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Abstract. Aim: The purpose of this investigation was to eval-
uate the ability of cat’s claw, an Amazonian medicinal plant,
to treat osteoarthritis of the knee, collect safety and tolerance
information and compare the antioxidant, and anti-inflam-
matory actions of Uncaria guianensis and Uncaria tomen-
tosa in vitro.
Materials and methods: Forty-five patients with osteoarthri-
tis of the knee were recruited, 30 were treated with freeze-
dried U. guianensis, and 15 with placebo. Hematological
parameters were assessed on entry and exit of the four-week
trial. Pain, medical and subject assessment scores and
adverse effects were collected at weeks 1, 2 and 4. The
antioxidant and anti-inflammatory activity of the cat’s claw
species was determined by the
a
,
a
-diphenyl-
b
-picrylhy-
drazyl (DPPH) free radical scavenging method. Inhibition of
TNF
a
and prostaglandin E
2
(PGE
2
) production was deter-
mined in RAW 264.7 cells by ELISA.
Results: Cat’s claw had no deleterious effects on blood or liv-
er function or other significant side-effects compared to
placebo. Pain associated with activity, medical and patient
assessment scores were all significantly reduced, with bene-
fits occurring within the first week of therapy. Knee pain at
rest or at night, and knee circumference were not significant-
ly reduced by cat’s claw during this brief trial. In vitro tests
indicated that U. guianensis and U. tomentosa were equiva-
lent at quenching DPPH radicals (EC
50
, 13.6–21.7 mg/ml) as
well as inhibiting TNF
a
production. However, the latter
action was registered at much lower concentrations (EC
50
,
10.2–10.9 ng/ml). Cat’s claw (10 mg/ml) had no effect on
basal PGE
2
production, but reduced LPS-induced PGE
2
release (P < 0.05), but at higher concentrations than that
required for TNF
a
inhibition.
Conclusion: Cat’s claw is an effective treatment for
osteoarthritis. The species, U. guianensis and U. tomentosa
Inflamm. res. 50 (2001) 442– 448
1023-3830/01/090442-07 $ 1.50+0.20/0
are equiactive. They are effective antioxidants, but their anti-
inflammatory properties may result from their ability to
inhibit TNF
a
and to a lesser extent PGE
2
production.
Key words: Inflammation – TNF
a
– Antioxidant – Prosta-
glandin – Complimentary medicine
Introduction
Cat’s claw is a medicinal plant from the Amazon River basin
that has been used for the treatment of chronic inflammation,
including arthritis, by indigenous cultures for centuries.
Despite its increasing popularity in the Western world, there
are no studies that have assessed its therapeutic potential for
arthritis in a placebo controlled trial. This present investiga-
tion was designed to assess this potential, and in addition,
compare the antioxidant and anti-inflammatory properties of
two species of cat’s claw. In the Western world Uncaria
tomentosa is better known than Uncaria guianensis, but both
species share the same traditional ethnomedical applications.
To date a direct comparison of these species in models of
inflammation is lacking.
Preclinical evaluation of cat’s claw has largely been
directed at Uncaria tomentosa. We have described that this
specie of cat’s claw protects against a multitude of oxidative
stresses, including peroxynitrite [1] which has been implicat-
ed as a mediator of arthritis [2] and other chronic inflamma-
tory disorders [3, 4], as well as UV radiation and free radical
(
a
,
a
-diphenyl-
b
-picrylhydrazyl, DPPH) induced cytotoxici-
ty [5]. Further, we have observed that cat’s claw prevents the
gastrointestinal damage from high dose NSAIDs, either as
acute gastritis [6] or chronic enteritis [5]. These observations
alone would suggest that cat’s claw be considered as an
adjunct therapy in the treatment of arthritis. However, as cat’s
claw may attenuate directly arthritic joint pain and dysfunc-
© Birkhäuser Verlag, Basel, 2001
Inflammation Research
Original Research Papers
Efficacy and safety of freeze-dried cat’s claw in osteoarthritis of the
knee: mechanisms of action of the species Uncaria guianensis
J. Piscoya
1
, Z. Rodriguez
1
, S. A. Bustamante
2
, N. N. Okuhama
3
, M. J.S. Miller
3
and M. Sandoval
3
1
Universidad Nacional Mayor de San Marcos, Facultad de Medicina, Lima, Peru
2
Rainforest Phytoceuticals, LLC, Delmar, NY, USA
3
Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Avenue (MC8), Albany, NY, 12208, USA, Fax: ++518 262 5241,
e-mail: sandovm@mail.amc.edu
Reveived 31 August 2000; returned for revision 10 November 2000; accepted by L.G. Letts 17 November 2000
Correspondence to: M. Sandoval
tion a detailed assessment in arthritis is warranted. Previous-
ly, many have erroneously considered cat’s claw as an
immune stimulant, a counter-intuitive concept for an anti-
inflammatory agent that arose from a patent on the oxindole
alkaloids present in Cat’s claw [7–9]. We have described that
cat’s claw is a remarkably potent inhibitor of NF-
k
B [1], a
critical transcription factor implicated in arthritis [10, 11].
Inhibition of NF-
k
B is a highly prized mechanism in the
development of new anti-inflammatory agents. We have
determined that cat’s claw (Uncaria tomentosa) is an effec-
tive inhibitor of TNF
a
gene expression in vitro and in vivo.
TNF
a
production is regulated at the transcriptional level,
largely by NF-
k
B [11]. The effectiveness of TNF
a
antibody
therapies for arthritis is proof positive that NF-
k
B activation
and TNF
a
production are critical elements of the disease
process [12, 13]. Consequently, any therapeutic agent that
shares this action has the potential to offer benefit in arthritis
[14]. In addition, considering that osteoarthritis (OA) is the
most common form of arthritis in developing countries and
the United States [15], and causes pain and disability in old-
er people [16–18], it is warranted to investigate the use of
this Amazonian medicinal plant for the treatment of OA. To
test this hypothesis, we set out to evaluate a cat’s claw specie,
Uncaria guianensis in osteoarthritis a specie low in oxindole
alkaloids, and to compare its in vitro actions with Uncaria
tomentosa.
Materials and methods
Materials
Except where noted, all chemicals were at least reagent grade and were
obtained from Sigma Chemical Company (St. Louis, MO). Cat’s claw
(Uncaria tomentosa and Uncaria guianensis) was collected from the
Upper Tropical Region of Peru. The authenticity of the two species of
cat’s claw was confirmed by Ing. Warren Rios, Professor at Universidad
Nacional Agraria de la Selva, Tingo Maria, Peru.
Cat’s claw preparation
For the clinical trial, an aqueous extraction of cat’s claw bark (Uncaria
guianensis) was prepared by boiling in hot water for 30 minutes, decant-
ed and total solids separated by filtration with a Whatman N
o
4 filter
paper. The filtrate was then freeze-dried in the laboratories of Universi-
dad Nacional Mayor de San Marcos, Lima, Peru. Then tablets were pre-
pared with the freeze-dried (100 mg + excipient). For the in vitro exper-
iments, Rainforest Phytoceuticals, LLC (Delmar, NY, www.amazon-
medicines.com), supplied purified freeze-dried extracts of Uncaria
tomentosa and Uncaria guianensis.
Patients
Forty-five male patients, ages 45-75 years, with symptomatic
osteoarthritis (OA) of the knee (grades II-III of the Kellgren/Lawrence
(K/L) classification [19], fulfilling the American College of Rheuma-
tology criteria for the knee [20], and with pain present most days of the
prior month were recruited for the study. Radiographic evidence of knee
OA was defined by the presence of osteophytes in at least 1 tibiofemoral
compartment. Criteria for entry into the study were osteoarthritis of the
knee that required NSAID therapy for at least 3 months prior to the
study, and there had to be evidence of knee pain on movement scored by
the patient [21]. Before entering the trial, patients underwent washout
periods of 7 days for any NSAIDs or 12 hours for analgesics. During the
trial, acetaminophen intake (500-mg tablets) was permitted in cases of
persistent pain, and the dose and duration were recorded. Entry also
required a normal liver and hematological function assessment (alanine
aminotransferase – ALT; aspartate aminotransferase – AST; erythrocyte
sedimentation rate – ESR, hematocrit and hemoglobin) at baseline as
previously described [22].
Patients were not retained for the study if they had serious con-
comitant medical illness (pre-existing renal, cardiovascular, gastroin-
testinal, hepatic or hematological complications, and history of alco-
holism or drug abuse), secondary OA, radiographic grade IV by the K/L
classification, hypersensitivity reactions to salicylates nor patients tak-
ing oral anticoagulants, systemic or treated with intraarticular injection
of glucocorticoids for at least three months before the study.
Study design
This was a prospective, multicenter, randomized, double blind, placebo-
controlled, parallel trial of 4-week duration. This duration was chosen
according to personal communication from previous patients taking
freeze-dried cat’s claw, and also to gain more information about cat’s
claw safety profile. The study was conducted in accordance with the
Helsinki Declaration (1964) and its revision (1975). Patients entered the
study after fulfilling the inclusion and exclusion criteria and signing an
informed consent.
Cat’s claw administration
Patients were randomly assigned to two treatment groups. One group
(n = 15) received placebo (1 capsule daily), the second group (n = 30)
received 100 mg of freeze-dried cat’s claw (1 capsule of 100 mg daily).
Placebo tablets contained the same excipient but without cat’s claw.
Physicians and patients were blind to the treatment nature, and identical
procedures were also used in the laboratory analysis.
Evaluation of efficacy
Subjects were assessed at the commencement of the study for pain at
rest, at night and during exercise. Tenderness was scored on a 4-point
scale [21], (0 = no tenderness, 1 = patient complained of pain, 2 =
patient complained of pain and winced, 3 = patient complained of pain,
winced and withdrew the joint). The global tolerance to the study treat-
ment was assessed by the patient and the investigator at weeks 1–4 of
the trial, as described previously [23 –25] with a scoring system using a
5-point scale (very good, good, moderate bad and very bad). Subjects
were also assessed at the conclusion of the study for ALT, AST, ESR,
hematocrit and hemoglobin. All adverse effects (AEs) reported by the
patients during the study treatment were recorded on the case report
form (CRF) and described their nature, frequency and severity.
Free radical scavenging assay.
The DPPH free radical scavenging method previously reported [26] was
modified as follows. The soluble solids content of the cat’s claw extracts
were standardized to give stock solutions containing 20 mg/ml water.
An aliquot of the freeze-dried cat’s claw extracts (U. tomentosa or U.
guianensis) were placed in a cuvette and a 60 mM ethanolic solution of
DPPH were added (final vol 1 ml). The decrease in absorbance at 515
nm was determined continuously with data capturing at 30-sec intervals
with a Beckman Coulter DU-640 spectrophotometer (Beckman Instru-
ments, Fullerton, CA). All determinations were performed in triplicate.
The DPPH scavenging capacity of cat’s claw was determined as previ-
ously described [5]. Ascorbic acid (10 –100 mM) was used as a refer-
ence antioxidant-control to compare the efficacy of DPPH inhibition.
Vol. 50, 2001 Osteoarthritis and cat’s claw 443
Inhibition of TNF
a
production
The ability of cat’s claw to inhibit TNF
a
synthesis/release in vitro was
determined by stimulating TNF
a
production in RAW 264.7 cells
(1 ¥ 10
5
cells/well), a murine macrophage cell line, after administration
of lipopolysaccharide (LPS, 50 ng/ml). Cells were either pretreated with
cat’s claw (Uncaria tomentosa or Uncaria guianensis) with concentra-
tions ranging from 1 to 1000 ng/ml for two h and/or treated with LPS
(50 ng/ml) for 1 h. The media was then replaced and cells were incu-
bated at 37 °C for 16 h. Culture medium was collected for determination
of TNF
a
levels using the Quantikine M mouse TNF
a
Immunoassay kit
(R & D Systems Inc., Minneapolis, MN). Samples were processed for
ELISA determinations following the manufacturer’s recommendations.
Inhibition of PGE
2
production
RAW 264.7 cells (1 ¥ 10
6
cells/well) were used to determine the capac-
ity of cat’s claw (Uncaria tomentosa) to decrease the production of LPS-
induced prostaglandin E
2
(PGE
2
). Cells were pretreated with cat’s claw
(10 mg/ml) for 1 h, then the media was replaced with medium contain-
ing LPS (50 ng/ml), and cells were incubated at 37 °C for 4 h. At the end
of the incubation period, medium was collected and PGE
2
was quanti-
fied using a Prostaglandin E
2
EIA kit-monoclonal (Cayman Chemical,
Ann Arbor, MI).
Data analysis
Clinical trial data was evaluated by one-way ANOVA followed by post
hoc analysis with the Kruskal-Wallis and Mann-Whitney test. Results
are expressed as the mean ± SE. Statistical analysis for the in vitro
experiments was performed using t-test and one-way ANOVA. Post hoc
comparison of means was done by Least Significant Difference test and
unpaired t-test. A probability value of < 0.05 was considered signifi-
cant.
Results
Clinical Trial
At the commencement of the study there was no difference
between the treatment groups in all variables assessed –
hematological and disease activity scores, indicating effec-
tive randomization (Table 1). Compared to placebo, the cat’s
claw group had a significant improvement in the pain associ-
ated with activity (Fig. 1), patient and medical assessment
scores (Fig. 2). Importantly, all of these indices were found to
be improved significantly after one week of the trial, with the
exception of the medical assessment score which bordered
on significance (P = 0.0715) but improvement was highly
significant at weeks 2 and 4 (P < 0.001). In addition, there
was a significant improvement in these disease indices with
time of treatment (P < 0.05), with scores at week 4 lower than
baseline or week 1 values.
In contrast, pain at rest or at night, and knee circumfer-
ence (Table 2) were not significantly altered in either place-
bo or cat’s claw groups during the course of the study. No
change in hematological determinations was observed in
either group, over the course of the study (Table 3). There
was also no difference in the incidence and form of side
effects reported by the two groups. Specifically, at week one,
in the cat’s claw group one patient presented with vomiting
444 J. Piscoya et al. Inflamm. res.
Table 1. Patient demographics and baseline characteristics.
Placebo 100 mg/day
(n = 15) Freeze-dried
cat’s claw
(n = 30)
Age, years 60.9 ± 6.5 59.9 ± 8.4
Rest pain score 4.2 ± 2.9 4.4 ± 2.6
Activity pain score 6.8 ± 1.9 5.7 ± 2.6
Night pain score 4.6 ± 2.8 4.6 ± 2.3
Right knee perimeter 41.2 ± 8.4 39.0 ± 7.4
Left knee perimeter 40.0 ± 7.1 38.6 ± 8.4
Values are the mean ± SD. No statistical differences between the two
groups.
Fig. 1. Pain on activity scores in placebo (n = 15) and cat’s claw (n = 30)
treated groups at the commencement of the trial, as well as determina-
tions at week 1, 2 and 4. The single * indicates significant difference
from placebo (P < 0.01) and ** indicates significant difference from
placebo (P < 0.001).
Fig. 2. Physician (medical) and patient assessment scores of disease
activity in placebo (n = 15) and cat’s claw (n = 30) treated groups, as
determined at week 1, 2 and 4 of the trial. The * indicates a significant
difference from placebo (P < 0.05), and the † indicates significant dif-
ference from placebo (P < 0.001).
and another with dizziness. At week two, the cat’s claw group
had 5 patients reporting headache (P = 0.1526), and at week
four, three patients in the cat’s claw group and one patient in
the placebo group presented with headache; one patient in
the placebo group reported dizziness and another reported
ringing in the ears (P = 0.3842).
Free radical scavenging
DPPH gives a steady absorbance reading at 515 nm.
Absorbance declined in the presence of cat’s claw (Fig. 3),
indicating radical quenching. The effectiveness of Uncaria
guianensis and Uncaria tomentosa as DPPH scavengers is
shown in Figure 3. The EC
50
for both species were 13.6 vs
21.7 mg/ml, respectively (Table 4). While the rate of quench-
ing may have been marginally greater for Uncaria guianen-
sis at some concentrations this had no impact on total antiox-
idant activity. Thus, we regard their antioxidant activity in
this system to be comparable.
Inhibition of TNF
a
production
Murine macrophages (RAW 264.7 cells) when stimulated
with LPS release substantial quantities of TNF
a
into the
media. Inclusion of cat’s claw into the media prior to LPS
administration, resulted in a dose-dependent reduction in
TNF
a
levels (Fig. 4, P < 0.001). As observed with the DPPH
assay, the potency of Uncaria tomentosa and Uncaria guia-
nensis extracts as inhibitors of TNF
a
synthesis were equiva-
lent in this assay. It is important to note however that the con-
centrations required to inhibit TNF
a
production were con-
siderably lower than that needed to quench DPPH radicals
(Table 4).
Inhibition of PGE
2
production
Murine macrophages (RAW 264.7 cells) were also used to
assess PGE
2
release. Cat’s claw had no effect on basal
(unstimulated) PGE
2
production, indicating that cyclooxyge-
nase-1 (COX-1) activity was not influenced. However, the
marked increase in PGE
2
production induced by LPS
(0.5 mg/ml) was significantly reduced (P < 0.05) by cat’s claw
(Figure 5), suggestive of an inhibition of cyclooxygenase-2
(COX-2) expression. The dose of cat’s claw (10 mg/ml) was
greater than that required suppressing TNF
a
production but
less than concentrations required for antioxidant activity.
Vol. 50, 2001 Osteoarthritis and cat’s claw 445
Table 2. Effect of cat’s claw (Uncaria guianensis) on measures of pain
at rest and night.
Assessment Placebo Freeze-dried cat’s claw
of pain
Entry Week 4 Entry Week 4
Score at rest 4.15 ± 0.77 3.94 ± 0.69 4.41 ± 0.48 3.42 ± 0.33
Score at night 4.60 ± 0.74 4.17 ± 0.69 4.63 ± 0.42 3.06 ± 0.37
Values are mean ± SE from participants of the study.
Table 3. Effect of cat’s claw (Uncaria guianensis) on hematological
parameters.
Assessment Placebo Freeze-dried Cat’s claw
Entry Week 4 Entry Week 4
Hemoglobin, 14.41 ± 2.01 12.67 ± 0.31 12.75 ± 0.23 13.89 ± 1.05
g/dL
Hematocrit, 37.29 ± 2.41 39.15 ± 1.29 38.00 ± 0.67 36.87 ± 1.30
%
ESR, mm/h 20.97 ± 1.49 16.56 ± 0.98 17.80 ± 1.08 17.75 ± 1.18
AST, U/L 32.82 ± 8.59 25.31 ± 2.17 21.77 ± 1.37 29.69 ± 8.11
ALT, U/L 19.41 ± 2.65 21.12 ± 2.08 21.04 ± 1.51 19.38 ± 1.63
Values are mean ± SE from participants of the study as described in
materials and methods. Erythrocyte sedimentation rate (ESR), Aspar-
tate aminotransferase (AST), and Alanine aminotransferase (ALT).
Fig. 3. Antioxidant activity of cat’s claw assessed by DPPH free radical
method. The DPPH scavenging capacity of cat’s claw Uncaria guianen-
sis (solid bars) and Uncaria tomentosa (open bars) was quantified spec-
trophotometrically at 515 nm. In vitro reactions were carried out for
5 min and the degree of DPPH inhibition is expressed as absorbance
depletion as described in Materials and methods. Values are mean ± SE
of three experiments with three samples each. No significant difference
between the species was noted in their ability to quench DPPH. Inset:
DPPH inhibition by ascorbic acid as antioxidant of reference r = 0.9784
(EC
50
, 4.8 mM).
Table 4. Comparison of the antioxidant and anti-TNF
a
activities of
cat’s claw species.
Assay Freeze-dried cat’s claw
Uncaria tomentosa Uncaria guianensis
EC
50
Max EC
50
Max
Inhibition, % Inhibition, %
Antioxidant 21.7 mg/ml 85.5 13.6 mg/ml 90.5
(DPPH)
Anti-TNF
a
10.2 ng/ml 79.0 10.9 ng/ml 73.0
Freeze-dried cat’s claw was used for these experiments. The antioxidant
activity was assayed by in vitro scavenging of the free radical DPPH
(60 mM), and quantified spectrophotometrically at 515 nm. The anti-
TNF
a
activity was determined using the Quantikine M mouse TNF
a
immunoassay as described in Materials and methods.
Discussion
This placebo-controlled double blind study clearly defines
that cat’s claw (Uncaria guianensis) is an effective treatment
for osteoarthritis of the knee. Within the four-week study
protocol the major benefits of cat’s claw treatment were in
alleviating pain associated with exercise, patient and physi-
cian assessment scores. Improvement in knee circumference
and pain at rest or at night was not observed but this may
reflect the duration of treatment, as therapeutic trends were
evident with cat’s claw and treatment duration was a signifi-
cant factor in the disease assessment scores and pain with
exercise. Cat’s claw therapy was not associated with any
changes in liver or hematological function, and the incidence
and frequency of side effects was not different from placebo
control. In this limited study we confirm the ethnomedical
reputation of cat’s claw for being well tolerated and safe.
Whether the more popular specie of cat’s claw, Uncaria
tomentosa, is more effective in treating arthritis is unknown
and was not the goal of this study. However, we attempted to
address this issue in the laboratory setting. Uncaria tomen-
tosa and Uncaria guianensis displayed comparable antioxi-
dant activity using the DPPH free radical scavenging assay.
Certainly oxidative stress and free radical damage has been
implicated in arthritis [27 – 29] and other chronic inflamma-
tory diseases [3, 5]. The antioxidant function of cat’s claw
may explain its ability to offer benefit to patients with
osteoarthritis. On the other hand, the therapeutic benefits of
antioxidants alone can be questioned.
In the TNF
a
production assay, species were equivalent,
producing substantial reductions in TNF
a
synthesis. A criti-
cal finding was that suppression of TNF
a
production was
noted at concentrations that were far less than that required
for antioxidant activity (Table 4). The cytokine TNF
a
is
regarded as a critical mediator of chronic inflammation [30,
31], including arthritis [13, 14, 32]. The success of Inflix-
imab™, the TNF
a
antibody therapy in bringing active dis-
ease into quiescence is proof positive that TNF
a
is a legiti-
mate therapeutic target. Whether the benefits of cat’s claw are
solely due to inhibition of TNF
a
production is unknown.
Indeed, the use of TNF
a
antibody therapy is usually confined
to rheumatoid arthritis and here we have examined the effects
of cat’s claw in osteoarthritis. However, inflammatory medi-
ators are activated in both forms of joint inflammation
although differences in cellular source and etiology exist
[33]. We have demonstrated that cat’s claw inhibits TNF
a
gene expression in gastric mucosa in NSAID gastritis [6]: an
action that is the result of its ability to inhibit the activation
of NF-
k
B [1]. The transcription factor NF-
k
B, is a redox-sen-
sitive transcription factor that regulates the expression of
over 28 different genes involved in inflammation [12], coor-
dinating many aspects of the inflammatory process (adhesion
molecules, cytokines, chemokines, enzymes). Inducible
nitric oxide synthase is an example of a NF-
k
B regulated
gene, that has been implicated in osteoarthritis [28, 29],
whose expression can be reduced by either cat’s claw direct-
ly [1] or by anti-TNF
a
antibody [32]. Thus, suppression of
NF-
k
B activation is critical target for treating inflammation,
as has been demonstrated with antisense technology [34].
While NF-
k
B is activated by oxidants, there was a clear dis-
crepancy in the concentrations required for these two species,
Uncaria tomentosa and Uncaria guianensis to act either as
antioxidants or anti-TNF
a
agents. We interpret this to mean
that the different constituents in this decoction are responsi-
ble for antioxidant and anti-TNF
a
activities, or alternatively
these components are functionally more directed at tran-
scriptional inhibition than antioxidant activity.
The importance of this study is that it provides therapeu-
tic information as to the application of a medicinal plant in
446 J. Piscoya et al. Inflamm. res.
Fig. 4. Effect of cat’s claw (Uncaria tomentosa and Uncaria guianen-
sis) on LPS-induced TNF
a
production by macrophages (RAW 264.7).
Cells were seeded at 1 ¥ 10
5
cells/well. Freeze-dried concentrates from
both species of cat’s claw inhibited TNF
a
production in an equivalent
dose-dependent manner. Bars represent TNF
a
release into the media for
Uncaria tomentosa (horizontal) and Uncaria guianensis (cross). Cells
were treated with LPS (50 ng/ml) for 1 h or pretreated with freeze-dried
cat’s claw for 2 h then challenged with LPS for 1 h, and incubated for
16 h as described in Materials and methods. All data represent mean ±
SE for triplicate determinations. * significant decrease (P < 0.05) from
LPS alone for Uncaria guianensis. ** significant decrease (P < 0.01)
from LPS alone, for both species.
Fig. 5. Effect of cat’s claw (Uncaria tomentosa) on prostaglandin E
2
(PGE
2
) production. Murine macrophages (RAW 264.7 cells) were
pretreated with cat’s claw (10 mg/ml) for 1 h and/or treated with LPS
(50 ng/ml) for 4 h. PGE
2
release into the media was assessed by ELISA
as described in Materials and methods. All data represent mean ± SE
for triplicate determinations. * significant decrease (P < 0.05) from
LPS alone.
the treatment of osteoarthritis. This type of information,
along with safety and tolerability data, will assist health care
professionals to make informed and educated decisions as to
the utility of cat’s claw. It should be noted that this freeze-
dried formulation was quite potent. Dosing at 100 mg once a
day reflects a potency that one normally associates with a
pharmaceutical rather than a medicinal plant preparation. On
the other hand, we have determined that the micropulveriza-
tion preparative method, which is the standard formulation in
the Western world, is approximately 20-fold less potent [5],
in which case gram quantities will be needed to achieve the
same effects.
Cat’s claw has had enjoyed a remarkable clinical experi-
ence in South America, and it is highly regarded for the treat-
ment of chronic inflammation [35]. This study as well as our
previous investigations [1, 5, 6], supports this ideology. Of
particular interest in the treatment of arthritis is the ability of
cat’s claw to not only confer benefit to the joints but also
negate the side effects of NSAIDs on the stomach and intes-
tine [5, 6]. With the observation that cat’s claw significantly
lowered PGE
2
production by macrophages, presumably due
to an inhibition of COX-2 expression, concomitant with in
vivo benefits on pain, it is likely that cat’s claw administra-
tion may lower the need for arthritic patients to consume
NSAIDs. Thus, this Amazonian botanical not only treats the
arthritic disease process but also reduces the toxic side
effects of the current standard pharmaceuticals used in the
management of arthritis. The concept that botanicals can be
used to reduce the toxicity of pharmaceuticals is an intrigu-
ing and greatly under-explored area of investigation.
Another complimentary medicine approach to osteo-
arthritis that is more commonly appreciated is the use of glu-
cosamine and chondroitin sulfate [36]. While the mecha-
nisms of action of these nutraceuticals have not been com-
pletely elucidated [37], their actions appear to be quite dis-
tinct from cat’s claw. Glucosamine and chondroitin are sub-
strates for cartilage and as such, assist in replacing chondro-
cyte material that is lost during the inflammatory process.
There is no evidence for a direct action on gene expression or
antioxidant activity, in contrast to the present observations
with cat’s claw. Thus, it is clear that this disease can be
approached therapeutically from different perspectives.
However, we believe that an approach that directly interrupts
the disease process has a better chance for therapeutic bene-
fits in a large proportion of the population than an approach
that is designed to arithmetically replace substrates lost as a
result of ongoing inflammation. In that regards, cat’s claw is
also distinct from NSAIDs as they only treat the symptoms
of the condition (pain, swelling) and not the underlying dis-
ease process. Given the ability of cat’s claw to negate the side
effects of NSAIDs, it is possible that a combination of cat’s
claw and NSAID would be a significant improvement in the
management of arthritis, and a cost-effective alternative to
COX-2 inhibitors.
We conclude that cat’s claw is a medicinal plant that
deserves further consideration in the treatment of arthritis
and other chronic inflammatory disorders.
Acknowledgements. We gratefully acknowledge the assistance of: Drs.
Herman Silva, Raúl Díaz, Inés Segami, César Ugarte, Felipe Becerra,
Pedro Mendoza, José Escalante, Graciela Alonso, Raúl Marañón, Jorge
Zapata and Dennis Elera for providing advice, and active participation
during the course of the study. The clinical trial was performed under
the sponsorship of Seguro Social del Peru (ESSALUD). The in vitro
experiments were supported by grants RO1 HD 31885 and PO1 CA
28842 from the National Institutes of Health, Bethesda, MD (to
M.J.S.M).
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