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The Veronica genus, with more than 200 species, belongs to the Plantaginaceae family and is distributed over most of the Northern Hemisphere and in many parts of Southern Hemisphere. These plants are traditionally used in medicine for wound healing, in the treatment of rheumatism, and in different human diseases. This paper reviews the chemical composition of some valuable Veronica species, the possibilities Veronica extracts have in food preservation and as food ingredients, and their functional properties. Veronica species represent a valuable source of biological active secondary metabolites, including iridoid glycosides and phenolic compounds. In particular, due to presence of these phytochemicals, Veronica species exhibit a wide spectrum of biological activities, including antimicrobial and antioxidant. In fact, some studies suggest that some Veronica extracts can inhibit foodborne pathogens, such as Listeria monocytogenes, but only a few of them were performed in food systems. Moreover, anticancer, anti-inflammatory, and other bioactivities were reported in vitro and in vivo. The bioactivity of Veronica plants was demonstrated, but further studies in food systems and in humans are required.
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molecules
Review
Veronica Plants—Drifting from Farm to Traditional
Healing, Food Application, and Phytopharmacology
Bahare Salehi 1, Mangalpady Shivaprasad Shetty 2, Nanjangud V. Anil Kumar 3,
Jelena Živkovi´c 4, Daniela Calina 5, Anca Oana Docea 6, Simin Emamzadeh-Yazdi 7,
Ceyda Sibel Kılıç 8, Tamar Goloshvili 9, Silvana Nicola 10 , Giuseppe Pignata 10,
Farukh Sharopov 11,* , María del Mar Contreras 12,* , William C. Cho 13,* ,
Natália Martins 14,15,* and Javad Sharifi-Rad 16,*
1
Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 44340847, Iran
2Department of Chemistry, NMAM Institute of Technology, Karkala 574110, India
3Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education,
Manipal 576104, India
4Institute for Medicinal Plants Research “Dr. Josif Panˇci´c”, Tadeuša Koš´cuška 1, Belgrade 11000, Serbia
5Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova 200349,
Romania
6Department of Toxicology, University of Medicine and Pharmacy of Craiova, Craiova 200349, Romania
7Department of Plant and Soil Sciences, University of Pretoria, Gauteng 0002, South Africa
8Department of Pharmaceutical Botany, Faculty of Pharmacy, Ankara University, Ankara 06100, Turkey
9
Department of Plant Physiology and Genetic Resources, Institute of Botany, Ilia State University, Tbilisi 0162,
Georgia
10 Department of Agricultural, Forest and Food Sciences, University of Turin, I-10095 Grugliasco, Italy
11 Department of Pharmaceutical Technology, Avicenna Tajik State Medical University, Rudaki 139,
Dushanbe 734003, Tajikistan
12 Department of Chemical, Environmental and Materials Engineering, University of Jaén, 23071 Jaén, Spain
13 Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR 999077, China
14 Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
15
Institute for Research and Innovation in Health (i3S), University of Porto–Portugal, 4200-135 Porto, Portugal
16 Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences, Zabol 61615-585, Iran
*Correspondence: farukhsharopov@gmail.com (F.S.); mmcontreras@ugr.es (M.d.M.C.);
williamcscho@gmail.com (W.C.C.); ncmartins@med.up.pt (N.M.); javad.sharifirad@gmail.com (J.S.-R.);
Tel.: +992-93-995-0370 (F.S.); +34-953-212799 (M.d.M.C.); +852-3506-6284 (W.C.C.); +351-22-5512100 (N.M.);
+98-21-8820-0104 (J.S.-R.)
Academic Editors: Federica Pellati, Laura Mercolini and Roccaldo Sardella
Received: 15 May 2019; Accepted: 30 June 2019; Published: 4 July 2019


Abstract:
The Veronica genus, with more than 200 species, belongs to the Plantaginaceae family and is
distributed over most of the Northern Hemisphere and in many parts of Southern Hemisphere. These
plants are traditionally used in medicine for wound healing, in the treatment of rheumatism, and in
dierent human diseases. This paper reviews the chemical composition of some valuable Veronica
species, the possibilities Veronica extracts have in food preservation and as food ingredients, and
their functional properties. Veronica species represent a valuable source of biological active secondary
metabolites, including iridoid glycosides and phenolic compounds. In particular, due to presence
of these phytochemicals, Veronica species exhibit a wide spectrum of biological activities, including
antimicrobial and antioxidant. In fact, some studies suggest that some Veronica extracts can inhibit
foodborne pathogens, such as Listeria monocytogenes, but only a few of them were performed in food
systems. Moreover, anticancer, anti-inflammatory, and other bioactivities were reported
in vitro
and
in vivo
. The bioactivity of Veronica plants was demonstrated, but further studies in food systems and
in humans are required.
Molecules 2019,24, 2454; doi:10.3390/molecules24132454 www.mdpi.com/journal/molecules
Molecules 2019,24, 2454 2 of 35
Keywords: Veronica plants; speedwell; iridoids; phenolic compounds; natural preservatives
1. Introduction
The genus Veronica at present belongs to the family Plantaginaceae, while it was previously
classified in the family Scrophulariaceae [
1
]. There are many suggestions (problems) related to the
classification and rearrangement of this genus [
2
,
3
]. The family includes 120 plant genera with 7055
scientific plant names, of which 1614 are accepted species names [
4
]. The Plant List includes 1520
scientific plant names for the Veronica genus. Of these, 234 are accepted species names, 335 are
synonyms, and 951 are unassessed. Thus, the total number of species belonging to the genus Veronica
depends on synonym acceptance. These species are distributed over the Northern Hemisphere and into
the Australasian region (Australia, New Zealand, New Guinea), with centers of diversity in western
Asia and New Zealand [
2
]. Most of the species of Veronica occur in regions with a Mediterranean
precipitation regime from the sea to high alpine elevations. Despite the importance in many habitats,
aquatic plants of Veronica are mostly researched in modern biosystematic studies. The common member
of the semi-aquatic plants in the Mediterranean region is Veronica sect. beccabunga [
5
]. Some other
common species of Veronica genus are represented in Table 1.
Table 1. List of some common Veronica species, their edibility, and medicinal uses [6].
Latin Name Common Name Edibility Medicinal Use
Veronica agrestis L. Field speedwell, green field speedwell Yes Yes
Veronica americana Schwein. ex Benth. American brooklime, American speedwell Yes Yes
Veronica anagallis-aquatica L. Water speedwell Yes Yes
Veronica arvensis L. Corn speedwell No Yes
Veronica beccabunga L. Brooklime, European speedwell Yes Yes
Veronica catenata Pennell Yes No
Veronica chamaedrys L. Germander speedwell Yes Yes
Veronica hederifolia L. Ivy-leaf speedwell No Yes
Veronica longifolia L. Garden speedwell, long-leaf speedwell Yes No
Veronica ocinalis L. Common speedwell Yes Yes
Veronica peregrina L. Necklace weed, neckweed, hairy purslane
speedwell No Yes
Veronica polita Fr. Gray field speedwell Yes Yes
Veronica scutellata L. Marsh speedwell, skullcap speedwell Yes No
Veronica spuria L. Bastard speedwell Yes No
Veronica undulata Wall. Undulate speedwell Yes Yes
Veronica strum virginicum (L.) Farw. Beaumont’s root, Culver’s root, Bowman’s
root, Culver’s root, Black root No Yes
Traditional medicine is a sum of great knowledge about health, disease prevention, treatment,
and physical and mental illnesses. There are dierent types of traditional medicine such as ancient
Iranian medicine, traditional Chinese medicine, Ayurveda, traditional African medicine, acupuncture,
and so on [
7
]. In 2019, the World Health Organization published a global report on traditional and
complementary medicine and stated that 88% of its member states, corresponding to 170 member
states, reported that their population uses traditional medicines to treat illnesses [
8
]. The wide diverse
distribution of Veronica plants, from aquatic to dry steppe habitats and from sea-level to high alpine
regions [
9
], could be related to the wide range of traditional uses within these cultures (Table 1).
As an example, Veronica peregrina L. is useful for treating hemorrhage, gastric ulcer, infections, and
diseases related to macrophage-mediated inflammatory disorders, as illustrated in Korean traditional
medicine [10]. Tea made from Veronica spicata L. is a well-known remedy in traditional medicine [11].
Veronica species have cytotoxic and anti-inflammatory activity. Veronica ocinalis L. (common speedwell)
is used for treating liver, eczema, ulceration, snake bites, wound healing, and skin lesions in Balkan
traditional medicine [
12
]. Veronica species are used in traditional medicine for the treatment of
Molecules 2019,24, 2454 3 of 35
rheumatism [
13
], hemoptysis, laryngopharyngitis, hernia [
14
], and lung and respiratory diseases (e.g.,
against cough or as an expectorant) [
15
]. They also have properties such as antiscorbutic and diuretic,
as well as wound healing [
16
]. Three Veronica species, namely, V. ocinalis,Veronica chamaedrys L.,
and Veronica herba DAC, are used in traditional Austrian herbal drugs [
17
]. V. ocinalis is a popular
medicinal plant, used as a commercial herbal product in many European countries [
18
]. There are
around 79 Veronica species in Turkish flora, 26 of which are endemic. Dierent parts of Veronica species
are used as a diuretic, for wound healing, and against rheumatic pains in Turkish folk medicine [19].
Thus, based on this knowledge, Veronica plants are potential sources of nutraceuticals and
functional ingredients with a wide spectrum of bioactivities. In fact, Veronica species represent a valuable
source of biological active compounds. Among others, the extracts of Veronica plants show antioxidant,
antimicrobial, antifungal, anti-inflammatory, scolicidal, and anti-cancer activities, as well as inhibitory
potential on acetylcholinesterase, tyrosinase, lipoxygenase, and xanthine oxidase [
20
]. Overall, these
species might be considered good candidates for industrial or pharmacological applications. Therefore,
this review covers information about the phytochemical composition of Veronica plants, mainly
focused on phenolics and iridoids. Their biological properties are also detailed, as well as recent
food applications.
2. Phytochemical Characterization of Veronica Plants
Several phytoconstituents isolated from the plant extracts were studied by means of mass
spectrometry (MS) and spectroscopy techniques such as nuclear magnetic resonance (NMR). In the year
1973, Grayer-Barkmeijer and co-workers reported that catalpol (1) derivatives, i.e., caeoyl-catalpol
(2), isoferuloyl-catalpol (3), protocatechuoyl-catalpol (4), benzoyl-catalpol (5), p-hydroxybenzoyl
catalpol (catalposide) (6), vanilloyl-catalpol (7), and cinnamoyl-aucubin (9), were isolated from several
Veronica species, including sect. Paederota, Pseudolysimachia, Veronicastrum, Omphalospora, and
Chamaedrys [
21
] (Figure 1). It depends on the species, e.g., neither of them was detected in Veronica
virginica L. (sect. Paederota) and most of them were in Veronica persica Poir (Sect. Omphalospora).
Verproside (6-O-protocatechuoylcatalpol) (4) was also isolated from V. ocinalis [
22
]. In fact, Johansen
and co-authors reported that 6-O-rhamnopyranosylcatalpol esters are chemical markers of Veronica
sect. Hebe [23].
Molecules 2019, 24, x 4 of 26
R = H, Catalpol (1)
R = Caffeoyl (2)
R = Isoferuloyl (3)
R = Protocatechuoyl (4)
R = Benzoyl (5)
R = p-Hydroxybenzoyl (6)
R = Vanilloyl (7)
R = H, Aucubin (8)
R = Cinnamoyl (9)
Figure 1. Catalpol and aucubin derivatives described in several Veronica plants, including sect.
Paederota, Pseudolysimachia, Veronicastrum, Omphalospora, and Chamaedrys.
In Veronica, a larger variety of flavone aglycones was also found, e.g., luteolin (10), apigenin
(11), chrysoeriol (12), tricin (13), and 6-hydroxyflavones (14) [24]. In fact, eight flavone aglycones
were detected in 52 samples of 29 species of Veronica, and the most common ones were apigenin (11)
and luteolin (10) (Figure 2) [25]. The observed exudate flavonoid aglycone profiles appeared to be
characteristic for some related groups within Veronica genus, in consonance with the morphological,
karyological, molecular, and other chemical data [25]. The presence of flavone glycosides was
reported in several species, such as Veronica gentianoides Vahl., Veronica alpine L., and Veronica
fruticans Jacq. The petals of the species of Veronica, like Veronica gentianoides Vahl, Veronica arvensis L.,
V. persica, Veronica filiformis Sm., Veronica hederifolia L., and V. chamaedrys, also showed the presence of
the anthocyanidin delphinidin (15).
Figure 2. Common flavonoid aglycones in several Veronica species.
Furthermore, the structure of other particular compounds in Veronica species is detailed in this
section; in addition to the expected iridoid glucosides, Veronica species are sources of new
phytochemicals.
2.1. Veronica Filiformis
A non-common flavone glycoside was isolated from the whole plant of V. filiformis and
identified by means of
13
C NMR spectroscopy as isoscutellarein 4-methyl ether
7-O-β-(6′′′-O-acetyl-2′′-O-allosylglucoside) (16) (Figure 3). This was the first report of
2-allosylglucose as a disaccharide unit of flavonoids [26].
Figure 1.
Catalpol and aucubin derivatives described in several Veronica plants, including sect.
Paederota, Pseudolysimachia, Veronicastrum, Omphalospora, and Chamaedrys.
In Veronica, a larger variety of flavone aglycones was also found, e.g., luteolin (10), apigenin
(11), chrysoeriol (12), tricin (13), and 6-hydroxyflavones (14) [
24
]. In fact, eight flavone aglycones
were detected in 52 samples of 29 species of Veronica, and the most common ones were apigenin (11)
and luteolin (10) (Figure 2) [
25
]. The observed exudate flavonoid aglycone profiles appeared to be
characteristic for some related groups within Veronica genus, in consonance with the morphological,
karyological, molecular, and other chemical data [
25
]. The presence of flavone glycosides was reported
Molecules 2019,24, 2454 4 of 35
in several species, such as Veronica gentianoides Vahl., Veronica alpine L., and Veronica fruticans Jacq. The
petals of the species of Veronica, like Veronica gentianoides Vahl, Veronica arvensis L., V. persica, Veronica
filiformis Sm., Veronica hederifolia L., and V. chamaedrys, also showed the presence of the anthocyanidin
delphinidin (15).
Molecules 2019, 24, x 4 of 34
R = Caffeoyl (2)
R = Isoferuloyl (3)
R = Protocatechuoyl (4)
R = p-Hydroxybenzoyl (6)
R = Vanilloyl (7)
R = Cinnamoyl (9)
Figure 1. Catalpol and aucubin derivatives described in several Veronica plants, including sect.
Paederota, Pseudolysimachia, Veronicastrum, Omphalospora, and Chamaedrys.
In Veronica, a larger variety of flavone aglycones was also found, e.g., luteolin (10), apigenin
(11), chrysoeriol (12), tricin (13), and 6-hydroxyflavones (14) [24]. In fact, eight flavone aglycones
were detected in 52 samples of 29 species of Veronica, and the most common ones were apigenin (11)
and luteolin (10) (Figure 2) [25]. The observed exudate flavonoid aglycone profiles appeared to be
characteristic for some related groups within Veronica genus, in consonance with the morphological,
karyological, molecular, and other chemical data [25]. The presence of flavone glycosides was
reported in several species, such as Veronica gentianoides Vahl., Veronica alpine L., and Veronica
fruticans Jacq. The petals of the species of Veronica, like Veronica gentianoides Vahl, Veronica arvensis L.,
V. persica, Veronica filiformis Sm., Veronica hederifolia L., and V. chamaedrys, also showed the presence of
the anthocyanidin delphinidin (15).
R = OH, Luteolin (10)
R = H, Apigenin (11)
R = OCH3, Chrysoeriol (12)
Tricin (13)
Delphinidin (15) 6-Hydroxyflavones (14)
Figure 2. Common flavonoid aglycones in several Veronica species.
Furthermore, the structure of other particular compounds in Veronica species is detailed in this
section; in addition to the expected iridoid glucosides, Veronica species are sources of new
phytochemicals.
2.1. Veronica Filiformis
A non-common flavone glycoside was isolated from the whole plant of V. filiformis and
identified by means of 13C NMR spectroscopy as isoscutellarein 4-methyl ether
7-O-β-(6′′′-O-acetyl-2′′-O-allosylglucoside) (16) (Figure 3). This was the first report of
2-allosylglucose as a disaccharide unit of flavonoids [26].
Figure 2. Common flavonoid aglycones in several Veronica species.
Furthermore, the structure of other particular compounds in Veronica species is detailed
in this section; in addition to the expected iridoid glucosides, Veronica species are sources of
new phytochemicals.
2.1. Veronica filiformis
A non-common flavone glycoside was isolated from the whole plant of V. filiformis
and identified by means of
13
C NMR spectroscopy as isoscutellarein 4
0
-methyl ether
7-O-
β
-(6
000
-O-acetyl-2
00
-O-allosylglucoside) (16) (Figure 3). This was the first report of 2-allosylglucose
as a disaccharide unit of flavonoids [26].
2.2. Veronica linariifolia Pall. ex Link
A new flavonoid glycoside, linariifolioside (18) (Figure 3), was isolated from the
alcohol extract of the dried whole herb. In addition, four known compounds,
luteolin-7-O-
β
-d-glucosyl-(1-2)-
β
-d-glucoside (17), apigenin-7-O-
α
-l-rhamnoside (19), luteolin (10),
and apigenin (11) were isolated from the same fraction and identified [
27
]. Another work
showed the presence of 3
0
,4
0
,5,6,7-pentahydroxyflavone-7-O-
β
-d-glucosyl-(1
00
2
0
)-
β
-d-glucoside,
4
0
,5,7-trihydroxy-3
0
,6-dimethoxyflavone-7-O-
β
-d-glucoside, apigenin-7-O-
β
-d-glucuronide methyl
ester, apigenin-7-O-
β
-d-glucuronide ethyl ester, apigenin-7-O-
β
-d-glucuronide buthyl ester, apigenin
(11), luteolin (10), vanillic acid, p-hydroxybenzoic acid, protocatechuic acid, protocatechuic acid ethyl
ester, isoerulic acid, catechol, and emodin [
28
]. Alternatively, the essential oil was extracted by
steam distillation approaches. The main compounds isolated were cyclohexene (21),
β
-pinene (22),
1S-α-pinene (23), β-phellandrene (24), β-myrcene (25), and germacrene-d(26) (Figure 4) [29].
Molecules 2019,24, 2454 5 of 35
Figure 3. Flavone derivatives found in Veronica filiformis and Veronica linariifolia.
2.3. Veronica fushii
From the methanolic extract of the aerial parts of V. fuhsii, Ozipek and co-workers isolated and
reported fushioside (27) and 2-(3,4-dihydroxyphenyl)ethyl 6-O-protocatechuoyl-
β
-d-glucopyranoside
(28), along with a known phenylethanoid glycoside, plantamajoside (29), and a flavone glucoside,
luteolin 7-O-glucoside (30) (Figure 5) [
30
]. Note that this species is endemic of Middle Anatolia [
30
],
and it is not included in the plant list.
Molecules 2019,24, 2454 6 of 35
Molecules 2019, 24, x 6 of 34
Cyclohexene (21)
Veronicoside (20) β-Pinene (22)
1S-α-Pinene (23)
β-Phellandrene (24)
β-Myrcene (25) Germacrene-D (26)
Figure 4. Phytochemicals from Veronica linariifolia essential oil.
2.3. Veronica Fushii
From the methanolic extract of the aerial parts of V. fuhsii, Ozipek and co-workers isolated and
reported fushioside (27) and 2-(3,4-dihydroxyphenyl)ethyl
6-O-protocatechuoyl-β-D-glucopyranoside (28), along with a known phenylethanoid glycoside,
plantamajoside (29), and a flavone glucoside, luteolin 7-O-glucoside (30) (Figure 5) [30]. Note that
this species is endemic of Middle Anatolia [30], and it is not included in the plant list.
Fushioside (27)
2-(3,4-Dihydroxyphenyl)ethyl 6-O-protocatechuoyl-β-D-glucopyranoside (28)
Figure 4. Phytochemicals from Veronica linariifolia essential oil.
Molecules 2019, 24, x 6 of 34
Cyclohexene (21)
Veronicoside (20) β-Pinene (22)
1S-α-Pinene (23)
β-Phellandrene (24)
β-Myrcene (25) Germacrene-D (26)
Figure 4. Phytochemicals from Veronica linariifolia essential oil.
2.3. Veronica Fushii
From the methanolic extract of the aerial parts of V. fuhsii, Ozipek and co-workers isolated and
reported fushioside (27) and 2-(3,4-dihydroxyphenyl)ethyl
6-O-protocatechuoyl-β-D-glucopyranoside (28), along with a known phenylethanoid glycoside,
plantamajoside (29), and a flavone glucoside, luteolin 7-O-glucoside (30) (Figure 5) [30]. Note that
this species is endemic of Middle Anatolia [30], and it is not included in the plant list.
Fushioside (27)
2-(3,4-Dihydroxyphenyl)ethyl 6-O-protocatechuoyl-β-D-glucopyranoside (28)
Figure 5. Cont.
Molecules 2019,24, 2454 7 of 35
Molecules 2019, 24, x 7 of 34
Plantamajoside (29)
Luteolin 7-O-glucoside (30)
Figure 5. Phytoconstituents in Veronica fushii.
2.4. Veronica Cymbalaria Bodard
The main iridoids and iridoid-phenolic constituents of extracts from this plant were catalpol (1),
amphicoside (31), and verproside (32), together with alpinoside (33), aucubin (8),
6-O-veratroylcatalpol (34), and verminoside (35) (Figure 6). The iridoid alpinoside with a 8,9-double
bond was found for the first time in genus Veronica [31]. In V. cymbalaria, other authors found the
iridoid glucosides aucubin (8), catalpol (1), veronicoside (20), verproside (32), amphycoside,
verminoside (35), catalposide (6), 6-O-veratroylcatalposide (34), and 6-O-isovanilloylcatalpol [32].
Amphicoside (31)
Verproside (32)
Figure 5. Phytoconstituents in Veronica fushii.
2.4. Veronica cymbalaria Bodard
The main iridoids and iridoid-phenolic constituents of extracts from this plant were catalpol (1),
amphicoside (31), and verproside (32), together with alpinoside (33), aucubin (8), 6-O-veratroylcatalpol
(34), and verminoside (35) (Figure 6). The iridoid alpinoside with a 8,9-double bond was found for the
first time in genus Veronica [
31
]. In V. cymbalaria, other authors found the iridoid glucosides aucubin
(8), catalpol (1), veronicoside (20), verproside (32), amphycoside, verminoside (35), catalposide (6),
6-O-veratroylcatalposide (34), and 6-O-isovanilloylcatalpol [32].
Molecules 2019, 24, x 7 of 34
Plantamajoside (29)
Luteolin 7-O-glucoside (30)
Figure 5. Phytoconstituents in Veronica fushii.
2.4. Veronica Cymbalaria Bodard
The main iridoids and iridoid-phenolic constituents of extracts from this plant were catalpol (1),
amphicoside (31), and verproside (32), together with alpinoside (33), aucubin (8),
6-O-veratroylcatalpol (34), and verminoside (35) (Figure 6). The iridoid alpinoside with a 8,9-double
bond was found for the first time in genus Veronica [31]. In V. cymbalaria, other authors found the
iridoid glucosides aucubin (8), catalpol (1), veronicoside (20), verproside (32), amphycoside,
verminoside (35), catalposide (6), 6-O-veratroylcatalposide (34), and 6-O-isovanilloylcatalpol [32].
Amphicoside (31)
Verproside (32)
Figure 6. Cont.
Molecules 2019,24, 2454 8 of 35
Molecules 2019, 24, x 8 of 34
Alpinoside (33)
6-O-veratroylcatalposide (34)
Verminoside (35)
Figure 6. Phytoconstituents from Veronica cymbalaria.
2.5. Veronica Anagallis-aquatica L.
Aquaticol (36), an unusual bis-sesquiterpene, was isolated from the methanol extracts of V.
anagallis-aquatica. The other 11 well-known compounds are aucubin (8), geniposidic acid (37),
mussaenoside (38), catalposide (6), verproside (32), amphicoside (31), catalpol (1), boschnaloside
(39), shanzhiside methyl ester (40), sitosterol (41), and β-stigmast-4-en-6β-ol-3-one (42) (Figure 7)
[33].
Figure 6. Phytoconstituents from Veronica cymbalaria.
2.5. Veronica anagallis-aquatica L.
Aquaticol (
36
), an unusual bis-sesquiterpene, was isolated from the methanol extracts of
V. anagallis-aquatica. The other 11 well-known compounds are aucubin (
8
), geniposidic acid (
37
),
mussaenoside (
38
), catalposide (
6
), verproside (
32
), amphicoside (
31
), catalpol (
1
), boschnaloside (
39
),
shanzhiside methyl ester (40), sitosterol (41), and β-stigmast-4-en-6β-ol-3-one (42) (Figure 7) [33].
2.6. Veronica persica
V. persica, “common field speedwell” or “Persian speedwell”, is a neophytic weed originally
from southwest Asia and widely distributed in the temperate regions. In dichloromethane extracts of
this plant, calendin (
43
), tyrosol (
44
), and two benzoic acid derivatives were isolated [
34
] (Figure 8).
Moreover, in the aerial parts of V. persica, a new phenylethanoid glycoside, persicoside (
45
), and
three known phenylethanoid glycosides, acteoside (
46
), isoacteoside (
47
), and lavandulifolioside (
48
)
(Figure 8), were isolated and the structure was confirmed by spectroscopic techniques.
Molecules 2019,24, 2454 9 of 35
Molecules 2019, 24, x 9 of 34
Aquaticol (36)
Geniposidic acid (37) Mussaenoside (38)
Boschnaloside (39) Shanzhiside methyl ester (40)
Sitosterol (41) β-Stigmast-4-en-6β-ol-3-one (42)
Figure 7. Selected phytochemicals from Veronica anagallis-aquatica and others.
2.6. Veronica Persica
V. persica, “common field speedwell” or “Persian speedwell”, is a neophytic weed originally
from southwest Asia and widely distributed in the temperate regions. In dichloromethane extracts
of this plant, calendin (43), tyrosol (44), and two benzoic acid derivatives were isolated [34] (Figure
8). Moreover, in the aerial parts of V. persica, a new phenylethanoid glycoside, persicoside (45), and
three known phenylethanoid glycosides, acteoside (46), isoacteoside (47), and lavandulifolioside (48)
(Figure 8), were isolated and the structure was confirmed by spectroscopic techniques.
In addition to phenylethanoid glycosides, hexitol, dulcitol, and seven known iridoid glucosides,
aucubin (8), veronicoside (20), amphicoside (31), 6-O-veratroyl-catalpol (34), catalposide (6),
verproside (32), and verminoside (35) were isolated from this plant species [35].
Figure 7. Selected phytochemicals from Veronica anagallis-aquatica and others.
In addition to phenylethanoid glycosides, hexitol, dulcitol, and seven known iridoid glucosides,
aucubin (
8
), veronicoside (
20
), amphicoside (
31
), 6-O-veratroyl-catalpol (
34
), catalposide (
6
), verproside
(32), and verminoside (35) were isolated from this plant species [35].
Molecules 2019,24, 2454 10 of 35
Molecules 2019, 24, x 10 of 34
Calendin (43) Tyrosol (44)
Persicoside (45) Acteoside (46)
Isoacteoside (47) Lavandulifolioside (48)
Figure 8. Phytoconstituents from Veronica persica.
2.7. Veronica Longifolia L. and Veronica Liwanensis K. Koch
Two new acylated 5,6,7,3,4-pentahydroxyflavone (6-hydroxyluteolin) glycosides and two
unusual allose-containing acylated 5,7,8,4-tetrahydroxyflavone (isoscutellarein) glycosides were
isolated from V. longifolia and V. liwanensis and characterized by NMR spectroscopy as
6-hydroxyluteolin 4-methyl ether 7-O-α-rhamnopyranosyl(1′′′2′′)[6-O-acetyl-β-glucopyranoside]
(49) and 6-hydroxyluteolin 7-O-(6-O-(E)-caffeoyl)-β–glucopyranoside (50), respectively (see Table 2
and Figure 9) [36]. Moreover, three chlorinated iridoid glucosides, asystasioside E (92) and its
6-O-esters, named longifoliosides A and B (93, 94), were also detected [37].
Table 2. Phytoconstituents obtained from ethanol extracts of some Veronica species (based on
Reference [3]).
Species Extract Compounds
Veronica argute-serrata Ethanol
Mannitol (65), catalpol (1), aucubin (8), gardoside (69), ajugol
(63), mussaenosidic acid (70), epiloganica acid (71),
arborescosidic acid (72), verbascoside-like compounds,
acetyl-flavone glycoside
Figure 8. Phytoconstituents from Veronica persica.
2.7. Veronica longifolia L. and Veronica liwanensis K. Koch
Two new acylated 5,6,7,3
0
,4
0
-pentahydroxyflavone (6-hydroxyluteolin) glycosides and two unusual
allose-containing acylated 5,7,8,4
0
-tetrahydroxyflavone (isoscutellarein) glycosides were isolated from
V. longifolia and V. liwanensis and characterized by NMR spectroscopy as 6-hydroxyluteolin 4
0
-methyl
ether 7-O-
α
-rhamnopyranosyl(1
000
2
00
)[6
00
-O-acetyl-
β
-glucopyranoside] (
49
) and 6-hydroxyluteolin
7-O-(6
00
-O-(E)-caeoyl)-
β
–glucopyranoside (
50
), respectively (see Table 2and Figure 9) [
36
]. Moreover,
three chlorinated iridoid glucosides, asystasioside E (
92
) and its 6-O-esters, named longifoliosides A
and B (93,94), were also detected [37].
Molecules 2019,24, 2454 11 of 35
Table 2. Phytoconstituents obtained from ethanol extracts of some Veronica species (based on Reference [3]).
Species Extract Compounds
Veronica argute-serrata Ethanol
Mannitol (65), catalpol (1), aucubin (8), gardoside (69),
ajugol (63), mussaenosidic acid (70), epiloganica acid
(71), arborescosidic acid (72), verbascoside-like
compounds, acetyl-flavone glycoside
Veronica arvensis L. Ethanol
Mannitol (65), cornoside (64), ajugol (63), salidroside (66),
verbascoside-like compounds
Veronica biloba schreb. ex L. Ethanol
Catalpol (1), aucubin (8), ajugol (63), epiloganic acid (71),
alpinoside (33)
Veronica campylopoda Boiss. Ethanol Mannitol (65), catalpol (1), aucubin (8), ajugol (63),
verminoside (35), acetyl-flavone glycoside
Veronica chamaedryoides Engl. Ethanol Verbascoside-like compounds; some iridoid
Veronica dillenii Crantz Ethanol Verbascoside (67) and cornoside (64)
Veronica longifolia L. Ethanol Mannitol (65), catalpol (1), aucubin (8), verposide,
catalposide (6), verminoside (35), catalpol ester, flavones
Veronica magna M.A.Fisch. Ethanol Verbascoside-like compounds
Veronica micans (M.A.Fisch.)
Landolt Ethanol Verbascoside (67) and cornoside
Veronica micrantha Homanns.
& Link Ethanol Mannitol (65), aucubin (8), verpectoside B (68),
triterpene glycosides
Veronica orbelica Ethanol Verbascoside-like compounds
Veronica vindobonensis (M.A.Fisch.)
M.A.Fisch. Ethanol Verbascoside (67) and cornoside (64)
2.8. Veronica orientalis Mill.
Isoscutellarein 7-O-(6
000
-O-acetyl)-
β
-allopyranosyl(1
000
2
00
)-
β
-glucopyranoside (51) and its
4
0
-methyl ether (52) were obtained from V. orientalis species (Figure 9). The former was also found in
Veronica intercedens Bornm. [36], although it is still an unresolved name [4].
Molecules 2019, 24, x 11 of 34
Veronica arvensis L. Ethanol Mannitol (65), cornoside (64), ajugol (63), salidroside (66),
verbascoside-like compounds
V
eronica biloba schreb.
ex L. Ethanol Catalpol (1), aucubin (8), ajugol (63), epiloganic acid (71),
alpinoside (33)
Veronica campylopoda
Boiss. Ethanol Mannitol (65), catalpol (1), aucubin (8), ajugol (63), verminoside
(35), acetyl-flavone glycoside
Veronica
chamaedryoides Engl. Ethanol Verbascoside-like compounds; some iridoid
Veronica dillenii Crantz Ethanol Verbascoside (67) and cornoside (64)
Veronica longifolia L. Ethanol Mannitol (65), catalpol (1), aucubin (8), verposide, catalposide
(6), verminoside (35), catalpol ester, flavones
Veronica magna
M.A.Fisch. Ethanol Verbascoside-like compounds
Veronica micans
(M.A.Fisch.) Landolt Ethanol Verbascoside (67) and cornoside
Veronica micrantha
Hoffmanns. & Link Ethanol Mannitol (65), aucubin (8), verpectoside B (68), triterpene
glycosides
Veronica orbelica Ethanol Verbascoside-like compounds
Veronica vindobonensis
(M.A.Fisch.)
M.A.Fisch.
Ethanol Verbascoside (67) and cornoside (64)
2.8. Veronica Orientalis Mill.
Isoscutellarein 7-O-(6-O-acetyl)-β-allopyranosyl(1‴→2)-β-glucopyranoside (51) and its
4-methyl ether (52) were obtained from V. orientalis species (Figure 9). The former was also found in
Veronica intercedens Bornm. [36], although it is still an unresolved name [4].
Figure 9. Phytoconstituents from Veronica longifolia, Veronica liwanensis, and Veronica orientalis.
2.9. Veronica Thymoides P. H. Davis
From V. thymoides subsp. pseudocinerea, a new acylated flavone glucoside,
3-hydroxyscutellarein 7-O-(6-O-protocatechuoyl)-β-glucopyranoside (53), and a new phenol
glucoside, 3,5-dihydroxyphenethyl alcohol 3-O-β-glucopyranoside were isolated, along with seven
flavone, phenol, and lignan glycosides:
3-hydroxyscutellarein-7-O-(6-O-trans-feruloyl)-β-glucopyranoside (54), 3-hydroxy,
6-O-methylscutellarein 7-O-β-glucopyranoside (55), luteolin 7-O-β-glucopyranoside (56),
isoscutellarein 7-O-(6-O-acetyl)-β-allopyranosyl (1‴→2)-β-glucopyranoside (57),
Figure 9. Phytoconstituents from Veronica longifolia,Veronica liwanensis, and Veronica orientalis.
2.9. Veronica thymoides P. H. Davis
From V. thymoides subsp. pseudocinerea, a new acylated flavone glucoside, 3
0
-hydroxyscutellarein
7-O-(6
00
-O-protocatechuoyl)-
β
-glucopyranoside (53), and a new phenol glucoside, 3,5-dihydroxyphenethyl
Molecules 2019,24, 2454 12 of 35
alcohol 3-O-
β
-glucopyranoside were isolated, along with seven flavone, phenol, and
lignan glycosides: 3
0
-hydroxyscutellarein-7-O-(6
00
-O-trans-feruloyl)-
β
-glucopyranoside (54),
3
0
-hydroxy, 6-O-methylscutellarein 7-O-
β
-glucopyranoside (55), luteolin 7-O-
β
-glucopyranoside
(56), isoscutellarein 7-O-(6
000
-O-acetyl)-
β
-allopyranosyl (1
000
2
00
)-
β
-glucopyranoside (57),
3,4-dihydroxyphenethyl alcohol 8-O-
β
-glucopyranoside (58), benzyl alcohol 7-O-
β
-xylopyranosyl
(1
00
2
0
)-
β
-glucopyranoside (59), and (+)-syringaresinol 4
0
-O-
β
-glucopyranoside (60) (Figure 10) [
38
].
Molecules 2019, 24, x 12 of 34
3,4-dihydroxyphenethyl alcohol 8-O-β-glucopyranoside (58), benzyl alcohol 7-O-β-xylopyranosyl
(12)-β-glucopyranoside (59), and (+)-syringaresinol 4-O-β-glucopyranoside (60) (Figure 10) [38].
Figure 10. Phytoconstituents from Veronica thymoides.
2.10. Veronica Arvensis
The water extracts of this plant revealed the presence of cornoside aglycone and rengyolone
(62). The iridoid glucoside, ajugol (63), and the phenylethanoid glucoside, cornoside (64) (Figure 11),
were isolated from species of Veronica for the first time [39]. Other compounds are described in Table
2.
Figure 10. Phytoconstituents from Veronica thymoides.
2.10. Veronica arvensis
The water extracts of this plant revealed the presence of cornoside aglycone and rengyolone (62).
The iridoid glucoside, ajugol (63), and the phenylethanoid glucoside, cornoside (64) (Figure 11), were
isolated from species of Veronica for the first time [39]. Other compounds are described in Table 2.
2.11. Veronica turrilliana Stoj. & Stef.
From V. turrilliana aerial parts, two phenylethanoid glycosides, turrilliosides A and
B, and a steroidal saponin, turrillianoside, were isolated and their structures elucidated as
β
-(3,4-dihydroxyphenyl) ethyl-4-O-E-caeoyl-O-[
β
-glucopyranosyl-(1
4)-
α
-rhamnopyranosyl
-(1
6)]-
β
-glucopyranoside (73),
β
-(3,4-dihydroxyphenyl)ethyl-4-O-E-caeoyl-[6-O-E-feruloyl
-
β
-glucopyranosyl-(1
4)-
α
-rhamnopyranosyl-(1
6)]-
β
-glucopyranoside (74), and (23S,25S)-12
β
,23-
dihydroxyspirost-5-en-3
β
-yl O-
α
-rhamnopyranosyl-(1
4)-
β
-glucopyranoside (75) (Figure 12),
respectively. Other glucosides were reported, namely, catalpol (1), catalposide (6), verproside (32),
amphicoside (31), isovanilloylcatalpol, aucubin (8), arbutin (76), and 6-O-E-caeoylarbutin (77) [40].
Molecules 2019,24, 2454 13 of 35
Molecules 2019, 24, x 13 of 34
Figure 11. Phytoconstituents reported in Veronica arvensis and other species (Table 2).
2.11. Veronica Turrilliana Stoj. & Stef.
From V. turrilliana aerial parts, two phenylethanoid glycosides, turrilliosides A and B, and a
steroidal saponin, turrillianoside, were isolated and their structures elucidated as
β-(3,4-dihydroxyphenyl) ethyl-4-O-E-caffeoyl-O-[β-glucopyranosyl-(14)-α-rhamnopyranosyl
-(16)]-β-glucopyranoside (73), β-(3,4-dihydroxyphenyl)ethyl-4-O-E-caffeoyl-[6-O-E-feruloyl
-β-glucopyranosyl-(14)-α-rhamnopyranosyl-(16)]-β-glucopyranoside (74), and (23S,25S)-12β,23-
Figure 11. Phytoconstituents reported in Veronica arvensis and other species (Table 2).
Molecules 2019,24, 2454 14 of 35
Molecules 2019, 24, x 14 of 34
dihydroxyspirost-5-en-3β-yl O-α-rhamnopyranosyl-(14)-β-glucopyranoside (75) (Figure 12),
respectively. Other glucosides were reported, namely, catalpol (1), catalposide (6), verproside (32),
amphicoside (31), isovanilloylcatalpol, aucubin (8), arbutin (76), and 6-O-E-caffeoylarbutin (77) [40].
Figure 12. Phytoconstituents from Veronica turrilliana.
2.12. Veronica Cuneifolia D. Don
Column chromatography of iridoid fractions of V. cuneifoia subsp. cuneifolia methanol extract
resulted in the isolation of verproside (32), verminoside (35), amphicoside (31), veronicoside (20),
catalposide (6), and catalpol (1). The comparison of the iridoid fractions of V. cuneifolia subsp.
cuneifolia and V. cymbalaria using an HPLC diode array detector (DAD) system with 40% MeOH
showed that iridoid fractions of V. cymbalaria contained veratroylcatalpol (34), isovanilloylcatalpol,
and aucubin (8) in addition to the compounds found in iridoid fractions [19]. Additionally, seven
iridoid glucosides, aucubin (8), catalpol (1), veronicoside (20), verproside (32), amphycoside,
verminoside (28), and catalposide (6), were identified [32].
2.13. Veronica Derwentiana Andrews and Veronica Catarractae G. Forst.
Three unusual substituted benzoyl esters of aucubin were obtained from V. derwentiana and a
chlorinated iridoid glycoside (catarractoside) (78) (Figure 13) from V. catarractae, in addition to other
iridoids common to the genus. The chemical profile of V. perfoliata is similar to that of Northern
Hemisphere species of Veronica because of the presence of characteristic 6-O-catalpol esters. The
profile of V. derwentiana is unique, since 6-O-esters of aucubin rather than of catalpol dominate;
however, the acyl groups are the same as those present in catalpol esters found in some other
Veronica sections. V. catarractae also contains one of the catalpol esters characteristic of Veronica, in
addition to three 6-O-rhamnopyranosyl substituted iridoid glycosides, one of which is
6-O-rhamnopyranosylcatalpol (79) (Figure 13) [41].
Figure 12. Phytoconstituents from Veronica turrilliana.
2.12. Veronica cuneifolia D. Don
Column chromatography of iridoid fractions of V. cuneifoia subsp. cuneifolia methanol extract
resulted in the isolation of verproside (32), verminoside (35), amphicoside (31), veronicoside (20),
catalposide (6), and catalpol (1). The comparison of the iridoid fractions of V. cuneifolia subsp. cuneifolia
and V. cymbalaria using an HPLC diode array detector (DAD) system with 40% MeOH showed that
iridoid fractions of V. cymbalaria contained veratroylcatalpol (34), isovanilloylcatalpol, and aucubin (8)
in addition to the compounds found in iridoid fractions [
19
]. Additionally, seven iridoid glucosides,
aucubin (8), catalpol (1), veronicoside (20), verproside (32), amphycoside, verminoside (28), and
catalposide (6), were identified [32].
2.13. Veronica derwentiana Andrews and Veronica catarractae G. Forst.
Three unusual substituted benzoyl esters of aucubin were obtained from V. derwentiana and a
chlorinated iridoid glycoside (catarractoside) (78) (Figure 13) from V. catarractae, in addition to other
iridoids common to the genus. The chemical profile of V. perfoliata is similar to that of Northern
Hemisphere species of Veronica because of the presence of characteristic 6-O-catalpol esters. The profile
of V. derwentiana is unique, since 6-O-esters of aucubin rather than of catalpol dominate; however,
the acyl groups are the same as those present in catalpol esters found in some other Veronica sections.
V. catarractae also contains one of the catalpol esters characteristic of Veronica, in addition to three
6-O-rhamnopyranosyl substituted iridoid glycosides, one of which is 6-O-rhamnopyranosylcatalpol
(79) (Figure 13) [41].
2.14. Veronica sibirica L.
Eight compounds were isolated from V. sibirica L. and identified as 1,2-dehydrocryptotanshinone,
sibiriquinone A (80), sibiriquinone B (81), cryptotanshinone (82), ferruginol (83), dihydrotanshinone I
(84), tanshinone I (85), and tanshinone IIA (86) [
42
]. A new iridoid glycoside, versibirioside (87), and a
known iridoid glycoside, verbaspinoside (88) (Figure 14), were also reported from the whole plant. In
addition, versibirioside was isolated from the whole plant of V. sibirica [43].
Molecules 2019,24, 2454 15 of 35
Molecules 2019, 24, x 15 of 34
Figure 13. Structures of isolated compounds catarractoside and 6-O-rhamnopyranosylcatalpol
(species Veronica derwentiana and Veronica catarractae).
2.14. Veronica Sibirica L.
Eight compounds were isolated from V. sibirica L. and identified as
1,2-dehydrocryptotanshinone, sibiriquinone A (80), sibiriquinone B (81), cryptotanshinone (82),
ferruginol (83), dihydrotanshinone I (84), tanshinone I (85), and tanshinone IIA (86) [42]. A new
iridoid glycoside, versibirioside (87), and a known iridoid glycoside, verbaspinoside (88) (Figure 14),
were also reported from the whole plant. In addition, versibirioside was isolated from the whole
plant of V. sibirica [43].
2.15. Veronica Peregrina L.
Eight iridoid glycosides and four phenolic compounds were isolated from the ethyl acetate
extract of V. peregrine. The compounds were identified as protocatechuic acid, luteolin (10),
veronicoside (20), minecoside (89), specioside (90), amphicoside (31), catalposide (6),
6-O-cis-p-coumaroyl catalpol, p-hydroxybenzoic acid methyl ester, verproside (32), verminoside
(35), and chrysoeriol 7-glucuronide (91) by spectroscopic analysis (Figure 14) [12]. In the methanolic
extract, the presence of chrysoeriol (12), diosmetin (95), 4-hydroxybenzoic acid, apigenin (11), caffeic
acid methylester (96), and protocatechuic acid was reported [44]. The phenolic acid
4-hydroxybenzoic acid was also found by other authors [45].
Figure 13.
Structures of isolated compounds catarractoside and 6-O-rhamnopyranosylcatalpol (species
Veronica derwentiana and Veronica catarractae).
2.15. Veronica peregrina L.
Eight iridoid glycosides and four phenolic compounds were isolated from the ethyl acetate extract
of V. peregrine. The compounds were identified as protocatechuic acid, luteolin (10), veronicoside
(20), minecoside (89), specioside (90), amphicoside (31), catalposide (6), 6-O-cis-p-coumaroyl catalpol,
p-hydroxybenzoic acid methyl ester, verproside (32), verminoside (35), and chrysoeriol 7-glucuronide
(91) by spectroscopic analysis (Figure 14) [
12
]. In the methanolic extract, the presence of chrysoeriol (12),
diosmetin (95), 4-hydroxybenzoic acid, apigenin (11), caeic acid methylester (96), and protocatechuic
acid was reported [
44
]. The phenolic acid 4-hydroxybenzoic acid was also found by other authors [
45
].
2.16. Veronica montana L., Veronica polita Fr., and Veronica spuria L.
The phenolic compounds of V. montana,V. polita, and V. spuria showed that flavones were the
major compounds (V. montana: seven phenolic acids, five flavones, four phenylethanoids, and one
isoflavone; V. polita: 10 flavones, five phenolic acids, two phenylethanoids, one flavonol, and one
isoflavone; V. spuria: 10 phenolic acids, five flavones, two flavonols, two phenylethanoids, and one
isoflavone). V. spuria possessed the highest contents in all groups of phenolic compounds, except
flavones [46].
2.17. Veronica spicata
Six 6-hydroxyluteolin glycosides acylated with phenolic acids were elucidated in this species, three
of which were new compounds and called spicoside (61) derivatives. A flavonoid survey of seven more
species belonging to subgenus Pseudolysimachium and eight species of V. subgenus Pentasepalae showed
that all the Pseudolysimachium species and four of the Pentasepalae species produced 6-hydroxyflavone
glycosides, whereas the remaining four Pentasepalae species contained acetylated 8-hydroxyflavone
glycosides [
39
]. Moreover, from the species, 10 phenolic compounds were characterized: chrysin (98),
rutin (99), and quercitrin (100), as well as cichoric (101), ferulic (102), protocatechuic (103), syringic
(104), rosmarinic (105), and tannic acids (106) (Figure 15) [11].
Molecules 2019,24, 2454 16 of 35
Molecules 2019, 24, x 16 of 34
Figure 14. Several phytoconstituents in Veronica sibirica and Veronica peregrina.
2.16. Veronica Montana L., Veronica Polita Fr., and Veronica Spuria L.
The phenolic compounds of V. montana, V. polita, and V. spuria showed that flavones were the
major compounds (V. montana: seven phenolic acids, five flavones, four phenylethanoids, and one
isoflavone; V. polita: 10 flavones, five phenolic acids, two phenylethanoids, one flavonol, and one
isoflavone; V. spuria: 10 phenolic acids, five flavones, two flavonols, two phenylethanoids, and one
Figure 14. Several phytoconstituents in Veronica sibirica and Veronica peregrina.
Molecules 2019,24, 2454 17 of 35
Molecules 2019, 24, x 17 of 34
isoflavone). V. spuria possessed the highest contents in all groups of phenolic compounds, except
flavones [46].
2.17. Veronica Spicata
Six 6-hydroxyluteolin glycosides acylated with phenolic acids were elucidated in this species,
three of which were new compounds and called spicoside (61) derivatives. A flavonoid survey of
seven more species belonging to subgenus Pseudolysimachium and eight species of V. subgenus
Pentasepalae showed that all the Pseudolysimachium species and four of the Pentasepalae species
produced 6-hydroxyflavone glycosides, whereas the remaining four Pentasepalae species contained
acetylated 8-hydroxyflavone glycosides [39]. Moreover, from the species, 10 phenolic compounds
were characterized: chrysin (98), rutin (99), and quercitrin (100), as well as cichoric (101), ferulic
(102), protocatechuic (103), syringic (104), rosmarinic (105), and tannic acids (106) (Figure 15) [11].
(97) (98) (99)
(100) (101)
(102) (103) (104)
(105) (106)
Figure 15. Other phytoconstituents in Veronica spicata.
2.18. Veronica Officinalis
Figure 15. Other phytoconstituents in Veronica spicata.
2.18. Veronica ocinalis
The main phenolic compounds characterized in V. ocinalis L. were p-coumaric acid (107), ferulic
acid (108), luteolin (10), apigenin (11), quercitrin (100), hispidulin (109), quercetin (110) (Figure 16),
and the sterol
β
-sitosterol (41). Some of these compounds (ferulic acid, coumaric acid, apigenin, and
luteolin) were also found in V. teucrium L. and V. orchidea Crantz. Aglycones hispidulin, eupatorin
(111), and eupatilin (112) (Figure 16) were also detected for the first time in the Veronica genus, mainly
after hydrolysis, suggesting the presence of glycosylated forms. Eupatilin was found only in V. orchidea
extracts. This chemical composition showed intravarietal dierences [47].
Molecules 2019,24, 2454 18 of 35
Molecules 2019, 24, x 18 of 34
The main phenolic compounds characterized in V. officinalis L. were p-coumaric acid (107),
ferulic acid (108), luteolin (10), apigenin (11), quercitrin (100), hispidulin (109), quercetin (110)
(Figure 16), and the sterol β-sitosterol (41). Some of these compounds (ferulic acid, coumaric acid,
apigenin, and luteolin) were also found in V. teucrium L. and V. orchidea Crantz. Aglycones
hispidulin, eupatorin (111), and eupatilin (112) (Figure 16) were also detected for the first time in the
Veronica genus, mainly after hydrolysis, suggesting the presence of glycosylated forms. Eupatilin
was found only in V. orchidea extracts. This chemical composition showed intravarietal differences
[47].
2.19. Veronica Ciliata Fisch.
Five main compounds, including two iridoid glycosides (catalposide (6), verproside (32)) and
three phenolic compounds (luteolin (10), 4-hydroxy benzoic acid, and 3,4-dihydroxy benzoic acid
(113)) (Figure 16), were isolated from the crude extract of V. ciliata by high-speed countercurrent
chromatography [48].
2.20. Veronica Rosea Desf.
The phytochemical study of butanolic extract of aerial parts of V. rosea led to the isolation and
identification of four phytoconstituents: apigenin-7-O-β-glucopyranoside (114) (Figure 16),
isoscutellarein-7-O-β-d-glucopyranoside, isoscutellarein7-O-[(6’’-O-acetyl-β-
D
-allopyranosyl
-(12)]-β-glucopyranoside, and mannitol (65) [49].
Figure 16. Structures of compounds reported in several Veronica species: Veronica officinalis, Veronica ciliata, and
Veronica rosea.
2.21. Others Phytochemicals and Species
Veronica americana Schwein. ex Benth. methanolic extracts revealed new iridoids identified as
4β-hydroxy-6-O-(p-hydroxybenzoyl)-tetrahydrolinaride (115) and 10-O-protocatechuyl-catalpol
(116), along with four known aromatic compounds, veratric acid (97), p-methoxybenzoic acid (117),
p-hydroxybenzoic acid (118), and protocatechuic acid (119) (Figure 17) [50]. Kroll-Møller and
co-workers isolated iridoid glucosides from Veronica hookeri (Buchanan) Garn.-Jones and Veronica
pinguifolia Hook. f. from New Zealand [51]. Thirty-three water-soluble compounds were isolated
from Veronica pulvinaris (Hook. f.) Cheeseman and Veronica thomsonii (Buchanan) Cheeseman. Most
of the isolated compounds were esters of phenylethanoid and iridoid glycosides [52]. A
Figure 16.
Structures of compounds reported in several Veronica species: Veronica ocinalis,Veronica
ciliata, and Veronica rosea.
2.19. Veronica ciliata Fisch.
Five main compounds, including two iridoid glycosides (catalposide (6), verproside (32)) and
three phenolic compounds (luteolin (10), 4-hydroxy benzoic acid, and 3,4-dihydroxy benzoic acid
(113)) (Figure 16), were isolated from the crude extract of V. ciliata by high-speed countercurrent
chromatography [48].
2.20. Veronica rosea Desf.
The phytochemical study of butanolic extract of aerial parts of V. rosea led to the isolation
and identification of four phytoconstituents: apigenin-7-O-
β
-glucopyranoside (114) (Figure 16),
isoscutellarein-7-O-
β
-d-glucopyranoside, isoscutellarein7-O-[(6
0
”-O-acetyl-
β
-d-allopyranosyl-(1
2)]-
β-glucopyranoside, and mannitol (65) [49].
2.21. Others Phytochemicals and Species
Veronica americana Schwein. ex Benth. methanolic extracts revealed new iridoids identified
as 4
β
-hydroxy-6-O-(p-hydroxybenzoyl)-tetrahydrolinaride (115) and 10-O-protocatechuyl-catalpol
(116), along with four known aromatic compounds, veratric acid (97), p-methoxybenzoic acid (117),
p-hydroxybenzoic acid (118), and protocatechuic acid (119) (Figure 17) [
50
]. Kroll-Møller and co-workers
isolated iridoid glucosides from Veronica hookeri (Buchanan) Garn.-Jones and Veronica pinguifolia Hook.
f. from New Zealand [
51
]. Thirty-three water-soluble compounds were isolated from Veronica pulvinaris
(Hook. f.) Cheeseman and Veronica thomsonii (Buchanan) Cheeseman. Most of the isolated compounds
were esters of phenylethanoid and iridoid glycosides [
52
]. A chemosystematic investigation of the
water-soluble compounds in Veronica cheesemanii and Veronica hookeriana Walp. showed that both
species contained mannitol (65), in considerable amounts, and some iridoids such as aucubin (8),
catalpol (1), and their esters [53].
Molecules 2019,24, 2454 19 of 35
Molecules 2019, 24, x 19 of 34
chemosystematic investigation of the water-soluble compounds in Veronica cheesemanii and Veronica
hookeriana Walp. showed that both species contained mannitol (65), in considerable amounts, and
some iridoids such as aucubin (8), catalpol (1), and their esters [53].
The phenolic compounds baicalin (120), hyperoside (121), isoquercetin (122), and chlorogenic
acid (123), as well as quinic acid (124), were the main components in aqueous-acetone extracts of
Veronica jacquinii Baumg., Veronica teucrium L., and Veronica urticifolia Jacq. (Figure 17) [13]. A new
phenylethanoid triglycoside, chionoside J (125), was isolated from Veronica beccabunga L. (brooklime)
[54], while two new spirostane glycosides, chamaedrosides C (126) and C1 (127), two new furostane
glycosides, chamaedrosides E (128) and E1 (129), and two new furospirostane glycosides were found
in V. chamaedrys (Figure 18) [55]. Compounds in other species are detailed in Table 2, i.e., Veronica
argute-serrata, Veronica biloba schreb. ex L., Veronica campylopoda Boiss., Veronica chamaedryoides Engl.,
Veronica dillenii Crantz, Veronica magna M.A.Fisch., Veronica micans (M.A.Fisch.) Landolt, Veronica
micrantha Hoffmanns. & Link, Veronica orbelica, and Veronica vindobonensis (M.A.Fisch.) M.A.Fisch.
Figure 17. Structures of compounds reported in several Veronica species: Veronica americana, Veronica
jacquinii, Veronica teucrium, and Veronica urticifolia.
3. Antimicrobial Activities of Veronica Plants
(118)
HO
OH
OH
O
(121)
O
O
HO
OH
OH
OH
OH
O
HO
O
OH
OH
(116)
(115)
(117)
(124)
(119)
(120)
(122) (123)
(125)
R
1
: caffeoyl; R
2
: glucosyl
Figure 17.
Structures of compounds reported in several Veronica species: Veronica americana,Veronica
jacquinii,Veronica teucrium, and Veronica urticifolia.
The phenolic compounds baicalin (120), hyperoside (121), isoquercetin (122), and chlorogenic
acid (123), as well as quinic acid (124), were the main components in aqueous-acetone extracts
of Veronica jacquinii Baumg., Veronica teucrium L., and Veronica urticifolia Jacq. (Figure 17) [
13
].
A new phenylethanoid triglycoside, chionoside J (125), was isolated from Veronica beccabunga L.
(brooklime) [
54
], while two new spirostane glycosides, chamaedrosides C (126) and C1 (127), two new
furostane glycosides, chamaedrosides E (128) and E1 (129), and two new furospirostane glycosides
were found in V. chamaedrys (Figure 18) [
55
]. Compounds in other species are detailed in Table 2, i.e.,
Veronica argute-serrata,Veronica biloba schreb. ex L., Veronica campylopoda Boiss., Veronica chamaedryoides
Engl., Veronica dillenii Crantz, Veronica magna M.A.Fisch., Veronica micans (M.A.Fisch.) Landolt, Veronica
micrantha Homanns. & Link, Veronica orbelica, and Veronica vindobonensis (M.A.Fisch.) M.A.Fisch.
Molecules 2019,24, 2454 20 of 35
Molecules 2019, 24, x 20 of 34
Many plants were used since ancient times to treat infections caused by bacteria that are now
resistant to antibiotics [56]. There are several traditional uses of the genus Veronica that could be
related to antimicrobial properties. For example, these species are used as expectorants, restoratives,
tonics, and for the treatment of influenza and other respiratory diseases in traditional Chinese
medicine [57]. In Romanian medicine, aerial parts of Veronica plants are known for their
wound-healing properties and are also used for the treatment of cough and catarrh [47]. Despite
their widespread usage in folk medicine, there is a lack of information about the antimicrobial
activity. Only a few studies confirmed that certain Veronica species showed noticeable bioactivity
such as antibacterial, antifungal, and antiviral activity.
Figure 18. Structures of compounds reported in Veronica beccabunga L.
3.1. Antibacterial Activity
Although Veronica species are traditionally used for their antibacterial effect, there are only a
few studies that showed its strong antibacterial effect. The antibacterial activity against
Gram-positive and Gram-negative species depends on the extract type (solvent used, part extracted,
species, etc.). As an example, the antimicrobial properties of aerial parts of V. spicata extracts with
ethyl-acetate, methanol, or water using the diffusion method and microdilution method were
examined. The bacterial strains used in study were found to be susceptible toward methanol and
ethyl-acetate extracts, with minimum inhibitory concentration (MIC) values between 1.25 and 5
mg/mL using the microdilution method, while aqueous extracts were inactive. The extracts prepared
from leaves showed larger zones of inhibition compared to flowers and steam extracts of V. spicata,
indicating stronger antimicrobial activity [11,58]. In another work and using the microdilution
method, Živković et al. (2014) investigated the antibacterial effect of the V. urticifolia methanol extract
against the Gram-negative bacteria Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa,
and Gram-positive bacteria Staphylococcus aureus, L. monocytogenes, and Bacillus cereus [59]. After the
measurement of the minimum bactericidal concentration (MBC) and MIC values, it was found that
the most sensitive germ was Staphylococcus aureus. The antistaphylococcal effect is due to a main
phenolic compound acteoside, which could inhibit the incorporation of leucine and disturb protein
synthesis. The same antistaphylococcal effects were found in other studies [20]. Other chemical
compounds could be also responsible for this antibacterial activity, e.g., β-sitosterol, campesterol,
Figure 18. Structures of compounds reported in Veronica beccabunga L.
3. Antimicrobial Activities of Veronica Plants
Many plants were used since ancient times to treat infections caused by bacteria that are now
resistant to antibiotics [
56
]. There are several traditional uses of the genus Veronica that could be related
to antimicrobial properties. For example, these species are used as expectorants, restoratives, tonics,
and for the treatment of influenza and other respiratory diseases in traditional Chinese medicine [
57
].
In Romanian medicine, aerial parts of Veronica plants are known for their wound-healing properties
and are also used for the treatment of cough and catarrh [
47
]. Despite their widespread usage in
folk medicine, there is a lack of information about the antimicrobial activity. Only a few studies
confirmed that certain Veronica species showed noticeable bioactivity such as antibacterial, antifungal,
and antiviral activity.
3.1. Antibacterial Activity
Although Veronica species are traditionally used for their antibacterial eect, there are only a few
studies that showed its strong antibacterial eect. The antibacterial activity against Gram-positive and
Gram-negative species depends on the extract type (solvent used, part extracted, species, etc.). As an
example, the antimicrobial properties of aerial parts of V. spicata extracts with ethyl-acetate, methanol,
or water using the diusion method and microdilution method were examined. The bacterial strains
used in study were found to be susceptible toward methanol and ethyl-acetate extracts, with minimum
inhibitory concentration (MIC) values between 1.25 and 5 mg/mL using the microdilution method,
while aqueous extracts were inactive. The extracts prepared from leaves showed larger zones of
inhibition compared to flowers and steam extracts of V. spicata, indicating stronger antimicrobial
activity [
11
,
58
]. In another work and using the microdilution method, Živkovi´c et al. (2014) investigated
the antibacterial eect of the V. urticifolia methanol extract against the Gram-negative bacteria Escherichia
coli, Enterococcus faecalis, and Pseudomonas aeruginosa, and Gram-positive bacteria Staphylococcus aureus,
L. monocytogenes, and Bacillus cereus [
59
]. After the measurement of the minimum bactericidal
concentration (MBC) and MIC values, it was found that the most sensitive germ was Staphylococcus
Molecules 2019,24, 2454 21 of 35
aureus. The antistaphylococcal eect is due to a main phenolic compound acteoside, which could inhibit
the incorporation of leucine and disturb protein synthesis. The same antistaphylococcal eects were
found in other studies [
20
]. Other chemical compounds could be also responsible for this antibacterial
activity, e.g.,
β
-sitosterol, campesterol, stigmasterol, hispidulin, and flavonoids. These results are
important for human health because S. aureus is a pathogen germ dicult to treat with the development
of antibiotic resistance. For this reason, natural alternative therapies to solve this problem are useful.
Other studies showed the antibacterial activity of methanol, ethanol, or aqueous extracts from Veronica
urticifolia Jacq., Veronica orchidea Crantz, V. persica, and Veronica montana L. against Gram-positive and
Gram-negative bacteria [
20
,
47
,
57
,
59
]. The summary of the antimicrobial activity of dierent Veronica
species is represented in Table 3.
As commented before, not all results were positive. Dulger and Ugurlu (2005) evaluated the
antimicrobial activity of the methanol extracts obtained from endemic Plantaginaceae members
from Turkey, including Veronica lycica E. Lehm. The antimicrobial activity was determined in E. coli
(American Type Culture Collection (ATCC) 11230), S. aureus (ATCC 6538P), Klebsiella pneumoniae (UC57),
P. aeruginosa (ATCC 27853), Proteus vulgaris (ATCC 8427), B. cereus (ATCC 7064), Mycobacterium smegmatis
(Czech Collection of Microorganisms (CCM) 2067), L. monocytogenes (ATCC 15313), Micrococcus luteus
(CCM 169), Candida albicans (ATCC 10231), Rhodotorula rubra (German Collection of Microorganisms
(DSM) 70403), and Kluyveromyces fragilis (ATCC 8608) using the disc diusion method. In this case,
V. lycica had weak antimicrobial eect against the tested microorganisms [
60
]. V. anagallis-aquatica
was tested using the agar well diusion assay against five bacterial and two yeast strains. None of
the extracts of this Veronica species showed significant inhibition comparing to the positive control
(gentamicin) [61].
Table 3.
Summary of the antimicrobial activity of dierent Veronica species. MIC—minimum inhibitory
concentration; MBC—minimum bactericidal concentration.
Species Plant Part Extract Eect Reference
Veronica spicata L. Flowers and stem Methanol and
ethyl-acetate
extracts
MIC values were between 1.25 and
5 mg/mL against Staphylococcus aureus,
Microccocus flavus, Listeria
monocytogenes, Enterobacter cloacae,
Escherichia coli, Bacillus cereus, and
Pseudomonas aeruginosa
[11,58]
Veronica urticifolia
Jacq.
The aerial parts Methanol extract The most sensitive germ was
Staphylococcus aureus (MIC and MBC
=7.5 mg/mL)
[59]
Veronica lycica E.
Lehm.
The aerial parts Methanol extract The antimicrobial activity was
determined against E. coli,S. aureus,
Klebsiella pneumoniae,P. aeruginosa,
Proteus vulgaris,B. cereus,
Mycobacterium smegmatis,
L. monocytogenes,Micrococcus luteus,
Candida albicans,Rhodotorula rubra,
and Kluyveromyces fragilis. The weak
antimicrobial eect was observed
against the tested microorganisms
[60]
Veronica
anagallis-aquatica L.
The aerial parts Methanol extract The extracts were tested against five
bacterial and two yeast strains. They
showed significant inhibition
compared to the positive control
(gentamicin)
[61]
Molecules 2019,24, 2454 22 of 35
Table 3. Cont.
Species Plant Part Extract Eect Reference
Veronica ocinalis
L., Veronica
teucrium L.,
Veronica orchidea
Crantz
The aerial parts
70% ethanol extract
Two anaerobic bacterial strains were
used: Peptostreptococcus anaerobius and
Fusobacterium nucleatum.V. teucrium
and V. orchidea presented a higher
activity (MIC =31.25 mg/mL and
MBC =62.5 mg/mL) than V. ocinalis
(MIC and MBC of 62.5 mg/mL), with
the most sensitive strain being
Peptostreptococcus anaerobius
[62]
V. ocinalis,
V. teucrium,
V. orchidea
The aerial parts
70% ethanol extract
Eight bacterial strains were used:
Staphylococcus aureus, Bacillus cereus,
Listeria monocytogenes, Listeria ivanovii,
Pseudomonas aeruginosa, Enterococcus
faecalis, Salmonella typhimurium, and
Escherichia coli. The most sensitive
strains were Staphylococcus aureus,
Listeria monocytogenes, and Listeria
ivanovii with MIC values between 3.9
and 15.62 mg/mL
[47]
Veronica persica Poir
The aerial parts 70% methanol
extract
V. persica extract demonstrated an
antifungal eect against Candida
albicans and Aspergillus niger at a
concentration 300 µg/mL of extract
[20]
In some cases, the antimicrobial activity of the isolated compounds was determined. In a
study conducted by Mocan and collaborators, V. ocinalis,V. teucrium, and V. orchidea were selected
from Romanian natural flora and investigated for their antioxidant and antimicrobial eects against
anaerobic bacterial strains with emphasis on the isolated compounds, caeic and chlorogenic acids.
V. teucrium and V. orchidea presented a higher activity (MIC =31.25 mg/mL and MBC =62.5 mg/mL)
than V. ocinalis (MIC and MBC of 62.5 mg/mL), with the most sensitive strain being Peptostreptococcus
anaerobius. All analyzed species contained both caeic and chlorogenic acids, where the richest source
of caeic acid was V. ocinalis and the highest amount of chlorogenic acid was found in V. teucrium [
62
].
3.2. Antifungal, Antiviral, and Antiparasitic Activity
Other studies demonstrated the antifungal eect of Veronica species [
11
,
20
,
47
]. Mocan and
co-workers investigated the antifungal properties of V. persica against Aspergillus niger and Penicillium
hirsutum using the Kirby–Bauer diusimetric method. The antifungal eect was higher for A. niger
than P. hirsutum and it is due to phenolic compounds [
47
]. Using the same method, antifungal eects
of V. persica extract against Candida albicans and A. niger were demonstrated in another study [
20
].
The results showed that the highest antifungal eect for both fungal pathogens was obtained at a
concentration 300
µ
g/mL of extract. Dunkic et al. demonstrated in another study the antifungal eect
of methanol V. spicata extract at MIC values ranging from 1.25 mg/mL to 5 mg/mL. In addition, the
methanol extract prepared only from V. spicata’s leaves also had an eect against the dermatophyte
Microsporum gypseum [
11
]. As a result of these positive data, Veronica plants can be considered good
natural therapeutic alternatives for mild fungal infections.
A new biological property, i.e., antiviral activity (against herpes simplex viruses HSV1 and
HSV2), of V. persica was demonstrated in a recent research conducted by Sharifi-Rad et al. (2018) [
63
].
In this study, the ethanol extract of V. persica was tested on Vero cells infected with both types of
viruses. The stronger antiviral activity was found in the 80% methanol fraction of V. persica extract
during and after infection of the cells with viruses, thus suggesting the interference of the extract
with the intracellular entry of the virus and a possible inhibition of the viral intracellular replication
of endogenous herpetic viruses. HSV1 was much more sensitive to the action of the methanolic
fraction compared to HSV2. In addition, the 80% MeOH fraction of V. persica extract administered
Molecules 2019,24, 2454 23 of 35
to the cells at the same time with aciclovir (antiviral drug) showed a synergistic eect in reducing
plaque formation by herpetic viruses [
63
]. This antiviral action indicates the usefulness of the V. persica
extract in combination with the antiviral medication (such as aciclovir) for decreasing the severity of
symptomatic episodes of oral herpetic infection, which relapses when the immune system is weak.
Moreover, in a recent investigation conducted by these authors,
in vitro
and
in vivo
susceptibility
of Leishmania major to V. persica extract was evaluated. Antileishmanial activity of plant extract
was investigated on cultured L. major promastigotes and in mice.
In vitro
tests showed a high and
dose-dependent inhibitory activity of plant extract, which was able to reduce the survival time of
promastigotes in a concentration-dependent manner; for example, the survival time of promastigotes
decreased to 10% at 750
µ
g/mL after 72 h of exposure time. There was a significant influence of V. persica
extracts
in vivo
on accelerating the healing process, as well as reducing the overall disease burden, in
an animal model by inducing nitric oxide production in macrophage cells [64].
4. Antioxidant Activities of Veronica Plants
4.1. In Vitro Studies
Medicinal plants, including Veronica species, are excellent sources of phytochemicals with
potent antioxidant activities. Extracts from several species were tested
in vitro
through several
methods such as DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical scavenging, the phosphomolybdate
method [
56
,
65
68
], hydrogen peroxide scavenging and bleomycin-dependent deoxyribonucleic acid
(DNA) damage test [
69
], oxygen radical absorbance capacity (ORAC) assay [
12
], ferric-reducing
antioxidant power test [
70
], and ABTS (2,2-azinobis 3- ethylbenzothiazoline-6-sulfonate) radical
scavenging ability [56].
Mocan and co-workers reported that ethanolic extracts of V. ocinalis,V. teucrium, and V. orchidea,
which contain phenolic acids and flavonoids, showed potent antioxidant activity [
47
]. The Trolox
equivalent (TE) antioxidant capacity (TEAC) assay indicated that V. ocinalis (157.99
±
6.58 mg TE/g dry
weight (d.w.)) and V. orchidea (155.41
±
1.58 mg TE/g d.w.) exhibited similar antioxidant capacities, but
higher than that of V. teucrium (96.67
±
0.26 mg TE/g d.w.). This was also suggested using antioxidant
activity measured with electron paramagnetic resonance (EPR) spectroscopy using Fremy’s salt. In
another work, 14 Veronica species were tested for their radical scavenging activity against DPPH,
superoxide (SO), and nitric oxide (NO) radicals. V. chamaedrys was the most active against SO radical
(half maximal inhibitory concentration (IC
50
) 113.40
µ
g/mL) and V. ocinalis against DPPH (IC
50
40.93
µ
g/mL) and NO radicals (IC
50
570.33
µ
g/mL) [
68
]. In another work, the antioxidant potential of
various extracts obtained from aerial flowering parts of three Veronica species, V. teucrium,V. jacquinii,
and V. urticifola, was evaluated
in vitro
by DPPH free-radical scavenging activity (IC
50
values 12.58 to
66.34
µ
g/mL) and ferric-reducing antioxidant power assays (0.97 to 4.85 mmol Fe
2+
/g) [
70
]. V. spicata
extracts obtained by dierent solvents (water, methanol, and ethyl-acetate) also demonstrated a
radical scavenging eect [
11
], especially methanol ones. Although butylated hydroxytoluene and
butylhydroxyanisole are generally more active [11,70], the former is a source of natural ingredients.
Antioxidant activities of Veronica species could be attributed to their content of iridoids and
phenolic acids [
65
]. Moreover, acylated flavonoids and phenol glycosides from V. thymoides subsp.
pseudocinerea exhibited potent radical scavenging activity against DPPH radicals [
38
]. The two
phenylethanoid glycosides, turrilliosides A and B, isolated from Veronica turrilliana Stoj. & Stef.
were found to be potent DPPH radical scavengers, approximately 1.6-fold better than the flavonoid
quercetin [
40
]. In another work, the antioxidant capacity of V. persica phenolic-rich extracts was
correlated with their total phenol content [56].
Molecules 2019,24, 2454 24 of 35
4.2. In Vivo Studies
The antioxidant activity of three Veronica species, V. teucrium, V. jacquinii, and V. urticifola, was
examined
in vivo
in rats, and their eect on several hepatic antioxidant systems was tested, i.e., on
the activity of glutathione peroxidase, glutathione reductase (GR), peroxidase (Px), catalase (CAT),
and xanthine oxidase, as well as glutathione (GSH) content and level of thiobarbituric acid reactive
substances (TBARS). Treatment with Veronica extracts (methanolic, aqueous-acetone, and water extracts)
(100 mg/kg) inhibited CCl
4
-induced liver injury by decreasing TBARS level, increasing GSH content,
and bringing the activities of antioxidative enzymes CAT, Px, and GR to control levels. The study
suggested that the extracts analyzed could protect the liver cells from CCl
4
-induced liver damage by
their antioxidative eect on hepatocytes [
70
]. Veronica ciliata Fisch. is also a considerable candidate for
protecting liver injuries due to its antioxidant and anti-apoptosis properties [71].
The antioxidant activity of other Veronica extracts was associated with other bioactivities.
As an example, Lu and co-authors reported that isolated compounds from V. ciliata showed
anti-hepatocarcinoma activities against HepG2 liver hepatocellular carcinoma cells, which could
be associated with its antioxidant activity [
48
]. Lee and co-workers evaluated the antioxidant activity,
cytotoxicity, and collagen synthesis activity
in vitro
in order to test the anti-wrinkle eect of a formulated
cream containing V. ocinalis extract. Antioxidant evaluation was performed in fibroblast cells. The
ethanolic extract showed good antioxidant activity against DPPH free radicals (103.50
µ
g/mL) and also
exhibited a significant eect on collagen synthesis activity without cytotoxicity. In a placebo-controlled
trial on women, the treatment with the formulated cream (Scoti-Speedwell) for 56 days significantly
resulted in anti-wrinkle activity [72].
5. Anticancer Activities of Veronica Species
Plant-derived metabolites are beneficial sources of new anti-cancer drugs with reduced cytotoxicity
and increased activity. More than 60% of today’s drugs with proven anticancer properties originated
from plants [
73
]. Extracts obtained from the aerial parts of various Veronica species are globally used
as folk medicine for the therapy of cancer [
16
]. Despite this fact, only a few amounts of Veronica
species were investigated for their cytotoxic and anticancer activities (as an example, see Table 4). With
the exception of one
in vivo
confirmation, all of the investigations were performed
in vitro
against
various cancer cell lines. Also, there is a lack of mechanistic studies for compounds isolated from
Veronica species.
5.1. In Vitro Studies
Methanolic and water extracts of several Veronica species were tested against cancer cells
in vitro
.
Harput and collaborators studied the cytotoxic activity of five Veronica species: V. cymbalaria,V. hederifolia,
Veronica pectinata L., V. persica, and V. polita. Their methanolic extracts showed dose-dependent
cytotoxicity against KB (human epidermoid carcinoma) and B16 (mouse melanoma) cells. Additional
fractionation of investigated extracts pointed out that the active compounds occurred in the chloroform
fraction, but not the water one. Moreover, KB cells were more sensitive to the CHCl
3
-soluble parts of the
extracts compared to B16 cells. Except for V. cymbalaria,Veronica species exhibited similar activity against
KB cells, while V. persica,V. polita, and V. pectinata demonstrated potent activity against B16 cells [
74
].
Saracoglu et al. (2011) evaluated the cytotoxicity of aqueous extracts (10–800
µ
L) of V. cuneifolia
subsp. cuneifolia and V. cymbalaria using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay against various cell lines, Hep-2 (human epidermoid carcinoma), RD (human
rhabdomyosarcoma), and L-20B (transgenic murine L-cells), as well as in non-cancerous Vero cells
(African green monkey kidney cells). Both samples showed cytotoxic activity against used cell lines,
but V. cuneifolia subsp. cuneifolia showed a stronger eect with IC
50
values ranging from 250.4 (for RD
line) to 410.9 (for Vero cell line)
µ
g/mL [
75
]. Moreover, a previous pharmacological investigation on
edible V. americana (Raf.) Schwein species (American speedwell) showed that the methanolic extract of
Molecules 2019,24, 2454 25 of 35
the aerial parts exhibited cytotoxic activity against colon (HF-6) and prostate (PC-3) human cancer cell
lines with IC50 values of 0.169 and 1.460 µg/mL, respectively [76].
Other studies focused on the elucidation of the active compounds. As an example, the authors of
Reference [
50
] conducted bioassay-guided fractionation of V. americana methanolic extract, employing
the cytotoxic activity against two previously mentioned cancer cell lines in order to determine active
components. Compounds in this extract that demonstrated activity higher than camptothecin
(used as the positive control) were 4
β
-hydroxy-6-O-(p-hydroxybenzoyl)-tetrahydrolinaride and
10-O-protocatechuyl catalpol. Their activity was higher against HF-6 cells with IC
50
values of 0.031
and 0.066
µ
M for americanoside and 10-O-protocatechuyl-catalpol, respectively. Also, according to
the calculated selectivity index (SI), both compounds showed more selective cytotoxicity against
applied cancer cell lines than against human normal MRC-5 (fetal lung fibroblast) cells. Yin
and co-workers investigated anti-hepatocarcinoma activity of 95% ethanol extract of V. ciliata
aerial parts and its fractions, using human hepatocellular carcinoma cells HepG2 and the 3-(4,
5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test. They demonstrated that active
compounds were concentrated in the ethyl acetate fraction of the extract [
77
]. Iridoid compounds
veronicoside, catalposide, amphicoside, and verminoside strongly inhibited HepG2 cell proliferation in
a dose-dependent manner. Their inhibition rates (with the exception of veronicoside) were significantly
higher compared to that of 5-fluorouracil used as a positive control, i.e., IC
50
values ranged from 15.54
to 28.32
µ
g/mL, while the 5-fluorouracil IC
50
value was 29.62
µ
g/mL. In the later study conducted by
the same group of authors [
48
], the anti-hepatocarcinoma activities of five other compounds isolated
from V. ciliata were also determined
in vitro
against the HepG2 cell line using the Cell Counting Kit-8
(CCK-8) method. The results showed that the proliferation of HepG2 cells was notably inhibited by
these five compounds in a dose-dependent manner, and their activities decreased in the following
order: luteolin >verproside >catalposide >3,4-dihydroxy benzoic acid >4-hydroxybenzoic acid,
with IC
50
values ranging from 102.36 to 444.76
µ
g/mL. The authors hypothesized that the exhibited
activity of isolated compounds could be associated, at least in part, with their antioxidant activity.
According to them, the higher cytotoxic potential of luteolin compared to analyzed iridoid glucosides
and phenolic acids could be attributed to the higher number of phenolic groups in the molecule.
In a recent study, the cytotoxic properties of eight compounds isolated from V. sibirica were tested
in vitro
through the MTT assay against two cell lines: human neuroblastoma (SK-N-SH) and human
hepatocellular carcinoma (BEL-7402). Compounds sibiriquinone A, cryptotanshinone, ferruginol,
dihydrotanshinone I, tanshinone I, and tanshinone IIA showed beneficial inhibitory eects on the
SK-N-SH cell growth, while compounds sibiriquinone A, cryptotanshinone, dihydrotanshinone I,
and tanshinone IIA inhibited growth of the BEL-7402 cell line [
42
]. Moreover, the cytotoxic activity
of iridoid compounds characteristic for Veronica species (aucubin, catalpol, and catalpol derivatives)
was also determined against previously mentioned cell lines Hep-2, RD, and L-20B. Among tested
compounds, verminoside showed very strong activity with IC
50
values of 128
µ
M, 70
µ
M, and 103
µ
M,
respectively. The activities of amphicoside and veronicoside were lower, while verminoside, verproside,
and 6-O-veratroylcatalposide showed cytostatic activity [
78
]. Moreover, the
in vitro
antitumor activity
of diterpenes, chemical compounds from V. sibirica, was also shown using the SK-N-SH human
neuroblastoma cell line and BEL-7402 human hepatoma cell line [42].
Molecules 2019,24, 2454 26 of 35
Table 4. Some bioactive eects of Veronica plants and potential active compounds.
Type of Studies Primary Outcomes Active
Compounds Veronica spp. References
In vitro
Human neuroblastoma
cell line SH-SY5Y
Neuroprotective
against H2O2
induced
cytotoxicity
Iridoid glucosides
acteoside, and
aucubin (only in
V. urticifolia)
Veronica
urticifolia Jacq.
Veronica
teucrium L.
Veronica jacquinii
Baumg.
[79]
Human endothelial
cells EA.hy 926 Angiogenic Phenylpropanoids
and flavonoids
V. jacquinii
V. teucrium
V. urticifolia
Human lung epithelial
cells A549
Anti-inflammatory
in lung diseases
(anti-asthmatic)
Iridoid glycosides
(verminoside,
verproside)
Veronica
ocinalis L. [15]
Human cancer cell
lines HF-6 (colon),
PC-3 (prostate) human
normal MRC-5 cells
(fetal lung fibroblast)
Cytotoxic Iridoids
Veronica
americana
Schwein. ex Benth.
[50]
SK-N-SH human
neuroblastoma cell
line, BEL-7402 human
hepatoma cell line
Cytotoxic Diterpenes
Veronica sibirica L.
[42]
In vivo
Phenyl-p-benzoquinone
writhing test and
carrageenan induced
hind paw edema
model in mice
Antinociceptive
and
anti-inflammatory
Iridoid glucosides,
catalposide and
verproside
Veronica
anagallis-aquatica
L.
[16]
Rats0paw edema
induced by dextran Anti-inflammatory
Phenolic
compounds and
iridoids
Veronica persica
Poir [65]
Clinical
Study design:
randomized, placebo
controlled for 58 days
Anti-wrinkles,
antiaging of skin Verbascoside V. ocinalis [72]
5.2. In Vivo Studies
Tumors and dierent types of cancers are dicult to treat, but classical conventional chemotherapy
can be combined with cytotoxic natural remedies. Živkovi´c and co-workers evaluated the antitumor
activity of V. urticifolia methanolic extract
in vivo
in animals with Ehrlich ascites carcinoma (EAC) [
59
].
It is an aggressive, fast-growing carcinoma initially described as a spontaneous murine mammary
adenocarcinoma [80]. The antitumor properties of V. urticifolia methanolic extract were estimated via
determination of the tumor cell count, ascites volume, and cell viability, and the results were compared
with those achieved for positive control N-acetyl-l-cysteine. Pretreatment (2 mg/kg body weight) for
seven days before EAC implantation showed a statistically significant decrease in tumor cell viability,
while ascites volume and tumor cell count were reduced to some extent, but not statistically significant.
There are too few data about the
in vivo
antitumor eects of compounds isolated from
Veronica species. Acteoside (phenylpropanoid compound dominant in V. urticifolia extract)
applied intraperitoneally (i.p.) in a concentration of 50 mg/kg in C57BL/6 mice as pretreatment
for 13 days before implantation of melanoma cells induced a statistically significant increase
in survival rate in animals [
81
]. According to the aforementioned
in vitro
studies, other
candidates for the development of eective anticancer therapeutic agents could be verminoside,
4β-hydroxy-6-O-(p-hydroxybenzoyl)-tetrahydrolinaride, and 10-O-protocatechuyl catalpol.
Molecules 2019,24, 2454 27 of 35
6. Anti-Inflammatory Activity
6.1. In Vitro Studies
The anti-inflammatory properties of several Veronica species were evaluated in vitro and in vivo
(Table 4). In particular, the anti-inflammatory eect of Veronica peregrina L. was demonstrated in a recent
study [
10
]. Dierent concentrations of V. peregrina methanolic extracts were incubated with C57BL/6
mouse peritoneal macrophages and the release of pro-inflammatory mediators, cyclooxygenase-2
(COX
2
) and nitric oxide (NO), mediated by lipopolysaccharides was assessed; these were reduced
dependent on the concentration of the extract. The mechanism of anti-inflammatory action was also
highlighted: the inhibition of inducible nitric oxide synthase (iNOS) enzyme and consecutive decrease
of NO production [
10
]. This study revealed the usefulness of V. peregrina extract as synergistic natural
therapy in inflammatory diseases mediated by activated mast cells, such as arthritis, obesity, and
atherosclerosis [
82
]. A similar study conducted by Harput et al. demonstrated the same biological
anti-inflammatory activity of a methanol extract of five Veronica species which inhibited NO release
from activated macrophages [74].
In another study, aqueous-acetone extracts of V. teucrium,V. jacquinii, and V. urticifola were
tested for this eect on calcium ionophore-stimulated platelets, which release pro-inflammatory
enzymes 12-lipoxygenase (12-LOX) and cyclooxygenase-1 (COX-1) with tromboxane B
2
(TXB
2
) and
prostaglandin E2 (PGE
2
). COX
1
and its metabolite PGE
2
were inhibited by V. urticifolia extract,
while the 12-LOX enzyme was blocked only by the V. jacquinii extract (IC
50
=1.072 mg/mL). This
anti-inflammatory activity is correlated with the presence of the main chemical compounds genistein,
baicalin, isoquercetin, and hyperoside, but the mechanism of action is not yet completely known [
13
].
The results of these studies are important for human health, because natural remedies can successfully
complete anti-inflammatory medical treatments.
Extracts of V. chamaedrys and V. ocinalis also revealed
in vitro
anti-inflammatory activity
on peroxisome proliferator-activated receptors (PPARs) and on the pro-inflammatory mediators,
interleukin-8 (IL-8) and E-selectin [
17
]. Among the active constituents, V. ocinalis extract rich in
iridoid glycosides (verproside and verminoside) inhibited pro-inflammatory mediators via the nuclear
factor kappa B (NF-κB) signaling pathway in a human lung cell line [15].
In another study, the anti-inflammatory action of V. ocinalis extract in allergic inflammatory
lung diseases was evaluated using A549 human lung epithelial cells. The results showed that the
V. ocinalis extract (40 to 160
µ
g/mL) inhibited in a dose-dependent manner the release of the main
pro-inflammatory mediators IL-6 and IL-8, prostaglandin E
2
, and eotaxin. The data of the study did
not clarify the mode of action of V. ocinalis extract, but it is supposed that there is a link between the
most abundant and important active compounds, iridoid glycosides (verminoside and verproside),
and the anti-inflammatory eect [
15
]. These positive molecular results are in contrast to other studies
that showed that the oral bioavailability of verproside is very low [
83
]. Nonetheless, more studies are
required to elucidate the metabolites formed and their bioactivity. Moreover, an alternative way to
administer V. ocinalis extracts could be the pulmonary route using a spray for inhalation with the
direct release of active substances to the lung epithelium [83].
6.2. In Vivo Studies
Inflammatory bowel diseases (IBD) (Crohn
0
s disease and ulcerative colitis) are a heterogeneous
group of diseases with incomplete elucidate pathogenesis defined by inflammation, persistence,
or recurrence in the gastrointestinal tract, dierent in terms of extension of lesions, symptoms,
prognosis, and treatment [
84
]. The triggers of these diseases are complex and mediated by
cytokines (interleukins, IL) [
85
] and signal transducer activator of transcription 3 (STAT3) [
86
,
87
],
pro-inflammatory enzymes such as cyclooxygenase-2 (COX
2
) [
88
], and non-specific pro-inflammatory
mediators, e.g., thromboxanes, prostaglandins, leukotrienes, oxygen free radicals, and NO [
89
].
Understanding these mechanisms led to research of new therapies, including natural alternatives.
Molecules 2019,24, 2454 28 of 35
Thus, Akanda and co-workers investigated the anti-inflammatory property of V. polita species on
experimental colitis induced in mice using dextran sulfate sodium (DSS) [
90
]. Forty mice divided
into four groups were included in the study: control, mice treated with DSS, mice treated with DSS
plus V. polita extract (200 mg/kg), and the last group received DSS associated with dexamethasone.
The results of the study were surprising because, for the mice treated with V. polita associated
with dexamethasone compared to those treated with DSS alone, the following data were obtained:
pro-inflammatory cytokines (IL-1
β
, IL-6, tumor necrosis factor alpha (TNF-
α
)) were not activated
and NO production in the intestine was reduced. In addition, COX-2, NF-
κ
B, and the Janus kinase 2
(JAK2)/STAT3 signaling pathway were blocked in mice co-treated with DSS and V. polita, similarly to
the group of mice co-treated with DSS and dexamethasone [
90
]. This can be attributed to the high
content of total phenols and flavonoids of this species [46].
Kupeli et al. conducted a study concerning the antinociceptive and anti-inflammatory eect of
the methanol and aqueous extracts of the species V. anagallis-aquatica, using a phenyl-p-benzoquinone
(PBQ) writhing test and carrageenan-induced hind paw edema model in mice. Only the methanolic
extract (500 mg/kg) showed significant antinociceptive and anti-inflammatory eects, which could be
related to the presence of iridoid glucosides, catalposide and verproside. In addition, no toxic and
adverse irritant gastric eects were revealed [16].
A new pharmaceutical formulation consisting of a microemulsion of V. persica was tested for
anti-inflammatory eects on rat paw edema induced by two dierent substances—kaolin, stimulating
pro-inflammatory cytokines, and dextran, increasing the release of histamine and consequently
inducing vascular permeability. Inflammation induced by dextran was totally reduced following the
co-administration of V. persica microemulsion compared to the kaolin inflammation. This eect was
correlated with its high content of polyphenols and iridoids [65].
7. Other Properties
The neuroprotective and angiogenic eects of the methanolic and aqueous-acetone extracts of three
Veronica species, V. teucrium,V. jacquinii, and V. urticifolia, were determined on human SH-SY5Y cell line
neuroblastoma. The neurotoxicity was induced on the cells by oxidative and nitrosative stress using
H
2
O
2
and nitroprusside sodium, respectively. The six extracts showed a moderate neuroprotective
eect, and this eect was higher for the cytotoxicity induced by oxidative stress and using V. urticifolia
extract. Moreover, these authors showed that Veronica extracts, especially the V. jacquinni methanol
extract and V. teucrium aqueous-acetone extract, showed antiangiogenic properties by preventing the
formation of tubular structures in a Matrigel assay. Although this eect was probably due to the
content of acteoside and aucubine, the mechanisms of action are unclear [79].
8. Food Applications of Veronica Plants and Other Uses
The enzymatic activity in foodstus result in some chemical reactions leading to food spoilage,
thus making foods inedible or decreasing their qualities [
91
,
92
]. In addition to being an important
health issue, which may sometimes lead to death, it may also yield great economic losses [
93
]. The
World Health Organization reported that unsafe food resulted in illnesses in approximately two billion
people throughout the world, and some of the cases were actually fatal [
94
]. There are some other
methods that could prevent food spoilage, such as thermal processing; however, this technique might
also result in a decrease in the nutritional value and quality of the food while reducing vegetative
microorganisms. Therefore, to prevent food-related diseases and even death, a preservative should be
used and this preservative has to be appropriate for the health of consumers and should not yield toxic
materials [
95
]. Food manufacturers also search for compounds that could meet the expectations of
healthy food trends, and this is also an important issue since synthetic preservatives are known to yield
unwanted health results [
96
]. Veronica species have widespread traditional use throughout the world
and, in addition to this usage, stems and leaves of some of the species are consumed as food in certain
regions. Moreover, according to the Food Additive Status List by the Food and Drug Administration
Molecules 2019,24, 2454 29 of 35
(FDA), Veronica species are listed as substances in conjunction with flavors that can be used in alcoholic
beverages only [
97
]. However, since some members of this genus are also consumed by humans and
used in traditional medicine, we can consider that usage of this plant is relatively safe [57].
Thus, the use of Veronica species in food preservation could be plausible with no adverse eects
since some of them were demonstrated to possess antimicrobial eects (see Section 4). Although
not directed on their use in food matrices, these studies also proved that the species extracts possess
antibacterial eects and, thus, this genus has a potential to be used in food preservation [
11
,
47
,
98
100
].
In this sense, the antimicrobial eect of Veronica plants extracts against foodborne pathogenic and
food contaminant bacteria was demonstrated by several authors, but with modest activity. As an
example, the results of the experiment conducted by Mocan et al. (2015) on the antibacterial activity of
V. ocinalis,V. teucrium, and V. orchidea ethanolic extracts, tested using the microdilution assay, revealed
that the most sensitive bacterial strains to V. ocinalis were Listeria monocytogenes (ATCC 19114) and
Listeria ivanovii (ATCC 19119), with the same values of minimum inhibitory (MIC) and minimum
bactericidal concentration (MBC) of 7.81 mg/mL. In the case of V. teucrium antibacterial activity, the
strains of Staphylococcus aureus (ATCC 49444), Bacillus cereus (ATCC 11778), and Enterococcus faecalis
(ATCC 29212) showed equal values for MIC and MBC (7.81 mg/mL), being the most sensitive. The
ethanolic extract of V. orchidea inhibited L. monocytogenes and L. ivanovii with MIC =3.9 mg/mL and
MBC =7.81 mg/mL. Regarding the V. ocinalis extract, Bacillus cereus,Pseudomonas aeruginosa (ATCC
27853), and Escherichia coli (ATCC 25922) were the most resistant species with MIC and MBC values
higher than 15.62 mg/mL. According to Mocan et al. (2015), the activity of these extracts against
Gram-positive bacteria like Listeria species and S. aureus could be related to their high
β
-sitosterol,
campesterol, and stigmasterol content. Phenolic constituents such as apigenin, luteolin, and their
glycosides could also contribute [
11
,
20
,
47
]. Another work also suggested that V. montana L. water
extract and its main phenolic compound, protocatechuic acid, showed the highest antibacterial eect
against S. aureus (ATCC 6538) (MIC and MBC, 7.5 mg/mL) but a poor eect against B. cereus (human
isolate) (MIC =22.5 mg/mL; MBC 45 mg/mL) [57].
The incorporation of these species in a food system was investigated recently. In this sense, the
water extract of V. montana exerted antimicrobial eects against six pathogenic bacteria, but it was
more eective against L. monocytogenes (MIC, 7.5 mg/L; MBC, 15.0 mg/mL). Its major compound,
protocatechuic acid (15.7 mg/g), also showed antibacterial properties (MIC, 0.75 mg/L; MBC, 1.0 mg/mL)
and it was evaluated after its incorporation in cream cheese, using this bacterium as a cheese
contaminant. This compound preserved cream cheese by inhibiting the growth of L. monocytogenes at
room temperature and in the refrigerator after three days of inoculation, without compromising the
sensory properties. The compound was shown to alter the permeability of the bacterial cytoplasmic
membrane, and this makes this plant species and its major component promising antibacterial food
preservatives [57].
The antioxidant properties (see Section 5) can be also exploited to preserve food quality and
reduce rancidity and o-flavors, but these studies were not carried out on food systems. In this context,
further studies are required to establish their real applicability as natural preservatives instead of
synthetic ones, including dosages, advantages, and disadvantages.
In another context, some wild edible plants are attracting attention as novel food ingredients for
gourmet in agro-tourism, for example, for salads and refreshing candy products. Ricola
®
(Laufen,
Switzerland) sweets are made with V. ocinalis in conjunction with other medicinal plants, used to
refresh the mouth and throat. Blanco-Salas et al. (2019) suggested that V. anagallis-aquatica, among
other wild plants in “Sierra Grande de Hornachos” (Spain), already entered the high Spanish hotel
industry and small selected market niches, due to its sensory and nutritional characteristics [
101
]. As
commented before, this is a natural source of iridoids and other phytochemicals.
Molecules 2019,24, 2454 30 of 35
9. Conclusions
More than 100 phytochemicals were identified in Veronica plants, which mainly belong to iridoid
glycosides and phenolic compounds, particularly flavones and terpenoids. Veronica plants are described
in traditional medicine for the treatment of many diseases, especially related to inflammatory disorders.
In addition, they represent importance in cosmetic and food industries. The review of the literature
highlights that Veronica plants have good antioxidant, anti-inflammatory, antimicrobial, and anticancer
abilities, which are mainly related to the presence of iridoid glucosides and phenolic constituents.
The antioxidant properties of Veronica species were determined through dierent
in vitro
and
in vivo
studies. In addition, Veronica plants showed interesting antimicrobial eects, and most studies
focused on its eects against both Gram-positive and Gram-negative bacteria. This also included
foodborne pathogens, such as L. monocytogenes. The anti-inflammatory studies agreed with the use of
Veronica remedies for anti-inflammatory medical treatments. Many authors also hypothesized that the
cytotoxic activity of Veronica plants is associated with their antioxidant and anti-inflammatory eects.
However, studies proving the therapeutic eects of the Veronica genus in humans are scarce, with the
exception of V. ocinalis as an anti-wrinkle agent. Only few studies were conducted
in vivo
, while the
molecular mechanisms of the pharmacotherapeutic eects remain still unknown. When looking at the
food applications of Veronica plants, promissory reports showed that its incorporation into several
food matrices, such as dairy products, results in an improvement of the shelf-life, through exerting
antimicrobial and antioxidant eects. Thus, these plants may be conceived as upcoming and eective
natural food preservatives.
Author Contributions:
All authors contributed to the manuscript. Conceptualization, B.S. and J.S.-R.; validation,
investigation, resources, data reviewing, and writing, all authors; review and editing, J.S.-R., M.d.M.C., F.S., N.M.,
and W.C.C. All authors read and approved the final manuscript.
Funding: This research received no external funding.
Acknowledgments:
M.d.M.C. is grateful for funding from the “Acci
ó
n 6 del Plan de Apoyo a la Investigaci
ó
n
de la Universidad de Ja
é
n, 2017–2019”. N. Martins would like to thank the Portuguese Foundation for Science
and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “NORTE2020 - Northern
Regional Operational Program” (NORTE-01-0145-FEDER-000012).
Conflicts of Interest: The authors declare no conflicts of interest.
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