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Medicinal plants are used worldwide due to their lower risk of side effects and eco-friendly, cost-effective production when compared to chemical drugs, encouraging researchers to further exploit the therapeutic potential of the former. One of the most popular medicinal plants is Vitex agnus-castus L., grown in tropical and sub-tropical regions, to which different health benefits have already been attributed. In this perspective article, the in vitro and in vivo therapeutic properties of V. agnus-castus L. have been analyzed and reviewed with a special focus on its health-promoting effects and potential nutraceutical applications.
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Perspective
Vitex agnus-castus L.: Main Features and
Nutraceutical Perspectives
Eliana B. Souto 1, 2, *, Alessandra Durazzo 3, Amirhossein Nazhand 4, Massimo Lucarini 3,
Massimo Zaccardelli 5, Selma B. Souto 6, Amelia M. Silva 7,8 , Patricia Severino 9, 10, 11 ,
Ettore Novellino 12 and Antonello Santini 12, *
1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências
da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
2CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
3CREA-Research Centre for Food and Nutrition, Via Ardeatina 546, 00178 Roma, Italy;
alessandra.durazzo@crea.gov.it (A.D.); massimo.lucarini@crea.gov.it (M.L.)
4Department of Biotechnology, Sari Agricultural Science and Natural Resource University, 9th km of Farah
Abad Road, Sari 48181 68984, Mazandaran, Iran; nazhand.ah@gmail.com
5CREA-Research Centre for Vegetable and Ornamental Crops, Via Cavalleggeri 25,
84098 Pontecagnano (Salerno), Italy; massimo.zaccardelli@crea.gov.it
6Department of Endocrinology of Braga Hospital, Sete Fontes, 4710-243 São Victor, Braga, Portugal;
sbsouto.md@gmail.com
7Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD),
Quinta de Prados, P-5001-801 Vila Real, Portugal; amsilva@utad.pt
8
Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of
Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal
9Industrial Biotechnology Program, University of Tiradentes (UNIT), Av. Murilo Dantas 300,
49032-490 Aracaju, Brazil; pattypharma@gmail.com
10 Tiradentes Institute, 150 Mt Vernon St., Dorchester, MA 02125, USA
11 Laboratory of Nanotechnology and Nanomedicine (LNMED), Institute of Technology and Research (ITP),
Av. Murilo Dantas, 300, 49010-390 Aracaju, Brazil
12 Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy;
ettore.novellino@unina.it
*Correspondence: ebsouto@.uc.pt (E.B.S.); asantini@unina.it (A.S.); Tel.: +351-239-488-400 (E.B.S.);
+39-81-253-9317 (A.S.)
Received: 14 May 2020; Accepted: 10 July 2020; Published: 16 July 2020


Abstract:
Medicinal plants are used worldwide due to their lower risk of side eects and eco-friendly,
cost-eective production when compared to chemical drugs, encouraging researchers to further
exploit the therapeutic potential of the former. One of the most popular medicinal plants is
Vitex agnus-castus L.
, grown in tropical and sub-tropical regions, to which dierent health benefits
have already been attributed. In this perspective article, the
in vitro
and
in vivo
therapeutic properties
of V. agnus-castus L. have been analyzed and reviewed with a special focus on its health-promoting
eects and potential nutraceutical applications.
Keywords:
chaste tree; Vitex agnus-castus L.; bioactive compounds;
in vitro
studies;
in vivo
studies;
nutraceuticals; health-promoting properties.
1. Introduction
Medicinal wild plants and herbs have been considered worldwide for centuries as valuable tools
in the management of dierent diseases, due to their ease of use and improved cost-eectiveness
when compared to chemical remedies obtained from synthesis [
1
]. Plants have recently been exploited
Forests 2020,11, 761; doi:10.3390/f11070761 www.mdpi.com/journal/forests
Forests 2020,11, 761 2 of 16
for nutraceutical purposes, as they play a key role in the development of food and plant-derived
phytocomplexes with medicinal properties, to be used in health conditions as preventive or curative
tools [
2
23
]. A popular medicinal plant with recognized beneficial eects on human health is
Vitex agnus-castus L.
, belonging to the Lamiaceae family (formerly included in the Verbenaceae family),
native to the Mediterranean area and diused in Europe, Asia, and North Africa [
24
,
25
]. It has been
used by people in Italy, Iran, Greece, and Egypt for over 2500 years, mainly to treat gynecologic
disorders [
26
]. It is a globally famous plant known by dierent names, e.g. Fruit de gattilier (French),
Sauzgatillo (Spanish), Mönchspfeerfrüchte (German), Panj-angosht (Persian), Frutto di Agnocasto
(Italian), and Chaste tree (English) [27].
The term agnus-castus combines the Greek (
Forests 2020, 11, x FOR PEER REVIEW 2 of 17
cost-effectiveness when compared to chemical remedies obtained from synthesis [1]. Plants have
recently been exploited for nutraceutical purposes, as they play a key role in the development of
food and plant-derived phytocomplexes with medicinal properties, to be used in health conditions
as preventive or curative tools [2–23]. A popular medicinal plant with recognized beneficial effects
on human health is Vitex agnus-castus L., belonging to the Lamiaceae family (formerly included in
the Verbenaceae family), native to the Mediterranean area and diffused in Europe, Asia, and North
Africa [24,25]. It has been used by people in Italy, Iran, Greece, and Egypt for over 2500 years, mainly
to treat gynecologic disorders [26]. It is a globally famous plant known by different names, e.g. Fruit
de gattilier (French), Sauzgatillo (Spanish), Mönchspfefferfrüchte (German), Panj-angosht (Persian),
Frutto di Agnocasto (Italian), and Chaste tree (English) [27].
The term agnus-castus combines the Greek meaning pure, chaste) and the Latin (castus from
“castitas” meaning chastity), repeating the term chaste for “pure”, which refers to the anaphrodisiac
properties of this plant and its use by monks to maintain celibacy (thus the “monk’s pepper”
synonym). The word “castushas been used for centuries to remark further the meaning or purity
associated with this plant. Homer, the semi-legendary author of the Iliad and the Odyssey epic
poems, defines agnus-castus as a “tendril for braiding”, explaining the origin of the genus “Vitex”.
Dioscorides, the Greek physician, used to suggest V. agnus-castus to decrease libido. Pliny the
Elder, the famous Roman author, naturalist, and natural philosopher, commented that this herb was
scattered on the beds of Athenian women when husbands went to war to ensure their loyalty.
Pietro Andrea Mattioli, an Italian physician and botanist of the XVI century, commented in his text
“Compendium de Plantis Omnibus una cum Earum Iconibus” (1571) with reference to the
properties of V. agnus-castus L. that: “… it forces the impulses of Venus when eaten either fried or
raw ... …..it is believed that not only eating or drinking it will make chaste men but even lying on it
...". V. agnus-castus is also known as “monk’s pepper” since the fruits of this plant have a bitter taste,
and the plant used to be cultivated by monks in their gardens as an anaphrodisiac, according to a
legend, to help them not betray their vow of chastity.
Vitex agnus-castus L. fruits have been traditionally consumed as food to enhance milk volume
and to treat flatulence and diarrhea as well as cyclic breast pain, menopause, acne, infertility,
premenstrual dysphoric disorder and other menstrual disorders (amenorrhea, dysmenorrhea) [28].
The European Medicines Agency and the German Health Commission have reported many
health benefits of this medicinal plant, including regulation of the menstrual cycle and treatment of
premenstrual syndrome, and mastalgia [29]. This paper is focused on a perspective analysis of the
health-promoting effects of V. agnus-castus L. and its nutraceutical potential. There are many
reported data on the different beneficial health-promoting potentials of this plant, including
antioxidant, immunomodulatory, cytotoxic, antimutagenic, antimicrobial, antifungal,
antinociceptive, opioidergic, antiepileptic, and anti-inflammatory properties, as well as benefits for
osteopenic syndromes, as shown in Figure 1 [30–34].
γν
o
Forests 2020, 11, x FOR PEER REVIEW 2 of 17
cost-effectiveness when compared to chemical remedies obtained from synthesis [1]. Plants have
recently been exploited for nutraceutical purposes, as they play a key role in the development of
food and plant-derived phytocomplexes with medicinal properties, to be used in health conditions
as preventive or curative tools [2–23]. A popular medicinal plant with recognized beneficial effects
on human health is Vitex agnus-castus L., belonging to the Lamiaceae family (formerly included in
the Verbenaceae family), native to the Mediterranean area and diffused in Europe, Asia, and North
Africa [24,25]. It has been used by people in Italy, Iran, Greece, and Egypt for over 2500 years, mainly
to treat gynecologic disorders [26]. It is a globally famous plant known by different names, e.g. Fruit
de gattilier (French), Sauzgatillo (Spanish), Mönchspfefferfrüchte (German), Panj-angosht (Persian),
Frutto di Agnocasto (Italian), and Chaste tree (English) [27].
The term agnus-castus combines the Greek meaning pure, chaste) and the Latin (castus from
“castitas” meaning chastity), repeating the term chaste for “pure”, which refers to the anaphrodisiac
properties of this plant and its use by monks to maintain celibacy (thus the “monk’s pepper”
synonym). The word “castushas been used for centuries to remark further the meaning or purity
associated with this plant. Homer, the semi-legendary author of the Iliad and the Odyssey epic
poems, defines agnus-castus as a “tendril for braiding”, explaining the origin of the genus “Vitex”.
Dioscorides, the Greek physician, used to suggest V. agnus-castus to decrease libido. Pliny the
Elder, the famous Roman author, naturalist, and natural philosopher, commented that this herb was
scattered on the beds of Athenian women when husbands went to war to ensure their loyalty.
Pietro Andrea Mattioli, an Italian physician and botanist of the XVI century, commented in his text
“Compendium de Plantis Omnibus una cum Earum Iconibus” (1571) with reference to the
properties of V. agnus-castus L. that: “… it forces the impulses of Venus when eaten either fried or
raw ... …..it is believed that not only eating or drinking it will make chaste men but even lying on it
...". V. agnus-castus is also known as “monk’s pepper” since the fruits of this plant have a bitter taste,
and the plant used to be cultivated by monks in their gardens as an anaphrodisiac, according to a
legend, to help them not betray their vow of chastity.
Vitex agnus-castus L. fruits have been traditionally consumed as food to enhance milk volume
and to treat flatulence and diarrhea as well as cyclic breast pain, menopause, acne, infertility,
premenstrual dysphoric disorder and other menstrual disorders (amenorrhea, dysmenorrhea) [28].
The European Medicines Agency and the German Health Commission have reported many
health benefits of this medicinal plant, including regulation of the menstrual cycle and treatment of
premenstrual syndrome, and mastalgia [29]. This paper is focused on a perspective analysis of the
health-promoting effects of V. agnus-castus L. and its nutraceutical potential. There are many
reported data on the different beneficial health-promoting potentials of this plant, including
antioxidant, immunomodulatory, cytotoxic, antimutagenic, antimicrobial, antifungal,
antinociceptive, opioidergic, antiepileptic, and anti-inflammatory properties, as well as benefits for
osteopenic syndromes, as shown in Figure 1 [30–34].
ς
, meaning pure, chaste) and the Latin (castus
from “castitas” meaning chastity), repeating the term chaste for “pure”, which refers to the anaphrodisiac
properties of this plant and its use by monks to maintain celibacy (thus the “monk’s pepper” synonym).
The word “castus” has been used for centuries to remark further the meaning or purity associated
with this plant. Homer, the semi-legendary author of the Iliad and the Odyssey epic poems, defines
agnus-castus as a “tendril for braiding”, explaining the origin of the genus “Vitex”. Dioscorides,
the Greek physician, used to suggest V. agnus-castus to decrease libido. Pliny the Elder, the famous
Roman author, naturalist, and natural philosopher, commented that this herb was scattered on the
beds of Athenian women when husbands went to war to ensure their loyalty. Pietro Andrea Mattioli,
an Italian physician and botanist of the XVI century, commented in his text “Compendium de Plantis
Omnibus una cum Earum Iconibus” (1571) with reference to the properties of V. agnus-castus L. that:
. . .
it forces the impulses of Venus when eaten either fried or raw
. . . . . .
..it is believed that not only
eating or drinking it will make chaste men but even lying on it
. . .
". V. agnus-castus is also known as
“monk’s pepper” since the fruits of this plant have a bitter taste, and the plant used to be cultivated by
monks in their gardens as an anaphrodisiac, according to a legend, to help them not betray their vow
of chastity.
Vitex agnus-castus L. fruits have been traditionally consumed as food to enhance milk volume and
to treat flatulence and diarrhea as well as cyclic breast pain, menopause, acne, infertility, premenstrual
dysphoric disorder and other menstrual disorders (amenorrhea, dysmenorrhea) [28].
The European Medicines Agency and the German Health Commission have reported many
health benefits of this medicinal plant, including regulation of the menstrual cycle and treatment
of premenstrual syndrome, and mastalgia [
29
]. This paper is focused on a perspective analysis of
the health-promoting eects of V. agnus-castus L. and its nutraceutical potential. There are many
reported data on the dierent beneficial health-promoting potentials of this plant, including antioxidant,
immunomodulatory, cytotoxic, antimutagenic, antimicrobial, antifungal, antinociceptive, opioidergic,
antiepileptic, and anti-inflammatory properties, as well as benefits for osteopenic syndromes, as shown
in Figure 1[3034].
Forests 2020,11, 761 3 of 16
Forests 2020, 11, x FOR PEER REVIEW 3 of 17
Figure 1. Scheme of the beneficial properties of Vitex agnus-castus L.
2. Main Substances of Nutraceutical Interest in Vitex agnus-castus
The chemical composition of Vitex agnus-castus L. includes many different chemical
compounds, among which are: vitexilactone, rolundifuran, ketosteroids, diterpenoids (vitexlactam,
vitexilactone, viteagnusin I, and rotundifuran), flavonoids (orientin, kaempferol, penduletin,
luteolin, artemetin, vitexin, and casticin), and iridoids (agnuside, agnusoside, agnucastosid A/B, and
aucubin) [35–37]. The identification and quantification of agnuside (Figure 2), together with
p-hydroxy benzoic acid, can be achieved by high-performance liquid chromatography HPLC) [38].
This method has been validated for extracts of the species Vitex negundo L. and Vitex trifolia L., with
limits of quantification and detection of 25 µg/mL and 10 µg/mL, respectively [38].
Figure 1. Scheme of the beneficial properties of Vitex agnus-castus L.
2. Main Substances of Nutraceutical Interest in Vitex agnus-castus
The chemical composition of Vitex agnus-castus L. includes many dierent chemical compounds,
among which are: vitexilactone, rolundifuran, ketosteroids, diterpenoids (vitexlactam, vitexilactone,
viteagnusin I, and rotundifuran), flavonoids (orientin, kaempferol, penduletin, luteolin, artemetin,
vitexin, and casticin), and iridoids (agnuside, agnusoside, agnucastosid A/B, and aucubin) [
35
37
].
The identification and quantification of agnuside (Figure 2), together with p-hydroxy benzoic acid,
can be achieved by high-performance liquid chromatography HPLC) [
38
]. This method has been
validated for extracts of the species Vitex negundo L. and Vitex trifolia L., with limits of quantification
and detection of 25 µg/mL and 10 µg/mL, respectively [38].
Forests 2020,11, 761 4 of 16
Forests 2020, 11, x FOR PEER REVIEW 4 of 17
(a) (b)
Figure 2. Chemical structure of vitexin (a) and of agnuside (b).
Gokbulut et al. measured the levels of vitexin (Figure 2), isolated from V. agnus-castus L. fruit
and leaf extracts, using the RP-HPLC-DAD (diode array detector) technique, and the results showed
that this flavonoid was present in considerable amounts (0.342 ± 0.0153% and 0.252 ± 0.0089%,
respectively) [39].
Agnuside together with casticin (a tetramethoxyflavone) have been used as fingerprint markers
to evaluate the quality of Japanese commercial products containing V. agnus-castus L. [40]. Another
marker validated for quality assessment was reported by Yahagi et al., using a liquid
chromatography–mass spectrometry (LC-MS)-based metabolomic technique and nuclear magnetic
resonance (NMR) spectroscopy to detect 3-O-trans-feruloyl tormentic acid, which was isolated from
the V. agnus-castus L. fruit extract [41]. In another study, using a rapid ultra-high performance liquid
chromatography diode array detector (UHPLC-DAD-QTOF-MS), seven markers of V. agnus-castus L.
fruit extract were claimed to be used as reference compounds for quality validation of medicinal
products containing this extract, in particular, vitetrifolin D (labdane diterpenoid),
5-hydroxykaempferol-3,6,7,4’-tetramethylether, casticin, isovitexin, and agnuside compounds [42].
A study conducted to compare the chemical markers occurring in food supplements and in V.
agnus-castus L. extracts, using the liquid chromatography electrospray triple quadrupole tandem
mass spectrometry (LC/ESI/(QqQ)MSMS) method in multiple reaction monitoring (MRM) mode as a
quantitative analysis, reported the presence of aucubin, orientin, luteolin-7-O-glucoside, agnuside,
isovitexin, homoorientin, and casticin compounds [43]. According to the findings from
RP-HPLC-DAD analysis, V. agnus-castus L. leaf and fruit extracts contained chlorogenic and caffeic
acid phenolic compounds with average concentrations of 0.27% and 0.32% (w/w), respectively [44].
Li et al. isolated eighteen compounds from V. agnus-castus L. fruit extract, using 1D/2D NMR and
mass spectrometry methods, and their chemopreventive potential was studied in Hepa 1c1c7 cells,
which showed NADP(H): quinone oxidoreductase type 1 (QR1) induction potential related, with
vitetrifolin D and vitexlactam C being the most promising [45]. In another study, the method of
supercritical carbon dioxide was used to detect the compounds dihydroselarene, α-terpinyl acetate,
trans-caryophyllene, sabinene, and 1,8-cineole [46]. Ono et al. applied HPLC coupled with NMR
analysis to determine the chemical constituents of V. agnus-castus L. fruits, reporting that
viteagnuside was the main compound present [47].
3. An Updated Snapshot of In Vitro and In Vivo Studies on Vitex agnus-castus
In-depth knowledge of the phytochemical composition of any potential medicinal plant is the
first step for the determination of its beneficial health properties. In the following, the main findings
Figure 2. Chemical structure of vitexin (a) and of agnuside (b).
Gokbulut et al. measured the levels of vitexin (Figure 2), isolated from V. agnus-castus L. fruit
and leaf extracts, using the RP-HPLC-DAD (diode array detector) technique, and the results showed
that this flavonoid was present in considerable amounts (0.342
±
0.0153% and 0.252
±
0.0089%,
respectively) [39].
Agnuside together with casticin (a tetramethoxyflavone) have been used as fingerprint markers to
evaluate the quality of Japanese commercial products containing V. agnus-castus L. [
40
]. Another marker
validated for quality assessment was reported by Yahagi et al., using a liquid chromatography–mass
spectrometry (LC-MS)-based metabolomic technique and nuclear magnetic resonance (NMR)
spectroscopy to detect 3-O-trans-feruloyl tormentic acid, which was isolated from the V. agnus-castus L.
fruit extract [
41
]. In another study, using a rapid ultra-high performance liquid chromatography diode
array detector (UHPLC-DAD-QTOF-MS), seven markers of V. agnus-castus L. fruit extract were claimed
to be used as reference compounds for quality validation of medicinal products containing this extract,
in particular, vitetrifolin D (labdane diterpenoid), 5-hydroxykaempferol-3,6,7,4’-tetramethylether,
casticin, isovitexin, and agnuside compounds [
42
]. A study conducted to compare the chemical markers
occurring in food supplements and in V. agnus-castus L. extracts, using the liquid chromatography
electrospray triple quadrupole tandem mass spectrometry (LC/ESI/(QqQ)MSMS) method in multiple
reaction monitoring (MRM) mode as a quantitative analysis, reported the presence of aucubin,
orientin, luteolin-7-O-glucoside, agnuside, isovitexin, homoorientin, and casticin compounds [
43
].
According to the findings from RP-HPLC-DAD analysis, V. agnus-castus L. leaf and fruit extracts
contained chlorogenic and caeic acid phenolic compounds with average concentrations of 0.27%
and 0.32% (w/w), respectively [
44
]. Li et al. isolated eighteen compounds from V. agnus-castus L. fruit
extract, using 1D/2D NMR and mass spectrometry methods, and their chemopreventive potential was
studied in Hepa 1c1c7 cells, which showed NADP(H): quinone oxidoreductase type 1 (QR1) induction
potential related, with vitetrifolin D and vitexlactam C being the most promising [
45
]. In another
study, the method of supercritical carbon dioxide was used to detect the compounds dihydroselarene,
α
-terpinyl acetate, trans-caryophyllene, sabinene, and 1,8-cineole [
46
]. Ono et al. applied HPLC
coupled with NMR analysis to determine the chemical constituents of V. agnus-castus L. fruits, reporting
that viteagnuside was the main compound present [47].
3. An Updated Snapshot of In Vitro and In Vivo Studies on Vitex agnus-castus
In-depth knowledge of the phytochemical composition of any potential medicinal plant is the
first step for the determination of its beneficial health properties. In the following, the main findings
Forests 2020,11, 761 5 of 16
regarding beneficial health eects from
in vitro
and
in vivo
studies are reported. This information
gives an updated picture of the many activities of the compounds contained in this plant, outlining its
possible prospective application in the prevention and even in the treatment of pathological conditions.
3.1. Health-Promoting Activities of Vitex agnus-castus L. In Vitro
The
in vitro
health-promoting potential of V. agnus-castus L. has been reported in the past [
48
].
Table 1summarizes the main results of
in vitro
studies. V. agnus-castus fruit extract showed
in vitro
anticancer activity against HL-60 cells by arresting the cell cycle at the G2/M phase and by inducing
apoptosis [
49
]. Abdel-Lateef et al. [
50
] analyzed the chemical composition of V. agnus-castus L.
leaf extract and found it to be composed of phenolic acids, flavonoids, and iridoids, which could
significantly prevent HepG2 cell proliferation by inducing apoptosis through caspase-3 activation,
with the butanolic fraction being the most active (IC
50
=13.42
±
0.17 mg/mL). The cytotoxic eect of
agnuside was assayed in a colon cancer cell line (COLO 320 DM), showing an IC
50
value of 15.99
µ
g/mL,
and 76.1% cytotoxic activity at 200
µ
g/mL [
51
]. Cytotoxic activity of V. agnus-castus L. fruit extract
against other another human colon carcinoma cell line (COLO 201) was shown, by inducing activation
of caspase 3/9 leading to apoptosis [
52
]. Ribat et al. [
53
] described antiproliferative and anticancer
properties of
V. agnus-castus L.
fruit methanol extract, showing that normal rat embryonic fibroblast
cells were much less sensitive than AMN3 cells (mouse mammary gland adenocarcinoma cell line),
with IC
50
values of 1324
µ
g/mL and 129
µ
g/mL, respectively. A synergistic eect was observed with
co-administration of 5-fluorouracil and 10
µ
g/mL vitex (ethanolic extract of V. agnus-castus L. fruits),
using colon cancer cell lines [
54
]. Casticin extracted from V. agnus castus L. showed cytotoxic and
immunomodulatory properties by inhibiting phytohemagglutinin (PHA) induced T-cell proliferation,
phagocytosis, and chemotaxis [
55
]. Sarac et al. reported 56.18% and 72.25% antimutagenic activities for
the ethanolic extracts of V. agnus castus L. seed and leaf at the doses of 2.5 mg/plate and 0.125 mg/plate,
respectively [56].
Table 1. In vitro reported activities for V. agnus-castus L.
Condition Plant Part Extract Activity Eect Reference
In vitro Fruits Ethyl acetate Antioxidant
activity
Lipid peroxidation was inhibited by
casticin with an IC
50
value of 0.049 mM.
[57]
In vitro Leaves Supercritical
CO2
Antifungal
activity
The antifungal potential of essential oil
with an MIC value of 0.64 µL/mL. [58]
In vitro Leaves
Hydrodistillation
Antifungal
activity
The antimutagenic activity of V.
agnus-castus leaf extract against
Salmonella typhimurium.
[56]
In vitro Aerial parts
Methanolic
extract (Cr.
MeOH Ext.)
Antimicrobial
activity
The V. agnus-castus leaf essential oil
showed an antibacterial eect against
Staphylococcus aureus with an MIC value
of 0.31% v/v.
[59]
In vitro Seed n-hexane Antifungal
activity
Essential oil was eective against
Candida species with an MIC50 value of
1.75 mg/mL.
[60]
In vitro
Ripened fruits and
fruitless aerial
parts
Ethanol Anticancer
activity
Cytotoxic eect of V. agnus-castus fruit
extract against MCF-7 cancer cells with
IC50 =88 µg/mL.
[61]
In vitro Fruits
Chloroform–
methanol
(250:1)
Anticancer
activity
The cytotoxicity was due to
dierentiation of the hematopoietic cell
line.
[62]
In vitro Fruits Ethanol Anticancer
activity
Enhanced apoptosis and decreased
intracellular ROS levels. [49]
In vitro Leaves Methanol Antioxidant
eect
The free radical scavenging eect of V.
agnus-castus methanol extract with an
IC50 value of 126.79 mg/mL.
[63]
Forests 2020,11, 761 6 of 16
The health of humans, animals, and the food chain is directly and indirectly influenced by
various pathogens. Thus, extensive studies have been conducted to control such microorganisms
using dierent approaches, among which the use of cost-eective and more eective natural plant
extracts or essential oil has attracted further attention; for example, V. agnus-castus L. has been
studied against several pathogenic species such as Staphylococcus aureus,Escheria coli,Bacillus subtilis,
and Pseudomonas aeruginosa. Habbab et al. [
64
] evaluated the antifungal activity of V. agnus-castus
flower and leaf essential oils against Aspergillus flavus and Penicillium escpansum, as well as the
antibacterial activity of V. agnus-castus L. seed and leaf essential oils against P. aeruginosa,E. coli,
and Klebsiella pneumonia.
Vitex agnus-castus L.
essential oil was shown to exhibit antibacterial activity
against Staphylococcus aureus [
65
].
Afarin et al.
[
66
] observed
in vitro
antimicrobial activity for
V. agnus-castus L.
essential oil at doses of 112.5 and 56.25
µ
g/mL against Candida albicans and S. aureus,
respectively. Katiraee et al. [
67
] found radical scavenging (IC
50
=27.16
µ
g/mL) and antifungal properties
for V. agnus-castus L. essential oil. Others reported that V. agnus-castus L. essential oil showed antifungal
potential against Sclerotinia sclerotiorum and Verticillium dahlia with LC
50
values of 3.322
µ
g/mL and
1.063
µ
g/mL, and 9.729
µ
g/mL and 7.313
µ
g/mL, respectively [
68
]. Stojkovi´c et al. [
69
] reported
antimicrobial potential for V. agnus-castus L. fruit and leaf essential oils attributed to the presence of
α
-pinene and 1,8-cineole. The administration of active ethyl acetate extract of V. agnus-castus L. leaf
exhibited antibacterial potential against methicillin-resistant S. aureus (MIC =0.312 mg/mL) owing to
steroids, terpenoids, and flavonoids [
70
]. Vitex agnus-castus L. leaf essential oil eliminated the cariogenic
bacteria Streptococcus mutans (MIC =15.6
µ
g/mL) [
71
]. In another study, alcoholic and aqueous extracts
had an antifungal eect on C. albicans isolated from clinical vaginal infections [
72
]. Vitex agnus-castus L.
seed essential oil showed antifungal activity against Candida species (
IC50 =1.072 mg/mL
) and also
antioxidant potential [73].
The anticancer activity of Vitex agnus-castus L. seed extracts against MCF-7 cells showed
DNA-damaging, cytotoxic, and apoptotic eects, and this extract also showed antioxidant
properties [
74
]. Rashed et al. [
75
] stated that the antioxidant eect of ethyl acetate extract of
V. agnus castus
could be attributed to flavonoids and tannins, as the main compounds. The antioxidant
eect of V. agnus-castus L. fruit and leaf extract was confirmed by the decolorization of the radical
monocation of 2,2
0
-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay [
76
].
Malta¸s et al.
described a H
2
O
2
scavenging eect for V. agnus-castus L. extract with antioxidant activity of
93.5 ±0.8%
[
77
]. In another study, using ethanolic extract of V. agnus-castus L. leaf, containing mainly
flavonoids and phenols as active ingredients, it was revealed that there was a direct correlation between
these compounds and antioxidant properties [
78
]. Ahmad et al. [
79
] reported that vitexcarpan, isolated
from the aerial parts of V. agnus-castus L. by extraction using ethyl acetate, showed anti-inflammatory
activity in activated human neutrophils. The presence of casticin in V. agnus-castus L. extract exhibited
anti-inflammatory potential with an ecacy of 69.51% and an IC50 value of 302.1 µg/mL [80].
Vitex agnus-castus L. fruit extract showed antiangiogenic activity due to the presence of
antiangiogenic compounds, confirmed by phytochemical analysis [81].
3.2. Health-Promoting Activities of Vitex agnus-castus L. in Animals
There are numerous therapeutic eects of V. agnus-castus L. described in animal models. Table 2
reports the results of the main animal model studies. Oral administration of V. agnus-castus L. extract
(200 mg/kg) in Sprague–Dawley rats with a mammary tumor for 15 days improved the oxidative status
of the mammary tumor tissue and treated tumor regression properties [82].
Forests 2020,11, 761 7 of 16
Table 2. Animal model reported activities for V. agnus-castus L.
Condition Plant Part Extract Activity Eect Reference
Animal model Leaves
Hydrodistillation
Antinociceptive
activity and
analgesic eect
The analgesic activity was
due to the activation of
muscarinic receptors of the
cholinergic system and
endogenous opioidergic
system.
[83]
Animal model Stems and
leaves Ethanol
Treatment of
polycystic ovary
syndrome
V. agnus-castus exhibited
hypoglycemic, antioxidant,
and antihyperlipidemic
activities in rats.
[84]
Animal model Fruits
Chloroform,
methanol, and
water
Antihyperlipidemic
activity
The V. agnus-castus extract
(500 mg/kg for 28 days)
decreased the levels of
VLDL, LDL, TG, and TC.
[85]
Animal model Fruits
Hexane, ethyl
ether, and
n-butanol
Protected against
nonalcoholic fat
liver disease
Prevented oxidative stress
and treated nonalcoholic fat
liver disease.
[86]
Animal model Berries Ethanol Anti-inflammatory
activity
Inhibited the production of
reactive oxygen species, the
release of cytokines, and the
formation of leukotriene.
[87]
Animal model Leaves Chloroform Antiangiogenic
activity
Prevented growth of
psoriasis, cataract, and
tumor.
[88]
Animal model Fruits Ethanol Antiaging eects
Improved
d-galactose-induced aging
symptoms, including
enhanced serum LH and
FSH levels, follicle
degeneration, and
endometrial atrophy.
[89]
Animal model Fruits Methanol Antiepileptic
activity
Reduced stage 5 duration
and after-discharge
duration.
[90]
Animal model Fruits Ethanol Osteoprotective
eects
Enhanced biomechanical
stability of bone via
connectivity density in the
orchidectomized rats and
improved the trabecular
microarchitecture.
[91]
Animal model Leaves Methanol Anti-inflammatory
eect
The V. agnus-castus methanol
extract (400 mg/kg) reduced
IL-6 and TNF-αlevels.
[92]
Animal model -
Methanol,
n-hexane, and
Ethyl acetate
Antioxidant and
antiapoptotic
eects
Vitexilactone extracted from
V. agnus-castus reduced
caspase-3 and apoptosis
marker expression in
Sprague–Dawley rats.
[93]
The administration of casticin extracted from V. agnus-castus L. fructus (1, 2, and 10 mg/Kg per day)
for two weeks protected inflammatory lung diseases in a mouse model due to an anti-inflammatory eect
by decreasing epithelium thickness, perivascular inflammatory cells, and peribronchial infiltration,
as well as reduced the numbers of total cells, lymphocytes, macrophages, and neutrophils [
94
].
The administration of V. agnus-castus L. fruit extract (165 mg/Kg/day) in rats controlled prostate
cancer by inducing apoptosis and showed an anti-inflammatory eect by inhibiting cyclooxygenase-2
activity [95]. Webster et al. reported that V. agnus-castus attenuates pre-menstrual syndrome [96].
Forests 2020,11, 761 8 of 16
Vitex agnus-castus administered for five days protected mice against lipopolysaccharide
(LPS)-induced acute lung damage, due to an antioxidant eect [
97
]. The methanol extract of
V. agnus-castus leaf showed an antiangiogenic eect in an ex vivo rat aorta, and also antioxidant
activity with an IC50 value of 126.79 µg/mL [88].
Moreover, administration of V. agnus castus ethanolic extract (8 and 80 mg/Kg/day) for three
months in ovariectomized rats improved memory and learning via decreasing uterine weight and
increasing the estrogen receptor ER
α
gene expression, respectively, suggesting a solution for memory
loss in postmenopausal women [
98
]. The hydroalcoholic extract of V. agnus-castus fruits (600 mg/Kg
twice a day) reduced age-related changes in a female mice model after 7 days [99].
V. agnus-castus extract was administered to a mouse model of permanent middle cerebral artery
occlusion for 30 days, and it was observed that the anti-inflammatory and estrogenic activities reduced
stroke injuries. Moreover, this study also reported neuroprotective activity by reducing matrix
metalloproteinase-9 (MMP-9), increasing interleukin 10, and improving adhesive removal and wire
hanging test performance [100].
3.3. Health-Promoting Activities of Vitex agnus-castus L. in Humans, with Particular Regard to Clinical Trials
Many clinical trials confirm the health-promoting eects of V. agnus-castus L. [
101
108
]. Table 3
reports the results of the main clinical trial studies. Naseri et al. [
109
] reported a reduction in menopausal
symptoms after taking V. agnus-castus L. extracts. The authors allocated the participants into two placebo
groups and a Vitex-treated group, and then assessed menopausal symptoms before and after an 8-week
intervention using the Greene Questionnaire [
110
]. After the intervention, the Vitex group showed
a reduction in vasomotor dysfunction, anxiety, and total menopausal disorder.
Yavarikia et al.
[
111
]
administered V. agnus-castus L. capsules to female participants three times a day for four months,
and obtained data with the Higham five-stage chart (for 1 month before the treatment and 4 months
during the treatment) [
112
] and a demographic questionnaire. They found a 47.6% decrease in bleeding
in the V. agnus-castus L. group. Oral administration of ethanolic extract of V. agnus-castus L. (4.0 mg),
dried as film-coated tablets, in Chinese women with premenstrual syndrome (PMS) reduced the
PMS score of the third cycle from 27.10 to 14.59 in the case group [
113
]. Daily administration of
V. agnus-castus L.
extract-containing tablets in Chinese women with premenstrual syndrome (PMS)
decreased the PMS scores of symptoms such as pain, food cravings, and water retention [
114
].
A self-assessment questionnaire was completed for the symptoms of PMS in women after taking
40 drops of V. agnus-castus L. extract for 6 days, the results of which showed mild to moderate relief in
PMS symptoms [
115
]. In a recent clinical trial, it was reported that the administration of
V. agnus-castus L.
in women with polycystic ovary syndrome reduced the level of dehy-droepiandrosterone sulfate
(DHEA-S) and normalized the menstrual cycle [
116
]. Healthy menopausal women co-administrated
V. agnus-castus L. and Nigella sativa with citalopram once a day for 8 weeks showed superior scores
in three of the Menopause-specific Quality of Life Questionnaire (MENQOL) domains: psychosocial
(p=0.001), physical (p=0.036), and vasomotor (p<0.001) [117].
Forests 2020,11, 761 9 of 16
Table 3. Clinical trials reporting V. agnus-castus L. activities.
Condition Activity Administration Eect Reference
Clinical trial
Treatment of
vasomotor
symptoms.
The administration of V.
agnus-castus (40 mg) once a
day for a month in women
with postmenopausal
symptoms.
Improvement of
sleep satisfaction. [118]
Clinical trial Treatment of
mastalgia.
The administration of V.
agnus-castus in patients with
mastalgia.
Reduction in
prolactin level after
three months.
[119]
Clinical trial
Treatment of
premenstrual
syndrome.
Administration of V.
agnus-castus extract (20 mg)
once a day for three
menstrual cycles in Japanese
women.
The symptoms of
premenstrual
syndrome were
improved.
[120]
Clinical trial
Treatment of
premenstrual
syndrome.
The administration of V.
agnus-castus (40 mg) once a
day for three months in
migrainous women with
premenstrual syndrome.
The symptoms of
premenstrual
syndrome were
reduced in 66
women.
[121]
Clinical trial
Treatment of
premenstrual
syndrome.
The administration of V.
agnus-castus extract Ze 440
(20 mg) once a day.
The symptoms of
premenstrual
syndrome were
relieved in women.
[122]
Clinical trial
Treatment of
menopausal
syndrome.
The administration of V.
agnus-castus extract (40
drops) once a day for 8
weeks in women.
Hot flashes were
positively
influenced by Vitex
in women.
[123]
Clinical trial
Treatment of
premenstrual
syndrome.
The co-administration of V.
agnus-castus with Hypericum
perforatum twice a day for 16
weeks in women with
premenstrual syndrome.
Symptoms such as
hydration clusters
and anxiety were
alleviated.
[124]
Clinical trial
Treatment of
premenstrual
syndrome.
The administration of V.
agnus-castus extract (40
drops) for 4 months.
The pregnancy rate,
endometrial
thickness,
ovulation, and
fertility were
increased in
women.
[125]
Clinical trial
Prolactin-inhibiting
activity.
The daily administration of
Agnus-castus extract
(BP1O95E1) at a
concentration of 480 mg for
two weeks in healthy male
subjects.
Decreased
prolactin profile
levels.
[126]
Vitex agnus-castus L. extracts have reportedly exhibited many health-promoting eects, but some
limitations have been shown for human health such as agitation, headache, nausea, tachycardia,
fatigue, dry mouth, urticaria, and gastrointestinal problems [
78
]. In a study by Owolabi et al. [
127
],
it was also reported that increasing the dose and long-term administration of the Vitex genus induced
toxicity in rats.
Forests 2020,11, 761 10 of 16
4. Conclusions
Considering the naturally occurring bioactive compounds with therapeutic potential that it
contains, V. agnus-castus L. is one of the best-selling and most widely used medicinal herbs worldwide.
Nevertheless, there is a need for further
in vivo
and
in vitro
research and more clinical trials to assess
the beneficial health compounds content of this plant and the related mechanisms of action in the
treatment of various diseases, as it is so far been largely limited to animal model trials and
in vitro
studies. The clinical trial studies in humans focus on a limited number of health conditions, suggesting
the need to exploit what is observed in animal trials and possible in prospective assess also possible
applications in humans. The beneficial properties of V. agnus-castus L. trigger interest in the possibility
of developing novel nutraceutical formulations, which can help to support health conditions before the
need of a pharmacological therapy, in particular for individuals who do not qualify for a conventional
drug-based treatment. It should be noted also that there is a need for more comprehensive clinical
trials over a long timeframe in order to draw definitive conclusions about the findings related to the
various eects and consequences of a long-term consumption of V. agnus-castus L.
Author Contributions:
E.B.S., A.D., A.N., M.L., E.N., and A.S. conceived and designed the work. E.B.S., A.D.,
A.N., M.L., M.Z., A.M.S., P.S., E.N., and A.S. wrote the work. A.D., A.N., M.L., M.Z., S.B.S., A.M.S., and P.S.
validated and elaborated data information and figures. All authors have read and agreed to the published version
of the manuscript.
Funding:
The authors acknowledge the support of the research project: Nutraceutica come supporto
nutrizionale nel paziente oncologico, CUP: B83D18000140007. E.B.S. acknowledges the sponsorship of
the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020 (strategic fund); A.M.S. acknowledges
UIDB/04033/2020 (CITAB), receiving support from the Portuguese Science and Technology Foundation, Ministry
of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER under the Partnership
Agreement PT2020.
Conflicts of Interest: The authors declare no conflict of interest.
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2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
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(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
... A despeito da nossa aclamada biodiversidade vegetal e disseminado uso tradicional de plantas com finalidades medicinais, ainda são bastante modestas as iniciativas no país para traduzir a riqueza material e imaterial em benefícios para a população. Lembrei 2 Choudhary et al. 5 demonstraram que o extrato dos frutos apresentou atividade inibidora da enzima lipoxigenase em um estudo in vitro. Embora seja utilizado para problemas ginecológicos, existem resultados contraditórios em relação à ligação dos princípios ativos contidos no extrato ao receptor de estrogênio e a ligação preferencial a receptores β ou α. ...
... Existem apenas dados pré-clínicos limitados para o uso do fruto ou suas preparações medicinais. Um artigo de revisão recente foi publicado por Souto et al. 5 sobre os estudos in vitro e in vivo usando extratos de V. agnus-castus. A utilização de fitoterápicos pela população tem sido cada vez maior nos últimos anos. ...
... anisatum) 4 . Casos frequentes de fraudes com danos econômicos também são identificados em fiscalizações, como os azeites adulterados e as impurezas acima dos limites em alguns cafés 5 . Segundo a Organização Pan-Americana da Saúde, quase um a cada dez indivíduos no mundo adoecem após a ingestão de alimentos contaminados, com 420 mil mortes a cada ano. ...
... No safety concerns are reported for the usage of VAC fruits or its extracts (EMA, 2017), with LD50 (Median Lethal Dose) of 1.65 g/kg for Vitex agnus castus L. extract (VACE) (Ibrahim et al., 2017). Promising nutraceutical and health-promoting potentials of Vitex agnus castus were previously reported (Souto et al., 2020). For instance, the broad antioxidative and anti-inflammatory effects of Vitex agnus castus L. have been confirmed by several studies (Hajdú et al., 2007;Röhrl et al., 2016;Sarikurkcu et al., 2009). ...
... These effects could contribute to its pharmacological actions of relieving premenstrual syndrome, uterine contraction and bleeding, and breast pain (Verkaik et al., 2017). Moreover, antimutagenic, antifungal, antimicrobial, and immunomodulatory effects of VAC were previously reported (Röhrl et al., 2016;Souto et al., 2020). The relevance of VAC in mining for natural anti-inflammatory agents has increased due to its abundant flavonoids such as vitexin and casticin. ...
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Vitex agnus castus L. extract (VACE) was investigated for its gastroprotective properties and possible molecular mechanisms in rats. VACE (60 or 120 mg/kg) or Esomeprazole (20 mg/kg) were orally administered for 3 weeks before the induction of gastropathy using indomethacin (30 mg/kg, single oral dose). VACE ameliorated the indomethacin-induced gastric juice acidity and pathological changes. VACE significantly preserved GSH, SOD, NO and PGE2 contents, while decreased lipid-peroxide, TNF-α and MPO contents. Moreover, VACE downregulated NF-κB1, COX-2, Caspase-3 and upregulated Bcl-2 and HSP-70 expression. Ultra-high-performance liquid chromatography (UPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (qTOF-MS) enabled the tentative identification of 87 compounds allocated in seven main classes including flavonoids, glycosylated iridoid and labdane diterpenes. Notably, different agnuside derivatives and diterpenoids were reported in VACE for the first time. In conclusion, VACE contains an arsenal of bioactive metabolites which may exhibit gastroprotection by inhibiting inflammation, oxidative stress, and apoptosis.
... V. agnus-castus L., commonly known as chaste tree or chaste berry, is an herbal plant often used for various medicinal purposes. In pharmacology, V. agnus-castus L. was reported to have antibacterial, anti-inflammatory, anti-fungal, anti-microbial, antioxidant, and anticancer effects [152]. Four patents for the Vitex genus were recorded, most of which employ the V. agnus-castus L. species. ...
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The genus Vitex is also known as a chaste tree, in which it is a large shrub native to the tropical and subtropical regions of the world. A diverse range of species is distributed throughout Southern Europe, the Mediterranean, and Central Asia. The Vitex tree, including its leaves and fruits, has been used for herbal remedies in the form of pastes, decoctions, and dried fruits since ancient times. This article aimed to prepare a comprehensive review of traditional uses and secondary metabolites derived from Vitex sp., including the chemical compounds, biological activities, application of Vitex in human clinical trials, toxicology and safety, marketed products, and patents. The scientific findings were obtained using a number of search engines and databases, including Google Scholar, PMC, and ScienceDirect. Vitex species are well known in pharmacology to have medicinal values, such as anti-inflammatory, antibacterial, antifungal, antimicrobial, antioxidant, and anticancer properties. Previous studies reported that some species are proven to be effective in treating diseases, such as diabetes, and improving female health. A total of 161 compounds from different Vitex species are reported, covering the literature from 1982 to 2022. A chemical analysis report of various studies identified that Vitex exhibited a wide range of phytoconstituents, such as iridoid, diterpenoid, ecdysteroid, and flavonoid and phenolic compounds. Apart from that, the review will also discuss the application of Vitex in human clinical trials, toxicology and safety, marketed products, and patents of the genus. While the extracts of the genus have been made into many commercial products, including supplements and essential oils, most of them are made to be used by women to improve menstrual conditions and relieve premenstrual syndrome. Among the species, Vitex agnus-castus L. is the only one that has been reported to undergo clinical trials, mainly related to the use of the genus for the treatment of mastalgia, menstrual bleeding problems, amenorrhea, menorrhagia, luteal insufficiency, and premenstrual syndrome. Overall, the review addresses recent therapeutic breakthroughs and identifies research gaps that should be explored for prospective research work.
... Its trunk is covered with short, dense, soft and grey hairs. It is a deciduous shrub native to Europe and Central Asia (Stojković et al. 2011;Hürkul and Köroğlu 2018;Souto et al. 2020;Ilhan 2021). This plant is naturally found in many cities throughout Turkey, including Amasya, Antalya, Bursa, Muğla, Trabzon and Çanakkale (Yilar et al. 2016). ...
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In this study, genetic diversity and phylogenetic analysis of some Vitex agnus-castus L. populations were conducted based on ISSR-PCR and chloroplast DNA trnL intron, and trnL-F sequence analyses. Vitex agnus-castus populations were detected in Aydın province, Turkey. Fresh leaf samples from the populations were collected and brought to the laboratory for genomic DNA isolation. 15 ISSR primers were used to determine the genetic diversity ofe Vitex agnus-castus populations. A total of 138 bands were obtained in ISSR analysis, 85 of which were polymorphic and 53 were monomorphic. Polymorphism rate was determined as 61.59 %. trnC, trnD, trnE, and trnF primers were used for PCR amplification of the chloroplast trnL intron and trnL-F region. A total of 138 bands were obtained by ISSR analysis. For trnL intron analyses, nucleotide lengths of 13 populations were between 508 and 516. The average nucleotide composition consisted of 38.5 % T, 18.3 % C, 27.5 % A and 15.7 % G. In trnL-F assays, the nucleotide lengths of the 13 populations ranged from 330 to 353. The average nucleotide composition consisted of 29.4 % T, 18.1 % C, 32.9 % A and 19.6 % G. The results of the phylogenetic trees constructed using some trnL intron and trnL-F sequences of Vitex doniana, Vitex trifolia, Vitex triflora, Vitex turczaninowii, Vitex queenslandica, Vitex axillariflora, Vitex rotundifolia and Vitex negundo species obtained from NCBI were compared. As a result of the study, polymorphisms were obtained at a rate of 61.59% from the ISSR analysis. In addition, the phylogenetic relationship between chloroplast trnL intron and trnL-F sequences of Vitex agnus-castus populations along with the other species was revealed.
... BNO 1095, a Standardized Dry Extract from the Fruits of Vitex agnus-castus, Impairs Angiogenesis-related Endothelial Cell Functions In Vitro fungal impact [5]. According to the HMPC, a hydroethanolic dry extract (ethanol 60 %, drug-extract ratio 6-12 : 1) from the fruits of V. agnus-castus can be applied for the treatment of premenstrual syndrome as well-established use herbal medicinal product. ...
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BNO 1095, a standardized dry extract from the fruits of Vitex agnus-castus, represents an approved herbal medicinal product for the treatment of premenstrual syndrome. Angiogenesis, the formation of new blood vessels from pre-existing capillaries, plays a major role in physiological situations, such as wound healing or tissue growth in female reproductive organs, but it is also of great importance in pathophysiological conditions such as chronic inflammatory diseases or cancer. Angiogenesis is a highly regulated multi-step process consisting of distinct key events that can be influenced pharmacologically. Few studies suggested anti-angiogenic actions of V. agnus-castus fruit extracts in in vivo and ex vivo models. Here, we provide for the first time profound in vitro data on BNO 1095-derived anti-angiogenic effects focusing on distinct angiogenesis-related endothelial cell functions that are inevitable for the process of new blood vessel formation. We found that V. agnus-castus extract significantly attenuated undirected and chemotactic migration of primary human endothelial cells. Moreover, the extract efficiently inhibited endothelial cell proliferation and reduced the formation of tube-like structures on Matrigel. Of note, the treatment of endothelial cell spheroids almost blocked endothelial sprouting in a 3D collagen gel. Our data present new and detailed insights into the anti-angiogenic actions of BNO 1095 and, therefore, suggest a novel scope of potential therapeutic applications of the extract for which these anti-angiogenic properties are required.
... The discussion of the role of forest foods rich in compounds with nutrients and biologically active compounds to complement people's diet and the contribution of forest foods to a healthy diet has been exploited, adding information to the area of interest. The beneficial potential of medicinal plants and herbs has been investigated in different papers [9][10][11][12]. Functionally, extracts and biologically active components [13][14][15][16][17][18] from forest products are experiencing great interest for both research and potential application in nutraceutical, pharmaceutical, and cosmetic fields [19,20]. ...
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Forest ecosystems are an important biodiversity environment resource for many species. Forests and trees play a key role in food production and have relevant impact also on nutrition. Plants and animals in the forests make available nutrient-rich food sources, and can give an important contributions to dietary diversity, quality, and quantity. In this context, the Special Issue, entitled “Forest, Food and Nutrition”, is focused on the understanding of the intersection and linking existing between forests, food, and nutrition.
Article
The potential use of a lignocellulosic fi ller, Vitex agnus-castus plant (Chaste tree), which is a deciduous invasive shrub, in thermoplastic composites was investigated. The stems of chaste trees with a diameter of 5-10 cm from Mugla city, Western Turkey, were used for the study. The different amounts (0 to 50 wt%, by 10 % increments) of the wood fl our passing through the screen openings of 0.237 mm were added to the polypropylene matrix. Pre-mixed raw materials were put into the volumetric feeder of the twin-screw extruder. The extruder barrel temperature was gradually increased from 170 °C (feeding zone) to the die zone (190 °C) at a constant screw speed (40 rpm). Then, the dried granules were hotpressed into the 4 mm thick WPC panels at 2 MPa and 190 °C for 15 min. 3 wt% of maleic anhydride grafted polypropylene (MAPP) was added as compatibilizer into the formulation. The WPCs showed an increase in the thickness swelling (0.58 to 5.68 %) as the amount of the fi ller increased from 10 to 50 wt% in the polypropylene. The bending strength of the polypropylene composites increased from 33.9 to 44.8 MPa as the amount of the chaste wood fl our was increased to 30 wt%, but further increase caused the decrease in the tensile strength (25.7 MPa). As for the bending modulus, it increased from 815 to 3250 MPa when the wood content reached 50 wt%. The tensile modulus increased from 1690 to 2253 MPa when the wood content arised from 10 to 50 wt%. The tensile strength, tensile modulus, fl exural strength and fl exural modulus of the un-fi lled polypropylene were found to be 19.6 MPa, 1505 MPa, 30.2 MPa and 664 MPa, respectively. According to the test results, it was concluded that the 30-40 wt% of Vitex agnus-castus wood could be effi ciently used in the polypropylene composites for the semi-building applications such as decking or siding. The evaluation of underused invasive chaste wood in the production of tWPC production may result in an effective way to utilize this resource. SAŽETAK • U radu je istražena potencijalna primjena lignoceluloznog punila u termoplastičnim kompozitima od biljke Vitex agnus-castus (konopljike), koja je listopadni invazivni grm. Stabljike konopljike promjera 5-10 cm nabavljene su iz grada Mugla, iz zapadne Turske. U polipropilensku matricu dodane su različite količine drvnog brašna (0-50 wt. %, uz povećanje od 10 %) koje je prolazilo kroz sito otvora 0,237 mm. Prethodno pomiješane 1 Authors are professor and forest industrial engineer at This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Ayrilmis, Yildiz: Physical and Mechanical Properties of Thermoplastic Composites Filled with Wood Flour of Underutilized... 496 73 (4) 495-501 (2022) sirovine stavljene su u lijevak dvovijčanog ekstrudera. Temperatura spremnika ekstrudera postupno je povećava-na od 170 °C (zona uvlačenja) do 190 °C (zona istiskivanja), uz konstantnu brzinu vijka (40 okr./min). Zatim su osušene pelete 15 min vruće prešane pri 2 MPa i 190 °C u oblik WPC ploče debljine 4 mm. Kao kompatibilizator formulaciji je dodan MAPP (3 wt. %). Kako se količina punila u polipropilenu povećavala s 10 na 50 wt. %, kom-poziti su pokazivali povećanje debljinskog bubrenja (od 0,58 do 5,68 %). S povećanjem količine čistoga drvnog brašna na 30 wt. %, čvrstoća na savijanje polipropilenskih kompozita povećala se s 33,9 na 44,8 MPa, ali daljnje je povećanje dovelo do smanjenja vlačne čvrstoće (25,7 MPa). Kada je udio drva dosegnuo 50 wt. %, modul savi-janja povećao se s 815 na 3250 MPa. Pri povećanju udjela drva s 10 na 50 wt%, modul elastičnosti pri vlačnom se naprezanju povećao s 1690 na 2253 MPa. Utvrđeno je da su vlačna čvrstoća, modul elastičnosti pri vlačnom naprezanju, čvrstoća na savijanje i modul na savijanje polipropilena bez punila redom 19,6 MPa, 1505 MPa, 30,2 MPa i 664 MPa. Prema rezultatima ispitivanja, zaključeno je da se 30-40 wt. % drva konopljike može učinkovito iskoristiti u polipropilenskim kompozitima za primjenu u graditeljstvu kao što su podne ili zidne obloge. Istraživa-nje slabo iskorištene konopljike u proizvodnji WPC-a može rezultirati učinkovitim načinom upotrebe te sirovine.
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The potential use of a lignocellulosic filler, Vitex agnus-castus plant (Chaste tree), which is a deciduous invasive shrub, in thermoplastic composites was investigated. The stems of chaste trees with a diameter of 5-10 cm from Mugla city, Western Turkey, were used for the study. The different amounts (0 to 50 wt%, by 10 % increments) of the wood flour passing through the screen openings of 0.237 mm were added to the polypropylene matrix. Premixed raw materials were put into the volumetric feeder of the twin-screw extruder. The extruder barrel temperature was gradually increased from 170 °C (feeding zone) to the die zone (190 °C) at a constant screw speed (40 rpm). Then, the dried granules were hot-pressed into the 4 mm thick WPC panels at 2 MPa and 190 °C for 5 min. 3 wt% of maleic anhydride grafted polypropylene (MAPP) was added as compatibilizer into the formulation. The WPCs showed an increase in the thickness swelling (0.58 to 5.68 %) as the amount of the filler increased from 10 to 50 wt% in the polypropylene. The bending strength of the polypropylene composites increased from 33.9 to 44.8 MPa as the amount of the chaste wood flour was increased to 30 wt%, but further increase caused the decrease in the tensile strength (25.7 MPa). As for the bending modulus, it increased from 815 to 3250 MPa when the wood content reached 50 wt%. The tensile modulus increased from 1690 to 2253 MPa when the wood content arised from 10 to 50 wt%. The tensile strength, tensile modulus, flexural strength and flexural modulus of the unfilled polypropylene were found to be 19.6 MPa, 1505 MPa, 30.2 MPa and 664 MPa, respectively. According to the test results, it was concluded that the 30-40 wt% of Vitex agnus-castus wood could be efficiently used in the polypropylene composites for the semi-building applications such as decking or siding. The evaluation of underused invasive chaste wood in the production of tWPC production may result in an effective way to utilize this resource.
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This datasheet on Vitex agnus-castus covers Identity, Overview, Distribution, Dispersal, Biology & Ecology, Environmental Requirements, Natural Enemies, Impacts, Uses, Prevention/Control, Further Information.
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Vitex agnus-castus is a small tree or shrub, belonging to the family Verbenaceae. It is a deciduous shrub native to European, Mediterranean, and Central Asian countries. V. agnus castus has a long tradition as a herbal remedy and was used in ancient times not only as an anaphrodisiac but also against diverse disturbances of the female genital system. The major constituents in V. agnus-castus are flavonoids, essential oils, diterpenes, and glycosides. The flavonoids (casticin, quercetagetin, and isovitexin) have been shown in vitro to affect estrogen receptors. V. agnus-castus could be used to treat acne, digestive complaints, menstrual irregularities, premenstrual syndrome (PMS), mastalgia, and infertility, and also for lactation support. Although V. agnus-castus has been used for centuries and enjoys wide support from practitioners and the general public for many gynecological complaints, few clinical studies support its documented uses. The presence of phytochemical and pharmacological activities has proved that the plant has a leading capacity for the development of new good efficacy drug in future.
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Cisplatin (CP) is an antineoplastic drug; however, owing to its nephrotoxicity, its clinical use is limited. We investigated whether vitexilactone (vitex) is a safe and effective treatment for CP induced kidney injury. We allocated Sprague-Dawley rats into six groups: control group, low dose-high dose vitex groups (40 and 80 mg/kg vitex for 6 days before administration of CP), CP group (single 6 mg/kg dose on day 6) and CP + low dose vitex-CP + high dose vitex group (40 and 80 mg/kg vitex for 6 days, and a single 6 mg/kg dose of CP on day 6. Rats were euthanized 5 days after CP treatment. After exposure to CP and/or vitex, total oxidative stress and total antioxidant status were assessed. The histology of the kidney was examined using hematoxylin and eosin, and periodic acid-Schiff. We used immunohistochemical and fluorescence staining to detect expression of caspase-3. We also measured blood urea nitrogen, uric acid and creatinine levels. Nephroprotective effects of vitex were associated with decreased serum toxicity markers and increased antioxidant activity. Vitex also reduced the expression of the apoptosis marker, caspase-3. Treatment with CP increased blood urea nitrogen, uric acid, creatinine levels and total antioxidant status, and decreased total antioxidant status compared to the control group. Use of vitex for protection from CP induced nephrotoxicity appears to be a safe and efficacious alternative for treatment of kidney injury.
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The sector of food supplements is certainly varied and growing: an ever wider offer of new products is launched on the market every year. This is reflected in new reorganization of drug companies and new marketing strategies, in the adoption of new production technologies with resulting changes in dietary supplements regulation. In this context, information on composition reported in labels of selected dietary supplements was collected and updated for the development of a Dietary Supplement Label Database according to products’ availability on the Italian market and also including items consumed in the last Italian Dietary Survey. For each item, a code was assigned following the food classification and description system FoodEx2, revision 2. A total of 558 products have been entered into the database at present, trying to give a uniform image and representation of the major classes of food supplements, and 82 descriptors have been compiled. Various suggestions on how the number of FoodEx2 system descriptors could be expanded were noted during the compilation of the database and the coding procedure, which are presented in this article. Limits encountered in compiling the database are represented by the changes in the formulation of products on the market and therefore by the need for a constant database update. The database here presented can be a useful tool in clinical trials, dietary plans, and pharmacological programs.
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The primary product of the oenological sector is wine. Nonetheless, the grape processing produces large amounts of by-products and wastes, e.g., the grape seeds. In the context of a sustainable production, there is a strong push towards reutilizing these by-products and waste for making useful derivatives since they are rich of bioactive substances with high additional value. As it is true for the wine itself, bringing these by-products derivatives to the market calls for quality measures and analytical tools to assess quality itself. One of the main objectives is to collect analytical data regarding bioactive compounds using potentially green techniques. In the present work, the profile of fatty acids and the main phenolic compounds were investigated by conventional methods. The qualitative analysis of the main functional groups was carried out by Fourier Transform Infrared (FTIR) spectroscopy. Moreover, the successful use of FTIR technique in combination with chemometric data analysis is shown to be a suitable analytical tool for discriminating the grape seeds. Grape seeds of different origin have different content of bioactive substances, making this technique useful when planning to recover a certain substance with specific potential application in health area as food supplement or nutraceutical. For example, Cesanese d’Affile seeds were found to have a rather high fat content with a significant fraction of unsaturated fatty acids. On the other hand, the seeds of Nero d’Avola exhibit the highest amount of phenolic compounds.
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Objectives: Previous studies have indicated that phytoestrogens induce estrogenic as well as anti-inflammatory effects, and they are found in high abundance in the extracts of some herbs such as Vitex Agnus Castus (VAC). Therefore, we investigated the effect of VAC extract on ovariectomized mice after the induction of permanent middle cerebral artery occlusion (PMCAO) model. Materials and methods: In this study, 50 mice ranging from 25 to 35 g were divided into five experimental groups as follows: Control, VAC, Estrogen, Tamoxifen, and Tamoxifen-VAC. Animals were ovariectomized, and after 30 days of treatment, they were given PMCAO induction. Behavioral assessment (adhesive removal and wire hanging tests) was evaluated 24 hr, 48 hr, and one week after induction of stroke. The infarct volume, as well as serum levels of matrix metalloproteinase-9 (MMP-9) and interleukin-10 (IL-10), were measured one week after stroke. Results: One week after stroke, in both VAC and estrogen groups, the infarct size reduced in comparison with the control group. Estrogen and VAC extract improved adhesive removal and wire hanging test, increased the level of IL-10, and decreased the level of MMP-9 compared with the control group. In addition, co-administration of tamoxifen and VCA extract had no significant effect on measured indices compared with control and tamoxifen groups. Conclusion: Based on our findings, VAC extract has neuroprotective properties and can reduce stroke injuries in PMCAO-induced ovariectomized mice via anti-inflammatory and estrogenic properties.
Article
The chemical profile, cytotoxic and apoptotic effect, and antioxidant activity were determined of ethanolic extracts of Vitex agnus-castus L. (chaste tree). Ripened fruits and fruitless aerial parts were extracted with ethanol, and the chemical characterization of the extracts was determined by LC/ESI-MS-MS. Twelve compounds were tentatively identified in the extracts. The dose-dependent cytotoxic effects of the extracts were tested on C6, A549 and MCF-7 cells by using MTT assay; inhibition of DNA synthesis, and apoptotic and caspase-3 activation effects of the extracts were determined. The potential antioxidant activities of the extracts were evaluated by in vitro methods such as DPPH and ABTS scavenging activity, reducing power and β-carotene bleaching assays. The fruit extract showed noticeable cytotoxic activity against MCF-7 cells with an IC50 value of 88 μg/mL. Both extracts showed similar DPPH scavenging activity comparably with that of the standard.
Chapter
The plants have been used for thousands of years for therapeutic purposes. Hippocrates in the fifth century BC, already related the mood with food and plants [1]. The use of medicinal herbs flourished in Europe in the seventeenth century and the emigration of European people to America, moved to this continent the habit of using medicinal herbs [2]. In 1920 pharmacy drugs replaced herbal therapies in the USA, because the former had more lasting pharmacological effects and greater profitability.
Book
Plants have been a source of medicines and have played crucial role for human health. Despite tremendous advances in the field of synthetic drugs and antibiotics, plants continue to play a vital role in modern as well as traditional medicine across the globe. In even today, one-third of the world’s population depends on traditional medicine because of its safety features and ability to effectively cure diseases. This book presents a comprehensive guide to medicinal plants, their utility, diversity and conversation, as well as biotechnology. It is divided into four main sections, covering all aspects of research in medicinal plants: biodiversity and conservation; ethnobotany and ethnomedicine; bioactive compounds from plants and microbes; and biotechnology. All sections cover the latest advances. The book offers a valuable asset for researchers and graduate students of biotechnology, botany, microbiology and the pharmaceutical sciences. It is an equally important resource for doctors (especially those engaged in Ayurveda and allopathy); the pharmaceutical industry (for drug design and synthesis); and the agricultural sciences.