickel [11,59,64]. However, in the halophyte there are no toxic minerals such as cadmium and lead [11]. The nutritional value is also proven by the presence of vitamins and plant pigments [11,31]. Lutein and β-carotene are examples of plant pigmentsthat were found in the extract of S. maritima L. [11,31]. These pigments play an important role in maintaining eye health, while β-carotene is also an essential source of Vitamin A [11,67,68]. Vitamin A and Vitamin E are fat-soluble vitamins that are detected in the extract of S. maritima [11,31]. These vitamins are associated with strong antioxidant properties, and are also essential for the immune system and for the normal functioning of many organs. Vitamin C and Vitamin B6 are examples for water-soluble vitamins, found in S. maritima [11,31,64]. Vitamin C is a powerful antioxidant that is used in theprevention and treatment of many diseases, such as scurvy, coronary heart disease, stroke and cancer [11,69–71].

S. maritima L. is also a source of essential oil, which is associated with strong antimicrobial, antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral and insecticidal activity [65,72–74]. The extract from S. maritima mainly contains cirtonellyl propionate, cirtonellyl acetate, 2-hexyl-1-octanol, citronellal and aciphyllene [65].

Moreover, the antioxidant properties are also due to the presence of phenolic compounds and flavonoids in this halophyte plant, which are produced as a result of environmental stress, including salinity [11,75]. Flavonoids in S. maritima extract at a concentration of 0.8% (for the leaves) and 1.08% (for the stem) contribute to its hepatoprotective, anti-inflammatory and antineoplastic activity [76].

Recent studies reported that S. maritima has hepatoprotective effect due to the triterpenoids detected in its leaves [31,77]. Activity against hepatitis B virus and human immunodeficiency virus was also reported and it is considered to be a result of the polysaccharide found in the plant leaves [77]. It was also suggested that the antiviral activity is a result of the presence of flavonoids, phenolic compounds and tannins [59]. Other studies reported antibacterial and antioxidant properties [31,64,77]. Of great importance is the experimentally proven antibacterial activity against Pseudomonas aeruginosa [63]. This bacterium causes severe infections worldwide and is connected with multiantibiotic resistance [78]. The main biologically active compounds are summarized in Table 4.

Table 4. Biological activities of S. maritima L.

Study objectives	Study design	Study duration	Main results	References
Evaluation of the antimicrobial activity of S. maritima L.	The antimicrobial activities of different S. maritima L. extracts were examined by using agar disc diffusion method. Four bacterial strains were used, including Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Streptococcus pneumoniae. For positive control was used levofloxacin. The plates were incubated at 37° for 24 h. The antimicrobial activities were determined by calculating the diameter of the growth inhibition zones.	–	Demonstrated inhibition against the tested gram-positive and gram-negative bacterial strains.	[62]
Assessment of the antibacterial activity of S. maritima L. against Pseudomonas aureginosa.	Forty-five fish were used for the study. They were infected with Pseudomonas aureginosa. The fish were equally divided into five groups. The first group was control group. The second group received amoxicilline 25 mg/g. The third group received 25 mg/g crude leaf extract and the fourth group received 10 mg/g purified leaf extract.	5 days	Observed antimicrobial activity against Pseudomonas aeruginosa.	[63]
Examination of the antioxidant activity of S. maritima L. extract.	The antioxidant activity was determined in vitro with different concentrations of leaf exctract. For control was used Vitamin C. The DPPH assay, nitric oxide radical scavenging assay, superoxide radical scavenging assay and lipid peroxide radical scavenging assay were performed.	–	Demonstrated radical scavenging activity.	[59]
Assessment of the activity of S. maritima L. against Hepatitis B virus.	The assay was performed with extracts with different concentrations by the radiometric method. Control was used without the halophyte leaf extract. Liquid scintillation was used to determine the radiation. The percent of inhibition of the DNA polymerase activity was calculated.	–	Demonstrated inhibitory effect against the Hepatitis B virus DNA polymerase.	[59]
Evaluation of the inhibitory activity of S. maritima L.against HIV-1 reverse transcriptase.	The assay was performed by the radiometric method. Control was used without the halophyte leaf extract. Liquid scintillation was used to determine the radiation. The percent of inhibition was calculated.	–	Demonstrated inhibitory effect against the HIV-1 reverse transcriptase.	[59]
Evaluation of the toxicity of S. maritima L. extract.	Female albino rats were used for the experiment. The animals received 250 mg/kg body weight of the S. maritima L. leaf extract. The animals were observed for 24 h. If there was no observed mortality, the experiment was conducted with a higher dose − 300 mg/kg body weight.	24 h	A toxic effect was not observed.	[59]
Evaluation of the depressant activity of S. maritima L. extract relative to central nervous system.	Twenty mice were used for the study. They were divided equally into four groups. The first group was for control. The second group received 1 mg/kg of diazepam. The third and the forth group received 250 mg/kg and 500 mg/kg, respectively. The number of movements of the mice were scored to assess the central nervous system depressant activity.	1 h	Significant depressant activity relative to central nervous system.	[52]
Assessment of the effect of S. maritima L. extract on gastrointestinal motility activity.	Twenty mice were used for the study. They were divided equally into four groups. The first group was for control. The second group received loperamide 25 mg/kg. The third and the fourth group received 200 mg/kg and 400 mg/kg respectively. After 30 min, the distances traveled by charcoal meal were measured.	30 min	Reduction in gastrointestinal motility.	[52]
Examination of the cytotoxic effect of S. maritima L. extract.	Brine shrimp lethality test was used. The percent of mortality was determined.	24 h	Strong cytotoxic activity was observed.	[52]

The data obtained suggest the need for further investigation of specific compounds such as polyphenols, terpenoids, tannins and sterols.

Similar to the extract of S.europaea, the extract from S. maritima is not associated with side effects. However, more clinical studies regarding the safe use and the risk of side effects need to be conducted. In the future, there should be performed more in vivo studies and multicentre randomized double-blind studies.

Conclusions

Halophyte plants are plants that can grow on soils with a high salt concentration. Salt tolerance is the result of the phytochemicals they produce and the specific mechanisms they have developed. The phytochemicals isolated from S. europaea L. and S. maritima L. are associated with various health benefits. Compounds from different classes of biologically active substances have been found in the extracts of these two halophyte plants, such as saponins, flavonoids, chromones, lignans, caffeoylquinic acid derivatives, sterols, organic acids, vitamins, microelements and macroelements. These phytochemicals determine the pharmacological effects of S. europaea and S. maritima and they are characterised with anti-inflammatory, antimicrobial, antifungal, hepatoprotective, cytotoxic, antioxidant, neuroprotective, antidepressant, antiobesity, anti-atherosclerosis and antihypertensive effects. In our opinion, the halophyte plants in Bulgaria, especially S. europaea L. and S. maritima L., have great therapeutic potential due to their rich phytochemical composition. However, their biological activity needs further studies in more detail in cell cultures, mammals and randomised clinical trials.

Author contributions

VD: data collection, data analysis, methodology, writing; SI: conceptualisation, data analysis, methodology, writing, supervision, final approval; KI: conceptualisation, methodology, supervision; DK-B: conceptualisation, methodology, supervision, final approval; NB: results interpretation, writing, supervision; MB: data collection, data analysis; NK: data collection, data analysis. All authors have read and approved the final version of the paper.

Acknowledgements

The authors gratefully acknowledge the financial support of the Medical University of Plovdiv for this study.

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Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.