Cat’s Claw
[Download PDF]
Uncaria tomentosa (Willd.) DC.; Uncaria guianensis (Aubl.)
Gmel.
[Fam. Rubiaceae]
Overview
Cat’s claw, also known by its Spanish name, uña de gato, is an herb that has gained
recent popularity in the U.S. herb market. Uña
de gato is the common name for at least 20 plants (from 12 different
families) with sharp, curved thorns (Obregon, 1995; Cabieses, 1994). Among them
are two climbing, woody vines: Uncaria
tomentosa and U. guianensis, the
two species of Uncaria (there are
approximately 60 species) (Obregon, 1995; Cabieses, 1994) native to the South
and Central American tropical rain forests that are the subject of this
monograph. According to U.S. herb industry policy, the standardized common name
“cat’s claw” refers to only U. tomentosa
(McGuffin et al., 2000), presumably
because products containing U. guianensis
were not generally available in the U.S. market during most of the 1990s,
having been introduced in the past several years. [Editors’ note: For the purposes of this monograph, U. tomentosa will be abbreviated as “UT”
and U. guianensis will be abbreviated
as “UG.” Because the information on each species and preparation type may be
specific to that particular species or preparation type, it may have been
preferable to write two or three separate monographs instead of one. However,
the editors chose to include all the relevant information on “cat’s claw” in
this single monograph, with subheadings designating species and preparation
type, where applicable. In doing so, the editors acknowledge that actions and
uses based on one species or preparation type may not be transferable to
another.]
Both UT and UG are said to have a long history of use by
indigenous people to treat a diverse set of health problems, particularly
rheumatism, arthritis, and other chronic inflammatory disorders, gastric ulcers
and gastrointestinal disorders, tumors, and as a contraceptive (Cabieses, 1994;
Jones, 1995; Obregon, 1995; Anon.,1996; Miller, 2001a). Although no written
records are available describing their traditional use (Cabieses, 1994), a
study of the medicinal system of the Ashaninca (also spelled Asháninka) tribe
in Peru has been published. To the priests of this tribe, cat’s claw (UT) is a
sacred plant used to eliminate disturbance in the communication between body
and spirit (Keplinger et al., 1999).
One account of the Asháninka Indians states that the priests differentiate
between the two UT chemotypes and use only the pentacyclic oxindole alkaloid
(POA) chemotype (Keplinger et al.,
1999), but how the priests can distinguish between chemotypes without the
scientific tools of chemical analysis is not described. Despite some recent
interest in this herb’s potential immunomodulating activity, ethnomedical
evidence of such use is lacking.
Several types of cat’s claw preparations have grown in
popularity in the U.S. with the market defined by the following five types of
products offered mainly by three manufacturers, each with their own distinct
focus: (1) an aqueous-acid or hydroalcoholic extract of UT root standardized to
pentacyclic oxindole alkaloids (POAs) with no tetracyclic oxindole alkaloids
(TOAs) [herein referred to as UT-POA], (2) an aqueous UT extract standardized
to carboxy alkyl esters (CAEs) [herein referred to as UT-CAE], (3) and an
aqueous UG extract [herein referred to as UG]. Two additional types of cat’s
claw products are relatively generic and usually labeled as UT: extracts not
standardized to any particular constituent [herein referred to as
UT-unspecified] and raw root bark products powdered in capsules or tablets, or
finely cut for teas (decoctions, the traditional form of use). Little scientific research has been performed
on this fifth class of crude products. Occasionally, products labeled as “cat’s
claw” in ethnic markets have been shown to be mislabeled due to the vast number
of plants known by the common name cat’s claw, and the lack of adequate quality
control with some small importers and distributors.
Fourteen clinical trials on various preparations are
summarized herein. One controlled clinical trial with UG suggests efficacy in
the treatment of osteoarthritis of the knee (Piscoya et al., 2001). While
cat’s claw’s popularity is partly due to European reports of its clinical
effectiveness in combination with AZT (zidovudine) for AIDS treatment, these
findings lack confirmation by well-controlled clinical studies. Other current
studies report on cat’s claw’s anti-inflammatory and antioxidant properties,
and its ability to affect gene expression and thereby modulate the immune system.
Cat’s claw is not yet popular in mainstream retail markets,
being sold primarily in health food stores where it ranked 25th in total herb
sales in 2000 (Richman and Witkowski, 2001), mail order, and in the ethnic
Hispanic market.
Description
Cat’s claw preparations are made from extracts of the dried
stalk, stalk bark (commonly called “root” bark), or actual root of U. tomentosa (Willd.) DC. or U. guianensis (Aubl.) Gmel. [Fam. Rubiaceae]. Products standardized to
POAs will often use the root rather than the root (stalk) bark, as it contains
a higher concentration of POAs. However, this practice destroys the plant,
whereas use of the stalk or root bark allows the vine to regenerate. Given that
a considerable portion of cat’s claw is still wild harvested, from an
environmental/sustainability perspective it may be more prudent long-term to
utilize the stalk and root bark rather than the actual root, or cultivate the
plants if the actual root is desired. Uncaria
tomentosa and U. guianensis are
distinguished by flower color, thorn shape, and leaf characteristics (Jones,
1995; Cabrieses, 1994). In addition, U.
guianensis contains lower levels of alkaloids (35 times less) and flavanols
than U. tomentosa (Sandoval et al., 2002, 2000; Miller et al., 2001).The U. tomentosa plants
occur naturally as two chemotypes that appear botanically identical, but are
chemically different in their alkaloid content (Laus et al., 1997). One chemotype contains predominantly POAs with
little or no TOAs, and the other contains TOAs with either no POAs or up to a
considerable amount. TOAs are reported to act antagonistically to some POA
activity (Wurm et al., 1998). While
early studies focused on POAs as the active components, more recent studies
report that activity is well spread over a range of polar materials. Several
commercial preparations of U. tomentosa
are available: aqueous-acid and hydroalcoholic extracts standardized to POAs
(containing no TOAs); a nonstandardized mixture of both chemotypes; and an
aqueous extract, ultrafiltrated, containing a negligible level of oxindole
alkaloids, and standardized to CAEs. One U.
guianensis preparation is composed of a freeze-dried aqueous extract. No
monographs on any cat’s claw preparation have been published to date in any
official pharmacopeias.
Primary Uses
Anti-inflammatory
Osteoarthritis (of the knee)
UG: reduces pain (Piscoya et al., 2001)
Rheumatoid arthritis–adjunct therapy to conventional treatment
UT-POA: reduces number of painful and swollen joints
(Mur et al., 2002; Immodal, 1995, 2002)
Other Potential Uses
[Editors’ note: the
following potential uses are based on clinical trials unless otherwise noted.]
Anti-inflammatory/Gastrointestinal
UG: protects gastric epithelial cells against
NSAID-induced gastritis and apoptosis in in vitro tests (Sandoval et al., 2002)
UT-unspecified: protects gastric epithelial cells
against NSAID-induced gastritis and apoptosis in animal and in vitro tests
(Sandoval et al., 2002; Sandoval-Chacón et al., 1998)
UT-POA: ulcers and gastritis (Immodal 1995, 1999a)
Antioxidant
UG: effectively scavenges DPPH (a, a-diphenyl-b-picrylhydrazyl), protects against
deoxyribose degradation, and inhibits ABTS (2,2’-azinobis
[3-ethyl-benzthiazoline-6-sulfonic acid]) radicals in in vitro tests (Sandoval et
al., 2002); limits gastric epithelial cell death in response to oxidative
stress in vitro (Miller et al., 2001)
UT-unspecified: effectively scavenges DPPH, protects
against deoxyribose degradation, and inhibits ABTS radicals in in vitro tests
(Sandoval et al., 2002); cytoprotective against oxidative stress in vitro (Sandoval-Chacón
et al., 1998)
Cancer–adjunctive to chemotherapy & radiation
UT-POA: increases vitality and reduces side effects
(Immodal, 1995, 1999a, 2002)
DNA-Repair/Antimutagenic
UT-unspecified: decreased
mutagenicity of one smoker’s urine (Rizzi et
al., 1993)
UT-CAE: enhanced
DNA repair (Sheng et al., 2001)
External Use
UT-POA: Herpes simplex and Varicella-zoster (Immodal 1995, 1999a, 2002)
HIV–adjunctive to antiretroviral therapy
UT-POA: stabilizes and/or reduces CD4-cell count,
increases vitality and mobility, reduced HIV-related symptoms (Immodal, 1995,
1999a, 2002)
Immune system support
UT-CAE: extends immunity from pneumonia vaccine (Lamm
et al., 2001); increases white blood cells (Sheng et al., 2001, 2000a) in
animal study (Sheng et al, 2000b)
Protection against UV radiation
UT-unspecified: cytoprotective
against UV radiation in vitro
(Sandoval et al., 2000; Rizzi et al., 1993)
Dosages
Crude Preparations
[Editor’s Note:
There is little scientific or clinical documentation supporting the use of
crude cat’s claw products. Most clinical research has been conducted on special
standardized preparations of various types.]
Uncaria guianensis
Capsules:
aqueous extract of bark powder, freeze-dried: 100 mg 1–3 times daily (Piscoya et al., 2001; Miller, 2001a).
Uncaria tomentosa–chemotype and active component
unspecified
Capsules:
350–500 mg, 1–2 times daily (CAMR, 1999).
Decoction: 1 g
root bark boiled for 15 minutes in 250 ml water, 1–3 times daily (Access, 2000;
CAMR, 1999).
Tincture: 1–2
ml, 2–3 times daily (CAMR, 1999).
Standardized Preparations
Uncaria tomentosa–standardized to CAEs
Tablets: 350 mg
daily (Lamm et al., 2001; Sheng et al., 2001, 2000a).
Uncaria tomentosa–standardized to POAs
Capsules: 20 mg
(0.26 mg POAs), 3 times daily for the first 10 days, and one capsule daily
thereafter (Enzymatic Therapy, 2002).
Capsules: 1–3
capsules/day (in acute cases, triple dose for 1st wk) (Immodal, 1995).
Drops (d): Adults: 3x20 d/day; 3–6 yrs: 3x7 d/day; 7–9
yrs: 3x10 d/day; 10–12 yrs: 3x15 d/day; 12+ yrs: 3x20 d/day (Immodal, 1995).
Tea: 20 g
ground root bark in 1 L water, boiled 45 min, cooled 10 min, filtered water
added to make 1 L. Adults: 60 ml decoction in 60 ml hot water before breakfast;
Children: decoction in hot water before breakfast according to the following
amounts: 3–6 yrs: 20 ml in 20 ml;
7–9 yrs: 30 ml in 30 ml; 10–12 yrs: 50 ml in 50 ml; 12+ yrs: same as adult
(Immodal, 1995).
Ointment: applied externally several times daily
(Immodal, 1995).
Spray: applied externally several times daily
(Immodal, 1995).
Duration Of Administration
At this time, there is little scientific information other
than ethnobotanical observations and 14 clinical trials (including case reports
and treatment observations) on how long cat’s claw can be consumed. Published
clinical trials have been conducted from as short as 4 weeks to 1 year of
continuous internal use, while unpublished treatment observations using Krallendorn®
(Immodal Pharmaka GmbH) products report on continuous (uncontrolled) use for up
to 10 years. There are no known reports of adverse effects associated with the
use of cat’s claw preparations for extended periods.
Chemistry
Although chemical research on cat’s claw began with UG in
1952 (Cabieses, 1994), most of the chemical research since then has focussed on
UT and its alkaloids, particularly the oxindole alkaloids. However, these
alkaloids are a small component of cat’s claw (approximately 0.9% in UT and
0.03% in UG [Sandoval et al., 2002]),
which is rich in flavonoids, quinovic glycosides, polyhydroxylated triterpenes,
and tannins. While earlier studies reported alkaloids as the active components
of cat’s claw (Aguilar et al., 2000;
Laus et al., 1998; Stuppner et al., 1993; Kreutzkamp, 1984; Wagner et al., 1985a, 1985b), more recent
studies report that bioactivity is spread over a wide range of components
(Aguilar et al., 2002; Sandoval et al., 2002; Kitajima et al., 2000; Lee et al., 1999; Sheng et al.,
1998; Wirth and Wagner, 1997; Aquino et
al., 1991, 1989; Cerri et al.,
1988), and one study suggests that the anti-inflammatory and antioxidant
activities of cat’s claw are not affected by the presence or relative level of
alkaloids (Sandoval et al., 2002).
Uncaria guianensis
The little chemical research performed on UG has been
limited to its alkaloid, quinovic acid glycoside, and flavanol content. UG
contains very low levels of alkaloids—35 times less than UT (Sandoval et al., 2002; Miller et al., 2001)—including speciophylline,
mitraphylline, isomitraphylline, uncarine E, and uncarine C (Sandoval et al., 2002; Miller et al., 2001; Lee et al., 1999). UG also contains quinovic acid glycosides (Yépez et al., 1991), flavanols (catechin,
epigallocatechin, epicatechin, and epigallocatechin) (Sandoval et al., 2002; Miller et al., 2001), and polyphenols (Miller et al., 2001). UG has lower
concentrations of the flavanols (except for epigallocatechin) than does UT
(Sandoval et al., 2002).
Uncaria tomentosa
UT has two chemotypes: the pentacyclic alkaloid type and
tetracyclic alkaloid type. The first contains POAs, which some consider to be
the main active component of cat’s claw (Immodal 1995, 1999a, 1999b), with
little or no TOAs. The second chemotype contains predominantly TOAs with either
no POAs or up to a considerable amount of POAs (Laus et al., 1997). TOAs are considered antagonistic to the purported
beneficial effects of the POAs (Wurm et
al., 1998) and thus, the significance in distinguishing between the two
chemotypes. As in any determination of the source of bioactivity in an unknown
natural product any proposed active constituent must mimic the actions of the
extract from which it was derived, and exert these actions at a concentration
that reflects its relative amount within that botanical or botanical extract.
Studies demonstrating that purified POAs or TOAs share the same bioactivity of
cat’s claw preparations but enhanced for the relative concentrations in these
extracts are lacking. Therefore, these chemical constituents may be more useful
as marker compounds rather than mediating the bioactivity of the botanical.
POAs in UT include pteropodine (uncarine C), isopteropodine
(uncarine E), speciophylline (uncarine D), uncarine F, mitraphylline, and isomitraphylline
(Muhammad et al., 2001a; Laus et al., 1997; Stuppner et al., 1992; Wagner et al., 1985b). The TOAs present in UT
include rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine
(Keplinger et al., 1999; Laus et al., 1997; Wagner et al., 1985b). Other alkaloids in UT
include pentacyclic indol alkaloids (akuammigine, tetrahydroalstonine,
isoajmalicin) (Laus et al., 1997),
tetracyclic indol alkaloids (hirsutine, dihydrocorynantheine, hirsuteine,
corynantheine) (Keplinger et al.,
1999; Laus et al., 1997), and
precursor alkaloids (5a-carboxystrictosidine,
lyaloside) (Aquino et al., 1991).
In addition to alkaloids, UT contains triterpenes (ursolic
acid derivatives, quinovic acid glycosides, oleanolic acid derivatives) (Laus et al., 1997; Aquino et al., 1991, 1990, 1989; Cerri et al.¸1988), polyhydroxylated
triterpenes (Aquino et al., 1991,
1990, 1989; Cerri et al.¸1988),
procyanidins ([-]-epicatechin, cinchonain 1a, cinchonain 1b) (Wirth and Wagner,
1997), sterols (b-sitosterol,
stigmasterol, campesterol) (Senatore et
al., 1989), flavanols (catechin, epigallocatechin, epicatechin and
epigallocatechin) (Sandoval et al.,
2002), tannins (Wagner et al., 1985b)
and CAEs (Sheng et al., 2001).
Pharmacological Actions
Human
Uncaria guianensis
Anti-inflammatory:
significantly reduced pain associated with activity in patients with
osteoarthritis of the knee (Piscoya et al.,
2001).
Uncaria tomentosa–unspecified preparations
Antimutagenic:
ingestion for 15 days decreased mutagenicity of one smoker’s urine (Rizzi et al., 1993).
Uncaria tomentosa–standardized to CAEs
Immunomodulation/immune
support: enhanced response to pneumoccoccal vaccine by reducing
decay of antibody titers and elevating lymphocyte/neutrophil (Lamm et al., 2001); decreased DNA damage
(measured as single strand breaks in DNA) from single dose of hydrogen peroxide
and increased DNA repair (Sheng et al.,
2001); increased white blood cell levels in healthy males (Sheng et al., 2000a).
Antimutagenic:
decreased DNA damage (measured as single strand breaks in DNA) from single dose
of hydrogen peroxide and increased DNA repair (Sheng et al., 2001); enhances DNA repair (Sheng et al., 2000a).
Uncaria tomentosa–POA chemotype
Anti-inflammatory: reduced number of painful and tender
joints and decreased duration of morning stiffness in rheumatoid arthritis
patients (Mur et al., 2002; Immodal, 1995, 2002); eliminated symptoms and need
for antacids in ulcer and gastritis patients (Immodal 1995, 1999a).
Immunomodulation/immune support: increased vitality and
reduced side effects in cancer patients undergoing chemotherapy, radiation, or
surgery (Immodal 1995, 1999a, 2002); reduced HIV-related symptoms and increased
vitality of HIV patients receiving antiretroviral treatment, increased
lymphocyte numbers in HIV patients although total leukocyte numbers remained
unchanged, stabilized or increased CD4 cell count in HIV patients (Immodal
1995, 1999a, 2002).
Animal
Uncaria tomentosa–unspecified preparations
Anti-inflammatory:
significantly reduced paw volume in carrageen-induced rat paw edema (Aguilar et al., 2002, 2000; Aquino et al., 1991); protected against
NSAID-induced gastritis by reducing lesions and apoptosis of the mucosal
epithelial cells (Sandoval et al.,
2002); prevention of NSAID-induced enteropathy in rats (Sandoval-Chacón et al., 1998).
Uncaria tomentosa–standardized to CAEs
Immunomodulation/immune
support: increased DNA repair of single and double strand breaks
from whole body irradiation in rats (Sheng et
al., 2000a); increased white blood cell count sooner, and all fractions
proportionally, compared with control in rat model of chemotherapy-induced
leukopenia (Sheng et al, 2000b);
prolonged leukocyte survival in rats at daily doses of 125–500 mg/kg body
weight (Åkesson et al., 2003).
Uncaria tomentosa–POA chemotype
Anti-inflammatory:
significantly reduced paw volume in carrageen-induced rat paw edema (Aguilar et al., 2002, 2000).
Isolated components of Uncaria species
[Editors’ note: The studies referenced in this
subsection were performed with compounds isolated from U. rhynchophylla or U.
sinensis. While these compounds are also found in U. guianensis and/or U.
tomentosa, no studies have been performed on extracts or fractions derived
from UG or UT to verify that these
actions apply to them as well; thus their clinical significance is
undetermined. These studies have been included because some proponents of the
UT products standardized to POAs and no TOAs, cite them in support of the need
for removal of TOAs from cat’s claw products.]
Isorhynchophylline reduced blood pressure and heart rate
in rats and dogs (Shi et al., 1989);
rhynchophylline and isorhynchophylline reduced blood pressure and heart rate in
dogs, with isorhychophylline demonostrating a stronger effect (Shi et al., 1992).
In vitro
Uncaria guianensis
Anti-inflammatory:
reduces excessive production of cytokines and inflammatory mediators at the
genetic level (Sandoval et al., 2002;
Piscoya et al., 2001) with UG being
more potent than UT (Sandoval et al.,
2002), and at extract concentrations far lower than required for antioxidant
activity (Piscoya et al., 2001);
prevents and eliminates gastrointestinal injury and inflammation in
NSAID-induced gastritis (Sandoval et al.,
2002).
Antioxidant: scavenges DPPH (UG more potent than UT despite
lower concentrations of alkaloids and flavanols), protects against deoxyribose
degradation in a dose-dependent manner, and inhibits ABTS-radicals (Sandoval et al., 2002); effectively scavenges
free radicals and inhibits lipid peroxidation (Piscoya et al., 2001); protects human gastric epithelial cells from
apoptosis induced by DPPH, peroxynitrite and H2O2 (Miller
et al., 2001).
Uncaria tomentosa–unspecified preparations
Anti-inflammatory: reduces excessive production of
cytokines and inflammatory mediators at the genetic level with UG being more
potent than UT, and at extract concentrations far lower than required for
antioxidant activity (Sandoval et al., 2002; Piscoya et al., 2001); suppressed
tumor necrosis factor alpha (TNF)
production by 65–85% (Sandoval et al., 2000); prevents and eliminates
gastrointestinal injury and inflammation in NSAID-induced gastritis (Piscoya et
al., 2001; Sandoval et al., 2000; Sandoval-Chacón et al., 1998); reduces
cyclo-oxygenase-2 (COX-2) expression (Piscoya et al., 2001).
Antioxidant: scavenges DPPH (UG more potent than UT
reflected as lower IC50 value despite lower concentrations of alkaloids and
flavanols), protects against deoxyribose degradation in a dose-dependent
manner, and inhibits ABTS-radicals (Sandoval et al., 2002, 2000); effectively
scavenges free radicals and inhibits lipid peroxidation (Piscoya et al., 2001);
protects human gastric epithelial cells from apoptosis induced by DPPH,
peroxynitrite and hydrogen peroxide (Miller et al., 2001); reduces
peroxynitrite-induced apoptosis in human gastric epithelial cells and in
macrophages (Sandoval-Chacón et al., 1998); protective against UV
irradiation-induced cytotoxicity (Sandoval et al., 2000).
Immunomodulation/immune support: Increased cytokine
(IL-1 and IL-6) production in alveolar macrophages (Lemaire et al., 1999)
although high concentrations were used that might reflect a toxicologic
response and may be incompatible with in vivo efficacy (Sandoval et al., 2002).
Antimutagenic: protective against photomutagenesis,
(Rizzi et al., 1993).
Uncaria tomentosa–standardized to CAEs
Immunomodulation/immune
support: CAE: significantly increased PHA
(phytohemagglutinin)-stimulated lymphocyte proliferation in splenocytes and
significantly elevated white blood cell (WBC) count (Sheng et al., 2000a).
Antiproliferative:
inhibited proliferation and induced apoptosis in some tumor cell lines (Sheng et al., 1998) at high concentrations
that might reflect a toxicologic response (Sandoval et al., 2000).
Uncaria tomentosa–POA chemotype
Anti-inflammatory:
moderate to weak activity against cyclo-oxygenase-1 and -2 (COX-1 and COX-2)
(Aguilar et al., 2002).
Antiproliferative:
Inhibited proliferation of some human tumor cell lines (Immodal, 1999b).
Isolated Chemical Components from Cat’s Claw
[Editors’ note: As
in any determination of the source of bioactivity in an unknown natural
product, any proposed active constituent must mimic the actions of the extract
from which it was derived, and exert these actions at a concentration that
reflects its relative amount within that botanical or botanical extract.
Studies demonstrating that purified POAs or TOAs share the same bioactivity of
cat’s claw preparations but enhanced for the relative concentrations in these
extracts are lacking. Therefore, these chemical constituents may be more useful
as marker compounds rather than mediating the bioactivity of the botanical.]
Immunomodulation/Immune
Support: Phagocytosis was enhanced in vitro by pteropodine, isomitraphylline, and isorhynchophylline
(two POAs and one TOA, isolated from UT), but phagocytosis was enhanced in vivo only after addition of catechin
to POAs (Wagner et al., 1985a, 1985b;
Kreutzkamp, 1984); POAs isolated from UT induced endothelial cells to release a
factor that inhibited proliferation of normal human lymphoblasts and stimulated
proliferation of normal human resting lymphocytes, while TOAs dose-dependently
reduced these effects (Wurm et al.,
1998); POAs isolated from UT inhibited growth of HL60 and U-937 leukemic cells,
with uncarine F demonstrating the strongest effect; (Stuppner et al., 1993 cited in Keplinger et al., 1999); isopteropodine (POA
isolated from UT) increases the phagocytosis of granulocytes and
reticuloendothelial system (RES) cells (Kreutzkamp, 1984; Wagner et al., 1985a, 1985b).
Anti-inflammatory:
17 non-alkaloid HPLC fractions from UT reduced TNFa and nitrite production induced by lipopolysaccharide (LPS) in
RAW 264.7 cells (Sandoval et al.,
2002); one quinovic acid glycoside isolated from UT demonostrated
anti-inflammatory effects, but it appears that the strong anti-inflammatory
effects of cat’s claw extracts and fractions may be the result of the
synergistic activity of a combination of compounds (Aquino et al., 1991); moderate anti-inflammatory activity has been
demonstrated for b-sitosterol,
stigmasterol and campesterol isolated from UT (Senatore et al., 1989); one procyanidine (cinchonain Ib) isolated from UT
inhibited 5-lipoxygenase, demonstrating anti-inflammatory activity (Wirth and
Wagner, 1997).
Antiviral: 9 quinovic acid glycosides isolated from UT
showed moderate antiviral activity against vesicular stomatitis virus, but at
concentrations approaching cellular toxicity (Aquino et al., 1989); two quinovic acid glycocides isolated from UT (those
with free carboxyl groups) reduced by 50% the viral cytopathic effect of
rhinovirus type 1b infection (Aquino et
al., 1989).
Antiproliferative: Uncarine D showed weak cytotoxic activity
against SK-MEL, KB, BT-549 and SK-OV-3 cell lines with IC50 values between 30
and 40 mg/ml, while uncarine C exhibited weak cytocoxicity only against
ovarian carcinoma (IC50 at 37 mg/ml) (Muhammad et al., 2001b). However, given the concentration of uncarine C in
cat’s claw, the amount of cat’s claw that would have to be consumed to achieve
these concentrations in vivo may be
unrealistic. In addition to the antimutagenic activity, UT extracts and
factions exert a direct antiproliferative activity on the MCF7 human breast
cancer cell line. The bioassay-directed fraction from barks and leaves resulted
in the isolation of 2 active fractions, displaying an IC50 of 10 mg/ml and 20
mg/ml, respectively and an antiproliferative effect, with about 90% of
inhibition at a concentration of 100 mg/ml (Riva et al., 2001). As noted above, for the alkaloids uncarine D and C,
these fractions would require an unrealistic consumption of kilogram quantities
of cat’s claw to achieve these actions.
Isolated Chemical Components from other Uncaria species
[Editors’ note:
The studies referenced in this subsection were performed with compounds
isolated from U. rhynchophylla or U. sinensis. While these compounds are
also found in U. guianensis and/or U. tomentosa, no studies have been
performed on extracts or fractions derived from UG or UT to verify that these
actions apply to them as well; thus their clinical significance is
undetermined. These studies have been included because some proponents of the
UT products standardized to POAs and no TOAs, cite them in support of the need
for removal of TOAs from cat’s claw products.]
Rhynchophylline and isorhynchophylline produced negative
chronotropic and inotropic effects (Zhu and Guozing, 1993); rhynchophylline
inhibits platelet aggregation (Chen et al.,
1992; Jin et al., 1991);
rhynchophylline may be a calcium antagonist (Sun et al., 1988; Zhang et al.,
1987); rhynchophylline, corynoxeine, isorhynchophylline, isocorynoxeine, and
indole alkaloids such as hirsuteine and hirsutine inhibit Ca2+ influx which
protects against glutamate-induced neuronal death (Shimada et al, 1999; Yano et al.,
1991); corynantheine and dihydrocorynantheine have sedative action which in
toxic dosages may lead to respiratory paralysis and ataxia (Kanatani, 1985);
corynantheine and dihydrocorynantheine reduced specific [3H]5-HT binding and
were found to be partial agonists for 5-HT receptors (Kanatani, 1985).
Mechanisms Of Action
Uncaria guianensis
Anti-inflammatory
Modifies gene expression by inhibiting
redox-sensitive transcription factors (Piscoya et al., 2001; Sandoval et al.,
2002).
Inhibits transcription factor NF-kB thereby modifying
expression of genes involved in the inflammatory process including TNFa, inducible nitric oxide synthase (iNOS),
and COX-2 (Sandoval et al., 2002;
Piscoya et al., 2001).
Inhibits production of TNFa (Sandoval et al.,
2002; Piscoya et al., 2001) with UG
being more potent than UT (Sandoval et al.,
2002).
Decreases production of lipopolysaccharide-induced
prostaglandin E-2 (Piscoya et al.,
2001).
Antioxidant
Scavenges DPPH (UG more potent than UT despite lower
concentrations of alkaloids and flavanols), protects against deoxyribose
degradation in a dose-dependent manner, and inhibits ABTS-radicals (Sandoval et
al., 2002).
Effectively scavenges free radicals and inhibits
lipid peroxidation (Piscoya et al., 2001; Miller et al., 2001).
Protects human gastric epithelial cells from
apoptosis induced by DPPH, peroxynitrite and hydrogen peroxide (Miller et al.,
2001).
More effective in limiting the cellular response to
oxidants than degrading the oxidant itself (Miller et al., 2001; Piscoya et al.,
2001).
Uncaria tomentosa–unspecified
Anti-inflammatory
Modifies gene expression by inhibiting
redox-sensitive transcription factors (Piscoya et al., 2001; Sandoval et al.,
2000; Sandoval-Chacón et al., 1998).
Inhibits transcription factor NF-kB thereby modifying
expression of more than 28 genes involved in the inflammatory process including
TNFa, iNOS, and COX-2 (Aguilar et al., 2002; Sandoval et al., 2002; Piscoya et al., 2001; Sandoval-Chacón et al., 1998).
Inhibits lipopolysaccharide-induced iNOS gene
expression, nitrite formation, and cell death (Sandoval-Chacón et al., 1998).
Inhibits production of TNFa, iNOS, and COX-2 (Sandoval et
al., 2002; Piscoya et al., 2001;
Sandoval-Chacón et al., 1998).
Moderate to weak activity against COX-1 and COX-2
(Aguilar et al., 2002).
Decreased production of lipopolysaccharide-induced
prostaglandin E-2 (Piscoya et al.,
2001).
Suppressed TNFa
production (Sandoval et al., 2002;
Piscoya et al., 2001; Sandoval-Chacón
et al., 1998) by 65–85% (Sandoval et al., 2000).
Antioxidant
Scavenges DPPH (UG more potent than UT despite lower
concentrations of alkaloids and flavanols), protects against deoxyribose
degradation in a dose-dependent manner, and inhibits ABTS-radicals (Sandoval et al., 2002; 2000).
Effectively scavenges free radicals and inhibits
lipid peroxidation (Piscoya et al.,
2001).
Protects human gastric epithelial cells from
apoptosis induced by DPPH, peroxynitrite and H2O2 (Miller et al., 2001).
Reduces peroxynitrite-induced apoptosis in human
gastric epithelial cells and in macrophages (Sandoval-Chacón et al., 1998).
Cytoprotective against UV irradiation (Sandoval et al., 2000).
Immunomodulation/immune
support
Increased cytokine (IL-1 and IL-6) production in
alveolar macrophages (Lemaire et al., 1999) although high concentrations were
used suggesting that this action could only be observed in vivo with ingestion
of kilogram quantities; a dosing regimen that might reflect a toxicologic
response (Sandoval et al., 2002).
Stimulates interleukin-1 (IL-1) and interleukin-6
(IL-6) production at a rate of 10.0x and 7.5x control levels, respectively. The
effect is dose-dependent and diminishes when the dose exceeds the range of
0.025–0.1 mg/ml (Lemaire et al., 1999).
Uncaria tomentosa–standardized to
CAEs
Antimutagenic
Stimulation of DNA repair mechanisms (Sheng et al.,
2000a, 2001).
Immunomodulation/Immune
support
Stimulates lymphocyte proliferation and elevates
white blood cells (Sheng et al.,
2000a, 2000b; Lamm et al., 2001).
Anti-tumor
Suppresses tumor growth through selective induction
of apoptosis in two human leukemic cell lines (K562 and HL60) and one human
EBV-transformed B-lymphoma cell line (Raji) (Sheng et al., 1998); however, some authors have reported apoptosis in
these same cell lines due to inhibition of NF-kB (Sandoval et al., 2002; Mannick et al.,
1997; Beg and Baltimore, 1996).
Uncaria tomentosa–POA chemotype
Anti-inflammatory
Moderate to weak activity against COX-1 and COX-2
(Aguilar et al., 2002).
Inhibits synthesis of NF-kB (Aguilar et al., 2002; 2000).
Immunomodulation/Immune
Support
POAs induce the release of a lymphocyte-growth factor
from endothelial cells that regulates lymphocyte proliferation (Wurm et al., 1998), but does not change total
leukocyte numbers (Keplinger et al.,
1999). TOAs act antagonistically to this effect of POAs (Wurm et al., 1998; Keplinger et al., 1999).
Contraindications
Cat’s claw has been contraindicated for leukemia patients
awaiting bone marrow transplant, any patient awaiting organ transplant, persons
with iatrically-induced immunosuppression (e.g., organ transplants), autoimmune
disease, multiple sclerosis, or tuberculosis (CAMR, 1999). These
contraindications are based on the belief that cat’s claw is an
immunostimulant. However, some researchers disagree with this view (Miller,
2001b; Sandoval-Chacón et al., 1998;
Sandoval et al., 2000, 2002) and
suggest that cat’s claw may be helpful for transplant patients (Miller, 2001a).
The elevated production of TNFa is
a characteristic of numerous autoimmune disorders, including those in which
cat’s claw offers benefits (arthritis, gut inflammation) and lowering TNFa levels, as with cat’s claw, may be
desirable rather than contraindicated for these patients. HIV/AIDS patients
should proceed with caution when introducing any new therapeutic agent (Miller,
2001b). Cat’s claw is not for use in children under 3 years due to lack of data
regarding its effects on the immature immune system (Immodal, 1995).
Pregnancy and Lactation: Not recommended
(Jones, 1995) due to lack of data regarding the effects of cat’s claw on the
immature immune system (Immodal, 1995).
Adverse Effects
Recent human trials have concluded that the various cat’s
claw preparations tested are safe, with no adverse effects reported in liver,
renal, central nervous system, or hematological function (Piscoya et al., 2001; Sheng et al., 2001, 2000a; Lamm et
al., 2001). Cat’s claw teas or crude extracts may cause mild nausea, due to
the bitter taste (Williams, 2001); however, this appears speculative as nausea
is not a frequently reported effect. In one case report, a patient with
systemic lupus erythematosus (SLE) experienced acute renal failure, which the
authors attributed to an idiosyncratic adverse reaction to the purported cat’s
claw preparation which was not adequately documented (Hilepo et al., 1997).
Uncaria guianensis
In one study infrequent reports of headache, dizziness, and
vomiting were reported but the incidence and frequency were the same as with
placebo (Piscoya et al., 2001).
Uncaria tomentosa–standardized
to CAEs
None reported.
Uncaria tomentosa–POA
chemotype
In AIDS patients and patients receiving large doses of
chemotherapy, individual cases of a mild erythrocytosis have been reported.
During the first 1–2 weeks of ingesting cat’s claw tea (Krallendorn®)
temporary constipation or mild diarrhea was sometimes observed. Increased
occurrence of acne symptoms has been reported in HIV patients with prior
symptoms. In rare cases, elevated uric acid values were observed in HIV and
cancer patients; extensive cell die-off in tumor patients may cause lytic fever
lasting 1–2 weeks (Immodal, 1999a, 1995).
Components from Other Species of Uncaria
Cat’s claw products containing larger
amounts of TOAs could possibly result in sedative effects and circulatory
complaints (e.g., reduced blood pressure, coronary blood flow, and heart rate;
inhibited platelet aggregation) (Reinhard, 1999), due to the reported effects
of TOAs in Uncaria species other than
UT or UG (Shi et al., 1992, 1989; Jin
et al., 1991). However, no such
effects have been reported in studies using products made with UT or UG.
Drug Interactions
Uncaria guianensis
None reported.
Uncaria tomentosa–unspecified
preparations
UT may potentially reduce the rate of metabolism and thus
increase serum levels of drugs taken orally as observed in an in vitro assay on an unspecified UT
tincture where the CYP3A4 isozyme production was inhibited (Budzinski et al., 2000).
Some authors warn that some unspecified forms of cat’s claw
may increase the effects of anticoagulants and antihypertensives (Fetrow and
Avila, 2000; CAMR, 1999; Spaulding-Albright, 1997; INPR, 1999). However, this
is based on research on TOA components isolated from Uncaria species other than UG or UT. While it is possible that
cat’s claw products rich in TOAs may interact with these classes of drugs,
there are no reliable data to support this conclusion. Further, there is little
evidence to support this interaction with cat’s claw products that contain
little or no TOAs such as UG products or the UT product Krallendorn®,
or C-Med-100® (AF Nutraceutical Group).
Uncaria tomentosa–standardized to
CAEs
None reported.
Uncaria tomentosa–POA chemotype
According to a communication to physicians and pharmacists
from the leading Austrian research and manufacturing company of cat’s claw, the
following advice should be given to patients, based on the products proposed
immunomodulatory effects:
Take between chemotherapy treatments and after completion,
but not with chemotherapy treatments; do not take in conjunction with passive
animal vaccines, intravenous hyperimmunoglobulin therapy; intravenous thymic
extracts, drugs using animal protein or peptide hormones (e.g., bovine or
porcine insulin), cryoprecipitates, or fresh blood plasma (Immodal, 1995).
American Herbal Products Association (AHPA) Safety Rating
Class 4:
Insufficient data available for classification (McGuffin et al., 1997).
[Editors’ Note:
Cat’s claw was not widely marketed during the time that the literature upon
which this book is based was published, mainly 1980s and early to mid-1990s. Of
potential relevance is the fact that numerous studies show cat’s claw to be
safe. Human, animal, and in vitro
studies demonstrate the antimutagenic activity of cat’s claw (Sheng et al., 2001, 2000a, 1998; Immodal,
1999b; Leon et al., 1996; Rizzi et al., 1993). One human trial found no
toxic effects at a dose of 350 mg/day of C-Med-100® for 6
consecutive weeks (Sheng et al.,
2000a). One animal study reports an LD50 of greater than 16 g/kg of body weight
using a freeze-dried aqueous extract of POA type UT (Kynoch and Lloyd, 1975),
while a second reports an LD50 of greater than 8 g/kg for C-Med-100. Another
study found daily oral administration of an aqueous-acid extract of UT at 1,000
mg/kg body weight for 28 days to be atoxic in rats (Svendson and Skydsgaard,
1986). In an additional test, an aqueous extract of UT was atoxic up to the
maximum dosage of 5 g/kg body weight administered orally, and up to a concentration
of 2 g/kg body weight administered intraperitoneally (Kreutzkamp, 1984). The
alkaloid fraction of UT was found to be atoxic up to the maximum dosage of 2
g/kg body weight orally, and 1 g/kg body weight intraperitoneally (Kreutzkamp,
1984).]
Regulatory Status
Austria:
Prescription drug Krallendorn® (pentacyclic chemotype).
Canada:
Status undetermined. No products containing cat’s claw are listed in the Health
Canada Drugs Product Database (Health Canada, 2001).
Germany: No
German Commission E monograph (Blumenthal et
al., 1998). No monograph in the German
Pharmacopoeia (DAB, 1999).
Sweden: No
products containing cat’s claw are listed in the Medical Products Agency (MPA)
“Authorised Natural Remedies” (MPA, 2001).
Switzerland: No
products containing cat’s claw are listed in the Swiss Drug Compendium (Morant and Ruppanner, 2001). No monograph in
the Swiss Pharmacopoeia.
U.K.: Not listed in the General
Sale List (GSL, 1994). No monograph in the British Pharmacopoeia.
U.S.: Dietary supplement (USC, 1994). No monograph in the
USP-NF.
Clinical Review
There are 14 clinical trials on various preparations made
from the two species of Uncaria summarized
in the Clinical Studies Tables in this monograph. In general, the studies are
relatively small, most are uncontrolled, and some have not been published. One
prospective (P), randomized (R), double-blind (DB), placebo-controlled (PC),
parallel group (PG), multi-center (MC) trial was conducted on 45 men who
consumed 100 mg of a freeze-dried aqueous extract of UG for 4 weeks for
osteoarthritis of the knee (Piscoya et
al., 2001). The study reports a significant improvement in pain associated
with activity, and medical and patient assessment scores, but no significant
improvement in pain at rest or at night, or knee circumference. There were no
significant side effects in the UG and placebo groups.
Three trials tested the UT-CAE preparation (C-Med-100®)
on immunomodulatory parameters. One small R, PC trial (n=23) resulted in no
loss of immunity after 5 months in patients given a pneumonia vaccine after 2
months of treatment with 700 mg per day of the UT-CAE extract when compared to
loss in the placebo group (Lamm et al.,
2001). Another small trial (n=12) reported an increase in DNA repair with no
adverse effects (Sheng et al., 2001).
An uncontrolled trial on healthy volunteers resulted in an increase in white
blood cells (Sheng et al., 2000a).
Three trials tested a proprietary extract of UT standardized
to POAs (Krallendorn®) for anti-inflammatory effects. One 52-week
trial on 40 people with rheumatoid arthritis (RA) used 60 mg per day of the
extract in capsules (Mur et al.,
2002). The first phase (24 weeks) was R, DB, PC; the second phase (28 weeks)
was not blinded—all patients received the treatment. There was a significant
decrease in pain and a shorter period of morning stiffness for the treatment
group compared to placebo after the first phase and a further reduction after
the second phase. The placebo-cat’s claw treatment group experienced some
reduction of symptoms in the second phase. Two small uncontrolled, unpublished
trials test the UT-POA extract on patients with RA (Immodal, 1995, 2002) and on
ulcers and gastritis (Immodal, 1995, 1999a).
Five trials tested the UT-POA extract for its effects on
immune function. All five trials were uncontrolled and unpublished, thereby
raising questions as to the significance of the results. Two trials tested the
UT-POA extract as an adjuvant therapy for cancer patients undergoing
chemotherapy, radiation, and/or surgery (Immodal 1995, 1999a, 2002) with
generally favorable results, including patients’ reports of a greater sense of
vitality and fewer side effects; three additional trials tested UT-POA extract
as an adjuvant therapy for HIV-positive patients (Immodal 1995, 1999a, 2002)
and reported stabilized or increased CD-4 cell counts, increased vitality, and
no adverse effects.
Two uncontrolled, unpublished trials were performed on the
UT-POA extract in topical preparations for use on lesions caused by Herpes simplex (Immodal, 1995, 1999a,
2002) and Varicella zoster (Immodal,
1995, 1999a, 2002), showing improvement and no adverse effects.
Branded Products
C-MED-100®: Campamed, LLC / 437 Madison Avenue /
New York, NY 10022 / U.S.A. / Tel: 212-616-6814 / Fax: 212-838-8918. Patented extract
of Uncaria tomentosa, standardized to
8% by carboxy alkyl esters. Ultrafiltrated, 100% water soluble extract
spray-dried and compressed into 350 mg tablets.
Krallendorn® Capsules: Immodal Pharmaka GmbH /
Bundesstrasse 44 / 6111 Volders / Austria / Tel: +43-05-22-45-7678 / Fax:
+43-05-22-45-7646. Cat’s claw root (pentacyclic chemotype) aqueous-acid extract
standardized to contain 1.3% POAs, and undetectable TOAs.
Krallendorn® Drops: Immodal Pharmaka GmbH. Cat’s
claw root (pentacyclic chemotype) aqueous-acid extract standardized to contain
1.3% POAs, and undetectable TOAs; each 100 g of drop solution contains 600 mg
cat’s claw extract, water, ethanol (95% by volume).
Krallendorn® Ointment: Immodal Pharmaka GmbH.
Cat’s claw root (pentacyclic chemotype) aqueous-acid extract standardized to
contain 1.3% POAs, and undetectable TOAs; each 75 g of ointment contains 300 mg
cat’s claw extract.
Krallendorn® Spray: Immodal Pharmaka GmbH. Cat’s
claw root (pentacyclic chemotype) aqueous-acid extract standardized to contain
1.3% POAs, and undetectable TOAs; each 100 g of spray solution contains 600 mg
cat’s claw extract.
Krallendorn® Tea: Immodal Pharmaka GmbH. Cat’s
claw root (pentacyclic chemotype), ground.
*American equivalents, if any, are found in the Product Table
beginning on page 398.
References
Access. Professional Reference to Conditions, Herbs and Supplements. Newton
(MA): Integrative Medicine Communications; 2000.
Aguilar JL, Rojas PA, Capcha RC, Plaza A, Merfortl I. Anti-inflammatory and
molecular activity of extracts of Uña de gato with different concentrations of
pentacyclic and tetracyclic alkaloids and of a freeze-dried extract. Congreso
Internacional FITO 2000; Lima, Peru.
Aguilar JL, Rojas P, Marcelo A, Plaza A, Bauer R, Reininger E, et al.
Anti-inflammatory activity of two different extracts of Uncaria tomentosa
(Rubiaceae). J Ethnopharmacol 2002;81(2):271–6.
Åkesson C, Pero RW, Ivars F. C-Med 100®, a hot water extract of Uncaria tomentosa,
prolongs leukocyte survival in vivo. Phytomedicine 2003;30 [in press].
Anonymous. Cat’s Claw. The Lawrence Review of Natural Products Apr
1996;1–3.
Aquino R, DeFeo V, DeSimone F, Pizza C, Cirino G. Plant metabolites. New
compounds and anti-inflammatory activity of Uncaria tomentosa. J Nat Prod
1991;54(2):453–459.
Aquino R, DeSimone F, Vincieri FF, Pizza C, Gaes-Baitz E. New
polyhydroxylated triterpenes from Uncaria tomentosa. J Nat Prod 1990
May-Jun:53(3):559–64.
Aquino R, DeSimone C, Pizza. Plant metabolites. Structure and in vitro
antiviral activity of quinovic acid glycosides from Uncaria tomentosa and Guettarda
platypoda. J Nat Prod 1989;52(4):679–685.
Beg AA, Baltimore D. An essential role for NF-kB in preventing TNFa-induced cell death. Science
1996;274:782–410. Cited in Sandoval M, Okuhama NN, Zhang X-J, Condezo LA, Lao
J, Angeles FM, Bobrowski P, Miller MSJ. Anti-inflammatory and antioxidant
activities of cat’s claw (Uncaria tomentosa and Uncaria guianensis) are
independent of their alkaloid content. Phytomed 2002;9(4):325–37.
Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW, Rister
RS, editors. Klein S, Rister RS (trans.). The Complete German Commission E
Monographs—Therapeutic Guide to Herbal Medicines. Austin (TX): American
Botanical Council; Boston: Integrative Medicine Communication; 1998.
Budzinski JW, Foster BC, Wandenhoek S, Arnason JT. An in vitro evaluation
of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts
and tinctures. Phytomedicine 2000 Jul;7(4):273–82.
Cabieses F. The saga of the cat´s claw. Lima, Peru: Via Lactea Editores;
1994.
CAMR. See: Center for Alternative Medicine Research.
Center for Alternative Medicine Research. Cat’s Claw Summary [University of
Texas, Health Science Center at Houston, School of Public Health web site]. 4
May 1999. Available at: http://www.sph.uth.tmc.edu/utcam/summary/cat.htm.
Accessed 18 Oct 1999.
Cerri R, Aquino R, De Simone F, Pizza C. New quinovic acid glycosides from Uncaria
tomentosa. J Nat Prod 1988;51:257–61. Cited in Sandoval M, Okuhama NN, Zhang
X-J, Condezo LA, Lao J, Angeles FM, Bobrowski P, Miller MSJ. Anti-inflammatory
and antioxidant activities of cat’s claw (Uncaria tomentosa and Uncaria
guianensis) are independent of their alkaloid content. Phytomed
2002;9(4):325–37.
Chen CX, Jin RM, Li YK, Zhong J, Yue L, Chen SC, Zhou JY. Inhibitory effect
of rhynchophylline on platelet aggregation and thrombosis. Acta Pharamacol Sin
1992;13(2):126-130.
DAB. See: Deutsches Arzneibuch.
Deutsches Arzneibuch (DAB). Stuttgart, Germany: Deutscher Apotheker Verlag;
1999.
Enzymatic Therapy. SaventaroÒ [product
information]. Accessed 26 Jul 2002. Available at URL: www.enzy.com/products.
Fetrow CW, Avila JR. The Complete Guide to Herbal Medicines.
Springhouse(PA):Springhouse Corporation; 2000. p. 113–4.
General Sale List (GSL). Statutory Instrument 1994 No. 2410: The Medicines
(Products Other than Veterinary Drugs). London, UK: Her Majesty’s Stationery
Office (HMSO); 1994.
GSL. See: General Sale List.
Health Canada. Drug Product Database (DPD) Product Information. Ottawa,
Ontario: Health Canada Therapeutic Products Programme; 2001.
Hilepo J, Bellucci A, Mossey R. Acute renal failure caused by cat’s claw
herbal remedy in a patient with systemic lupus erythematosus [letter]. Nephron
1997;77:361.
Immodal Pharmaka. Krallendorn® Uncaria tomentosa (Willd.) DC Root Extract:
Information for Physicians and Dispensing Chemists. 3rd revised ed. Volders,
Austria: Immodal; 1995. Available on request from immodal@volders.netwing.at.
Immodal Pharmaka. Radix Uncariae tomentosae (Willd.) DC., pentacyclic
chemotype (Krallendorn®): summarized research. Volders, Austria: Immodal; 2002.
Immodal Pharmaka. Summary and assessment of clinical examinations of
Krallendorn® products. Volders, Austria: Immodal; 1999a. Available on request
from immodal@volders.netwing.at.
Immodal Pharmaka. Summary and assessment of: Pharmacodynamical examinations
of extracts of Uncaria tomentosa (Willd.) DC. mod. pent. Volders, Austria:
Immodal; 1999b.
INPR. See: Institute for Natural Products Research.
Institute for Natural Products Research (INPR). The NPDR Quick
Reference—Cat’s Claw [INPR web site]. 1999. Available at URL:
http://www.naturalproducts.org/ public/qr/catsclaw.html. Accessed 4 Dec 2002.
Jin R, Chen C, Li Y, Xu, P. Effect of rhynchophylline on platelet
aggregation and experimental thrombosis. Acta Pharm Sinica 1991;26(4):246–249.
Jones K. Cat’s Claw–Healing Vine of Peru. Seattle (WA): Sylvan Press; 1995.
Kanatani H, Kohda H, Yamasaki K, Hotta I, Nakata Y, Segawa T. The active
principles of the branchlet and hook of Uncaria sinensis Oliv. examined with a
5-hydroxytryptamine receptor binding assay. J Pharm Pharmacol 1985;37:401–404.
Keplinger K, Laus G, Wurm M, Dierich MP, Teppner H. Uncaria tomentosa
(Willd.) DC–Ethnomedicinal use and new pharmacological, toxicological and
botanical results. J Ethnopharmacol 1999;64:23–34.
Kitajima M, Hashimoto K, Yokoya M, Takayama H, Aimi N, Sakai LI. A new
gluco indole alkaloid, 3, 4-dehydro-5-carboxystrictosidine, from Peruvian Una
de Gato (Uncaria tomentosa). Chem Pharm Bull (Tokyo) 2000;48(10):1410–2.
Kreutzkamp B. Niedermolekulare Inhaltsstoffe mit immunstimulierenden
Eigenschaften aus Uncaria tomentosa, Okoubaka aubrevillei und anderen Drogen
[dissertation]. Munich, Germany: University of Munich; 1984. Cited in Keplinger
K, Laus G, Wurm M, et al. Uncaria tomentosa (Willd.) DC–Ethnomedicinal use and
new pharmacological, toxicological and botanical results. J Ethnopharmacol
1999;64:23–34.
Kynoch SR, Lloyd GK. Acute oral toxicity to mice of substance E-2919.
Huntingdon Research Centre. Huntingdon, Cambridgeshire, England: 1975. Cited in
Reinhard K. Uncaria tomentosa (Willd.) D.C. Cat’s claw, una de gato, or
saventaro. J Alternative Complement Med 1999;5(2):143–51.
Lamm S, Sheng Y, Pero RW. Persistent response to pneumococcal vaccine in
individuals supplemented with a novel water soluble extract of Uncaria
tomentosa, C-Med-100®. Phytomedicine 2001;8(4):267–274.
Laus G, Brössner D, Keplinger K. Alkaloids of Peruvian Uncaria tomentosa. Phytochemistry
1997;45(4):855–860.
Laus G, Keplinger K, Wurm M, Dierich
MP. Pharmacological activities of two chemotypes of Uncaria tomentosa (Willd.)
DC. 46th Annual Congress of the Society for Medicinal Plant Research, Vienna,
Austria, 1998.
Lee KK, Zhou BN, Lingston DG Vaisberg AJ, Hammond GB. Bioactive indole
alkaloids from the bark of Uncaria guianensis. Planta Med 1999;65:759–60.
Lemaire I, Assinewe V, Cano P, Awang D, Arnason J. Stimulation of
interleukin-1 and -6 production in alveolar macrophages by the neotropical
liana, Uncaria tomentosa (Uña de Gato). J Ethnopharmacol 1999;64:109–115.
Leon FR, Ortiz N, Antunez de Mayolo A, Namisato T, Monge R. Antimutagnic
activity of a freeze-dried aqueous extract of Uncaria tomentosa in smokers and
non-smokers. Third European Colloquium on Ethnopharmacology, Genova, Italy
1996:255. Cited in Reinhard K. Uncaria tomentosa (Willd.) D.C. Cat’s claw, una
de gato, or saventaro. J Alternative Complement Med 1999;5(2):143–51.
Mannick EE, Mishra J, Marque J, Clavell M, Miller MJS, Oliver PD.
Inhibitors of nuclear factor Kappa B cause apoptosis in cultured macrophages. Mediators
Inflammation 1997;6:225–32. Cited in Sandoval et al., 2002 Sandoval M, Okuhama
NN, Zhang X-J, Condezo LA, Lao J, Angeles FM, Bobrowski P, Miller MSJ.
Anti-inflammatory and antioxidant activities of cat’s claw (Uncaria tomentosa
and Uncaria guianensis) are independent of their alkaloid content. Phytomed
2002;9(4):325–37.
McGuffin M, Kartesz JT, Leung AY, Tucker AO. The American Herbal Product
Association’s Herbs of Commerce, 2nd ed. Silver Spring (MD): American Herbal
Products Association; 2000.
McGuffin M, Hobbs C, Upton R, Goldberg A. American Herbal Products
Association’s Botanical Safety Handbook: Guidelines for the Safe Use and
Labeling for Herbs of Commerce. Boca Raton (FL): CRC Press; 1997.
Medical Products Agency (MPA). Naturläkemedel: Authorised Natural Remedies
(as of January 24, 2001). Uppsala, Sweden: Medical Products Agency; 2001.
Miller MJS. Personal communication to M. Blumenthal. Jun 4, 2001a.
Miller MJS. Alternative focus: Amazonian medicinals for gastrointestinal
health. HIV Resource Review 2001b;5:1–6.
Miller MJS, Angeles FM, Reuter BK, Bobrowski P, Sandoval M. Dietary
antioxidants protect gut epithelial cells from oxidant-induced apoptosis. BMC
Complement Altern Med 2001;1:11.
Morant J, Ruppanner H (eds.). Arzneimittel-Kompendium der Schweiz® 2001.
Basel, Switzerland: Documed AG; 2001.
MPA. See: Medical Products Agency.
Muhammad I, Khan IA, Fischer NH, Fronczek FR. Two stereoisomeric
pentacyclic oxindole alkaloids from Uncaria tomentosa: uncarine C and uncarine
E. Acta Cryst 2001a;C57:240–2.
Muhammad I, Dunbar DC, Khan RA, Ganzera M, Khan IA. Investigation of Una de
Gato. 7-deoxyloganic acid and 15N NMR spectroscopic studies on pentacyclic
oxindole alkaloids from Uncaria tomentosa. Phytochemistry 2001b;57(5):781–5.
Mur E, Hartig F, Eibl G, Schirmer M. Randomized double blind trial of an
extract from the pentacyclic alkaloid-chemotype of Uncaria tomentosa for the
treatment of rheumatoid arthritis. J Rheumatol 2002;29:678–81.
Obregon VL. Cat’s Claw. Genus Uncaria. Botanical, Chemical and
Pharmacological Studies of Uncaria tomentosa (Willd.) DC and Uncaria guianensis
(Aubl.). 1995; Lima, Peru: Institute of American Phytotherapy. (English
translation of work published in Spanish in 1994).
Piscoya J, Rodriguez Z, Bustamante SA, Okuhama NN, Miller MJS, Sandoval M.
Efficacy and safety of freeze-dried cat’s claw in osteoarthritis of the knee:
mechanisms of action of the species Uncaria guianensis. Inflamm Res 2001;50:442–8.
Reinhard K. Uncaria tomentosa (Willd.) D.C. Cat’s claw, una de gato, or
saventaro. J Alternative Complement Med 1999;5(2):143–151.
Richman A, Witkowski JP. Annual herb sales survey. Whole Foods 2001
Oct:23–30.
Riva L, Coradini D, Di Fronzo G, De Feo V, De Tommasi N, De Simone F, Pizza
C. The antiproliferative effects of Uncaria tomentosa extracts and fractions on
the growth of breast cancer cell line. Anticancer Res 2001;21(4A):2457–61.
Rizzi R, Re F, Bianchi A, De Feo V, de Simone F, Bianchi L, Stivala L.
Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts. J
Ethnopharmacol 1993;38:63–77 .
Sandoval M, Charbonnet R, Okuhama N, Roberts J, Krenova Z, Trentacosti A,
Miller M. Cat’s claw inhibits TNFa
production and scavenges free radicals: role in cytoprotection. Free Radic Biol
Med 2000;29(1):71–78.
Sandoval M, Okuhama NN, Zhang X-J, Condezo LA, Lao J, Angeles FM, Bobrowski
P, Miller MJS. Antiinflammatory and antioxidant activities of cat’s claw (Uncaria
tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine
2002;9(4):325–37.
Sandoval-Chacón M, Thompson JH, Lui X, Mannick E, Sadowska-Krowicka H,
Charbonnet R, Clark D, Miller M. Anti-inflammatory actions of Cat’s claw: the
role of NF-kappaB. Aliment Pharmacol Ther 1998;12:1279–1289.
Senatore A, Cataldo A, Iaccarino FP, Elberti MG. Phytochemical and
biological study of Uncaria tomentosa. Bulletin de la Societe Italie Speriment
1989;65:517–520.
Sheng Y, Pero R, Amiri A et al. Induction of apoptosis and inhibition of
proliferation in human tumor cells treated with extracts of Uncaria tomentosa.
Anticancer Res 1998;18:3363–3368.
Sheng Y, Li L, Holmgren C, Pero RW. DNA repair enhancement of aqueous
extracts of Uncaria tomentosa in a human volunteer study. Phytomedicine 2001;8(4)
275–282.
Sheng Y, Bryngelsson C, Pero R. Enhanced DNA repair, immune function and
reduced toxicity of C-Med-100®, a novel aqueous extract from Uncaria tomentosa.
J Ethnopharmacol 2000a;69:115–126.
Sheng Y, Pero R, Wagner H. Treatment of chemotherapy-induced leukopenia in
the rat model with aqueous extract from Uncaria tomentosa. Phytomedicine 2000b;7(2):137–143.
Shi JS, Huang B, Wu Q, Ren RX, Xie XL. Effects of rhynchophylline on motor
activity of mice and serotonin and dopamine in rat brain. Acta Pharm Sinico
1992; 14(2):114–7.
Shi JS, Liu GX, Wu Q, Zhang W, Huang XN. Hypotensive and hemodynamic
effects of isorhynchophylline in conscious rats and anesthetized dogs. Chin J
Pharmacol Toxicol. 1989;3(3):205–10.
Shimada Y, Goto H, Itoh T, Sakakibara I, Kubo M, Sasaki H, Terasawa K.
Evaluation of the protective effects of alkaloids isolated from the hooks and
stems of Uncaria sinensis on glutamate-induced neuronal death in cultured
cerebellar granule cells from rats. J Pharm Pharmacol 1999;51(6):715–22.
Spaulding-Albright N. A review of some herbal and related products commonly
used in cancer patients. J Am Diet Assoc 1997;97:S208–15.
Stuppner H, Sturm S, Geisen G, Zillian U, Konwalinka G. A differential sensitivity
of oxindole alkaloids to normal and leukemic cell lines. Planta Medica.
1993;59:Supplement,A583.
Stuppner H, Sturm S, Konwalinka G. HPLC analysis of the main oxindole
alkaloids of Uncaria tomentosa. Chromatographia 1992;34:597–600.
Sun A-S, Liu G-X, Wang X-Y, Zhang W, Luang X-N. Effects of rhynchophylline
on contraction of isolated rat uterus. [in Chinese]. Ch J Pharm Tox
1988;2(2):93–97.
Svendson O, Skydsgaard. Test report, Extratum Redicis Uncariae tomentosae:
28-day oral rat toxicity study. Uppsala: Scantox; 1986. Cited in Reinhard K. Uncaria
tomentosa (Willd.) D.C. Cat’s claw, una de gato, or saventaro. J Alternative
Complement Med 1999;5(2):143–51.
United States Congress (USC). Public Law 103–417: Dietary Supplement Health
and Education Act of 1994. Washington, DC: 103rd Congress of the United States;
1994.
USC. See: United States Congress.
Wagner H, Proksch A, Vollmar A, Kreutzkamp B, Bauer J. In vitro
phagocytosis stimulation by isolated plant materials in a
chemoluminescence-phagocytosis model [in German]. Planta Med 1985a
Apr;(2):139–44.
Wagner H, Kreutzkamp B, Jurcic K. The alkaloids of Uncaria tomentosa and
their phagocytosis-stimulating action [in German]. Planta Med 1985b
Oct;(5):419–23.
Williams JE. Review of antiviral and immunomodulating properties of plants
of the Peruvian rainforest with a particular emphasis on Uña de gato and Sangre
de grado. Altern Med Rev 2001 Dec;6(6):567–79.
Wirth C, Wagner H. Pharmacologically active procyanidines from the bark of Uncaria
tomentosa. Phytomedicine 1997;4(3):265–266.
Wurm M, Kacani L, Laus G, Keplinger K, Dierich M. Pentacyclic oxindole
alkaloids from Uncaria tomentosa induce human endothelial cells to release a
lymphocyte-proliferation-regulating factor. Planta Med 1998;64:701–704.
Yano S, Horiuchi H, Horie S, Aimi N, Sakai S, Watanabe K. Ca2+ channel
blocking effects of hirsutine, an indole alkaloid from Uncaria genus, in the
isolated rat aorta. Planta Med 1991;57:403–5.
Yepez AM, de Ugaz OL, Alvarez CM, De Feo V, Aquino R, De Simone F, et al. Quinovic
acid glycosides from Uncaria guianensis. Phytochemistry 1991;30(5):1635–7.
Zhang W, Liu GX, Huang XN. Effect of rhynchophylline on contraction of
rabbit aorta. Acta Pharmacol Sin 1987;8(5):425–429.
Zhu Y, Guoxing HX. Negative chronotropic and inotropic effects of
rhynchophylline and isorhynchophylline on isolated guinea pig arteria. Chin J
Pharmacol Toxicol 1993;7(2):117–121.