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Review

Phytochemical Profiles and Biological Activities of Frankenia Species: A Review

by
Meyada Khaled
1,
Rachid Ouache
2,
Patrick Pale
3,* and
Hassina Harkat
1,2,*
1
Department of Pharmacy, Faculty of Medicine, Batna 2 University, Batna 05000, Algeria
2
Laboratory of Physio-Toxicology, Cellular and Molecular Pathology-Biomolecules (LPTPCMB), Batna 2 University, Batna 05000, Algeria
3
Laboratory of Organic Synthesis & Catalysis, Institute of Chemistry (UMR-CNRS 7177), University of Strasbourg, 67000 Strasbourg, France
*
Authors to whom correspondence should be addressed.
Molecules 2024, 29(5), 980; https://doi.org/10.3390/molecules29050980
Submission received: 11 January 2024 / Revised: 12 February 2024 / Accepted: 16 February 2024 / Published: 23 February 2024
(This article belongs to the Special Issue Halophytes: Nutrients, Bioactive Compounds, Chemical Characterisation and Potential Applications)
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Abstract

:
The relatively small Frankeniaceae family is represented by halophyte plants, growing in arid and semi-arid climates in saline, alkaline or calcareous soils. Due to their living conditions, they usually produce a large diversity of compounds, which often exhibit bioactivities. Some species of this genus have long been used as traditional herbal medicines to treat dysentery, diarrhea, gonorrhea, vaginal leucorrhea, respiratory diseases and wounds. To date, several studies on either phytochemical or pharmacological aspects, or both, have revealed that this genus is a rich source of diverse and novel bioactive chemicals, including phenolics, flavonoids, alkaloids and fatty acids. This review describes all the reported chemical profiles of Frankenia species, as well as the corresponding biological properties, when available. The aim of this review is to show the potential of these plants for various applications, especially therapeutic ones.

Graphical Abstract

1. Introduction

According to a very recent report from the World Health Organization (WHO), ‘traditional medicine has a long history of contributing to conventional medicine and continues to hold promise’ [1]. Indeed, since early times, human beings have learned how to address their health problems and various so-called traditional medicines have emerged all over the world and are still used, according to the 2019 WHO global report on traditional and complementary medicine [2]. These traditional medicines usually rely on natural products and mixtures of them, issued mostly from plants [3], but also from animals and microorganisms [4].
Marine environments are known for their high biodiversity. Among them, coastal environments exhibit specific plants able to grow in highly saline areas, often under severe variations in temperature, light intensity and drought. These plants, named halophytes, are not limited to such coastal areas but can be found in a diverse array of highly saline soils (Figure 1) [5]. To withstand such severe conditions, these plants have developed several ways to control and/or take away salt, but they also exhibit strong antioxidant systems composed of enzymes and highly bioactive secondary metabolites, such as phenolic compounds and alkaloids [6]. Probably for these reasons, halophytes are traditionally used in folk medicine for their curative properties against infectious diseases [7]. Hence, halophytes are currently gaining interest due to their nutraceutical potential, powerful antioxidant abilities and therapeutic significance in treating a variety of pathologies [8].
Among the halophytes, the Frankeniaceae family constitutes a relatively small family with originally 2 to 4–5 genera, but a recent taxonomic revision based on molecular phylogenetic studies retained the Frankeniaceae as a single genus, Frankenia [9]. The latter contains between 70 and 82 species that are found in deserts and sandy coastal locations with dry areas [9]. Similarly, the Frankeniaceae and Tamaricaceae families were considered as a pair of families that together made up the order Tamaricales, however, genetic studies have allowed them to be distinguished [9,10].
The shrubby and herbaceous species of Frankenia are known to mainly grow in arid and semi-arid climates in extremely saline, alkaline or calcareous soils. They can be found on all continents but are most common in the Western Hemisphere, particularly in the Mediterranean region up to the Middle East (Figure 2) [11]. Indeed, Frankenia species have been recorded in North Africa, especially in Algeria and Tunisia, as well as in Egypt, Portugal, Spain and France, but also in Turkey, Syria, Lebanon, Jordan and Palestine. They can also be found in Iraq and neighboring regions, such as Qatar, Kuwait and Iran (Table 1).
Despite their relevance in medicine and industry, studies about the Frankenia genus are unexpectedly limited, probably due to the scarcity of these plant species. Nonetheless, only a few species have been investigated in some detail (Table 1). Their chemical profile and/or their biological properties have been explored, revealing a wide variety of natural products and bioactivities.
The purpose of this study was to collect and systematically review the published phytochemical compositions and biological activities of the medicinal Frankenia species.

2. Phytochemical Profile of Frankenia Plants

From the studies mentioned above, more than 200 phytocompounds obtained from Frankenia extracts have already been identified. Among them, polyphenols, such as phenolic acids and flavonoids, are the major constituents and essential chemotaxonomic indicators. Further isolated compounds include alkaloids, terpenoids, steroids, fatty acids and other molecules.

2.1. Polyphenols

2.1.1. Phenolics

Phenolics are a broad category of chemical compounds that have one or more hydroxyl groups linked to at least one aromatic hydrocarbon ring [37]. Due to their hydroxylated conjugated structure, phenolic compounds have considerable potential as antioxidants [38]. Furthermore, their stability could allow their use as therapeutic agents.
Phenolic natural products are abundant in the Frankenia genus, especially in F. laevis, and exhibit a large variability (Figure 3). They were mainly represented by gallic acid (1–9), hydroxybenzoic acid (10–13), ellagitannins (14–27) and hydroxycinnamic acid (28–41) derivatives (Table 2). Other phenolic compounds (42–53) were also identified (Figure 3). The dihydroxybenzenes (44) and (45) were present in significant amounts in F. pulverulenta [39]. Additionally, compounds (10), (28) [23] and (31) [39] were the most representative compounds in F. thymifolia, followed by (29) [23].

2.1.2. Flavonoids

The Frankenia species, especially F. laevis, F. pulverulenta and F. thymifolia, contain a wide range of flavonoids (Table 3), mainly represented by flavonols, such as kaempferol (54–61), quercetin (62–73), catechin (74–78) and isorhamnetin (79–81) derivatives. The compounds (74) and (75) were the most representative flavonoids in F. thymifolia and F. pulverulenta, respectively [23,39]. Additionally, the flavanone (82) and the O-glycosylated flavone (83) were described in F. thymifolia (Figure 4).

2.1.3. Lignans

Lignans do not appear to be extremely prevalent in Frankenia (Table 4). The arylated tetralin derivative (84) is the most common lignan found in these plants. A few tetrahydrofuranic lignans (85–87) have also been isolated and identified (Figure 5).

2.1.4. Coumarins

So far, a single example of coumarin, the simplest one (88), has been isolated and characterized from a Frankenia species (Table 4 and Figure 5).

2.2. Alkaloids

Surprisingly, only a few alkaloids could be found in Frankenia species, and they were mainly detected in F. pulverulenta (Table 5). The phytochemical investigation of this species has led to the identification of several compounds with a wide variety of structures (89–101). The alkaloid dihydrotecomanine (102) was detected in both F. pulverulenta and F. hirsuta (Figure 6). In F. aucheri(hirsuta), an α-amino acid metabolite, the N-acetyl serine (103), could also be observed and characterized. The same species also contains another peculiar amino acid with a heterocyclic core, the pterin-6-carboxylic acid (104), but an indoloquinolizine derivative (105) was also identified.

2.3. Terpenoids

As important building blocks in biosynthesis, terpenoids are widely represented in living species. This large class of natural compounds is extremely prevalent in the plant kingdom, where they play key roles in plant defense and communication [44]. They are frequently found in plant essential oils. Therefore, it is natural to find them in plants of the Frankenia genus. However, in Frankenia species, most of them have been identified as sesquiterpenes. Nevertheless, some mono- and diterpenes have also been found (Figure 7).

2.3.1. Monoterpenes

Monoterpenes are not common among Frankenia species. It was only in 2021 and 2022 that a few monoterpenes were identified in, respectively, F. pulverulenta and laevis. Indeed, the phytochemical analysis of F. laevis extracts revealed the presence of three tetrahydrobenzofuran-2(4H)-ones (106–108). In F. pulverulenta extracts, the bicyclic α-pinene (109) was detected (Table 6).

2.3.2. Diterpenes

A few compounds have been reported as diterpenes from Frankenia species. The acyclic diterpenoids (110–112) were isolated from F. laevis, while (113) and its derivative gibberellic acid (114) were present in the essential oil (EO) and methanolic leaf extract of F. pulverulenta, respectively (Table 6).

2.3.3. Sesquiterpenes

Sesquiterpenes are abundant in the Frankenia genus. Overall, 22 compounds belonging to this subclass of terpenoids were identified in the EO of F. laevis and F. pulverulenta, including eleven oxygenated sesquiterpenes (115–125) and eleven sesquiterpene hydrocarbons (126–136) (Table 6).
Nerolidol (116) and farnesyl acetate (119) were the most widespread sesquiterpenes present in F. laevis [43]. Furthermore, β-caryophyllene (135) was the major compound detected in F. pulverulenta. The second major compounds were cadinene (134), allo-aromadendrene (136), copaene (128) and ledol (121) [18].
However, the later terpenes (134), (135) and (136) were found to be present at a much lower amount in F. laevis [43].

2.4. Steroids

Although they do not seem to be common in Frankenia species, steroids have nevertheless been isolated and characterized (Figure 8 and Table 7). The majority of them have been isolated from F. foliosa and identified as secosteroids (137–141) [35]. It is worth noticing that the latter included vitamin D (139) as well as the unusual eringiacetal A (141). In addition, the two steroids (142) and (143) have been identified in F. pulverulenta [24], while the steroid (144) has been detected in F. hirsuta [36].

2.5. Alkanes and Alkenes

Long-chain alkanes are common in terrestrial plants, especially as part of their cuticular leaf wax. Therefore, alkanes are quite common in Frankenia species (Table 8). Overall, 15 alkane chemicals (145–158) were reported in both F. laevis and F. pulverulenta [18,43].
Most of these alkanes exhibit linear and long carbon chains, containing from 17 to 35 carbons. So far, a single example of an α-methylated chain alkane (156) has been reported in F. laevis. Similarly, the C20 linear alkane eicosane (159) has so far only been characterized in F. hirsuta [36].
In contrast, long-chain alkenes seem to be quite rare in Frankenia species. Indeed, only two alkenes (160) and (161) have been reported as the only alkenes in the genus [36,43]. Both exhibit a terminal vinyl group within a linear chain (C19 and C22, respectively).

2.6. Fatty Acids and Esters

Fatty acids and esters are ubiquitous in all living organisms and are essential to them, as they serve as membrane constituents, modulators in glycerolipids and as carbon and energy reserves in triacylglycerols, but also as signal molecules [45].
The Frankenia plants contain various fatty acids and esters. At least 20 different fatty acids and fatty acid esters were found within members of the genus Frankenia (Table 9), and grouped as saturated (162–171), monounsaturated (172–173) and polyunsaturated (174–178) fatty acids, saturated fatty acid methyl esters (179–180) and unsaturated fatty acid methyl esters (181–183). Palmitic acid (167) was the major compound of F. laevis, followed by (181) [43]. In addition, (167), (173) and (174) were reported as the major fatty acids in the oil of F. thymifolia [23].

2.7. Other Compounds

In addition to the large well-known natural product families mentioned above, compounds from other classes of natural chemicals have also been detected (Figure 9 and Table 10). A large variety of compounds was identified, such as alcohols (184–185), glycosides (186–191), aromatic compounds (192–195), heterocyclic compounds (196–198), aldehydes (199–200), ketones (201–202), organic acids (203–205) and esters (206–208).
Long-chain alkyl alcohols, unsaturated or not, (184–185) were detected in F. pulverulenta and F. laevis, respectively [24,43]. Surprisingly, the same hexadecane-1-ol (185) found in F. laevis was also observed in F. hirsuta but as its glycidyl ether (197) [32].
Highly abundant in organisms, especially in plants, glycosides were only scarcely found in Frankenia species. The common monosaccharides, glucose and mannose, were both detected in F. pulverulenta and F. hirsuta, but as, respectively, their 3-O-methylated or 6-O-acetylated derivatives (186–188) [24,32]. A desulfonylated allyl glucosinolate was also detected in F. hirsuta, (191) [32]. Such a sinigrin derivative is usually found in the Brassicaceae family. A di- and a trisaccharide were also detected in F. pulverulenta. The disaccharide was unexpectedly characterized as lactose (190) [24], while the trisaccharide was assigned as a β-analog of melezitose (189) [24]. Interestingly, the aromatized form of glucose, i.e., hydroxymethylfurfural (HMF) (199), was also detected in F. hirsuta [32].
Among the other aromatic compounds found (192–195), a demetallated chlorophyll, i.e., pheophytin A, was observed in Frankenia species, and more precisely in F. laevis [13]. Alternatively, the F. hirsuta species seems relatively rich in aromatic compounds, since the simple 1,3,5-trimethylbenzene (194), phthalate esters (206–207) and various benzyl or phenyl derivatives (192–193 and 208–209) have been observed [32,36]. A hexamethoxylated naphthalene derivative, i.e., (195), was detected in F. thymifolia [22].
A few jasmonoids, i.e., (204–205), were found in F. laevis [13], as well as a related cyclopentenyl bicyclic lactone in F. pulverulenta [24]. Interestingly, the macrolactone (201), related to the methyl ester (183), was also detected in F. pulverulenta [24].
Furthermore, the hydrazine (209) and the stable peroxide (210) were both reported from the F. hirsuta species [32].

2.8. Phytochemical Outcome

The phytochemical compositions of the various Frankenia species collected above reveal the rich chemical content of these plants and the variety of chemicals that have been detected, or isolated and characterized. These plants mainly produce phenol derivatives, which represent around one-quarter of all the so far identified chemicals. The other chemicals mostly observed belong to the flavonoid and terpenoid families (14–15% each), while alkaloids, fatty acids and esters represent approximately 10% of all Frankenia phytochemicals (Figure 10).
Overall, Frankenia species might be regarded as potentially rich sources of phenolics, flavonoids, sesquiterpenes and fatty acids or esters. Nevertheless, the phytochemical repartition is quite different from one species to another, as revealed in Figure 11.
Indeed, F. laevis and F. thymifolia are particularly rich in phenol derivatives, while F. pulverulenta and F. hirsuta exhibit less than 10% of such chemicals. Similarly, fatty acids or esters are mostly present in F. hirsuta and F. thymifolia, while they represent less than 10% of the phytochemical content of F. pulverulenta and F. laevis.
Flavonoids are mostly present in F. thymifolia and F. pulverulenta, and to a lesser extent in F. laevis. However, they are surprisingly almost absent in other species. The same surprising repartition can be observed for terpenoids, which are mostly present in F. pulverulenta and F. laevis, but also to a small extent in F. hirsuta and almost absent in other species.
Among Frankenia species, F. hirsuta seems to present the largest diversity. Indeed, in addition to the large and ubiquitous classes of compounds mentioned above, F. hirsuta also contains alkaloids, steroids, (oligo)saccharides and aromatic derivatives, as well as unexpected hydrazine and peroxide derivatives.
Such different repartitions may be useful as chemotaxonomic tools, complementing others. Indeed, previous research demonstrated that plants of the genus Frankenia may produce sulfated chemicals, where they serve as an indirect chemotaxonomic marker. Furthermore, their presence has been correlated to their affinity for saline environments [22].

3. Biological Activities of Frankenia Plants

3.1. In Traditional Medicine

As was reminded in the introduction, traditional medicine has a long history in human health and various variants have been developed around the world and are still practiced nowadays. In countries with limited access to modern therapy, traditional medicine is frequently the major source of primary healthcare requirements [1,2,46].
Used as traditional medicinal plants, Frankenia species appear to play a prominent role in the treatment of various diseases. Due to their astringent properties, Frankenia species are utilized in Asian and African (especially in Morocco) folk medicine for gargling or for topical application, either as tinctures or as herbal tea, e.g., with F. laevis or F. thymifolia. They are also used in these countries to treat a variety of clinical disorders, such as dysentery, diarrhea, gonorrhea, vaginal leucorrhea, mucus releases from the nose and catarrh-induced infections, again as plant infusions, with, e.g., F. pulverulenta, or as stupe, depending on the localization [17,18,47].
Gargle and decoction generated from the entire plant of F. pulverulenta are widely used in local medicine by the inhabitants of the Onaizah province in Saudi Arabia and are mostly used orally for their analgesic and carminative properties [18]. Also in Saudi Arabia, the powdered rhizome of F. aucheri (hirsuta) combined with milk is used to stimulate lactation in cows and camels, particularly in the winter [48].
It has also been reported that Puna inhabitants in South America used F. triandra as a forage but also as antiseptic in folk medicine [34].
Additionally, some Frankenia species can be converted into sticky glue mixtures, due to their specific natural product contents, e.g., kaempferol, quercetin and tannin. Therefore, they are used in totally different applications, notably to stick blade cutting edges and to seal stoneware (e.g., F. hirsuta) [32].
Overall, Frankenia plant species may thus be viewed as promising prospects for different applications in industry, and mostly in pharmaceutical applications.

3.2. In Vitro Biological Activities

Secondary plant metabolites, which are produced in large amounts by plant species, are crucial components for supporting human health. They contribute to the medicinal properties of plant species as antioxidants, anti-inflammatory, anti-carcinogenic and antibacterial agents [3,4], along with other capacities [46].
Because the large diversity of natural compounds discovered in Frankenia species mostly belong to well-known families of bioactive compounds, it is expected that these plants exhibit the corresponding biological activities. Therefore, several works have been performed to check these bioactivities. They are listed below.

3.2.1. Antioxidant Activity

The antioxidant activity of Frankenia species has been assessed using several methods, including the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical-scavenging analysis, 2,20-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) cation radical trapping, ferric ion reducing antioxidant power (FRAP), metal chelating activity (MCA), including copper (CCA)- and iron (ICA)-chelating activities, oxygen radical absorbance capacity (ORAC) assay and β-carotene oxidation test. The corresponding details have been collected in Table 11.
The aqueous acetone [17], methanol [13] and ethanol [41] extracts of F. laevis exhibited spectacular in vitro radical scavenging and copper chelating properties. However, the dichloromethane extract from this species was only able to chelate iron, probably due to the presence of various phenolics and flavonoids that can act as phytochelators [49], such as gallic acid, kaempferol and quercetin derivatives (see Table 2 and Table 3 and Figure 3 and Figure 4).
Likewise, F. pulverulenta ethyl acetate [19] and methanolic [39] extracts were investigated using DPPH, ABTS and ORAC assays, and potent antioxidant activity was reported. The antioxidant activity of the aqueous acetone extract of F. pulverulenta was also assessed [17]. The antioxidant potency can be linked to the well-known antioxidant compounds gallic acid (1), p-coumaric acid (34), quercetin (62) and catechin (74) which are abundantly present in this species. Ben Mansour et al. [21] demonstrated, in 2016, that F. thymifolia ethyl acetate extracts exhibited strong antioxidant activity in both shoots and roots. Furthermore, this extract has the highest TPC and antioxidant capacities [42]. Other studies investigated the methanolic and chloroformic extracts of F. thymifolia and demonstrated that the methanolic extract exhibited better antioxidant activity, again linked to the high level of phenolic compounds, including salicylic acid (10), cinnamic acid (28), 2-hydroxycinnamic acid (29), chlorogenic acid (31) and catechin (74) [23,39]. Torres Carro et al. showed, in 2016, the significant antioxidant activity of the ethanolic and soxhlet of F. triandra evaluated by the β-carotene assay [34].
Overall, plants from the Frankenia family are rich in polyphenols, and this richness is often, if not always, correlated to the strong antioxidant properties these plants exhibit [13,17].
Table 11. Collected experimental data on the antioxidant activity of Frankenia species.
Table 11. Collected experimental data on the antioxidant activity of Frankenia species.
Frankenia
Species		Extract/
Fraction		OrganAssayRef.
DPPHABTSFRAPCCAICAORACβ-CaroteneMCA
F. laevisaqueous acetone APIC50 = 0.12 mg/mLIC50 = 0.18 mg/mLn.dIC50 = 0.44 mg/mLIC50 > 1 mg/mLn.dn.dn.d[17]
methanol APEC50 = 0.25 mg/mLEC50 = 0.65 mg/mLEC50 = 0.51 mg/mLEC50 = 0.78 mg/mLEC50 > 1 mg/mLn.dn.dn.d[13]
dichloromethaneEC50 > 1 mg/mLEC50 > 1
mg/mL		EC50> 1 mg/mLEC50 > 1 mg/mLEC50 = 0.76 mg/mLn.dn.dn.d
ethanol ShIC50 = 48.3 µg/mLIC50 = 93.4 µg/mLn.dn.dIC50 = 240 µg/mLn.dn.dn.d[41]
F. pulverulentaaqueous acetone APIC50 = 0.10 mg/mLIC50 = 0.15 mg/mLn.dIC50 = 0.30 mg/mLIC50 = 0.50 mg/mLn.dn.dn.d[17]
ethyl acetateSh586 mg TE/g E 1453 mg TE/g E n.dn.dn.d821 mg TE/g E n.d37 mg EDTA/g E [19]
R750 mg TE/g E1319 mg TE/g En.dn.dn.d1054 mg TE/g En.d23 mg EDTA/g E
methanolAP1090.4 mg TE/g E3621.43
mg TE/g E 		n.dn.dn.d58.08
mg TE/g E 		n.d71.98 mg EDTA/g E [39]
F. thymifoliamethanolAPIC50 = 99 µg/mLn.dn.dn.dEC50 = 120 µg/mLn.dIC50 = 11 µg/mLn.d[23]
chloroformIC50 = 120 µg/mLn.dn.dn.dEC50 = >1000 µg/mLn.dIC50 = >1000 µg/mLn.d
ethyl acetateAPn.dn.dn.dn.dn.dn.d71.66 ± 1.24%
at 100 mg/mL		n.d[21]
n-butanoln.dn.dn.dn.dn.dn.d50.83 ± 1.65%
at 100 mg/mL		n.d
chloroformn.dn.dn.dn.dn.dn.d49.91 ± 1.06%
at 100 mg/mL		n.d
F. triandraethanolAPn.dSC50 = 37.22 µg/mLn.dn.dn.dn.dIC50 = 41.24 µg/mLRC50 =
15.08
µg/mL		[34]
soxhletn.dSC50 = 35.99 µg/mLn.dn.dn.dn.dIC50 = 43.33 µg/mLRC50 = 16.53 µg/mL
AP: aerial parts, Sh: shoots, R: roots. DPPH: 2,2-diphenyl-1-picrylhydrazyl. ABTS: 2,20-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid. FRAP: ferric ion reducing antioxidant power. MCA: metal chelating activity. CCA: copper chelating activity. ICA: iron chelating activity. ORAC: oxygen radical absorbance capacity. n.d: not determined. EC50: half maximal effective concentration. IC50: half maximal inhibitory concentration. SC50: scavenging concentration 50%. SC50: concentration for 50% reduction. Ref.: references.

3.2.2. Antimicrobial Activity

Bacteria were involved in many of the most devastating diseases and massive epidemics in human history, before the discovery of antibiotics. Due to the misuse of the latter, bacteria have now developed resistance to the commonly used antibiotics [50]. Therefore, it is imperative to identify new and advanced chemical agents in order to have more productive resistance to microorganisms [50]. Since synthetic chemicals are related to adverse effects and harmful residues, novel antibacterial, antifungal, antiviral and antiparasitic drugs from plant sources must be developed worldwide [31,51,52]. Accordingly, a few Frankenia species were collected and screened for their antimicrobial activities. The corresponding details have been collected in Table 12.
Jdey et al. showed, in 2017, that the ethanolic extract of F. laevis significantly inhibited the development of both Gram-positive (Gram+) and Gram-negative (Gram−) bacteria engaged in their study [41]. All these strains were indeed inhibited by more than 55%, and the best inhibitions were observed for Micrococcus luteus (83%) and Salmonella enterica (77%) at a concentration of 1 mg/mL. This antibacterial effect may be attributed to the chlorogenic acid (31) and catechin (74) contained in this species, probably by inducing structural or functional damage to the bacterial cell membranes [53]. Similarly, Saïdana et al. [43] demonstrated, in 2010, that EO from the aerial parts of F. laevis was efficient against Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, Escherichia coli and Salmonella typhimurium. According to the authors, the antimicrobial activity of the EO can be attributed to the presence of fatty acids [54] such as palmitic acid (167), fatty acid esters like methyl linoleate (181), sesquiterpenes [55] such as farnesyl acetate (119), aromatic compounds [56] such as benzyl benzoate (192) and benzyl cinnamate (193), and, to a lesser extent, eugenol (49), β-caryophyllene (135), phytol (110), isophytol (112), (E, E)-farnesol (117) and hexadecanol (185). However, no significant effect on Pseudomonas aeruginosa was detected [43]. This Gram− bacteria has already been demonstrated to be less susceptible to the action of several other plant EOs [57]. The antifungal activity of the EO was also investigated. Despite the presence of eugenol (49) and β-caryophyllene (135) in the oil composition, known to have antifungal effects [58], none of the tested fungi were successfully inhibited by the EO at the tested doses. This may be explained by the low amounts of such chemicals in the EO [57].
The antibacterial and antifungal activity of EO from F. pulverulenta was also investigated [18]. Despite being rich in β-caryophyllene (135), which represents its main constituent (32%), this EO did not prevent bacterial growth. This finding appears contradictory to previous research, which showed that the presence of β-caryophyllene enhances the biological activities of EO, including their antibacterial activity [59,60]. Furthermore, the F. pulverulenta EO displayed poor antifungal activity and was exclusively efficient against the basidiomycete Rhizoctonia solani [18]. In 2011, Megdiche-Ksouri et al. investigated the activity of methanolic (polar) and chloroformic (less polar) extracts from F. thymifolia against five bacteria and one fungus [23]. The chloroformic extract provided the best performance, being active against all the evaluated bacterial strains. Similar inhibition results have been observed with other halophytes (e.g., sea holly, sea fennel) [61]. Such an outcome has been correlated to the polarity of the extracting solvent and could be attributed to the presence of lipophilic compounds in these extracts. Indeed, it has been demonstrated that long-chain unsaturated fatty acids, notably oleic (172) and linoleic (174), exhibit a strong inhibiting activity against mycobacteria [62]. Furthermore, it has been reported that the relatively lipophilic flavonoids catechin (74) and epigallocatechino-3-gallate (76) exhibit protective and antibacterial effects [63]. Likewise, the n-butanol fraction from F. thymifolia exhibited a stronger antibacterial effect against all tested bacterial strains compared to the ethyl acetate fraction (Pseudomonas aeruginosa was the most vulnerable strain) [42]. The extracts investigated also presented anti-leishmanial and antiamoebic effects against Leishmania amazonensis and Acanthamoeba castellanii, respectively. The antiparasitic capacities of these extracts may be related to the presence of quercetin (62) [64].
Canli et al. demonstrated the antibacterial and antifungal activity of F. hirsuta ethanolic extract against seventeen bacteria and one fungus [36]. Except for the Gram˗ bacteria Enterobacter aerogenes and Escherichia coli, all of the examined strains were sensitive to the antimicrobial action of the F. hirsuta extract. The most sensitive strains were Gram+ bacteria, especially Staphylococcus epidermidis and Enterecoccus faecium, compared to Gram˗ bacteria. Such antibiotic activity was again associated with the presence in this extract of oleic and linoleic acid in high amounts [65]. The concomitant presence of mesitylene (194), eudesmic acid (8) and stearic acid (169) also suggested a possible role in the F. hirsuta antibacterial activity, because some mesitylene derivatives [66], eudesmic acid [67] and stearic acid analogs [68] are known as antibacterial agents.
The difference in sensitivity to plant extracts between Gram+ and Gram− bacteria observed for F. hirsuta ethanolic extract could be generalized according to Canli et al. in other studies [69].
It is worth reminding here that the antibacterial properties of certain unsaturated fatty acids (oleic (172) and linoleic (174) acids) and, to some extent, of palmitic and stearic acids (167, 169) are linked to their ability to inhibit enoyl-acyl carrier protein reductase (FabI) activity [65,70].
The antibacterial activity of an ethanolic extract of F. triandra was also investigated [71]. The antischistosomal action of the methanol extract from F. hirsuta can also be found [31]. Interestingly, the acetonic and methanolic extracts derived from the aerial part of F. pulverulenta exhibited antiviral activity against Herpes simplex virus type 1 (HSV-1) at a dose of 500 μg/mL [72]. F. pulverulenta is known to contain flavonoids, including the 7-bisulfate-3-glucuronide of kaempferol (61), isorhamnetins (79–80) and quercetin (62) [27,72]. As some flavonoids, notably quercetin and, to a lesser extent, catechin and hesperetin, have been reported to possess antiviral capacities against a number of viruses, including HSV-1, the antiviral activity of F. pulverulenta extracts may be linked to its content of flavonoids [73].
These investigations and their results clearly suggest that Frankenia plants might be a valuable source of antimicrobial substances.
Table 12. Collected experimental data on the antimicrobial activity of Frankenia species.
Table 12. Collected experimental data on the antimicrobial activity of Frankenia species.
Microbial StrainFrankenia
Species		Extract/
Fraction/EO		OrganAssayMIC
(mg/mL)		MSI (%)IZ
(mm)		Ref.
Gram+ bacteria
Micrococcus
luteus		F. laevisethanolAPmicrodilutionn.d83.16 ± 0.38n.d[41]
F. laevisEOAPdisc diffusion0.5n.dn.d[43]
Staphylococcus aureusF. laevisethanolAPmicrodilutionn.d66.66 ± 1.25n.d[41]
F. laevisEOAPdisc diffusion0.5n.dn.d[43]
F. pulverulentaEOAPwell diffusionn.dn.d-[18]
F. thymifoliamethanol
chloroform		Sh
Sh		disc diffusion
disc diffusion		n.d
n.d		n.d
n.d		8.6
8.0		[23]
F. thymifolian-butanol
ethyl acetate		APdisc diffusion
disc diffusion		n.d
n.d		n.d
n.d		9.0
11.0		[42]
Staphylococcus epidermidisF. laevisEOAPdisc diffusion0.8n.dn.d[43]
F. hirsutaethanolHdisc diffusionn.dn.d16.0[36]
Enterococcus
faecium		F. thymifoliamethanol
chloroform		Sh
Sh		disc diffusion
disc diffusion		n.d
n.d		n.d
n.d		9.5
8.5		[23]
F. hirsutaethanolHdisc diffusionn.dn.d16.0[36]
Gram− bacteria
Escherichia coliF. laevisethanolAPmicrodilutionn.d56.18 ± 1.13n.d[41]
F. pulverulentaEOAPwell diffusionn.dn.d-[18]
F. laevisEOAPdisc diffusion0.8n.dn.d[43]
F. thymifoliamethanol
chloroform		Sh
Sh		disc diffusion
disc diffusion		n.d
n.d		n.d
n.d		6.0
10.0		[23]
F. thymifolian-butanol
ethyl acetate		APdisc diffusion
disc diffusion		n.d
n.d		n.d
n.d		8.0
7.0		[42]
F. hirsutaethanolHdisc diffusionn.dn.d-[36]
Salmonella enterica ssp. arizonaeF. laevisethanolAPmicrodilutionn.d77.66 ± 0.14n.d[41]
Salmonella
typhimurium		F. laevisEOAPdisc diffusion0.5n.dn.d[43]
Salmonella typhiF. thymifoliamethanol
chloroform		Sh
Sh		disc diffusion
disc diffusion		n.dn.d6.0
10.5		[23]
Pseudomonas
aeruginosa		F. laevisEOAPdisc diffusion-n.dn.d[43]
F. thymifoliamethanol
chloroform		Sh
Sh		disc diffusion
disc diffusion		n.d
n.d		n.d
n.d		6.0
8.1		[23]
F. thymifolian-butanol
ethyl acetate		APdisc diffusion
disc diffusion		n.d
n.d		n.d
n.d		12.0
7.0		[42]
F. hirsutaethanolHdisc diffusionn.dn.d9.0[36]
F. triandraethanol
water		APmicrodilution
macrodilution		0.3n.dn.d[74]
Klebsiella
oxytoca		F. thymifolian-butanol
ethyl acetate		APdisc diffusion
disc diffusion		n.d
n.d		n.d
n.d		9.0
10.0		[42]
Enterobacter
aerogenes		F. hirsutaethanolHdisc diffusionn.dn.d-[36]
Morganella
morganii		F. triandraethanol-waterAPmicrodilution
macrodilution		0.15n.dn.d[74]
Fungi
Candida albicansF. thymifoliamethanol
chloroform		Sh
Sh		disc diffusion
disc diffusion		n.d
n.d		n.d
n.d		6.0
9.5		[23]
F. hirsutaethanolHdisc diffusionn.dn.d12.0[36]
Rhizoctonia solaniF. pulverulentaEOAPwell diffusionn.dn.d12.25[18]
Penicillium
simplicissimum		F. pulverulentaEOAPwell diffusionn.dn.d-[18]
Fusarium
oxysporum		F. pulverulentaEOAPwell diffusionn.dn.d-[18]
F. laevisEOAPdisc diffusion-n.dn.d[43]
Penicillium
citrinum		F. pulverulentaEOAPwell diffusionn.dn.d-[18]
Fusarium
fujikuroi		F. pulverulentaEOAPwell diffusionn.dn.d-[18]
Aspergillus nigerF. laevisEOAPdisc diffusion-n.dn.d[43]
Alternaria sp.F. laevisEOAPdisc diffusion-n.dn.d[43]
Penicillium sp.F. laevisEOAPdisc diffusion-n.dn.d[43]
Parasite
Acanthamoeba castellanii str. Neff. F. thymifolian-butanol
ethyl acetate		APmodified Alamar Blue®95.43
66.25 		n.d
n.d		n.d
n.d		[42]
Leishmania amazonensisF. thymifolian-butanol
ethyl acetate		APmodified Alamar Blue®100.13
99.36 		n.d
n.d		n.d
n.d		[42]
Leishmania donovaniF. thymifolian-butanol
ethyl acetate		APmodified Alamar Blue®-
-		n.d
n.d		n.d
n.d		[42]
Trypanosoma cruziF. thymifolian-butanol
ethyl acetate		APmodified Alamar Blue®-
-		n.d
n.d		n.d
n.d		[42]
Schistosoma mansoniF. hirsutamethanolHviability testn.d46.80/68.50n.d[31]
Virus
HSV-1F. pulverulentaacetone
methanol		AP
AP		neutral red incorporation n.d
n.d		n.d
n.d		489.5 486.2[75]
Gram+: Gram-positive. Gram−: Gram-negative. HSV-1: Herpes simplex virus type 1. (-): no activity detected. n.d: not determined. AP: aerial parts. Sh: shoots. H: herb. EO: essential oil. MIC: minimum inhibitory concentration. MSI: microbial susceptibility index. IZ: inhibition zone. IC50: half maximal inhibitory concentration. LC50: 50% lethal concentration. LC90: 90% lethal concentration. EC50: half maximal effective concentration. Ref.: references.

3.2.3. Neuroprotective Activity

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive and irreversible memory loss and other cognitive impairments. At the cellular level, AD is characterized by synaptic and neuronal loss, deposition of plaques made of β-amyloid peptide (Aβ) and the formation of fibrils in the brain made of tau-protein. Several data issued from genetic, neuropathological and biochemical studies have established the central role of the β-amyloid peptide (Aβ), which results from the cleavage of the so-called amyloid precursor protein (APP), a membrane glycoprotein [74,75]. However, its precise role in AD pathogenesis is still unclear.
One hypothesis suggests that oxidative damage in the brain may cause ROS generation in neurons, which in turn could potentiate the Aβ neurotoxicity and metabolism perturbation [76]. Therefore, limiting or inhibiting oxidative stress could be a way to treat AD. As various plants contain various antioxidant natural products, especially those of the Frankenia family (see Section 2.1.1 and Section 2.1.2), the neuroprotective properties of plants have been, and are, still being explored [77].
In order to determine whether Frankenia plant species may prevent Aβ-induced neuronal cell toxicity, neuroprotection tests were carried out. The neuroprotective potential of ethyl acetate fractions from F. pulverulenta shoots and roots was evaluated [19]. An Aβ(25–35)-induced cytotoxicity assay using pheochromocytoma-derived (PC12) cells was assessed. Both fractions remarkably prevented the cytotoxic response of Aβ(25–35) at levels around 57% and 80% at 100 and 200 μg/mL, respectively, compared with non-treated cells. At a higher concentration (300 μg/mL), the root fraction entirely counteracted the toxic effect of Aβ(25–35). Using the same process, the neuroprotective capacities of methanolic extracts from F. thymifolia and F. pulverulenta aerial parts were demonstrated in another study [39]. Both species exerted a powerful neuroprotective effect in a dose-dependent manner, and about 80% of the cell viability was restored at 100 μg/mL. Additionally, the ethyl acetate fractions from F. thymifolia shoots and roots demonstrated a strong neuroprotective effect on neuronal PC12 cells and totally counterbalanced the damaging effect of Aβ(25–35) at 25 and 50 μg/mL, respectively [21]. Most phenolics isolated from F. pulverulenta ethyl acetate fractions were shown to exhibit potent neuroprotective activities, particularly procyanidin dimers (78), which prevented Aβ-induced toxicity at levels close to 100% at 50 μM, while catechin (74) prevented it only at 70% at the same concentration, and quercetin (62) did not [19].
The strong capacity of F. thymifolia and F. pulverulenta extracts to inhibit Aβ(25–35) aggregation could be attributed to their significant antioxidant activities and phenolic contents. Various reports have indeed shown that phenolic substances may prevent neurodegenerative disorders, either by directly preventing the formation of Aβ fibril deposits in the brain [78] or by exhibiting protective effects through scavenging ROS [79]. Furthermore, a two-to-one complex between a polyphenol and the full Aβ peptide was observed by ESI-MS [78]. It was also reported that gallic acid (1), found in F. thymifolia roots, in its glucosylated form and the corresponding gallotannins effectively suppressed Aβ(25–35) aggregation in vitro [80]. Another study revealed that kaempferol-3-O-glucoside (56) presented a modest inhibitory effect on Aβ(25–35) aggregation, whereas kaempferol itself had a moderate effect. However, the reverse situation was observed with quercetin (62) and its 3′-O-glucoside (72), the latter exhibiting a good activity while the former had a modest one [81]. These results are quite surprising due to the structural similarity between these compounds (see Figure 4). Interestingly, the very similar hyperoside (73) significantly diminished Aβ-induced cytotoxicity and apoptosis by restoring Aβ-induced mitochondrial dysfunction [82]. Alternatively, it has been shown that caffeic acid (30), epigallocatechin (75) and its 3-O-gallate (76) exhibit a modest aggregation inhibition, and p-hydroxybenzoic acid (11) presents a moderate one, while the hydroxy derivatives of benzyl benzoate (192) exhibit interesting inhibition [83]. However, the latter have so far not been detected in Frankenia species.
Another approach to facing AD is to attempt to treat the synaptic and neuronal loss associated with AD. During the progression of AD, different types of neurons deteriorate, but the main loss occurs in forebrain cholinergic neurons, which play an important role in cognition. Therapies have thus been, and are still being, designed to reverse this cholinergic deficit. Cholinergic neurons rely on acetylcholine (ACh) as a neurotransmitter, which is hydrolyzed by acetylcholinesterase (AChE) in the synapse and to a lesser extent by the non-specific butyrylcholinesterase (BuChE) [84]. Furthermore, several studies have suggested that AChE can modulate APP processing in a way that enhances β-amyloid plaque deposition [85]. As a consequence, the inhibition of these enzymes is actively pursued. Various inhibitors have proven beneficial as a curative approach to AD, and a few are commercially available [84].
As some of the earliest inhibitors discovered were alkaloids issued from plants, plant extracts are now often evaluated as cholinesterase inhibitors. In Frankenia species, only a few have so far been evaluated. Interestingly, methanol extracts from F. laevis demonstrated significant AChE and BuChE inhibition (about 80% at 1 mg/mL) [13].

3.2.4. Tyrosinase Inhibition Activity

Tyrosinase is a multipurpose copper-containing oxidase that participates in melanin production and enzymatic browning processes that happen in damaged fruits during post-harvest processing [86]. Natural substances are widely utilized in cosmetic formulations as tyrosinase inhibitors to cure skin hyperpigmentation, melasma and post-inflammatory hyperpigmentation [87]. They are also applied in the food industry to prohibit enzymatic browning action in injured vegetables [86].
The inhibition of tyrosinase by F. laevis shoot extracts (50% ethanol) was conducted by performing both the inhibition of l-tyrosine hydroxylation to l-3,4-dihydroxyphenylalanine (L-DOPA) (monophenolase) and that of L-DOPA oxidation to dopaquinone (diphenolase) [41]. A strong inhibition of monophenolase and diphenolase functions was achieved (IC50 = 730.43 and 123.62 μg/mL, respectively). In agreement with previous studies [88,89], the high levels of phenolic compounds, such as chlorogenic acid (31) and quercetin (62), in F. laevis extracts are probably responsible for the anti-tyrosinase effect, making this species a prospective source of natural skin-lightening agents and conservatives [86,87].

3.2.5. Anti-Inflammatory Activity

Inflammation is induced by either external or internal causes. In the former, inflammation occurs in response to infection caused by microorganisms or to tissue injury. In the latter, cell death, cancer and other dysfunctions initiate a cascade of events leading to inflammation. In turn, various inflammatory mediators are produced, such as cytokines, chemokines, polyunsaturated fatty acids, etc., some acting as pro- and/or anti-inflammatory agents. The enzymes that are responsible for the generation of these inflammatory mediators, such as cyclooxygenase (COX), lipoxygenase (LOX) and hyaluronidase, are the major targets of anti-inflammatory therapies and a number of drugs have been developed [90]
For such common anti-inflammatory activity, the use of plants has been known since antiquity and is still applied. Although traditional medicines provide numerous anti-inflammatory extracts or plant parts, this activity is still being explored and remains one of the most sought-after bioactivities from plants [91].
The anti-inflammatory capacity of ethanolic and soxhlet extracts obtained from F. triandra aerial parts was evaluated [34]. The inhibition of LOX and COX2 capacities was assessed on the basis of the enzymatic oxidation of linoleic acid to the corresponding hydroperoxide and prostaglandin measurement, respectively. The extracts displayed a satisfactory ability to prevent LOX (IC50 = 134.5 ± 12.9 and 117.8 ± 1.8 μg/mL, respectively) and COX2 (54% and 50% inhibition, respectively) actions. Hence, it is thought that these inhibition values are high for a crude extract [92]. The authors have also examined the hyaluronidase activity by measuring the quantity of generated N-acetyl glucosamine (NAGA) [34]. Both soxhlet and ethanolic extracts demonstrated a high degree of inhibition, but the soxhlet extract was three times more effective than the ethanolic extract (IC50 = 146.3 ± 4.3 and 412.2 ± 8.9 μg/mL, respectively) as compared to the commercial anti-inflammatory, indomethacin (IC50 = 502.0 ± 7.1 μg/mL), and the control sample, quercetin (IC50 = 340.0 ± 12.0 μg/mL).
Numerous studies have shown a strong correlation between inflammation and oxidative species production. Consequently, plants with antioxidant capabilities frequently have anti-inflammatory characteristics [93].

3.2.6. Carbonic Anhydrase II Inhibition Activity

Carbonic anhydrase II (CA-II) belongs to the carbonic anhydrase family of enzymes, which are zinc metalloenzymes that catalyze the reversible conversion of carbon dioxide (CO2) to bicarbonate (HCO3) and a proton (H+) [94]. In addition to their key roles in transporting CO2 and maintaining acid–base balance, the 16 human carbonic anhydrases are also involved in several essential physiological processes, and, thus, their dysregulated expression and/or abnormal activity have important pathological consequences. For example, CA-II is mainly involved in the regulation of bicarbonate concentration in the eyes, and is thus linked to glaucoma, but also expressed in malignant brain tumors and renal, gastritis and pancreatic carcinomas. CA-II and other CAs are therefore interesting therapeutic targets for the treatment of related diseases. CA-II inhibitors are, for example, used in the treatment of several illnesses, including glaucoma, idiopathic intracranial hypertension, altitude sickness, congestive heart failure and epilepsy [95,96,97,98].
In order to look for some activity in such health problems, the EO extracted from the aerial parts of F. pulverulenta was screened against the CA-II enzyme. The experiment was done at a micromolar level using acetazolamide as a standard inhibitor (IC50 = 18.2 ± 1.2 μM). The EO demonstrated a substantial and spectacular CA-II inhibition effect (IC50 = 101.5 ± 2.35%) and might have application in the management of CA-related disorders [18].

3.2.7. Antidiabetic Activity

In type 2 diabetic patients postprandial hyperglycemia occurs because the peak insulin release is delayed, and levels are thus insufficient to control the accelerated blood glucose elevation. Such hyperglycemic spikes induce inflammatory reactions, oxidative stress and endothelial dysfunction, which in turn increase the occurrence of cardiovascular diseases.
To reduce postprandial hyperglycemia, the most common type 2 diabetes preventive therapy involves decreasing carbohydrate digestibility by blocking two important hydrolyzing enzymes, specifically, α-amylase and α-glucosidase [99].
The methanol and dichloromethane extracts of F. laevis were investigated for their capacity to inhibit α-glucosidase and α-amylase enzymes [13] using a standard in vitro inhibition assay [100]. The extracts showed a marked α-glucosidase inhibition (EC50 = 1.02 ± 0.01 mg/mL and 0.52 ± 0.04 mg/mL, respectively) compared to the positive control, acarbose (EC50 = 3.14 ± 0.23 mg/mL). On the other hand, the extracts had no significant effect on α-amylase activity.
Abundant in F. laevis extracts, linoleic acid (174) and its derivatives, as well as loliolide (107), isololiolide (106) and dihydroactinidiolide (108), were found to have a strong inhibitory effect on α-glucosidase. Their higher abundance in the dichloromethane extract may explain the anti-α-glucosidase activity of the F. laevis extracts. In addition, the antioxidant properties of these extracts may also help to decrease the incidence of diabetes complications related to oxidative stress, specifically microvascular and cardiovascular issues [101].

3.2.8. Anticancer Activity

Prior to human usage, substances or chemicals must undergo rigorous safety evaluations. Cytotoxic tests using various human cell lines are often performed to assess the potential toxicity of different substances in vitro [102]. The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test, a colorimetric approach that measures cell metabolic activity, is one of the most frequently used methods to determine how a substance affects cellular viability [102]. On the other hand, cytotoxicity could be useful to control tumor cell proliferation and thus treat cancers.
For the latter purpose, the anticancer and antiproliferative activities of extracts from the aerial parts of F. laevis were investigated against human hepatocarcinoma cells (HepG2) [13]. Sea heath dichloromethane extract showed potential anti-HepG2 activity (EC50 = 52.1 μg/mL). In contrast, methanol extract did not present significant cytotoxicity. This difference could be ascribed to the high content of certain metabolites and fatty acids in the dichloromethane extract.
It has indeed been reported that fatty acids, especially linoleic acid (174) which is abundant in this extract, have shown chemoprotective effects [103,104]. Furthermore, the monoterpenes loliolide (107) and isololiolide (106), also abundant in this extract, are known for their strong cytotoxic activities on HepG2 cells [105,106], as is dihydroactinidiolide (108) on human lung carcinoma cells (A549) [107] and human breast cancer cells [106,108]. The phytohormone oxophytodienoic acid (204) also present in this extract is also known for its cytotoxic activity on human breast cancer cells [109].
A similar study on a large series of halophyte plants, including both F. laevis and F. pulverulenta, has been performed [17]. The viability of four cancer cell types, including the same HepG2 cell line, was evaluated, and the F. laevis extract was found to significantly decrease it (71%), while F. pulverulenta did not.
Due to the abundance of the active compounds mentioned above, the F. laevis dichloromethane extract may represent an interesting natural alternative for treating some cancers. Furthermore, the natural products probably responsible for these antitumor activities could become promising candidates for new antitumor drugs.

3.2.9. Insecticidal Activity

The control of insect proliferation and of the so-induced destruction of agricultural plants is usually achieved with synthetic insecticides. However, their intensive and uncontrolled utilization has led to the development of resistance in insects and to various environmental damages. Although a few insecticides are issued from plants, such as pyrethrenoids, plants may provide potentially safer alternatives to the currently used insect-control agents.
In this context, petroleum ether and chloroformic and ethyl acetate extracts obtained from the aerial parts of F. laevis were evaluated for their antifeedant, toxic and insect growth inhibition activities against larvae and adults of the confused flour beetle Tribolium confusum [110]. At a concentration of 1%, the petroleum ether extract demonstrated moderate antifeedant properties. At the same concentration, the tested extracts considerably induced larval mortality (up to 97% inhibition with the ethyl acetate extract), while adult toxicity did not surpass 33%. Furthermore, the F. laevis extracts inhibited feeding, exhibited high toxicity and greatly affected the development of Tribolium confusum larvae when used at a dose of 1%. Therefore, this halophyte plant seems to have great potential for pest control; it would be worth identifying the compound(s) responsible for the interesting insecticidal activity of these extracts even at low concentrations [110].

4. Conclusions

In this review, we have described a series of Frankenia plant species known for their role in traditional medicine. These plants are indicated for the treatment of a variety of illnesses, including diarrhea, respiratory issues and wounds. The corresponding phytochemical investigations have been collected here and analyzed. These data revealed that these Frankenia species produce a wide range of interesting metabolites. They contain relatively high levels of specific substances, such as phenolics, flavonoids and terpenoids, as well as various fatty acids, as such or as derivatives, and alkanes. Some alkaloids and steroids have also been identified, but only a few lignans and coumarins have so far been observed.
Furthermore, the corresponding biological investigations have also been collected when available and the results have been interpreted as much as possible in terms of the chemical content of each extract or part of the plants. Interestingly, these in vitro studies revealed a variety of biological activities, from the classical antioxidant effects and the related anti-inflammatory activity to enzyme inhibitions, neuroprotection, anti-diabetic and anti-tumor activities, as well as insecticidal properties. All these bioactivities are obviously linked to the application of Frankenia plants in traditional medicine. However, the molecular mechanisms of these biological effects correlated to the chemicals recovered from Frankenia species remain unclear.
As shown here, the value of plants as sources of bioactive natural substances resides not only in their insecticidal, pharmacological or chemotherapeutic effects but also in their roles in the development of novel drugs [111]. However, the number of higher plant species on earth is estimated to be between 250,000 and 500,000, from which only 15% have been evaluated phytochemically and only 6–7% have been screened for biologic activity [112]. It is thus worth looking at more plants for their chemical profile and their biological activity. Unfortunately, only six species of the Frankenia genus were investigated in detail for their chemical composition and/or pharmacological activities.
In summary, research on Frankenia species is still in its infancy and needs to be developed further, in order to discover novel bioactive compounds and better understand the correlation between the identified natural substances and the corresponding biological activity. Additionally, future research should also expand on in vivo studies and clinical trials to learn more about the potential modes of action in human metabolic disorders and illnesses.

Author Contributions

Conceptualization, H.H.; validation, M.K., R.O., H.H. and P.P.; formal analysis, H.H. and P.P.; investigation and resources, M.K. and R.O.; writing—original draft preparation, H.H. and M.K.; writing—review and editing, P.P. All authors have read and agreed to the published version of the manuscript.

Funding

This work was partly founded by the French-Algerian Program PHC Tassili (PHC 43807UL).

Data Availability Statement

The original contributions presented in the present study are included in the cited articles; further inquiries can be directed to the corresponding authors.

Acknowledgments

M.K., R.O. and H.H. acknowledge the facility provided by the Algerian Ministry of Higher Education and Scientific Research. P.P. acknowledges the financial support of the French Ministry of Research and the CNRS.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. World Health Organization. Available online: https://www.who.int/news-room/feature-stories/detail/traditional-medicine-has-a-long-history-of-contributing-to-conventional-medicine-and-continues-to-hold-promise (accessed on 19 September 2023).
  2. World Health Organization Report. 2019. Available online: https://apps.who.int/iris/bitstream/handle/10665/312342/9789241515436-eng.pdf (accessed on 19 September 2023).
  3. Fabricant, D.S.; Farnworth, N.R. The value of plants used in traditional medicine for drug discovery. Environ. Health Perspect. 2001, 109, 69–75. [Google Scholar] [PubMed]
  4. Yuan, H.; Ma, Q.; Ye, L.; Piao, G. The traditional medicine and modern medicine from natural products. Molecules 2016, 21, 559. [Google Scholar] [CrossRef] [PubMed]
  5. Lee, J.-S.; Kim, J.-W. Dynamics of zonal halophyte communities in salt marshes in the world. J. Mar. Isl. Cult. 2018, 7, 84–106. [Google Scholar] [CrossRef]
  6. Ksouri, R.; Megdiche, W.; Falleh, H.; Trabelsi, N.; Boulaaba, M.; Smaoui, A.; Abdelly, C. Influence of biological, environmental and technical factors on phenolic content and antioxidant activities of Tunisian halophytes. C. R. Biol. 2008, 331, 865–873. [Google Scholar] [CrossRef] [PubMed]
  7. Ferreira, M.J.; Pinto, D.C.G.A.; Cunha, Â.; Silva, H. Halophytes as Medicinal Plants against Human Infectious Diseases. Appl. Sci. 2022, 12, 7493. [Google Scholar] [CrossRef]
  8. Arya, S.S.; Devi, S.; Ram, K.; Kumar, S.; Kumar, N.; Mann, A.; Kumar, A.; Chand, G. Halophytes: The Plants of Therapeutic Medicine. In Ecophysiology, Abiotic Stress Responses and Utilization of Halophytes; Hasanuzzaman, M., Nahar, K., Öztürk, M., Eds.; Springer: Singapore, 2019; pp. 271–287. [Google Scholar]
  9. Hernández-Ledesma, P.; Berendsohn, W.G.; Borsch, T.; Mering, S.V.; Akhani, H.; Arias, S.; Castañeda-Noa, I.; Eggli, U.; Eriksson, R.; Flores-Olvera, H.; et al. A taxonomic backbone for the global synthesis of species diversity in the angiosperm order Caryophyllales. Willdenowia 2015, 45, 281–383. [Google Scholar] [CrossRef]
  10. Gaskin, J.F.; Ghahremani-nejad, F.; Zhang, D.-y.; Londo, J.P. A Systematic Overview of Frankeniaceae and Tamaricaceae from Nuclear rDNA and Plastid Sequence Data. Ann. Mo. Bot. Gard. 2004, 91, 401–409. [Google Scholar]
  11. Missouri Botanical Garden. Available online: https://www.mobot.org/mobot/research/apweb/orders/caryophyllalesweb.htm (accessed on 11 November 2023).
  12. Altameme, H. Systematics study of Frankenia L. (Frankeniaceae) in Iraq. Res. J. Pharm. Biol. Chem. Sci. 2016, 7, 1232–1242. [Google Scholar]
  13. Rodrigues, M.J.; Jekő, J.; Cziáky, Z.; Pereira, C.G.; Custódio, L. The medicinal halophyte Frankenia laevis L.(sea heath) has in vitro antioxidant activity, α-glucosidase inhibition, and cytotoxicity towards hepatocarcinoma cells. Plants 2022, 11, 1353. [Google Scholar] [CrossRef]
  14. Hussein, S. Phenolic Sodium Sulfates of Frankenia laevis L. Pharmazie 2004, 59, 304–308. [Google Scholar] [CrossRef]
  15. Chegah, S.; Chehrazi, M.; Albaji, M. Effects of drought stress on growth and development Frankenia plant (Frankenia Leavis). Bulg. J. Agric. Sci. 2013, 19, 659–666. [Google Scholar]
  16. Malta Wild Plants. Available online: https://maltawildplants.com/FRNK/Frankenia_pulverulenta.php (accessed on 24 October 2023).
  17. Lopes, A.; Rodrigues, M.J.; Pereira, C.; Oliveira, M.; Barreira, L.; Varela, J.; Trampetti, F.; Custódio, L. Natural products from extreme marine environments: Searching for potential industrial uses within extremophile plants. Ind. Crops Prod. 2016, 94, 299–307. [Google Scholar] [CrossRef]
  18. Rehman, N.U.; Alsabahi, J.N.; Alam, T.; Rafiq, K.; Khan, A.; Hidayatullah; Khan, N.A.; Khan, A.L.; Al Ruqaishi, H.; Al-Harrasi, A. Chemical composition and biological activities of essential oil from aerial parts of Frankenia pulverulenta L. and Boerhavia elegans Choisy from Northern Oman. J. Essent. Oil-Bear. Plants 2021, 24, 1180–1191. [Google Scholar] [CrossRef]
  19. Ben Mansour, R.; Wided, M.K.; Cluzet, S.; Krisa, S.; Richard, T.; Ksouri, R. LC-MS identification and preparative HPLC isolation of Frankenia pulverulenta phenolics with antioxidant and neuroprotective capacities in PC12 cell line. Pharm. Biol. 2017, 55, 880–887. [Google Scholar] [CrossRef] [PubMed]
  20. Boissier, P.E. Diagnoses Plantarum Orientalium Novarum; Series 2; (Reedition by Nabu Press: Charleston, SC, USA, 2012); Apud B. Herrmann: Lipsiae, Germany, 1854. [Google Scholar]
  21. Ben Mansour, R.; Ksouri, W.M.; Cluzet, S.; Krisa, S.; Richard, T.; Ksouri, R. Assessment of Antioxidant Activity and Neuroprotective Capacity on PC12 Cell Line of Frankenia thymifolia and Related Phenolic LC-MS/MS Identification. Evid. Based Complement. Altern. Med. 2016, 2016, 2843463. [Google Scholar] [CrossRef] [PubMed]
  22. Harkat, H.; Haba, H.; Marcourt, L.; Long, C.; Benkhaled, M. An unusual lignan sulfate and aromatic compounds from Frankenia thymifolia Desf. Biochem. Syst. Ecol. 2007, 35, 176–179. [Google Scholar] [CrossRef]
  23. Megdiche-Ksouri, W.; Chaouachi, F.; M’Rabet, R.; Medini, F.; Zaouali, Y.; Trabelsi, N.; Ksoury, R.; Noumi, E.; Abdelly, C. Antioxidant and antimicrobial properties of Frankenia thymifolia Desf. fractions and their related biomolecules identification by gas chromatography/mass spectrometry (GC/MS) and high performance liquid chromatography (HPLC). J. Med. Plants Res. 2011, 5, 5754–5765. [Google Scholar]
  24. Altameme, H. A Chemical composition of Halophyte plant Frankenia pulverulenta L. (Frankeniaceae) in Iraq depending on GC-MS and FT-IR techniques. J. Chem. Pharm. Sci. 2017, 10, 26–33. [Google Scholar]
  25. Vahdati, N.; Tehranifar, A.; Kazemi, F. Assessing chilling and drought tolerance of different plant genera on extensive green roofs in an arid climate region in Iran. J. Environ. Manag. 2017, 192, 215–223. [Google Scholar] [CrossRef]
  26. Bueno, M.; Cordovilla, M.D. Spermidine Pretreatments Mitigate the Effects of Saline Stress by Improving Growth and Saline Excretion in Frankenia pulverulenta. Agronomy 2021, 11, 1515. [Google Scholar] [CrossRef]
  27. Harborne, J.B. Flavonoid bisulphates and their co-occurrences with ellagic acid in the Bixaceae, Frankeniaceae and related families. Phytochemistry 1975, 14, 1331–1337. [Google Scholar] [CrossRef]
  28. MaltaWildPlants. Available online: https://maltawildplants.com/FRNK/Frankenia_hirsuta.php (accessed on 24 October 2023).
  29. Vural, M.; Duman, H.; Aytac, Z.; Adigüzel, N. A new genus and three new species from Central Anatolia, Turkey. Turk. J. Bot. 2012, 36, 427–433. [Google Scholar] [CrossRef]
  30. Delitheos, A.; Tiligada, E.; Yannitsaros, A.; Bazos, I. Antiphage activity in extracts of plants growing in Greece. Phytomedecine 1997, 4, 117–124. [Google Scholar] [CrossRef] [PubMed]
  31. Yousif, F.; Hifnawy, M.S.; Soliman, G.; Boulos, L.; Labib, T.; Mahmoud, S.; Ramzy, F.; Yousif, M.; Hassan, I.; Mahmoud, K.; et al. Large-scale in Vitro Screening of Egyptian Native and Cultivated plants for schistosomicidal activity. Pharm. Biol. 2007, 45, 501–510. [Google Scholar] [CrossRef]
  32. Altameme, H. Phytochemical analysis of Frankenia aucheri Jaub. et Spach (Frankeniaceae) by GC-MS and FT-IR techniques. Plant Arch. 2018, 18, 2263–2269. [Google Scholar]
  33. Abarsaji, G.A.; Mahdavi, M.; Jouri, M.H. Determination of Soil Salinity in Frankenia hirsuta L. Habitat (Case Study: Saline and Alkaline Rangelands of Golestan Province). J. Rangel. Sci. 2012, 2, 491–495. [Google Scholar]
  34. Torres Carro, R.; D’Almeida, R.E.; Isla, M.I.; Alberto, M.R. Antioxidant and anti-inflammatory activities of Frankenia triandra (J. Rémy) extracts. S. Afr. J. Bot. 2016, 104, 208–214. [Google Scholar] [CrossRef]
  35. Tan, Y.P.; Savchenko, A.I.; Broit, N.; Boyle, G.M.; Parsons, P.G.; Williams, C.M. The First plant 5,6-secosteroid from the australian arid zone species Frankenia foliosa. Eur. J. Org. Chem. 2017, 2017, 1498–1501. [Google Scholar] [CrossRef]
  36. Canli, K.; Simsek, O.; Yetgin, A.; Altuner, E.M. Determination of the chemical composition and antimicrobial activity of Frankenia hirsuta. Bangladesh J. Pharmacol. 2017, 12, 463–469. [Google Scholar] [CrossRef]
  37. Hussain, M.I.; Farooq, M.; Syed, Q.A.; Ishaq, A.; Al-Ghamdi, A.A.; Hatamleh, A.A. Botany, nutritional value; Phytochemical composition and biological activities of quinoa. Plants 2021, 10, 2258. [Google Scholar] [CrossRef]
  38. Woldemichael, G.M.; Wink, M. Identification and Biological Activities of Triterpenoid Saponins from Chenopodium quinoa. J. Agric. Food Chem. 2001, 49, 2327–2332. [Google Scholar] [CrossRef] [PubMed]
  39. Ben Mansour, R.; Megdiche-Ksouri, W.; Cluzet, S.; Krisa, S.; Mkadmini, K.; Richard, T.; Ksouri, R. Potential antioxidant capacities and neuroprotective properties of six Tunisian medicinal species. Int. J. Med. Plant Nat. Prod. 2017, 3, 45–54. [Google Scholar]
  40. Hussein, S.A.M. Flavonoid and methoxyellagic acid sodium sulphates from Frankenia laevis L. Pharmazie 2004, 59, 484–487. [Google Scholar] [PubMed]
  41. Jdey, A.; Falleh, H.; Ben Jannet, S.; Mkadmini Hammi, K.; Dauvergne, X.; Ksouri, R.; Magné, C. Phytochemical investigation and antioxidant, antibacterial and anti-tyrosinase performances of six medicinal halophytes. S. Afr. J. Bot. 2017, 112, 508–514. [Google Scholar] [CrossRef]
  42. Mennai, I.; Hanfer, M.; Esseid, C.; Benayache, S.; Ameddah, S.; Menad, A.; Benayache, F. Chemical composition, in vitro antiparasitic, antimicrobial and antioxidant activities of Frankenia thymifolia Desf. Nat. Prod. Res. 2020, 34, 3363–3368. [Google Scholar] [CrossRef] [PubMed]
  43. Saïdana, D.; Mahjoub, M.A.; Mighri, Z.; Chriaa, J.; Daamiand, M.; Helal, A.N. Studies of the essential oil composition, antibacterial and antifungal activity profiles of Frankenia laevis L. from Tunisia. J. Essent. Oil-Bear. Plants 2010, 22, 349–353. [Google Scholar] [CrossRef]
  44. Pichersky, E.; Raguso, R.A. Why do plants produce so many terpenoid compounds? New Phytol. 2018, 220, 692–702. [Google Scholar] [CrossRef] [PubMed]
  45. Karimi, E.; Jaafar, H.Z.E.; Ghasemzadeh, A.; Ebrahimi, M. Fatty acid composition, antioxidant and antibacterial properties of the microwave aqueous extract of three varieties of Labisia pumila Benth. Biol. Res. 2015, 48, 9. [Google Scholar] [CrossRef]
  46. Rodriguez, E.B.; Flavier, M.E.; Rodriguez-Amaya, D.B.; Amaya-Farfán, J. Phytochemicals and functional foods. Current situation and prospect for developing countries. Segur. Aliment. Nutr. 2006, 13, 1–22. [Google Scholar] [CrossRef]
  47. Daoud, S.; Elbrik, K.; Tachbibi, N.; Bouqbis, L.; Brakez, M.; Harrouni, M.C. The potential use of halophytes for the development of marginal dry areas in Morocco. In Halophytes for Food Security in Dry Lands; Khan, M.A., Ozturk, M., Gul, B., Ahmed, M.Z., Eds.; Academic Press: San Diego, CA, USA, 2016; pp. 141–156. [Google Scholar]
  48. Alyemeni, M.N.; Sher, H.; Wijaya, L. Some observations on Saudi medicinal plants of veterinary importance. J. Med. Plants Res 2010, 4, 2298–2304. [Google Scholar]
  49. Kontoghiorghes, G.J.; Kontoghiorghe, C.N. Iron and chelation in biochemistry and medicine: New approaches to controlling iron metabolism and treating related diseases. Cells 2020, 9, 1456. [Google Scholar] [CrossRef] [PubMed]
  50. Alanis, A.J. Resistance to Antibiotics: Are We in the Post-Antibiotic Era? Arch. Med. Res. 2005, 36, 697–705. [Google Scholar] [CrossRef] [PubMed]
  51. Doenhoff, M.J.; Kusel, J.R.; Coles, G.C.; Cioli, D. Resistance of Schistosoma mansoni to praziquantel: Is there a problem? Trans. R. Soc. Trop. Med. Hyg. 2002, 96, 465–469. [Google Scholar] [CrossRef]
  52. Isman, M.B. Plant essential oils for pest and disease management. Crop Protect. 2000, 19, 603–608. [Google Scholar] [CrossRef]
  53. Ozçelik, B.; Kusmenoglu, Ş.; Turkoz, S.; Abbasoglu, U. Antimicrobial activities of plants from the Apicaceae. Pharm. Biol. 2004, 42, 526–528. [Google Scholar] [CrossRef]
  54. Casillas-Vargas, G.; Ocasio-Malavé, C.; Medina, S.; Morales-Guzmán, C.; Del Valle, R.G.; Carballeira, N.M.; Sanabria-Ríos, D.J. Antibacterial fatty acids: An update of possible mechanisms of action and implications in the development of the next-generation of antibacterial agents. Prog. Lipid Res. 2021, 82, 101093. [Google Scholar] [CrossRef] [PubMed]
  55. Boussaada, O.; Ammar, S.; Saidana, D.; Chriaa, J.; Chraif, I.; Daami, M.; Helal, A.N.; Mighri, Z. Chemical composition and antimicrobial activity of volatile components from capitula and aerial parts of Rhaponticum acaule DC growing wild in Tunisia. Microbiol. Res. 2008, 163, 87–95. [Google Scholar] [CrossRef] [PubMed]
  56. Solórzano-Santos, F.; Miranda-Novales, M.G. Essential oils from aromatic herbs as antimicrobial agents. Curr. Opin. Biotech. 2012, 23, 136–141. [Google Scholar] [CrossRef]
  57. Dorman, H.J.D.; Deans, S.G. Antimicrobial agents from plants: Antibacterial activity of plant volatile oils. J. Appl. Microbiol. 2000, 88, 308–316. [Google Scholar] [CrossRef]
  58. Cheng, S.-S.; Liu, J.-Y.; Hsui, Y.-R.; Chang, S.-T. Chemical polymorphism and antifungal activity of essential oils from leaves of different provenances of indigenous cinnamon (Cinnamomum osmophloeum). Bioresour. Technol. 2006, 97, 306–312. [Google Scholar] [CrossRef]
  59. Joshi, R.K. GC/MS analysis of the essential oil of Leucas indica from India. Nat. Prod. Commun. 2014, 9, 1607–1608. [Google Scholar] [CrossRef] [PubMed]
  60. El Hadidy, D.; El Sayed, A.M.; El Tantawy, M.; El Alfy, T. Phytochemical analysis and biological activities of essential oils of the leaves and flowers of Ageratum houstonianum Mill. cultivated in Egypt. J. Essent. Oil-Bear. Plants 2019, 22, 1241–1251. [Google Scholar] [CrossRef]
  61. Meot-Duros, L.; Le Floch, G.; Magné, C. Radical scavenging, antioxidant and antimicrobial activities of halophytic species. J. Ethnopharm. 2008, 116, 258–262. [Google Scholar] [CrossRef] [PubMed]
  62. Seidel, V.; Taylor, P.W. In vitro activity of extracts and constituents of Pelagonium against rapidly growing mycobacteria. Int. J. Antimicrob. Agents 2004, 23, 613–619. [Google Scholar] [CrossRef] [PubMed]
  63. Puri, B.; Hall, A. Phytochemical Dictionary: A Handbook of Bioactive Compounds from Plants; CRC Press: Boca Raton, FL, USA, 1998. [Google Scholar]
  64. Badria, F.; Hetta, M.; Sarhan, R.M.; El-Din, M.E. Lethal effects of Helianthemum lippii (L.) on Acanthamoeba castellanii cysts in vitro. Korean J. Parasitol. 2014, 52, 243–249. [Google Scholar] [CrossRef] [PubMed]
  65. Zheng, C.J.; Yoo, J.-S.; Lee, T.-G.; Cho, H.-Y.; Kim, Y.-H.; Kim, W.-G. Fatty acid synthesis is a target for antibacterial activity of unsaturated fatty acids. FEBS Lett. 2005, 579, 5157–5162. [Google Scholar] [CrossRef] [PubMed]
  66. Kirilmis, C.; Ahmedzade, M.; Servi, S.; Koca, M.; Kizirgil, A.; Kazaz, C. Synthesis and antimicrobial activity of some novel derivatives of benzofuran: Part 2. The synthesis and antimicrobial activity of some novel 1-(1-benzofuran-2-yl)-2-mesitylethanone derivatives. Eur. J. Med. Chem. 2008, 43, 300–308. [Google Scholar] [CrossRef]
  67. Bisignano, G.; Sanogo, R.; Marino, A.; Aquino, R.; D‘angelo, V.D.; Germano, M.P.; De Pasquale, R.; Pizza, C. Antimicrobial activity of Mitracarpus scaber extract and isolated constituents. Lett. Appl. Microbiol. 2000, 30, 105–108. [Google Scholar] [CrossRef]
  68. Jubie, S.; Ramesh, P.N.; Dhanabal, P.; Kalirajan, R.; Muruganantham, N.; Shanish Antony, A. Synthesis, antidepressant and antimicrobial activities of some novel stearic acid analogues. Eur. J. Med. Chem. 2012, 54, 931–935. [Google Scholar] [CrossRef]
  69. Canli, K.; Akata, I.; Altuner, E.M. In vitro antimicrobial activity screening of Xylaria hypoxylon. Afr. J. Tradit. Complement. Altern. Med. 2016, 13, 42–46. [Google Scholar] [CrossRef]
  70. Payne, D.J.; Warren, P.V.; Holmes, D.J.; Ji, Y.; Lonsdale, J.T. Bacterial fatty-acid biosynthesis: A genomics-driven target for antibacterial drug discovery. Drug Discov. Today 2001, 6, 537–544. [Google Scholar] [CrossRef] [PubMed]
  71. Zampini, I.C.; Cuello, S.; Alberto, M.R.; Ordoñez, R.M.; Almeida, R.D.; Solorzano, E.; Isla, M.I. Antimicrobial activity of selected plant species from “the Argentine Puna” against sensitive and multi-resistant bacteria. J. Ethnopharm. 2009, 124, 499–505. [Google Scholar] [CrossRef] [PubMed]
  72. Ben Sassi, A.; Harzallah-Skhiri, F.; Bourgougnon, N.; Aouni, M. Antiviral activity of some Tunisian medicinal plants against Herpes simplex virus type 1. Nat. Prod. Res. 2008, 22, 53–65. [Google Scholar] [CrossRef] [PubMed]
  73. Kaul, T.N.; Middleton, E.; Ogra, P.L. Antiviral effect of flavonoids on human viruses. J. Med. Virol. 1985, 15, 71–79. [Google Scholar] [CrossRef] [PubMed]
  74. Zhang, Y.; Chen, H.; Sterling, K.; Song, W. Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future. Sig. Transduct. Target Ther. 2023, 8, 248. [Google Scholar] [CrossRef] [PubMed]
  75. Rukmangadachar, L.A.; Bollu, P.C. Amyloid Beta Peptide; StatPearls Publishing: Treasure Island, FL, USA, 2022. [Google Scholar]
  76. Arias, C.; Montiel, T.; Quiroz-Báez, R.; Massieu, L. β-Amyloid neurotoxicity is exacerbated during glycolysis inhibition and mitochondrial impairment in the rat hippocampus in vivo and in isolated nerve terminals: Implications for Alzheimer’s disease. Exp. J. Neurol. 2002, 176, 163–174. [Google Scholar] [CrossRef] [PubMed]
  77. Kumar, G.P.; Kumar, K.R.A.; Naveen, S. Phytochemicals Having Neuroprotective Properties from Dietary Sources and Medicinal Herbs. Pharmacogn. J. 2015, 7, 1–17. [Google Scholar] [CrossRef]
  78. Richard, T.; Poupard, P.; Nassra, M.; Papastamoulis, Y.; Iglésias, M.-L.; Krisa, S.; Waffo-Teguo, P.; Mérillon, J.-M.; Monti, J.-P. Protective effect of ε-viniferin on β-amyloid peptide aggregation investigated by electrospray ionization mass spectrometry. Bioorg. Med. Chem. 2011, 19, 3152–3155. [Google Scholar] [CrossRef]
  79. Pamplona, S.; Sá, P.; Lopes, D.; Costa, E.; Yamada, E.; Silva, C.E.; Arruda, M.; Souza, J.; Da Silva, M. In Vitro Cytoprotective Effects and Antioxidant Capacity of Phenolic Compounds from the Leaves of Swietenia macrophylla. Molecules 2015, 20, 18777–18788. [Google Scholar] [CrossRef]
  80. Sylla, T.; Pouységu, L.; Da Costa, G.; Deffieux, D.; Monti, J.P.; Quideau, S. Gallotannins and tannic acid: First chemical syntheses and In vitro inhibitory activity on Alzheimer’s amyloid β-peptide aggregation. Angew. Chem. Int. Ed. 2015, 54, 8217–8221. [Google Scholar] [CrossRef]
  81. Zhu, J.T.T.; Choi, R.C.Y.; Chu, G.K.Y.; Cheung, A.W.H.; Gao, Q.T.; Li, J.; Jiang, Z.Y.; Dong, T.T.X.; Tsim, K.W.K. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells:  A comparison of different flavonoids in activating estrogenic effect and in preventing β-amyloid-induced cell death. J. Agric. Food Chem. 2007, 55, 2438–2445. [Google Scholar] [CrossRef] [PubMed]
  82. Zeng, K.-W.; Wang, X.-M.; Ko, H.; Kwon, H.C.; Cha, J.W.; Yang, H.O. Hyperoside protects primary rat cortical neurons from neurotoxicity induced by amyloid β-protein via the PI3K/Akt/Bad/BclXL-regulated mitochondrial apoptotic pathway. Eur. J. Pharmacol. 2011, 672, 45–55. [Google Scholar] [CrossRef] [PubMed]
  83. Rivière, C.; Richard, T.; Vitrac, X.; Mérillon, J.-M.; Valls, J.; Monti, J.-P. New polyphenols active on β-amyloid aggregation. Bioorg. Med. Chem. Lett. 2008, 18, 828–831. [Google Scholar] [CrossRef] [PubMed]
  84. Marucci, G.; Buccioni, M.; Dal Ben, D.; Lambertucci, C.; Volpini, R.; Amenta, F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmology 2021, 190, 108353–108368. [Google Scholar] [CrossRef] [PubMed]
  85. Carvajal, F.J.; Inestrosa, N.C. Interactions of AChE with Aβ aggregates in Alzheimer’s brain: Therapeutic relevance of IDN 5706. Front. Mol. Neurosci. 2011, 4, 19–29. [Google Scholar] [CrossRef] [PubMed]
  86. Chang, T.-S. An updated review of tyrosinase inhibitors. Int. J. Mol. Sci. 2009, 10, 2440–2475. [Google Scholar] [CrossRef]
  87. Gillbro, J.M.; Olsson, M.J. The melanogenesis and mechanisms of skin-lightening agents—Existing and new approaches. Int. J. Cosmet. Sci. 2011, 33, 210–221. [Google Scholar] [CrossRef]
  88. Neagu, E.; Paun, G.; Albu, C.; Radu, G.-L. Assessment of acetylcholinesterase and tyrosinase inhibitory and antioxidant activity of Alchemilla vulgaris and Filipendula ulmaria extracts. J. Taiwan Inst. Chem. Eng. 2015, 52, 1–6. [Google Scholar] [CrossRef]
  89. Sarikurkcu, C.; Zengin, G.; Oskay, M.; Uysal, S.; Ceylan, R.; Aktumsek, A. Composition, antioxidant, antimicrobial and enzyme inhibition activities of two Origanum vulgare subspecies (subsp. vulgare and subsp. hirtum) essential oils. Ind. Crops Prod. 2015, 70, 178–184. [Google Scholar] [CrossRef]
  90. Vane, J.R.; Botting, R.M. Anti-inflammatory drugs and their mechanism of action. Inflamm. Res. 1998, 2, S78–S87. [Google Scholar] [CrossRef]
  91. Azab, A.; Nassar, A.; Azab, A.N. Anti-Inflammatory Activity of Natural Products. Molecules 2016, 21, 1321. [Google Scholar] [CrossRef] [PubMed]
  92. Torres Carro, R.; Isla, M.I.; Ríos, J.L.; Giner, R.M.; Alberto, M.R. Anti-inflammatory properties of hydroalcoholic extracts of Argentine Puna plants. Food Res. Int. 2015, 67, 230–237. [Google Scholar] [CrossRef]
  93. Rastogi, S.; Iqbal, M.S.; Ohri, D. In vitro study of anti-inflammatory and antioxidant activity of some medicinal plants and their interrelationship. Asian J. Pharm. Clin. Res. 2018, 11, 195–202. [Google Scholar] [CrossRef]
  94. Lindskog, S. Structure and Mechanism of Carbonic Anhydrase. Pharmacol. Ther. 1997, 74, 1–20. [Google Scholar] [CrossRef] [PubMed]
  95. Masini, E.; Carta, F.; Scozzafava, A.; Supuran, C.T. Antiglaucoma carbonic anhydrase inhibitors: A patent review. Expert Opin. Ther. Pat. 2013, 23, 705–716. [Google Scholar] [CrossRef] [PubMed]
  96. Khan, A.; Khan, M.; Halim, S.A.; Khan, Z.A.; Shafiq, Z.; Al-Harrasi, A. Quinazolinones as competitive inhibitors of carbonic anhydrase-II (human and bovine): Synthesis, in-vitro, in-silico, selectivity, and kinetics studies. Front. Chem. 2020, 8, 598095. [Google Scholar] [CrossRef] [PubMed]
  97. Aslam, S.; Gupta, V. Carbonic Anhydrase Inhibitors; StatPearls (Internet): Treasure Island, FL, USA, 2022. [Google Scholar]
  98. Supuran, C.T. Applications of carbonic anhydrases inhibitors in renal and central nervous system diseases. Expert Opin. Ther. Pat. 2018, 28, 713–721. [Google Scholar] [CrossRef] [PubMed]
  99. Gong, L.; Feng, D.; Wang, T.; Ren, Y.; Liu, Y.; Wang, J. Inhibitors of α-amylase and α-glucosidase: Potential linkage for whole cereal foods on prevention of hyperglycemia. Food Sci. Nutr. 2020, 8, 6320–6337. [Google Scholar] [CrossRef]
  100. Rodrigues, M.J.; Custódio, L.; Lopes, A.; Oliveira, M.; Neng, N.R.; Nogueira, J.M.F.; Martins, A.; Rauter, A.P.; Varela, J.; Barreira, L. Unlocking the in vitro anti-inflammatory and antidiabetic potential of Polygonum maritimum. Pharm. Biol. 2017, 55, 1348–1357. [Google Scholar] [CrossRef]
  101. Asmat, U.; Abad, K.; Ismail, K. Diabetes mellitus and oxidative stress—A concise review. Saudi Pharm. J. 2016, 24, 547–553. [Google Scholar] [CrossRef]
  102. Nogueira, D.R.; Mitjans, M.; Infante, M.R.; Vinardell, M.P. Comparative sensitivity of tumor and non-tumor cell lines as a reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications. Int. J. Pharm. 2011, 420, 51–58. [Google Scholar] [CrossRef] [PubMed]
  103. Itoh, S.; Taketomi, A.; Harimoto, N.; Tsujita, E.; Rikimaru, T.; Shirabe, K.; Shimada, M.; Maehara, Y. Antineoplastic effects of gamma linolenic acid on hepatocellular carcinoma cell lines. J. Clin. Biochemi. Nutr. 2010, 47, 81–90. [Google Scholar] [CrossRef] [PubMed]
  104. Cui, H.; Han, F.; Zhang, L.; Wang, L.; Kumar, M. Gamma linolic acid regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DEN induced Hepatocellular carcinoma. Drug Des. Dev. Ther. 2018, 12, 4241–4252. [Google Scholar] [CrossRef] [PubMed]
  105. Gangadhar, K.N.; Rodrigues, M.J.; Pereira, H.; Gaspar, H.; Malcata, F.X.; Barreira, L.; Varela, J. Anti-hepatocellular carcinoma (HepG2) activities of monoterpene hydroxy lactones isolated from the marine microalga Tisochrysis lutea. Mar. Drugs 2020, 18, 567. [Google Scholar] [CrossRef] [PubMed]
  106. Vizetto-Duarte, C.; Custódio, L.; Gangadhar, K.N.; Lago, J.H.G.; Dias, C.; Matos, A.M.; Neng, N.; Nogueira, J.M.F.; Barreira, L.; Albericio, F.; et al. Isololiolide, a carotenoid metabolite isolated from the brown alga Cystoseira tamariscifolia, is cytotoxic and able to induce apoptosis in hepatocarcinoma cells through caspase-3 activation, decreased Bcl-2 levels, increased p53 expression and PARP cleavage. Phytomedicine 2016, 23, 550–557. [Google Scholar] [PubMed]
  107. Malek, S.N.A.; Shin, S.K.; Wahab, N.A.; Yaacob, H. Cytotoxic components of Pereskia bleo (Kunth) DC. (Cactaceae) leaves. Molecules 2009, 14, 1713–1724. [Google Scholar] [CrossRef] [PubMed]
  108. El-Mekkawy, S.; Hassan, A.Z.; Abdelhafez, M.A.; Mahmoud, K.; Mahrous, K.F.; Meselhy, M.R.; Sendker, J.; Abdel-Sattar, E. Cytotoxicity, genotoxicity, and gene expression changes induced by methanolic extract of Moringa stenopetala leaf with LC-qTOF-MS metabolic profile. Toxicon 2021, 203, 40–50. [Google Scholar] [CrossRef]
  109. Altiok, N.; Mezzadra, H.; Patel, P.; Koyuturk, M.; Altiok, S. A plant oxylipin, 12-oxo-phytodienoic acid, inhibits proliferation of human breast cancer cells by targeting cyclin D1. Breast Cancer Res. Treat. 2008, 109, 315–323. [Google Scholar] [CrossRef]
  110. Saidana, D.; Halima-Kamel, M.B.; Mahjoub, M.; Haouas, D.; Mighri, Z.; Helal, A. Insecticidal activities of Tunisian halophytic plant extracts against larvae and adults of Tribolium confusum. Tropicultura 2007, 25, 193–199. [Google Scholar]
  111. Phillipson, J.D. Natural products as drugs. Trans. R. Soc.Trop. Med. Hyg. 1994, 88, 17–19. [Google Scholar] [CrossRef]
  112. Verpoorte, R. Pharmacognosy in the new millennium: Leadfinding and Biotechnology. J. Pharm. Pharmacol. 2010, 52, 253–262. [Google Scholar] [CrossRef]
Molecules 29 00980 g001
Figure 1. World distribution of halophytes (adapted with permission from [7]).
Figure 1. World distribution of halophytes (adapted with permission from [7]).
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Figure 2. World distribution of Frankenia species (adapted from [11]).
Figure 2. World distribution of Frankenia species (adapted from [11]).
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Molecules 29 00980 g003
Figure 3. Chemical skeleton of phenolics (1–53) isolated from the genus Frankenia (for detailed structures, see Table 2).
Figure 3. Chemical skeleton of phenolics (1–53) isolated from the genus Frankenia (for detailed structures, see Table 2).
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Molecules 29 00980 g004
Figure 4. Chemical structures of flavonoids (54–83) isolated from the genus Frankenia (for more detailed structures, see Table 3).
Figure 4. Chemical structures of flavonoids (54–83) isolated from the genus Frankenia (for more detailed structures, see Table 3).
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Molecules 29 00980 g005
Figure 5. Chemical structures of lignans (84–87) and coumarins (88) isolated from the genus Frankenia (for the detailed structures of 86–87, see Table 4).
Figure 5. Chemical structures of lignans (84–87) and coumarins (88) isolated from the genus Frankenia (for the detailed structures of 86–87, see Table 4).
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Molecules 29 00980 g006
Figure 6. Chemical structures of alkaloids (89–105) isolated from the genus Frankenia (for more detailed structures, see Table 5).
Figure 6. Chemical structures of alkaloids (89–105) isolated from the genus Frankenia (for more detailed structures, see Table 5).
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Molecules 29 00980 g007
Figure 7. Chemical structures of terpenoids (106–136) isolated from the genus Frankenia (for more detailed structures, see Table 6).
Figure 7. Chemical structures of terpenoids (106–136) isolated from the genus Frankenia (for more detailed structures, see Table 6).
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Molecules 29 00980 g008
Figure 8. Chemical structures of steroids (137–144) isolated from the genus Frankenia (for more detailed structures of 137–138, see Table 7).
Figure 8. Chemical structures of steroids (137–144) isolated from the genus Frankenia (for more detailed structures of 137–138, see Table 7).
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Molecules 29 00980 g009
Figure 9. The chemical structures of various compounds (184–210) isolated from the genus Frankenia (for more detailed structures of 206–207, see Table 10).
Figure 9. The chemical structures of various compounds (184–210) isolated from the genus Frankenia (for more detailed structures of 206–207, see Table 10).
Molecules 29 00980 g009
Molecules 29 00980 g010
Figure 10. Repartition of the various phytochemicals so far observed in and/or isolated from Frankenia plants.
Figure 10. Repartition of the various phytochemicals so far observed in and/or isolated from Frankenia plants.
Molecules 29 00980 g010
Molecules 29 00980 g011
Figure 11. Distribution of phytochemicals in typical Frankenia species.
Figure 11. Distribution of phytochemicals in typical Frankenia species.
Molecules 29 00980 g011
Table 1. Typical Frankenia species, their common and synonym names, from which phytochemical profiles have been established, and their geographic distribution.
Table 1. Typical Frankenia species, their common and synonym names, from which phytochemical profiles have been established, and their geographic distribution.
Species NameSynonymCommon NameDistribution
Frankenia laevis L. a
Molecules 29 00980 i001		Hypericopsis Boissier. [12]
Frankenia canescens Presl.		Sea heath [13]Portugal, Spain, France [13]
Algeria, Morocco, Tunisia
Frankenia intermedia Costa. Egypt [14], Iran [15]
Frankenia laevis Habl. ex Bieb.
   
Frankenia pulverulenta L. b
Molecules 29 00980 i002		Frankenia nodiflora Lam. [16]European sea heath [17]
Annual sea heath [16]		Tunisia [18,19]
   
Frankenia thymifolia Desf. c
Molecules 29 00980 i003		Frankenia reuteri Boiss. [20]Thyme sea heathNorth Africa [21,22,23]
Oman [18], Iraq [24], Iran [25]
Spain [26], Portugal [17],
England [27]
Frankenia hirsuta L. d
Molecules 29 00980 i004		Frankenia aucheri Jaub. and Spach [12]
Frankenia hirsuta L. var. erecta Boiss.		Millaih, Shuwaiwa [15]
Hairy sea heath [28]		Saudi Arabia [18]
Frankenia salsuginea Turkey [29]
Frankenia hispida D. C. Greece [30], Egypt [31],
Iraq [32], Iran [33]
Frankenia triandra J. Rémy c
Molecules 29 00980 i005		 Yareta
Yaretilla [34]		Argentina, Chile
Bolivia [34]
Frankenia foliosa Leafy sea heathAustralia [35]
a Picture adapted from [13]; b Picture adapted from [24]; c Picture adapted from the website of the Royal Botanical Kew Garden, London, https://powo.science.kew.org/ accessed on 6 February 2024; d Picture adapted from [36].
Table 2. Phenolics from Frankenia species.
Table 2. Phenolics from Frankenia species.
CompoundSubstituentsSpeciesReferences
(1) gallic acid R1 = H; R2 = H; R3 = H; R4 = HF. laevis,
F. pulverulenta, F. thymifolia		[19,21,39,40,41]
(2) gallic acid-3-methyl ether R1 = R2 = H; R3 = H; R4 = CH3F. laevis[14,40]
(3) gallic acid-3-methyl ether-5-sodium sulphateR1 = R3 = H; R2 = SO3Na; R4 = CH3“ a[14]
(4) gallic acid sulfate R1 = R2 = R3 = H; R4 = SO3H“[13]
(5) methyl gallate-3,4-dimethyl ether R1 = R3 = R4 = CH3; R2 = HF. thymifolia[42]
(6) 3-O-methylgallic acid-5-O-sulfate R1 = R3 = H; R2 = CH3; R4 = SO3HF. laevis[13]
(7) 4-O-methylgallic acid R1 = R2 = H; R3 = CH3; R4 = SO3H““ b
(8) trimethylgallate (eudesmic acid)R1 = H; R2 = R3 = R4 = CH3F. hirsuta[36]
(9) 4,5-dimethoxy-3-hydroxybenzoic acid methyl esterR1 = R3 = R4 = CH3; R2 = H;F. thymifolia[22]
(10) salicylic acid R1 = OH; R2 = R3 = R4 = H“[23]
(11) p-hydroxybenzoic acid R1 = R2 = R4 = H; R3 = OH“[21]
(12) 2,5-dihydroxybenzoic acid R1 = R4 = OH; R2 = R3 = H;“[23]
(13) vanillic acid R1 = R2 = H; R3 = OH; R4 = OCH3“[23]
(14) ellagic acid R1 = R2 = R3 = R4 = HF. laevis[13,40]
(15) 3-O-methylellagic acid R1 = CH3; R2 = R3 = R4 = H““
(16) 3-O-methylellagic acid-4-O-sulfate R1 = CH3; R2 = SO3H; R3 = R4 = H“[13]
(17) 3,3′-di-O-methylellagic acid-4-O-sulfate R1 = R4 = CH3; R2 = SO3H; R3 = H;““
(18) 3,3′-di-O-methylellagic acid R1 = R4 = CH3; R2 = R3 = H;“[13,14]
(19) ellagic acid-3-methyl etherR1 = CH3; R2 = R3 = R4 = H“[14,40]
(20) ellagic acid-3-methyl ether-4′-sodium sulphateR1 = R3 = H; R2 = SO3Na; R4 = CH3“[40]
(21) ellagic acid-3,3′-dimethyl ether-4-sodium sulphateR1 = R4 = CH3; R2 = H; R3 = SO3Na;“[14]
(22) ellagic acid-3,3′-dimethyl ether-4,4′-di-sodium sulphateR1 = R4 = CH3; R2 = R3 = SO3Na““
(23) ellagic acid-3-methyl ether-4-sodium sulphateR1 = R2 = H; R3 = SO3Na; R4 = CH3““
(24) 3,3′,4-tri-O-methylellagic acid R1 = R2 = R4 = CH3; R3 = H“[13]
(25) 3,3′,4-tri-O-methylellagic acid-4′-O-sulfate R1 = R2 = R4 = CH3; R3 = SO3H;““
(26) 3-O-methylellagic acid-4′-O-glucoside R1 = R3 = H; R2 = glucose; R4 = CH3““
(27) 3,3′-di-O-methylellagic acid-4-O-glucoside R1 = CH3; R2 = glucose; R3 = H;R4 = CH3““
(28) E-cinnamic acid R1 = H; R2 = H; R3 = H; R4 = H; R5 = OHF. thymifolia[23]
(29) E-2-hydroxycinnamic acid R1 = R2 = R3 = H; R4 = R5 = OH““
(30) caffeic acid R1 = R2 = R5 = OH; R3 = R4 = H“[39]
(31) chlorogenic acid R1 = R2 = OH; R3 = R4 = H; R5 = 1,3,4-trihy droxycyclohexane-1-carboxylic acid“[23,39]
(32) sinapic acid R1 = OCH3; R2 = OH; R3 = OCH3; R4 = H; R5 = OH“[39]
(33) caffeic acid sulfate R1 = OSO3H; R2 = R5 = OH; R3 = R4 = H;F. laevis[13]
(34) p-coumaric acidR1 = R3 = R4 = H; R2 = R5 = OH“[41]
(35) p-coumaric acid 4-O-sulfate R1 = R3 = R4 = H; R2 = OSO3H; R5 = OH“[13]
(36) ferulic acid 4-O-sulfate R1 = R3 = OCH3; R2 = OSO3H; R4 = H; R5 = OH““
(37) coumaroyl hexose sulfate R1 = R3 = R4 = H; R2 = OH;
R5 = OCH2CHOSO3H(CHOH)3CH2OH		““
(38) caffeoyl pentose sulfate R1 = OH; R2 = OH; R3 = H; R4 = H; R5 = OCH2CHOSO3H(CHOH)2CH2OH““
(39) caffeoyl hexose sulfate R1 = OH; R2 = OH; R3 = H; R4 = H;
R5 = OCH2CHOSO3H(CHOH)3CH2OH		““
(40) feruloyl hexose sulfate R1 = OCH3; R2 = OH; R3 = H; R4 = H;
R5 = OCH2CHOSO3H(CHOH)3CH2OH		““
(41) N-cis-feruloyltyramineR1 = R3 = R4 = H; R2 = OH;
R5 = 4-(2-aminoethyl)phenol		““
(42) acetophenone-4-methyletherR = H“[14]
(43) acetophenone-4-methylether-2-sodium sulfateR = SO3Na“[14]
(44) catecholR1 = R2 = R5 = H; R3 = R4 = OH;F. pulverulenta[39]
(45) resorcinol R1 = R3 = OH; R2 = R4 = R5 = H “
(46) hydroxytyrosol R1 = CH2CH2OH; R2 = R5 = H; R3 = R4 = OH;F. thymifolia[21]
(47) butenylpyrocatechol sulfate R1 = OSO3H; R2 = OH; R3 = Butenyl; R4 = R5 = HF. laevis[13]
(48) butanoylpyrocatechol sulfate R1 = OSO3H; R2 = OH; R3 = CO(CH2)2CH3; R4 = R5 = H““
(49) eugenol R1 = CH2CHCH2; R2 = R5 = H; R3 = OCH3; R4 = OH“[43]
(50) 1,3-dithian-2-yl(phenyl)methanoneR1 = (1,3-dithian-2-yl)oxomethyl; R2 = R3 = R4 = R5 = HF. hirsuta[32]
(51) 3-tertbutyl-5-chloro-2-hydroxybenzo phenoneR1 = CO(phenyl); R2 = OH; R3 = C(CH3)3; R4 = H; R5 = ClF. pulverulenta[24]
(52) posthumulone F. thymifolia[21]
(53) α-tocopherol (vitamin E) F. hirsuta[36]
a The mark “ indicates that the same species as above is concerned. b The mark “ indicates that the same reference as above is concerned.
Table 3. Flavonoids from Frankenia species.
Table 3. Flavonoids from Frankenia species.
CompoundSubstituentsSpeciesReferences
(54) kaempferol sulfate R1 = SO3H; R2 = HF. laevis[13]
(55) kaempferol-3-sodium sulfateR1 = SO3Na; R2 = H“ a[40]
(56) kaempferol-3-O-glucoside R1 = glucosyl; R2 = HF. thymifolia[21]
(57) kaempferol-3-O-rutinosideR1 = rutinosyl; R2 = HF. pulverulenta[39]
(58) kaempferol-7-sodium sulfate R1 = H; R2 = SO3NaF. laevis[40]
(59) kaempferol-7-bisulfate R1 = H; R2 = SO3HF. pulverulenta[27]
(60) kaempferol-3,7-disodium sulfate R1 = SO3Na; R2 = SO3 NaF. laevis[40]
(61) kaempferol-7-bisulfate-3-glucuronideR1 = glucuronide; R2 = SO3HF. pulverulenta[27]
(62) quercetin R1 = H; R2 = H; R3 = HF. thymifolia[42]
(63) quercetin-3-O-methyl ether R1 = H; R2 = CH3; R3 = H““ b
(64) quercetin-3-sodium sulfate R1 = H; R2 = SO3Na; R3 = HF. laevis[40]
(65) quercetin-3-bisulfate R1 = H; R2 = SO3H; R3 = HF. pulverulenta[27]
(66) quercetin-7-bisulfateR1 = H; R2 = H; R3 = SO3H““
(67) quercetin-7-sodium sulfate R1 = R2 = H; R3 = (SO3)NaF. laevis[40]
(68) quercetin 7-bisulfate-3-glucuronide R1 = H; R2 = glucuronide; R3 = SO3HF. pulverulenta[27]
(69) quercetin-3,7-disodium sulfate R1 = H; R2 = SO3 Na; R3 = SO3NaF. laevis[40]
(70) quercetin-3′-bisulfate R1 = (SO3H) Na; R2 = R3 = HF. pulverulenta[27]
(71) quercetin-3′-O-β-galactopyranosideR1 = galactopyranosyl; R2 = R3 = HF. thymifolia[42]
(72) quercetin-3′-O-β-glucopyranosideR1 = glucopyranosyl; R2 = R3 = H““
(73) quercetin-3-O-galactoside (hyperoside)R1 = R3 = H; R2 = galactosyl;“[21]
(74) catechin R1 = R2 = HF. laevis,
F. pulverulenta, F. thymifolia		[19,23,39,41]
(75) epigallocatechin R1 = OH; R2 = HF. pulverulenta[39]
(76) epigallocatechino-3-gallate R1 = OH; R2 = gallateF. thymifolia[23]
(77) prodelphinidin B-4 “[21]
(78) procyanidin (dimer 1,2 and 3) F. pulverulenta[19]
(79) isorhamnetin-7-bisulfate R1 = H; R2 = SO3H“[27]
(80) isorhamnetin-7-bisulfate-3-glucuronide R1 = glucuronide; R2 = SO3H““
(81) isorhamnetin-O-pentosylhexosideR1 = pentosyl-hexoside; R2 = HF. laevis[13]
(82) naringenin F. thymifolia[42]
(83) luteolin-7-O-glucoside F. pulverulenta, F. thymifolia[21,39]
a The mark “ indicates that the same species as above is concerned. b The mark “ indicates that the same reference as above is concerned.
Table 4. Lignans and coumarins from Frankenia species.
Table 4. Lignans and coumarins from Frankenia species.
CompoundSubstituentsSpeciesReferences
(84) lyoniresinol sulfate F. laevis[13]
(85) lariciresinol “ a“ b
(86) pinoresinol R = HF. thymifolia[21]
(87) pinoresinol-4-sulfate R = OSO3H“[22]
(88) coumarin F. pulverulenta[39]
a The mark “ indicates that the same species as above is concerned. b The mark “ indicates that the same reference as above is concerned.
Table 5. Alkaloids from Frankenia species.
Table 5. Alkaloids from Frankenia species.
CompoundSubstituentsSpeciesReferences
(89) S-methyl, N-(2-methyl-3-oxobutyl) dithiocarbamate F. pulverulenta[24]
(90) 1,8-di-(4-nitrophenylmethyl)-3,6-diazahomoadamantan-9-one “ a“ b
(91) pyrrolizin-1,7-dione-6-carboxylic acid, methyl ester ““
(92) N-methyl, N-4-[1-(pyrrolidinyl)-2-butynyl] formamide ““
(93) N-cyclooct-4-enyl acetamide ““
(94) 2-(2-methyl-propenyl)-cyclohexanone oxime ““
(95) 1-propyl-3,6-diaza homoadamantan-9-ol R1 = H; R2 = (CH2)2CH3““
(96) 1,8-diethyl-3,6-diaza homoadamantan-9-olR1 = R2 = CH2CH3““
(97) 16,17-didehydrocuran R1 = R2 = R3 = H““
(98) (19S)-16,17-didehydrocuran-19,20-diol R1 = H; R2 = R3 = OH““
(99) 1-acetyl-20α-hydroxy-16-methylene strychnaneR1 = COCH3; R2 = OH; R3 = H““
(100) dasycarpidan-1-methanol acetate ““
(101) 2,7-diphenyl-1,6-dioxopyridazino [4,5:2′,3′]pyrrolo [4′,5′-d]pyridazine ““
(102) dihydrotecomanine F. pulverulenta, F. hirsuta[24,32]
(103) 2-acetylamino-3-hydroxypropionic acid F. aucheri (irsute)[32]
(104) pterin-6-carboxylic acid ““
(105) 18,19-didehydro-10-methoxycorynan-17-ol, acetate ““
a The mark “ indicates that the same species as above is concerned. b The mark “ indicates that the same reference as above is concerned.
Table 6. Terpenoids from Frankenia species.
Table 6. Terpenoids from Frankenia species.
CompoundSubstituentsSpeciesReferences
(106) isololiolide R = OHF. laevis[13]
(107) loliolide R = OH“ a“ b
(108) dihydroactinidiolide R = H““
(109) α-pinene F. pulverulenta[18]
(110) phytol R = OHF. laevis[43]
(111) (E)-phytyl acetate R = OCOCH3““
(112) isophytol ““
(113) (E,E,E)-geranylgeraniol F. pulverulenta[18]
(114) gibberellic acid “[24]
(115) caryophyllene oxide F. laevis[43]
(116) (E)-nerolidol ““
(117) (E,E)-farnesolR = CH2OH““
(118) (E,E)-farnesal R = CHO““
(119) (E,E)-farnesyl acetate R = CH2OCOCH3““
(120) α-copaene-11-ol F. pulverulenta[18]
(121) ledol ““
(122) α-cadinol ““
(123) tau-cadinol ““
(124) torreyol ““
(125) 6-epi-shyobunol F. hirsuta[32]
(126) germacrene D F. laevis[43]
(127) calarene ““
(128) α-copaene F. pulverulenta[18]
(129) β-humulene ““
(130) α-selinene ““
(131) β-selinene ““
(132) ledene ““
(133) δ-cadinene ““
(134) γ-cadinene F. laevis,
F. pulverulenta		[18,43]
(135) (E)-β-caryophyllene ““
(136) allo-aromadendrene ““
a The mark “ indicates that the same species as above is concerned. b The mark “ indicates that the same reference as above is concerned.
Table 7. Steroids from Frankenia species.
Table 7. Steroids from Frankenia species.
CompoundSubstituentsSpeciesReferences
(137) β-5,6-secosteroid R = EtF. foliosa[35]
(138) 5-oxo-5,6-seco-3-cholesten-6-oic acid R = H“ a“ b
(139) vitamin D (9,10-secosteroids) ““
(140) brassinolide (6,7-secosteroids) ““
(141) eringiacetal A ““
(142) ethyl iso-allocholate F. pulverulenta[24]
(143) 2-(3-acetoxy-4,4,14 trimethylandrost-8-en-17-yl)propanoic acid ““
(144) γ-sitosterol F. hirsuta[36]
a The mark “ indicates that the same species as above is concerned. b The mark “ indicates that the same reference as above is concerned.
Table 8. Alkanes and alkenes from Frankenia species, corresponding to the global formula below.
Table 8. Alkanes and alkenes from Frankenia species, corresponding to the global formula below.
CompoundSubstituents
Molecules 29 00980 i006		SpeciesReferences
(145) heptadecane R1 = H; R2 = (CH2)14CH3F. laevis[43]
(146) tricosane R1 = H; R2 = (CH2)20CH3“ a“ b
(147) tetracosane R1 = H; R2 = (CH2)21CH3F. laevis, F. pulverulenta[18,43]
(148) pentacosane R1 = H; R2 = (CH2)22CH3““
(149) hexacosane R1 = H; R2 = (CH2)23CH3F. laevis[43]
(150) heptacosane R1 = H; R2 = (CH2)24CH3““
(151) octacosane R1 = H; R2 = (CH2)25CH3““
(152) nonacosane R1 = H; R2 = (CH2)26CH3““
(153) triacontane R1 = H; R2 = (CH2)27CH3““
(154) docosane R1 = H; R2 = (CH2)19CH3F. pulverulenta[18]
(155) n-heneicosane R1 = H; R2 = (CH2)18CH3F. laevis“
(156) 2-methyloctacosane R1 = CH3; R2 = (CH2)25CH3““
(157) hentriacontane R1 = H; R2 = (CH2)28CH3““
(158) pentatriacontane R1 = H; R2 = (CH2)32CH3““
(159) eicosane R1 = H; R2 = (CH2)17CH3F. hirsuta[36]
(160) 1-docosene R1 = H; R2 = (CH2)18CHCH2F. laevis[43]
(161) 1-nonade-ceneR1 = H; R2 = (CH2)15CHCH2F. hirsuta[36]
a The mark “ indicates that the same species as above is concerned. b The mark “ indicates that the same reference as above is concerned.
Table 9. Fatty acids and esters from Frankenia species, corresponding to the global formula below.
Table 9. Fatty acids and esters from Frankenia species, corresponding to the global formula below.
CompoundSubstituents
Molecules 29 00980 i007		SpeciesReferences
(162) caproic acid R1 = (CH2)4CH3; R2 = HF. laevis[43]
(163) caprylic acid R1 = (CH2)6CH3; R2 = HF. hirsuta[32]
(164) pelargonic acid R1 = (CH2)7CH3; R2 = H“ a“ b
(165) lauric acid R1 = (CH2)10CH3; R2 = HF. laevis,
F. thymifolia		[23,43]
(166) myristic acid R1 = (CH2)12CH3; R2 = HF. thymifolia[23]
(167) palmitic acid R1 = (CH2)14CH3; R2 = HF. hirsuta,
F. laevis,
F. pulverulenta, F. thymifolia		[23,24,36,43]
(168) thapsic acid R1 = (CH2)14COOH; R2 = HF. laevis[43]
(169) stearic acid R1 = (CH2)16CH3; R2 = HF. hirsuta,
F. thymifolia		[23,32,36]
(170) behenic acid R1 = (CH2)20CH3; R2 = H“[23,36]
(171) lignoceric acid R1 = (CH2)22CH3; R2 = HF. hirsuta[36]
(172) oleic acid R1 = (Z)-heptadec-8-enyl; R2 = HF. hirsuta,
F. thymifolia		[23,36]
(173) elaïdic acid R1 = (E)-heptadec-8-enyl; R2 = HF. thymifolia[23]
(174) linoleic acid R1 = (8Z,11Z)-heptadeca-8,11-dienyl; R2 = HF. hirsuta,
F. thymifolia		[23,36]
(175) α-linolenic acid R1 = (8Z,11Z,14Z)-heptadeca-8,11,14-trienyl; R2 = HF. thymifolia[23]
(176) gamolenic acid R1 = (5Z,8Z,11Z)-hexadeca-5,8,11-trienyl; R2 = HF. pulverulenta[24]
(177) hydroxyoctadecadienoic acid R1 = (1E,3E)-1-hydroxyheptadec-3-enylidene; R2 = HF. laevis[43]
(178) malyngic acidR1 = (8S, 9E,11R,12R,13Z)-8,11,12-trihydroxyheptadeca-9,13-dienyl; R2 = H“[13]
(179) methyl cis-12,13-epoxyoctadecanoate R1 = cis-11,13-epoxyheptadecyl;
R2 = CH3		F. hirsuta[32]
(180) methyl palmitate R1 = pentadecyl; R2 = CH3F. laevis[43]
(181) methyl linoleate R1 = (8Z,11Z)-heptadeca-8,11-dienyl; R2 = CH3““
(182) methyl 12,15-octadecadiynoate R1 = heptadeca-11,14-diynyl; R2 = CH3F. hirsuta[32]
(183) methyl-11,13-dihydroxytetradec-5-ynoate R1 = 10,11-dihydroxytridec-4-ynyl;
R2 = CH3		F. pulverulenta[24]
a The mark “ indicates that the same species as above is concerned. b The mark “ indicates that the same reference as above is concerned.
Table 10. Miscellaneous compounds isolated from Frankenia species.
Table 10. Miscellaneous compounds isolated from Frankenia species.
CompoundSubstituentsSpeciesReferences
(184) 5,7-dodecadiyn-1,12-diol F. pulverulenta[24]
(185) hexadecan-1-ol F. laevis[43]
(186) 3-O-methyl-d-glucose F. pulverulenta, F. hirsuta[24,32]
(187) 6-acetyl-α-d-mannose F. hirsuta[32]
(188) 6-acetyl-β-d-mannose F. pulverulenta[24]
(189) α-d-glucopyranosyl-(1->3)-β-d-fructofuranosyl β-d-glucopyranoside “ a“ b
(190) 4-O-(β-d-galactopyranosyl)-β-d-glucopyranose ““
(191) desulphosinigrin F. hirsuta[32]
(192) benzyl benzoate R = phenyl““
(193) benzyl cinnamate R = styryl““
(194) mesitylene “[36]
(195) 1,2,3,4,5,7-hexamethoxynaphthalene F. thymifolia[22]
(196) pheophytin A F. laevis[13]
(197) [(hexadecyloxy)methyl]oxirane F. hirsuta[32]
(198) 8a-methyl-4H,5H-tetrahydropyrano[4,3-d]-1,3-dioxin F. pulverulenta[24]
(199) 2-formyl-5-(hydroxymethyl)furan F. hirsuta[32]
(200) 2-methyldecanal F. laevis[43]
(201) (Z)-12-hydroxy-14-methyl-oxacyclotetradec-6-en-2-one F. pulverulenta[24]
(202) 7-(1-hydroxypentyl)-2-oxabicyclo[3.3.0]oct-7-en-3-one R = C4H9““
(203) citric acid F. laevis[13]
(204) 12-oxophytodienoic acid ““
(205) tuberonic acid sulfate ““
(206) phthalic acid, butyl tetradecyl ester R1 = nBu; R2 = tetradecylF. hirsuta[32]
(207) phthalic acid, isobutyl octadecyl ester R1 = iBu; R2 = octadecyl““
(208) N,N’-bis(carbobenzyloxy)-l-lysinyl-l-valine methyl ester ““
(209) 5-phenyloxymethyl-2-phenylhydrazino-4,5-dihydro-1,3-oxazole ““
(210) 2,5-dihydroperoxy-2,5-dimethylhexane ““
a The mark “ indicates that the same species as above is concerned. b The mark “ indicates that the same reference as above is concerned.
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Khaled, M.; Ouache, R.; Pale, P.; Harkat, H. Phytochemical Profiles and Biological Activities of Frankenia Species: A Review. Molecules 2024, 29, 980. https://doi.org/10.3390/molecules29050980

AMA Style

Khaled M, Ouache R, Pale P, Harkat H. Phytochemical Profiles and Biological Activities of Frankenia Species: A Review. Molecules. 2024; 29(5):980. https://doi.org/10.3390/molecules29050980

Chicago/Turabian Style

Khaled, Meyada, Rachid Ouache, Patrick Pale, and Hassina Harkat. 2024. "Phytochemical Profiles and Biological Activities of Frankenia Species: A Review" Molecules 29, no. 5: 980. https://doi.org/10.3390/molecules29050980

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