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Uncaria tomentosa (Willd. ex Schult.) DC. (Family: Rubiaceae), commonly known as cat’s claw, is a tropical medicinal vine originating at the Amazon rainforest and other areas of South and Central America. It has been traditionally used to treat asthma, abscesses, fever, urinary tract infections, viral infections, and wounds and found to be effective as an immune system rejuvenator, antioxidant, antimicrobial, and anti-inflammatory agent. U. tomentosa is rich in many phytoconstituents such as oxindole and indole alkaloids, glycosides, organic acids, proanthocyanidins, sterols, and triterpenes. Biological activities of U. tomentosa have been examined against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium, Babesia and Theileria parasites. Several formulations of cat’s claw (e.g., tinctures, decoctions, capsules, extracts, and teas) are recently available in the market. The current review covers the chemical constituents, biological activities, pharmacokinetics, and toxic properties of U. tomentosa extracts.
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applied
sciences
Review
Uncaria tomentosa (Willd. ex Schult.) DC.: A Review
on Chemical Constituents and Biological Activities
Gaber El-Saber Batiha 1, 2, *,, Amany Magdy Beshbishy 1, , Lamiaa Wasef 2,
Yaser H. A. Elewa 3,4, Mohamed E. Abd El-Hack 5, Ayman E. Taha 6,
Adham Abdullah Al-Sagheer 7, Hari Prasad Devkota 8and Vincenzo Tufarelli 9
1National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary
Medicine, Nishi 2-13, Inada-cho, Obihiro 080-8555, Hokkaido, Japan; amanimagdi2008@gmail.com
2Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University,
Damanhour 22511, Al Beheira, Egypt; lamiaawasef@vetmed.dmu.edu.eg
3Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University,
Zagazig 44511, Egypt; y-elewa@vetmed.hokudai.ac.jp
4Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine,
Hokkaido University, Sapporo 060-0818, Hokkaido, Japan
5Department of Poultry, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt;
dr.mohamed.e.abdalhaq@gmail.com
6Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine,
Alexandria University, Edfina 22578, Egypt; Ayman.Taha@alexu.edu.eg
7Animal Production Department, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt;
adham_alsaht@zu.edu.eg
8Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku,
Kumamoto City, Kumamoto 862-0973, Japan; devkotah@kumamoto-u.ac.jp
9DETO—Section of Veterinary Science and Animal Production, University of Bari ‘Aldo Moro’ s.p.
Casamassima km 3, 70010 Valenzano, Italy; vincenzo.tufarelli@uniba.it
*Correspondence: dr_gaber_batiha@vetmed.dmu.edu.eg or gaberbatiha@gmail.com; Tel.: +20-45-271-6024;
Fax: +20-45-271-6024
Equally contributed.
Received: 20 January 2020; Accepted: 11 March 2020; Published: 13 April 2020


Abstract:
Uncaria tomentosa (Willd. ex Schult.) DC. (Family: Rubiaceae), commonly known as
cat’s claw, is a tropical medicinal vine originating at the Amazon rainforest and other areas of
South and Central America. It has been traditionally used to treat asthma, abscesses, fever, urinary
tract infections, viral infections, and wounds and found to be eective as an immune system
rejuvenator, antioxidant, antimicrobial, and anti-inflammatory agent. U. tomentosa is rich in many
phytoconstituents such as oxindole and indole alkaloids, glycosides, organic acids, proanthocyanidins,
sterols, and triterpenes. Biological activities of U. tomentosa have been examined against various
microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium,Babesia and
Theileria parasites. Several formulations of cat’s claw (e.g., tinctures, decoctions, capsules, extracts,
and teas) are recently available in the market. The current review covers the chemical constituents,
biological activities, pharmacokinetics, and toxic properties of U. tomentosa extracts.
Keywords: Uncaria tomentosa; cat’s claw; biological activities; pharmacokinetics; phytoconstituents
1. Introduction
Medicinal plants have been used for various therapeutic purposes from ancient times and they
have also served as an important source for drug discovery [
1
3
]. A large proportion of the population
living in developing countries in Asia and Africa depend on plant-based traditional medicines for
Appl. Sci. 2020,10, 2668; doi:10.3390/app10082668 www.mdpi.com/journal/applsci
Appl. Sci. 2020,10, 2668 2 of 12
primary healthcare [
4
,
5
]. One of the main reasons for the wide use of plants is due to their easy
accessibility and low-cost [
6
8
]. Essentially, herbal therapies contain parts of herbs or unpurified
herbal extracts that involve a variety of phytoconstituents that are usually thought to act synergistically
together and can be used as a lead compound to discover a huge number of compounds that can be
used recently in the treatment of several diseases [7,8].
Uncaria tomentosa (Willd. ex Schult.) DC is commonly known as cat’s claw that is derived from the
Spanish word Uña de Gato that identifies the small, curved-back thorns on the stem at the leaf junction.
It is a tropical medicinal vine of the Rubiaceae family that is widely distributed in the Amazon rainforest
and other areas of South and Central America [
9
,
10
]. Thirty-four Uncaria species have been reported
including U. guianensis and U. tomentosa that are found in South America. Traditionally, U. tomentosa
has been reported to be used to asthma, abscesses, fever, urinary tract infections, viral infections,
and wounds [
9
]. It is also reported to be eective as an immune system rejuvenator, antioxidant,
antimicrobial, and anti-inflammatory. U. tomentosa is a potent complimentary herb for treating most
parasites [
11
]. Various chemical constituents are reported from the extracts of U. tomentosa along with
their biological activities. The main objective of this review is to review the available scientific literature
regarding the chemical constituents, biological activities of U. tomentosa along with the reported side
eects and precautions related to drug-drug interactions.
2. Chemical Constituents of U. tomentosa
Previous studies reported the chemical constituents of several Uncaria species and recognized
the dierent molecules present in dierent parts of the plant. It is worth noting that more than 50
phytochemical molecules have been identified and isolated from U. tomentosa, some of them are
considered new to that species [
12
]. U. tomentosa leaves contain higher oxindole alkaloid content than
that present in stem bark and branches. This result is compatible with a study previously described
by Laus et al. [
13
], who documented the accumulation of speciophylline and uncarine F (the main
oxindole alkaloids) in leaves that can occur as tetracyclic oxindole alkaloid (TOA) or pentacyclic
oxindole alkaloid (POA) derivatives. Both TOA and POA are liable to isomerization that depends
mainly on medium polarity, pH, and temperature [13].
A recent study about the chemical variation of a wild population of cat’s claw from Peru reported the
existence of three specific chemotypes that producing dierent alkaloidal constituents [
14
]. Chemotype I
is mainly composed of the POA with the intersection of D/E ring, chemotype II consists primarily of POA
with trans D/E ring junction, while chemotype III consists primarily of TOA derivative. Uncarine C and
uncarine E are two POA stereoisomers, while mitraphylline, rhynchophylline, and isorhynchophylline
are TOAs found in cat’s claw. On the basis of these results, the U.S. Pharmacopeia revealed that dried raw
material of cat’s claw included 0.05% (w/w) of the TOA concerning the POA amount, whereas cat’s claw
powdered dried extract, tablets, and capsules contained up to 25% (w/w). Cat’s claw contains several
active compositions including ajmalicine, campesterol, carboxyl alkyl esters, akuammigine, sitosterols,
rutin, chlorogenic acid, speciophylline, catechin, cinchonain [
15
], corynoxeine, harman, daucosterol,
epicatechin, hirsuteine, corynantheine, hirsutine, loganic acid, mitraphylline, iso-pteropodine, oleanolic
acid, ursolic acid, lyaloside [
16
], rhynchophylline, palmitoleic acid, pteropodine quinovic acid
glycosides, procyanidins [
10
], stigmasterol, 3,4-dehydro-5-carboxystrictosidine, vaccenic acid, uncarine
A thru F, and strictosidines [
10
,
17
]. Moreover, other reports revealed that various compounds other
than oxindole alkaloids such as rotundifoline and isorotundifolune, coumarins, flavonoids, quinovic
acid glycosides, and triterpenes may be responsible for the cat’s claw medicinal eects [18,19].
3. Biological Activities of U. tomentosa Extracts and Compounds
3.1. Traditional Uses
U. tomentosa bark and root have been traditionally used as a therapy in tropical South America for
many conditions, like inflammations, cancer, gastric ulcers, arthritis, and infections. Moreover, it was
Appl. Sci. 2020,10, 2668 3 of 12
documented to be used for blood purifications, after child delivery as a wash for wounds to allow
skin healing, cleansing the kidneys, asthma, inhibition of several diseases, menstrual irregularity and
hemorrhages, fevers, and possess a normalizing activity on body systems [
20
]. It also was used for the
treatment of various ailments including abscesses, urinary tract infections, contraception, rheumatism,
and weakness. Additionally, it was used as a treatment option for mental disorders (e.g., anxiety).
Some indigenous people in America used the water stored in the stem to quench thirst, and as a
restorative drink [21]. Few pharmacological eects of U. tomentosa have shown in Figure 1.
Appl. Sci. 2020, 10, x FOR PEER REVIEW 3 of 12
3. Biological Activities of U. tomentosa Extracts and Compounds
3.1. Traditional Uses
U. tomentosa bark and root have been traditionally used as a therapy in tropical South America
for many conditions, like inflammations, cancer, gastric ulcers, arthritis, and infections. Moreover, it
was documented to be used for blood purifications, after child delivery as a wash for wounds to
allow skin healing, cleansing the kidneys, asthma, inhibition of several diseases, menstrual
irregularity and hemorrhages, fevers, and possess a normalizing activity on body systems [20]. It also
was used for the treatment of various ailments including abscesses, urinary tract infections,
contraception, rheumatism, and weakness. Additionally, it was used as a treatment option for mental
disorders (e.g., anxiety). Some indigenous people in America used the water stored in the stem to
quench thirst, and as a restorative drink [21]. Few pharmacological effects of U. tomentosa have shown
in Figure 1.
Figure 1. Schematic representation of different pharmacological activities of Uncaria tomentosa (cat’s
claw).
3.2. Antioxidant Activity
The antioxidant activities of U. tomentosa have been attributed to the existence of alkaloids,
flavan-3-ol monomers, and polyphenols. The preclinical assessment revealed that the cat’s claw
defends toward various oxidative stresses, involving peroxynitrite that has been included in arthritis
and other chronic inflammatory diseases along with inhibiting acute or chronic gastritis caused by
high doses of nonsteroidal anti-inflammatory drugs (NSAIDs) [22,23].
U. tomentosa aqueous extract
was found to protect against oxidative stress in human erythrocytes and relieve chronic intestinal
inflammation in rats caused by indomethacin [24,25].
Another study documented that
hydroxybenzoic acids, proanthocyanidins acids hydroxycinnamic were responsible for potent radical
scavenging and anti-inflammatory activities of the cat’s claw [26,27]. In an in vitro experiment, U.
tomentosa bark showed high antioxidant efficacy manifested by trolox equivalent antioxidant
capacity, free radical diphenylpicrylhydrazyl capacity, superoxide radical scavenging activity, and
peroxyl radical-trapping capacity. Moreover, it protected membrane lipids from the peroxidation
caused by the iron/ascorbate system and was also evaluated by the formation of thiobarbituric acid-
reactive substances (TBARs) [26]. Another in vitro study revealed that the cat’s claw prevented the
inducible nitric oxide synthase (iNOS) gene expression caused by lipopolysaccharide, nitrite
Figure 1.
Schematic representation of dierent pharmacological activities of Uncaria tomentosa
(cat’s claw).
3.2. Antioxidant Activity
The antioxidant activities of U. tomentosa have been attributed to the existence of alkaloids,
flavan-3-ol monomers, and polyphenols. The preclinical assessment revealed that the cat’s claw
defends toward various oxidative stresses, involving peroxynitrite that has been included in arthritis
and other chronic inflammatory diseases along with inhibiting acute or chronic gastritis caused by
high doses of nonsteroidal anti-inflammatory drugs (NSAIDs) [
22
,
23
]. U. tomentosa aqueous extract
was found to protect against oxidative stress in human erythrocytes and relieve chronic intestinal
inflammation in rats caused by indomethacin [
24
,
25
]. Another study documented that hydroxybenzoic
acids, proanthocyanidins acids hydroxycinnamic were responsible for potent radical scavenging and
anti-inflammatory activities of the cat’s claw [
26
,
27
]. In an
in vitro
experiment, U. tomentosa bark
showed high antioxidant ecacy manifested by trolox equivalent antioxidant capacity, free radical
diphenylpicrylhydrazyl capacity, superoxide radical scavenging activity, and peroxyl radical-trapping
capacity. Moreover, it protected membrane lipids from the peroxidation caused by the iron/ascorbate
system and was also evaluated by the formation of thiobarbituric acid-reactive substances (TBARs) [
26
].
Another
in vitro
study revealed that the cat’s claw prevented the inducible nitric oxide synthase
(iNOS) gene expression caused by lipopolysaccharide, nitrite formation, cell death, and the NF-kappaB
activation. Cat’s claw possessed a cytoprotective eect due to its ability to interact with the injurious
oxidant, therefore, it may act on regulating cell death [22].
Appl. Sci. 2020,10, 2668 4 of 12
3.3. Anti-Neoplastic Activity
Cat’s claw was supposed to have antitumor and immunostimulatory eects because of its oxindole
alkaloids content [
10
,
23
,
28
]. U. tomentosa extracts were found to have antiproliferative ecacy against
SW620 colon adenocarcinoma, MCF7 breast cancer, and AGS gastric cells [
19
]. Interestingly, several
studies suggested the antiproliferative eect of U. tomentosa against several cancer cell lines, namely
cervical carcinoma, osteosarcoma, and breast cancer. For instance, an
in vitro
study reported that
U. tomentosa hot water extract prevents inflammatory responses as well as tumor cell proliferation by
inhibiting the transcriptional regulator nuclear factor kappa beta (NF-
κ
B) activation without interfering
with interleukin-2 (IL-2) production or IL-2 receptor signaling [29]. Cheng et al. [30] documented the
antiproliferative eect of cat’s claw extracts against several cell lines, including glioma, premyelocytic
leukemia, MCF7 breast cancer, acute lymphoblastic leukaemia, and neuroblastoma.
3.4. Anti-Inflammatory Activity
Recently, POA isolated from U. tomentosa extract has been documented to enhance the lymphocyte
proliferation-regulating factor released from human endothelial cells; however, TOA was found to
reduce POA activity on these cells in a dose-related manner [
22
,
31
]. Additionally, U. tomentosa stem
bark extracts have been revealed to stimulate the
in vitro
production of IL-6 and IL-1 in rat alveolar and
lipopolysaccharide-stimulated macrophages in a dose-related manner and its suppressive activities on
cancer cell multiplication appear to be due to apoptosis induction [
18
,
32
]. Moreover, Xiao et al. [
33
]
examined the hypotensive ecacy of isorhynchophylline in rats and dogs, whereas Xiang et al. [
34
]
documented the ability of rhynchophylline to suppress rabbit and rat platelet accumulation ex vivo.
Additionally, the anti-inflammatory activity of the standardized aqueous extract of U. tomentosa (AC
11
of U. tomentosa extract) was attributed to NF-
κ
B inhibition [
35
]. Recently, several studies reported the
antioxidant, anti-neoplastic and immunomodulant activities of the alkaloids isolated from the cat’s
claw [
36
38
]. For instance, Lopes et al. [
39
] revealed that U. tomentosa extract encourages the myeloid
precursor’s proliferation by increasing serum colony-stimulating growth factors (CSFs). Moreover,
in vivo
studies demonstrated the eectiveness of aqueous U. tomentosa extract on leukocyte counts in
healthy animals and doxorubicin-induced neutropenia [
23
,
40
,
41
]. Interestingly, Cisneros et al. [
42
]
reported that lung inflammation was reduced in all mice treated with U. tomentosa bark extract.
Additionally, Dreifuss et al. [
19
] examined the
in vivo
anti-inflammatory ecacy of quinovic acid
glycoside separated from the aqueous cat’s claw extracts.
3.5. Antimicrobial, Antiprotozoal and Antiviral Activities
The previous study documented the antimicrobial eect of U. tomentosa bark extracts against
several morphological forms of Borrelia burgdorferi and respiratory pathogens namely Enterococcus
faecalis,Pseudomonas aeruginosa and Staphylococcus aureus and this activity were attributed to the presence
of proanthocyanidins, including dimers and oligomers up to undecamers [
43
]. U. tomentosa showed
remarkable antifungal ecacy against various anidulafungin, terbinafine and fluconazole-resistant
non-albicans species [
44
]. The antiprotozoal activity has been recently documented by Batiha et al. [
45
]
against Babesia and Theileria parasites and this ecacy was attributed to its ability to digest harmful
microorganisms. In addition to that, it has been documented to treat many parasites except Giardia.
Therefore, U. tomentosa could be a good complementary antiprotozoal herb [
11
,
45
]. The antiviral activity
of quinovic acid glycosides has been demonstrated
in vitro
against vesicular stomatitis, ribonucleic
acid (RNA), a minus-strand RNA virus, and rhinovirus 1B [
25
]. Caon et al. [
46
] assessed the
in vitro
antiherpetic activity of hydroethanolic U. tomentosa extract, as well as the purified fractions of oxindole
alkaloids and quinovic acid glycosides against herpes simplex virus (HSV) infections as well as the
protective activity of these preparations on UV-induced DNA damage.
Appl. Sci. 2020,10, 2668 5 of 12
3.6. Immunomodulatory Activity
Smith et al. [
47
] reported that the POA isolated from U. tomentosa extracts improved the cellular
immune system, while the TOA suppressed this immunostimulating eect of this POA
in vitro
. Another
in vitro
study showed the eect of dierent cat’s claw extracts and mixtures of alkaloids in modulating
the immunobiochemical pathways enhanced by interferon-gamma [
48
]. Notably,
in vivo
experiments
revealed that U. tomentosa extracts exhibited immunomodulatory activity indirectly and promoted a
higher provide of myeloid progenitors in the bone marrow as a result of the release of biologically
active cytokines (e.g., CSFs, IL-6, and IL-1) [
49
]. Moreover, Allen-Hall et al. [
50
] documented that
U. tomentosa extracts prevented the mitogen-activated protein kinases (MAPK) signaling pathway and
change cytokine expression in the human acute monocytic leukemia cell line THP-1.
3.7. Cardiovascular Activity
Hirsutine isolated from U. rhynchophylla extract was found to decrease intracellular calcium
concentrations in rat aortas by inhibiting the calcium channels and eecting calcium stores [
51
].
Moreover, it showed a vasodilated, negative chronotropic, and antiarrhythmic eect. TOA namely
corynoxeine, isocorynoxiene, rhynchophylline, and isorhynchophylline exhibited a Ca
2+
channel
blocking eect, which resulted in low blood pressure and may aect the central nervous system [52].
3.8. Anti-Alzheimer’s Disease (AD) Activity
U. tomentosa is reported to act as a strong medicinal extract eliminator of A
β
plaques and
it is considered as a potential plant for Alzheimer’s Disease (AD) therapy. This activity was
attributed to the fact that U. tomentosa contains newly identified polyphenolic components namely
specific proanthocyanidins that possess both “plaque and tangle” reducing and inhibitory eects.
Proanthocyanidin B2 (epicatechin-4
β
-8-epicatechin) is one major cat’s claw-identified specific
polyphenol that markedly diminished the brain plaque load and enhanced short-term memory
in younger and older A
β
precursor protein (APP) transgenic mice “plaque-producing”. Moreover,
proanthocyanidin B2 has been shown to be a strong inhibitor of the brain inflammation as evidenced
by a decrease in astrocytosis and gliosis in TASD-41 transgenic mice [
53
]. List of some of POA and
TOA alkaloids along with their structures and biological activities are provided in Table 1.
Table 1. List of some of bioactive alkaloids isolated from Uncaria tomentosa.
Compounds Molecular Formula Structure Biological Activity References
Pentacyclic oxindole alkaloids (POA)
Uncarine F C21H24 N2O4
Appl. Sci. 2020, 10, x FOR PEER REVIEW 5 of 12
purified fractions of oxindole alkaloids and quinovic acid glycosides against herpes simplex virus
(HSV) infections as well as the protective activity of these preparations on UV-induced DNA damage.
3.6. Immunomodulatory Activity
Smith et al. [47] reported that the POA isolated from U. tomentosa extracts improved the cellular
immune system, while the TOA suppressed this immunostimulating effect of this POA in vitro.
Another in vitro study showed the effect of different cat’s claw extracts and mixtures of alkaloids in
modulating the immunobiochemical pathways enhanced by interferon-gamma [48]. Notably, in vivo
experiments revealed that U. tomentosa extracts exhibited immunomodulatory activity indirectly and
promoted a higher provide of myeloid progenitors in the bone marrow as a result of the release of
biologically active cytokines (e.g., CSFs, IL-6, and IL-1) [49]. Moreover, Allen-Hall et al. [50]
documented that U. tomentosa extracts prevented the mitogen-activated protein kinases (MAPK)
signaling pathway and change cytokine expression in the human acute monocytic leukemia cell line
THP-1.
3.7. Cardiovascular Activity
Hirsutine isolated from U. rhynchophylla extract was found to decrease intracellular calcium
concentrations in rat aortas by inhibiting the calcium channels and effecting calcium stores [51].
Moreover, it showed a vasodilated, negative chronotropic, and antiarrhythmic effect. TOA namely
corynoxeine, isocorynoxiene, rhynchophylline, and isorhynchophylline exhibited a Ca2+ channel
blocking effect, which resulted in low blood pressure and may affect the central nervous system [52].
3.8. Anti-Alzheimer’s Disease (AD) Activity
U. tomentosa is reported to act as a strong medicinal extract eliminator of Aβ plaques and it is
considered as a potential plant for Alzheimer’s Disease (AD) therapy. This activity was attributed to
the fact that U. tomentosa contains newly identified polyphenolic components namely specific
proanthocyanidins that possess both “plaque and tangle” reducing and inhibitory effects.
Proanthocyanidin B2 (epicatechin-4β-8-epicatechin) is one major cat’s claw-identified specific
polyphenol that markedly diminished the brain plaque load and enhanced short-term memory in
younger and older Aβ precursor protein (APP) transgenic mice “plaque-producing”. Moreover,
proanthocyanidin B2 has been shown to be a strong inhibitor of the brain inflammation as evidenced
by a decrease in astrocytosis and gliosis in TASD-41 transgenic mice [53]. List of some of POA and
TOA alkaloids along with their structures and biological activities are provided in Table 1.
Table 1. List of some of bioactive alkaloids isolated from Uncaria tomentosa.
Compounds Molecular
Formula Structure Biological Activity References
Pentacyclic oxindole alkaloids (POA)
Uncarine F C₂₁H₂₄NO
Anticancer activity [36]
Speciophylli
ne C21H24N2O4
Anti-neoplastic
activity [19]
Anticancer activity [36]
Speciophylline C21H24 N2O4
Appl. Sci. 2020, 10, x FOR PEER REVIEW 5 of 12
purified fractions of oxindole alkaloids and quinovic acid glycosides against herpes simplex virus
(HSV) infections as well as the protective activity of these preparations on UV-induced DNA damage.
3.6. Immunomodulatory Activity
Smith et al. [47] reported that the POA isolated from U. tomentosa extracts improved the cellular
immune system, while the TOA suppressed this immunostimulating effect of this POA in vitro.
Another in vitro study showed the effect of different cat’s claw extracts and mixtures of alkaloids in
modulating the immunobiochemical pathways enhanced by interferon-gamma [48]. Notably, in vivo
experiments revealed that U. tomentosa extracts exhibited immunomodulatory activity indirectly and
promoted a higher provide of myeloid progenitors in the bone marrow as a result of the release of
biologically active cytokines (e.g., CSFs, IL-6, and IL-1) [49]. Moreover, Allen-Hall et al. [50]
documented that U. tomentosa extracts prevented the mitogen-activated protein kinases (MAPK)
signaling pathway and change cytokine expression in the human acute monocytic leukemia cell line
THP-1.
3.7. Cardiovascular Activity
Hirsutine isolated from U. rhynchophylla extract was found to decrease intracellular calcium
concentrations in rat aortas by inhibiting the calcium channels and effecting calcium stores [51].
Moreover, it showed a vasodilated, negative chronotropic, and antiarrhythmic effect. TOA namely
corynoxeine, isocorynoxiene, rhynchophylline, and isorhynchophylline exhibited a Ca2+ channel
blocking effect, which resulted in low blood pressure and may affect the central nervous system [52].
3.8. Anti-Alzheimer’s Disease (AD) Activity
U. tomentosa is reported to act as a strong medicinal extract eliminator of Aβ plaques and it is
considered as a potential plant for Alzheimer’s Disease (AD) therapy. This activity was attributed to
the fact that U. tomentosa contains newly identified polyphenolic components namely specific
proanthocyanidins that possess both “plaque and tangle” reducing and inhibitory effects.
Proanthocyanidin B2 (epicatechin-4β-8-epicatechin) is one major cat’s claw-identified specific
polyphenol that markedly diminished the brain plaque load and enhanced short-term memory in
younger and older Aβ precursor protein (APP) transgenic mice “plaque-producing”. Moreover,
proanthocyanidin B2 has been shown to be a strong inhibitor of the brain inflammation as evidenced
by a decrease in astrocytosis and gliosis in TASD-41 transgenic mice [53]. List of some of POA and
TOA alkaloids along with their structures and biological activities are provided in Table 1.
Table 1. List of some of bioactive alkaloids isolated from Uncaria tomentosa.
Compounds Molecular
Formula Structure Biological Activity References
Pentacyclic oxindole alkaloids (POA)
Uncarine F C₂₁H₂₄NO
Anticancer activity [36]
Speciophylli
ne C21H24N2O4
Anti-neoplastic
activity [19]
Anti-neoplastic activity [19]
Mitraphylline C21H24 N2O4
Appl. Sci. 2020, 10, x FOR PEER REVIEW 6 of 12
Mitraphyllin
e C21H24N2O4
Anti-inflammatory,
antioxidant activities [54,55]
Isomitraphyl
line C21H24N2O4
Antioxidant activity [55]
Pteropodine C21H24N2O4
Immunomodulating
properties [48]
Isopteropodi
ne C21H24N2O4
Antimicrobial activity [37]
Tetracyclic oxindole alkaloid (TOA)
Corynoxeine C22H26N2O4
Antiproliferative
activity [56]
Rhynchophy
lline C22H28N2O4
Inhibit the platelet
aggregation and
thrombosis
[57]
Anti-inflammatory,
antioxidant activities [54,55]
Appl. Sci. 2020,10, 2668 6 of 12
Table 1. Cont.
Compounds Molecular Formula Structure Biological Activity References
Isomitraphylline C21H24 N2O4
Appl. Sci. 2020, 10, x FOR PEER REVIEW 6 of 12
Mitraphyllin
e C21H24N2O4
Anti-inflammatory,
antioxidant activities [54,55]
Isomitraphyl
line C21H24N2O4
Antioxidant activity [55]
Pteropodine C21H24N2O4
Immunomodulating
properties [48]
Isopteropodi
ne C21H24N2O4
Antimicrobial activity [37]
Tetracyclic oxindole alkaloid (TOA)
Corynoxeine C22H26N2O4
Antiproliferative
activity [56]
Rhynchophy
lline C22H28N2O4
Inhibit the platelet
aggregation and
thrombosis
[57]
Antioxidant activity [55]
Pteropodine C21H24N2O4
Immunomodulating
properties [48]
Isopteropodine C21H24N2O4
Appl. Sci. 2020, 10, x FOR PEER REVIEW 6 of 12
Mitraphyllin
e C21H24N2O4
Anti-inflammatory,
antioxidant activities [54,55]
Isomitraphyl
line C21H24N2O4
Antioxidant activity [55]
Pteropodine C21H24N2O4
Immunomodulating
properties [48]
Isopteropodi
ne C21H24N2O4
Antimicrobial activity [37]
Tetracyclic oxindole alkaloid (TOA)
Corynoxeine C22H26N2O4
Antiproliferative
activity [56]
Rhynchophy
lline C22H28N2O4
Inhibit the platelet
aggregation and
thrombosis
[57]
Antimicrobial activity [37]
Tetracyclic oxindole alkaloid (TOA)
Corynoxeine C22H26 N2O4
Appl. Sci. 2020, 10, x FOR PEER REVIEW 6 of 12
Mitraphyllin
e C21H24N2O4
Anti-inflammatory,
antioxidant activities [54,55]
Isomitraphyl
line C21H24N2O4
Antioxidant activity [55]
Pteropodine C21H24N2O4
Immunomodulating
properties [48]
Isopteropodi
ne C21H24N2O4
Antimicrobial activity [37]
Tetracyclic oxindole alkaloid (TOA)
Corynoxeine C22H26N2O4
Antiproliferative
activity [56]
Rhynchophy
lline C22H28N2O4
Inhibit the platelet
aggregation and
thrombosis
[57]
Antiproliferative activity
[56]
Rhynchophylline C22H28 N2O4
Appl. Sci. 2020, 10, x FOR PEER REVIEW 6 of 12
Mitraphyllin
e C21H24N2O4
Anti-inflammatory,
antioxidant activities [54,55]
Isomitraphyl
line C21H24N2O4
Antioxidant activity [55]
Pteropodine C21H24N2O4
Immunomodulating
properties [48]
Isopteropodi
ne C21H24N2O4
Antimicrobial activity [37]
Tetracyclic oxindole alkaloid (TOA)
Corynoxeine C22H26N2O4
Antiproliferative
activity [56]
Rhynchophy
lline C22H28N2O4
Inhibit the platelet
aggregation and
thrombosis
[57]
Inhibit the platelet
aggregation and
thrombosis
[57]
4. Reported Side Eects
The American Herbal Products Association (AHPA) classified cat’s claw as a class-4 safety rating,
although, it was known traditionally to be safe and nontoxic, indicating the lack of scientific data for herb
safety consideration [
31
]. Previous reports noted several adverse eects after administration of high
doses of cat’s claw including nausea, acute renal failure, slow heart rate, stomach discomfort, hormonal
eects, diarrhea, hepatotoxicity, decrease progesterone and estrogen levels, neuropathy [
58
,
59
], and
increased risk of bleeding when administered with blood thinner agents such as warfarin, therefore,
patients may be recommended to stop cat’s claw administration before surgeries [
31
,
60
,
61
]. Signs of
allergic reactions including swelling of face, lips, tongue, or throat, diculty breathing, and hives have
been observed [
62
]. Additionally, acute renal failure was noticed in systemic lupus erythematosus
patients after the daily administration of four capsules of the cat’s claw [31,63,64].
Appl. Sci. 2020,10, 2668 7 of 12
5. Precautions
5.1. Drug-Drug Interactions
5.1.1. Immunosuppressant Drugs
Theoretically, it was believed that POA isolated from cat’s claw possesses an immunostimulatory
eect, therefore, it is contraindicated to be used with immunosuppressant drugs including cyclosporine,
azathioprine, daclizumab, basiliximab, mycophenolate, muromonab-CD3, tacrolimus, sirolimus,
corticosteroids, prednisone, or other chemotherapeutic drugs recommended for autoimmune disease
treatment or after organ transplantation [39,62].
5.1.2. Anticoagulants
Cat’s claw contains TOA that increased risk of bleeding when administered with aspirin,
anticoagulant drugs such as warfarin or heparin, NSAIDs such as ibuprofen and naproxen, antiplatelet
drugs like clopidogrel due to rhynchophylline inhibitory ecacy on platelet aggregation, therefore,
patients may be recommended to stop cat’s claw administration before surgeries [31,61].
5.1.3. Diuretics
Cat’s claw has a diuretic eect, so it is contraindicated to be used with other diuretics, as they act
by the same mechanism and thus increases the risk of electrolyte imbalance. Moreover, it may interact
with hormonal drugs, cholesterol-lowering drugs, and drugs that aect the kidney [65].
5.1.4. Antihypertensive Drugs
Hirsutine extracted from cat’s claw was reported to have a hypotensive eect, therefore it is
not recommended to be used to hypotensive people or those administering antihypertensive drugs
(e.g., casein protein, coenzyme Q-10 (ubiquinone), fish oil, L-arginine, Lycium, or stinging nettle) due
to rhynchophylline and isorhynchophylline hypotensive eects as it may reduce the blood pressure to
be too low [33].
5.1.5. Cytochrome P450 Substrates
Cat’s claw prevents the microsomal CYP 3A4 activity, and thus, increased the serum levels of drugs
that are metabolized by CYP 3A4 suchlike nonnucleoside reverse-transcriptase inhibitors, cyclosporine,
and some benzodiazepines and increased the serious adverse eects of these drugs [
66
]. Moreover,
the cat’s claw may interact with allergic drugs like fexofenadine, anti-cancer agents as paclitaxel,
antifungals like ketoconazole, antiviral drugs, and oral contraceptives [67].
5.2. Drug Safety
Based on the possible safety data, U. tomentosa extracts appears to be safe when administered
to several cases of inflammation. Cat’s claw safety has not been documented in breastfeeding and
pregnant women, or children under three years of age because of insucient safety research [31,64].
6. Recommended Doses
The typical and recommended dose of U. tomentosa is one gram given two to three times daily.
A standardized extract attributed to specific chemotype of this species consisting of less than 0.5%
oxindole alkaloids and 8% to 10% carboxy alkyl esters has been used in doses of 250 to 300 mg in
several clinical studies [
68
,
69
]. In rats, it was determined that the average lethal dose for a single dose
of water extract from U. tomentosa is higher than 8 g/kg. In humans, no toxic symptoms were noticed
with frequent administration of 350 mg/day for 6 successive weeks [
18
,
70
,
71
]. Tinctures, decoctions,
capsules, extracts, and teas are recently prepared from the cat’s claw. For instance, 250–1000 mg capsule
Appl. Sci. 2020,10, 2668 8 of 12
is taken orally in divided doses per day [
31
], while in a decoction, up to 25 g of raw bark has been
used, although this based on traditional management practices. Although U. tomentosa is commercially
applicable in skin formulation, its typical dose has not yet been documented [31].
7. Conclusions
The existing review investigates the medicinal activities and all phytochemical molecules extracted
from U. tomentosa.U. tomentosa (cat’s claw) is used in the tradition medicine as a treatment option against
wide range of health problems, including immune system deficiencies, neurodegenerative disorders,
cancer, chronic fatigue syndrome, Crohn’s disease, digestive complaints, parasitic and microbial
infections, kidney cleanser, inflammatory problems, irritable and leaky bowel syndrome. Moreover,
U. tomentosa has many phytochemical molecules that are attributed to its therapeutic activities and exist
in dierent degrees in the herb. U. tomentosa acts as an eective natural herbal extract eliminator of A
β
protein “plaques”. Thence, U. tomentosa could be a potential herb for AD treatment. Although these
medicinal properties, the cat’s claw shows several adverse eects such as nausea, acute renal failure,
stomach discomfort, hormonal eects, diarrhea, hepatotoxicity, neuropathy and it is contraindicated to
be used with anticoagulants, antihypertensive, and immunosuppressant drugs.
Author Contributions:
G.E.-S.B., A.M.B., L.W., Y.H.A.E., M.E.A.E.-H., A.E.T., A.A.A.-S., and H.P.D. wrote the
paper. G.E.-S.B., A.M.B. and V.T. revised the paper. All authors have read and agreed to the published version of
the manuscript.
Funding: This research not receive external fund.
Conflicts of Interest: The authors declare no conflict of interest.
Abbreviations
HIV human immunodeficiency viruses
TOA tetracyclic oxindole alkaloid
POA pentacyclic oxindole alkaloid
IUPAC International Union of Pure and Applied Chemistry
NSAIDs nonsteroidal anti-inflammatory drugs
TBARs thiobarbituric acid-reactive substances
iNOS inducible nitric oxide synthase
IL-2 interleukin-2
AC11 of U. tomentosa extract standardized aqueous extract of U. tomentosa
CSFs colony-stimulating growth factors
RNA ribonucleic acid
HSV herpes simplex virus
MAPK mitogen-activated protein kinases
AD Alzheimer’s disease
Aβbeta-amyloid
AHPA The American Herbal Products Association
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(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
... Gracias a los compuestos bioactivos que presenta, los seres humanos han utilizado su raíz o corteza para el tratamiento de ciertas enfermedades (Liang et al., 2020). Por ejemplo, se ha empleado en el tratamiento de asma, abscesos, infecciones del tracto urinario, fiebre, artritis, tumores malignos, entre otras patologías (Batiha et al., 2020;Montserrat et al., 2016). Sin embargo, la cosecha de forma indiscriminada y la deforestación de su hábitat natural pueden situar a esta especie en peligro. ...
... Asimismo, las principales propiedades que posee esta planta son actividad antioxidante, antineoplásica, antiinflamatoria, antimicrobianas, antiprotozoarias y antivirales, inmunomodulador, cardiovascular y contra la enfermedad de Alzheimer (Batiha et al., 2020). Esto ocurre debido a las composiciones activas que se encuentran en las hojas, corteza de tallo y ramas de la planta. ...
... Nota. Traducido y tomado de Batiha et al. (2020) También presenta una actividad antioxidante, debido a que la planta brinda un mecanismo de defensa frente a los estreses oxidativos, como el peroxinitrito, que se encuentra incluido en la artritis y otras enfermedades inflamatorias crónicas. Además, se sabe que brinda un beneficio a los seres humanos por presentar una eficacia antiproliferativa contra varias líneas celulares, esto incluye enfermedades como la leucemia, cáncer de mama, entre otras. ...
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La Uncaria tomentosa representa a una de las plantas de la Amazonía peruana con un gran potencial en la medicina tradicional, cuya corteza se ha utilizado en una variedad de preparaciones terapéuticas populares. A lo largo de los años, su uso se ha intensificado por los descubrimientos y las diferentes aplicaciones de los extractos de esta planta. Por tal motivo, el objetivo de este artículo fue resaltar la importancia de U. tomentosa en el tratamiento y desinflamación de distintas enfermedades, además de su contexto en el Perú. En la búsqueda bibliográfica, se emplearon palabras clave como “planta amazónica, “uncaria tomentosa” o “uña de gato”; de este modo, se obtuvo que esta planta resulta de uso terapéutico cuando se obtienen los extractos de la hoja, tallo o corteza; con una mayor predominancia de esta última. Asimismo, se ha descubierto que tiene propiedades importantes como antioxidante, antineoplásica, antiinflamatoria y antimicrobiana. Su uso es muy variado, desde el consumo (infusión o vino) hasta la aplicación (crema gel), aunque la primera forma es la más empleada por las poblaciones locales. Por lo tanto, basado en los últimos trabajos y pruebas de estudio que se están realizando a nivel nacional e internacional, se concluye que la U. tomentosa promete ser una especie con potencial médico para el tratamiento de enfermedades, que beneficie a las sociedades humanas por su bajo costo y fácil acceso.
... Phytogenic feed additives obtained from herbal plant extracts are commonly used in poultry, particularly in laying hens. Phytogenics, also known as phytobiotics, have beneficial effects on gut health and performance due to the presence of bioactive compounds such as polyphenols with antimicrobial, antioxidant, immunomodulatory, and anti-inflammatory properties [1,2]. Polyphenol compounds are the most widely produced plant bioactive compounds that serve to protect plants from the pests and UV radiation that can be found in plant parts, including the fruit, seeds, roots, bark, and leaves [3]. ...
... Phytogenics, also known as phytobiotics, are plant bioactive compounds that have beneficial effects on gastrointestinal health and the performance of poultry due to the presence of phytogenic compounds such as polyphenols with antioxidant and immunomodulatory properties [1,41]. Various studies have been conducted to assess the efficacy of phytogenic feed additives in laying hens to minimise antibiotic use. ...
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Citation: Darmawan A, Hermana W, Suci DM, Mutia R, Sumiati S, Jayanegara A, Ozturk E. Dietary Phytogenic Extracts Favorably Influence Productivity, Egg Quality, Blood Constituents, Antioxidant and Immunological Parameters of Laying Hens: A Meta-Analysis. Animals. 2022; 12(17):2278. https://doi.org/10.3390/ani12172278
... Phytogenic feed additives obtained from herbal plant extracts are commonly used in poultry, particularly in laying hens. Phytogenics, also known as phytobiotics, have beneficial effects on gut health and performance due to the presence of bioactive compounds such as polyphenols with antimicrobial, antioxidant, immunomodulatory, and anti-inflammatory properties [1,2]. Polyphenol compounds are the most widely produced plant bioactive compounds that serve to protect plants from the pests and UV radiation that can be found in plant parts, including the fruit, seeds, roots, bark, and leaves [3]. ...
... Phytogenics, also known as phytobiotics, are plant bioactive compounds that have beneficial effects on gastrointestinal health and the performance of poultry due to the presence of phytogenic compounds such as polyphenols with antioxidant and immunomodulatory properties [1,41]. Various studies have been conducted to assess the efficacy of phytogenic feed additives in laying hens to minimise antibiotic use. ...
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The present study aimed to assess the impact of dietary phytogenic extracts on laying hen productivity, egg quality, blood constituents, antioxidant, and immunological parameters through a meta-analytical approach. A total of 28 articles (119 data points) reporting the influence of dietary phytogenic extracts on the productive performance, egg quality, blood constituents, immunological, and antioxidant parameters of laying hens were embedded into a database. Statistical analysis was performed using a mixed model, with different studies treated as random effects and phytogenic extract levels treated as fixed effects. This meta-analysis revealed that dietary phytogenic extracts quadratically (p < 0.05) improved egg production and egg mass as well as decreased (p < 0.05) the feed conversion ratio (FCR) with no adverse effect on egg weight and egg quality. Feed intake and egg yolk percentage tended to increase linearly (p < 0.1). Total serum cholesterol and low-density lipoprotein (LDL) declined quadratically (p < 0.001 and p < 0.05, respectively), high-density lipoprotein (HDL) increased linearly (p < 0.001), and malondialdehyde (MDA) decreased linearly (p < 0.01), with increasing levels of dietary phytogenic extract. In addition, immunoglobulin G (IgG), immunoglobulin A (IgA), glutathione peroxidase (GSH-Px), and total superoxide dismutase (TSOD) increased linearly (p < 0.05) in line with the increase in dietary phytogenic extract level. It was concluded that the inclusion of phytogenic extracts in the diet of laying hens had a positive effect on productive performance, feed efficiency, egg mass, immunity, and antioxidant activity without interfering with egg quality. The optimum level of feed photogenic extract for egg production and feed efficiency was determined to be around 300 mg/kg feed.
... This study showed that exposure to FA resulted in a significant decrease in anti-oxidant markers (Batiha et al., 2020b) and hepatic transaminases, triglycerides, and inflammatory markers increased. G. lucidum was ability to restore anti-oxidant, lipid, and antiinflammatory status conferred a protective impact (El-Rahman et al., 2020). ...
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... Each year several new cytotoxic secondary metabolites are isolated from the plants, as shown in Fig. 1, but few of them are selected for a laboratory test and clinical trial [17,18] as shown in Table. 1. For instance, Uncaria spp. was given special consideration and a series of alkaloids, such as corynoxeine, rhynchophylline, and isomitraphylline, [19,20] were isolated and their anticancer potential was determined [21]. With the data shown in Supplementary Table. ...
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Cancer has become the silent killer in less-developed countries and the most significant cause of morbidity worldwide. The accessible and frequently used treatments include surgery, radiotherapy, chemotherapy, and immunotherapy. Chemotherapeutic drugs traditionally involve using plant-based medications either in the form of isolated compounds or as scaffolds for synthetic drugs. To launch a drug in the market, it has to pass through several intricate steps. The multidrug resistance in cancers calls for novel drug discovery and development. Every year anticancer potential of several plant-based compounds and extracts is reported but only a few advances to clinical trials. The false-positive or negative results impact the progress of the cell-based anticancer assays. There are several cell-based assays but the widely used include MTT, MTS, and XTT. In this article, we have discussed various pitfalls and workable solutions. Graphical abstract
... Medicinal plants significantly contribute to worldwide therapeutic control, particularly in developing countries due to their easy accessibility and low cost [1]. According to the World Health Organization (WHO), approximately three billion people across the planet rely on so-called traditional medicine for their basic health needs as they are often the only therapeutic alternative for a large majority of the population. ...
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This work prepared and characterized microcapsule of Uncaria tomentosa (UT) in order to standardize a spray-dryer Uncaria tomentosa extract. The UT bark powder was subjected to extraction by maceration using hydro-ethanol solution. The Uncaria tomentosa extract was used to prepare the spray-dryer microcapsules UT-F1. The UT extract and microcapsules UT-F1 were submitted to chemical and physicochemical characterization tests. The phytochemical tests revealed the presence of alkaloids and phenolic compounds such as catechin. The UT extract and microcapsules UT-F1 showed high content of total phenols (28.48% ± 0.76 and 36.34% ± 0.22), high catechin content (47.95% ± 4.90 and 51.15% ± 4.20) and high antioxidant activity with IC50 values of 5.80 and 5.03 µg cm−3. The SEM, FTIR and TG analysis confirmed the morphology of spherical particles, the microencapsulation of the constituents of the UT extract, low moisture content, as well as stability of the microcapsules UT-F1. The DSC analysis and dissolution tests showed the technological influence of spray-dried starch combined UT extract considered water-poorly soluble resulting in vitro release (52.9%) of polyphenolic compounds from Uncaria tomentosa microcapsules. The combined use of disintegrants with a natural surfactant in the UT microcapsules has improved the release of polyphenols (catechin) from spray-dryer herbal composition reaching an equivalent release of 78.6% of catechin after 240 min. The in vitro release of microcapsules UT-F1 responds depending on the concentration of pharmaceutical excipients considered disintegrating and can easily achieve release greater than 80%. The microcapsules UT-F1 can be used as bulk material for herbal products in pharmaceutical industry.
... Medicinal plants exert favorable effects on animal and human health due to their content of secondary metabolites, such as polyphenols [6,7]. Polyphenols have been reported to have anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, anti-mutagenic, and anti-allergic properties [8,9]. ...
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The aim of the present study was to investigate the polyphenolic profile and the anti-inflammatory and anti-nociceptive activities of four traditionally used medicinal plants from Burkina Faso: Parkia biglobosa, Detarium microcarpum, Vitellaria paradoxa and Sclerocarya birrea. The analysis of the main phenolic compounds was performed by the HPLC-UV-MS method. The anti-inflammatory effect of the aqueous bark extracts was investigated by the λ-carrageenan-induced rat paw edema test. The anti-nociceptive activity was evaluated by the Randall–Selitto test under inflammatory conditions. Seven phenolic acids (gallic, protocatechuic, gentisic, vanillic, p-coumaric, ferulic, and syringic acids), and three flavonoids (catechin, epicatechin, and quercitrin) were identified in the plant samples. High contents of gallic acid were determined in the D. microcarpum, P. biglobosa and S. birrea extracts (190–300 mg/100 g), and V. paradoxa extract was the richest in epicatechin (173.86 mg/100 g). The λ-carrageenan-induced inflammation was significantly reduced (p < 0.001) by the P. biglobosa and D. microcarpum extracts (400 mg/kg p.o.). Under the inflammatory conditions, a significant anti-nociceptive activity (p < 0.001) was obtained after 2–3 h from the induction of inflammation. The effects of the tested extracts could be related to the presence of polyphenols and could be useful in the management of certain inflammatory diseases.
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Cat’s claw (Uncaria tomentosa (Willd. ex Schults) DC.), a plant that is exceptionally rich in phytochemicals, has been used for centuries by the indigenous people of South and Central America as a therapeutic and is currently widely exported for medicinal purposes. Extracts and individual components have shown considerable potential as antibacterials in the literature. The purpose of this review is twofold: first, to provide a substantiated, comprehensive collection of the known chemical constituents of U. tomentosa, including their detailed structures; second, to identify those components that offer some promise as antibacterials based on the research to date. Bacterial resistance to currently available antibiotics continues to increase and is widely recognized as an impending, potentially catastrophic, problem. There is research to suggest that U. tomentosa components may have antibacterial potential individually or synergistically with established antibiotics against microbes, including Borrelia burgdorferi, the causative agent of Lyme disease. It is our intention that this review will provide a valuable resource to investigators in search of new antimicrobials to meet the daunting challenge of antibiotic resistance.
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Gray mold (Botrytis cinerea Pers.), crown and fruit rot (Phytophthora cactorum (Lebert and Cohn) J.Schröt), and verticillium wilt (Verticillium dahliae Kleb.) are among the main diseases that affect the strawberry crop. In the study presented herein, the bark extract of Uncaria tomentosa (Willd. ex Schult.) DC, popularly known as “cat’s claw”, has been evaluated for its capability to act as a sustainable control method. The bioactive compounds present in the aqueous ammonia extract were characterized by gas chromatography–mass spectroscopy, and the antimicrobial activity of the extract—alone and in combination with chitosan oligomers (COS)—was assessed in vitro and as a coating for postharvest treatment during storage. Octyl isobutyrate (30.7%), 19α methyl-2-oxoformosanan-16-carboxylate (9.3%), tetrahydro-2-methyl-thiophene (4.7%), and α-methyl manofuranoside (4.4%) were identified as the main phytoconstituents. The results of in vitro growth inhibition tests showed that, upon conjugation of the bark extract with COS, complete inhibition was reached at concentrations in the 39–93.75 μg∙mL−1 range, depending on the pathogen. Concerning the effect of the treatment as a coating to prolong the storage life and control decay during post-harvest storage, high protection was observed at a concentration of 1000 μg∙mL−1. Because of this effectiveness, higher than that attained with conventional synthetic fungicides, the bark extracts of cat’s claw may hold promise for strawberry crop protection.
Chapter
In recent years, there is an increasing interest on the plant-based nutraceuticals, functional foods, and food supplements as potential agents for the maintenance of good health and the prevention and treatment of diseases. Phytochemicals, especially the polyphenols including flavonoids, phenolic acids, curcuminoids, and stilbinoids, are widely studied for their health beneficial properties. Among many other issues, one important issue is the continuous supply of active components in nutraceuticals to meet the market demand. As many phytochemicals present in nutraceuticals are specific to certain plant species, the conservation, cultivation, and sustainable utilization are equally important. Newer biotechnological tools such as tissue and cell culture have potential to provide the necessary amount of the specific nutraceutical compounds in future. For wider application, their chemical classification, biosynthetic routes, potential health beneficial activities, and market trends must be well understood. This chapter focuses mainly on the classification of these compounds, their biosynthesis in plants and role in human health.
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Uncaria tomentosa (Rubiaceae) has a recognized therapeutic potential against various diseases associated with oxidative stress. The aim of this research was to evaluate the antioxidant potential of an aqueous leaf extract (ALE) from U. tomentosa, and its major alkaloids mitraphylline and isomitraphylline. The antioxidant activity of ALE was investigated in vitro using standard assays (DPPH, ABTS and FRAP), while the in vivo activity and mode of action were studied using Caenorhabditis elegans as a model organism. The purified alkaloids did not exhibit antioxidant effects in vivo. ALE reduced the accumulation of reactive oxygen species (ROS) in wild-type worms, and was able to rescue the worms from a lethal dose of the pro-oxidant juglone. The ALE treatment led to a decreased expression of the oxidative stress response related genes sod-3, gst-4, and hsp-16.2. The treatment of mutant worms lacking the DAF-16 transcription factor with ALE resulted in a significant reduction of ROS levels. Contrarily, the extract had a pro-oxidant effect in the worms lacking the SKN-1 transcription factor. Our results suggest that the antioxidant activity of ALE in C. elegans is independent of its alkaloid content, and that SKN-1 is required for ALE-mediated stress resistance.
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Uncaria tomentosa, which is widely commercialized as an herbal medicine, constitutes an important source of secondary metabolites with diverse biological activities. For instance, we have previously reported, for the first time, of a polyphenolic profile rich in proanthocyanidins from extracts of U. tomentosa plants, as well as their antioxidant capacity, antimicrobial activity on aerial bacteria, and cytotoxicity on cancer cell lines. These promising results prompted this research to evaluate the polyphenolic contents of U. tomentosa commercial products. We report a detailed study on the polyphenolic composition of extracts from U. tomentosa bark products (n = 18) commercialized in Costa Rica and Spain. Using HPLC-DAD/TQ-ESI-MS, a total of 25 polyphenolic compounds were identified, including hydroxybenzoic and hydroxycinnamic acids, flavan-3-ol monomers, procyanidin dimers, procyanidin trimers, as well as propelargonidin dimers. Our findings on the polyphenolic profile for all commercial samples show analogous composition to previous reports on U. tomentosa bark material, for instance a 41–49% content of procyanidin dimers and the presence of propelargonidin dimers (8–15%). However, most of the 18 commercial samples exhibit low proanthocyanidin contents (254.8–602.8 µg/g), more similar to previous U. tomentosa inner bark reports, while some exhibit better results, with one sample (SP-2) showing the highest contents (2386.5 µg/g) representing twice the average value of all 18 commercial products. This sample also exhibits the highest total phenolics (TP) and total proanthocyanidins (PRO) contents, as well as the highest Oxygen Radical Absorbance Capacity (ORAC) value (1.31 µg TE/g). One-way Analysis of Variance (ANOVA) with a Tukey post hoc test indicated significant difference (p < 0.05) between products from Costa Rica and Spain for TP and PRO findings, with samples from Spain exhibiting a higher average value. In addition, Pearson correlation analysis results showed a positive correlation (p < 0.05) between TP, PRO, and ORAC results, and an especially important correlation between ORAC antioxidant values and procyanidin dimers (r = 0.843, p < 0.05), procyanidin trimers (r = 0.847, p < 0.05), and propelargonidin dimers (r = 0.851, p < 0.05) contents. Finally, Principal Component Analysis (PCA) results indicated some variability in the composition regardless of their origin. However, only one sample (SP-2) stands out significatively, showing the highest PC1 because of its particularly high proanthocyanidins contents, which could be attributed to the 15% bark polyphenolic extract labeled in this commercial product, which differentiate this sample from all other 17 commercial samples. Therefore, our findings confirmed previous results on the value of extracts in the elaboration of potential commercial products from U. tomentosa, rich in proanthocyanidins and exhibiting high antioxidant activity.
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Background: Treatment is the principle way to control and eliminate piroplasmosis. The search for new chemotherapy against Babesia and Theileria has become increasingly urgent due to parasite resistance to current drugs. Ivermectin (IVM) was the world's first endectocide, capable of killing a wide variety of parasites and vectors, both inside and outside the body. It is currently authorized to treat onchocerciasis, lymphatic filariasis, strongyloidiasis, and scabies. The current study documented the efficacy of IVM on the growth of Babesia and Theileria in vitro and in vivo. Methods: The fluorescence-based assay was used for evaluating the inhibitory effect of IVM on four Babesia species, including B. bovis, B. bigemina, B. divergens, B. caballi, and Theileria equi, the combination with diminazene aceturate (DA), clofazimine (CF), and atovaquone (AQ) on in vitro cultures, and on the multiplication of a B. microti-infected mouse model. The cytotoxicity of compounds was tested on Madin-Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3 T3), and human foreskin fibroblast (HFF) cell lines. Results: The half-maximal inhibitory concentration (IC50) values determined for IVM against B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi were 53.3 ± 4.8, 98.6 ± 5.7, 30.1 ± 2.2, 43.7 ± 3.7, and 90.1 ± 8.1 μM, respectively. Toxicity assays on MDBK, NIH/3 T3, and HFF cell lines showed that IVM affected the viability of cells with a half-maximal effective concentration (EC50) of 138.9 ± 4.9, 283.8 ± 3.6, and 287.5 ± 7.6 μM, respectively. In the in vivo experiment, IVM, when administered intraperitoneally at 4 mg/kg, significantly (p < 0.05) inhibited the growth of B. microti in mice by 63%. Furthermore, combination therapies of IVM-DA, IVM-AQ, and IVM-CF at a half dose reduced the peak parasitemia of B. microti by 83.7%, 76.5%, and 74.4%, respectively. Moreover, this study confirmed the absence of B. microti DNA in groups treated with combination chemotherapy of IVM + DA and IVM + AQ 49 days after infection. Conclusions: These findings suggest that IVM has the potential to be an alternative remedy for treating piroplasmosis.
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Background There are no effective vaccines against Babesia and Theileria parasites; therefore, therapy depends heavily on antiprotozoal drugs. Treatment options for piroplasmosis are limited; thus, the need for new antiprotozoal agents is becoming increasingly urgent. Ellagic acid (EA) is a polyphenol found in various plant products and has antioxidant, antibacterial and effective antimalarial activity in vitro and in vivo without toxicity. The present study documents the efficacy of EA and EA-loaded nanoparticles (EA-NPs) on the growth of Babesia and Theileria. Methods In this study, the inhibitory effect of EA, β-cyclodextrin ellagic acid (β-CD EA) and antisolvent precipitation with a syringe pump prepared ellagic acid (APSP EA) was evaluated on four Babesia species and Theileria equi in vitro, and on the multiplication of B. microti in mice. The cytotoxicity assay was tested on Madin-Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3) and human foreskin fibroblast (HFF) cell lines. Results The half-maximal inhibitory concentration (IC50) values of EA and β-CD EA on B. bovis, B. bigemina, B. divergens, B. caballi and T. equi were 9.58 ± 1.47, 7.87 ± 5.8, 5.41 ± 2.8, 3.29 ± 0.42 and 7.46 ± 0.6 µM and 8.8 ± 0.53, 18.9 ± 0.025, 11 ± 0.37, 4.4 ± 0.6 and 9.1 ± 1.72 µM, respectively. The IC50 values of APSP EA on B. bovis, B. bigemina, B. divergens, B. caballi and T. equi were 4.2 ± 0.42, 9.6 ± 0.6, 2.6 ± 1.47, 0.92 ± 5.8 and 7.3 ± 0.54 µM, respectively. A toxicity assay showed that EA, β-CD EA and APSP EA affected the viability of cells with a half-maximal effective concentration (EC50) higher than 800 µM. In the experiments on mice, APSP EA at a concentration of 70 mg/kg reduced the peak parasitemia of B. microti by 68.1%. Furthermore, the APSP EA-atovaquone (AQ) combination showed a higher chemotherapeutic effect than that of APSP EA monotherapy. Conclusions To our knowledge, this is the first study to demonstrate the in vitro and in vivo antibabesial action of EA-NPs and thus supports the use of nanoparticles as an alternative antiparasitic agent. Electronic supplementary material The online version of this article (10.1186/s13071-019-3520-x) contains supplementary material, which is available to authorized users.
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Background Chemotherapy is a principle tool for the control and prevention of piroplasmosis. The search for a new chemotherapy against Babesia and Theileria parasites has become increasingly urgent due to the toxic side effects of and developed resistance to the current drugs. Chalcones have attracted much attention due to their diverse biological activities. With the aim to discover new drugs and drug targets, in vitro and in vivo antibabesial activity of trans-chalcone (TC) and chalcone 4 hydrate (CH) alone and combined with diminazene aceturate (DA), clofazimine (CF) and atovaquone (AQ) were investigated. Methodology/Principal findings The fluorescence-based assay was used for evaluating the inhibitory effect of TC and CH on four Babesia species, including B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi, the combination with DA, CF, and AQ on in vitro cultures, and on the multiplication of a B. microti–infected mouse model. The cytotoxicity of compounds was tested on Madin–Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3), and human foreskin fibroblast (HFF) cell lines. The half maximal inhibitory concentration (IC50) values of TC and CH against B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi were 69.6 ± 2.3, 33.3 ± 1.2, 64.8 ± 2.5, 18.9 ± 1.7, and 14.3 ± 1.6 μM and 138.4 ± 4.4, 60.9 ± 1.1, 82.3 ± 2.3, 27.9 ± 1.2, and 19.2 ± 1.5 μM, respectively. In toxicity assays, TC and CH affected the viability of MDBK, NIH/3T3, and HFF cell lines the with half maximum effective concentration (EC50) values of 293.9 ± 2.9, 434.4 ± 2.7, and 498 ± 3.1 μM and 252.7 ± 1.7, 406.3 ± 9.7, and 466 ± 5.7 μM, respectively. In the mouse experiment, TC reduced the peak parasitemia of B. microti by 71.8% when administered intraperitoneally at 25 mg/kg. Combination therapies of TC–DA and TC–CF were more potent against B. microti infection in mice than their monotherapies. Conclusions/Significance In conclusion, both TC and CH inhibited the growth of Babesia and Theileria in vitro, and TC inhibited the growth of B. microti in vivo. Therefore, TC and CH could be candidates for the treatment of piroplasmosis after further studies.
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Cats claw Uncaria tomentosa , myrtle Myrtus communis , oregano Origanum vulgare , and cumin Cuminum cyminum have diverse medicinal properties. The current study evaluated the growth-inhibitory effects of these herbal extracts against Babesia and Theileria parasites in vitro and examined their cytotoxic properties. The half maximal inhibitory concentration IC 50 values against B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi for acetonic U. tomentosa extract were 16.1 0.7, 12.8 2.8, 29.5 1.5, 41.7 14.5, and 69.5 4.7 µg/ml, and those for acetonic M. communis extract were 88 35.1, 115.6 9.5, 33.8 1.9, 28.3 8.5, and 58.1 0.4 µg/ml, respectively. The half maximal effective concentration EC 50 values for acetonic U. tomentosa and M. communis extracts on Madin-Darby bovine kidney MDBK cell lines were 50.7 3.7 and 470 42.4 µg/ml, and those on human foreskin fibroblast HFF cell lines were 337.3 22.5 and 856 32.9 µg/ml, respectively. The ethanolic O. vulgare extract and methanolic C. cyminum extract exhibited IC 50 values of 240.4 9.7, 135.9 2.9, 116.6 1.6, 101.2 52.6, and 173.5 78.5 µg/ml and 293.3 3.1, 289.9 2.4, 243.2 6.8, 282.2 5.3, and 273.1 26.9 µg/ml against B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi, respectively, with EC 50 values on MDBK and HFF cell lines at 1000 44.6 and 1000 µg/ml, respectively. In conclusion, these extracts are effective against Babesia and Theileria in vitro without cytotoxic properties. Further research is necessary to identify the bioactive component of the herbal extracts and to evaluate the chemotherapeutic efficacy of the identified bioactive component against Babesia and Theileria in cattle and horses in the future.