"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
- TNF Alpha -
Names: Tumor Necrosis Factor Alpha
Dr. Ray Shahelien
tomentosa, Una de Gato, Samento)
See also TNF-alpha
There are several plants known as Cat's Claw. We are
interested in the Peruvian plant, Uncaria
tomentosa, commonly known as Cat's Claw or UŮa de gato. The theory is
that Alzheimer's disease (AD) may in some cases be caused by the
presence of excessive TNF-alpha, or extreme sensitivity to
it. The cause of elevated levels of TNF-alpha may be a
remote, chronic infection, such as an H.pylori infection
of the stomac, gum disease, etc. Therefore suppressing the
production or action of TNF-alpha may improve the condition of the
AD patient. This is the theory. Claims that
"perispinal injection" (Tobinick's patented procedure) of the
TNF-alpha inhibitor arthritis drug Enbrel have improved AD
symptoms in a matter of minutes lends some support for this idea.
I have found several claims on Cat's Claw (CC) supplement
manufactures and sellers web sites claiming that it crosses the
blood-brain barrier (BBB) in 2 minutes. I have not yet
located research to back this up. However, it may not be
necessary. If an increase level of TNF-alpha is caused by a
remote (to the brain) infection, then CC may not have to.
I'm also quite confused by the claims for CC. Some say it is
an immune system stimulant, others that it is
anti-inflammatory. Can these two properties exist
of Maryland Medical Center (UMMC)
The two are frequently confused but U. tomentosa is the more
heavily researched for medicinal use and immune modulation,
while U. guianensis may be more useful for osteoarthritis. U.
tomentosa is further divided into two chemotypes with different
properties and active compounds, a fact ignored by most
manufacturers that can have significant implications on both
its use as an alternative medicine and in clinical trials to
prove or disprove its efficacy...
Sahelian, M.D. Cat's Claw page:
claw (Uncaria tomentosa or Una do Gato) is a medicinal herb from
the Amazon River basin that is widely used for inflammatory
disorders. Cat's claw contains gluco indole alkaloids. This herb
is promoted as having anti-cancer, anti-inflammatory, and for
arthritis. In the traditional Peruvian medicine, hot aqueous
extracts have been used for the treatment of a wide range of
health problems, particularly digestive complaints and
arthritis. What does the research say?...
regard to the different types of Cat's Claw, I have found the
following. I am providing this only for information.
There may be clues here, but they may lead nowhere. It is
possible that the information is totally bogus, or that the author
misinterpreted something. Also, I am not endorsing the products
mentioned, and I am not vouching for the credibility of the
original authors. Except in the case of purposeful
deception, there may be some truth in misinterpreted information
and half-remembered anecdotes that will provide clues about what
to look for and where to go next.
How to Use Cat's Claw to Treat
Because some scientific studies suggest that cat's claw can stop
the beta-amyloid plaques that cause Alzheimer's disease from
forming in the brain, some people use it to treat and prevent
the condition. Preliminary findings suggest that cat's claw may
be an effective supplementary method for managing Alzheimer's
disease and preventing the condition from worsening...
The following article is from a web site about Lyme disease:
is supposedly what the Ashaninka Indians of South America call
Catís Claw (Uncaria tomentosa). However, Wikipedia links
Samento with Uncaria guianensis, a relative of U.tomentosa with
different medicinal properties. Wikipedia could be
wrong. All of the "Samento" advertizing I've seen says that
it is Uncaria tomentosa.
Samento is a form of catís claw from the Peruvian jungle that is
superior to typical forms. The beneficial effects of most catís
claw preparations are blunted by the presence of TOA
(tetracyclic oxindole alkaloids), which inhibit the real active
agents, called POA (pentacyclic oxindole alkaloids). The latter,
more favorable compounds are known to modulate and up-regulate
the immune system. Many commercially available catís claw
preparations contain up to 80 percent TOA. As little as one
percent TOA can reduce POA effectiveness up to 80 percent. In
addition, the specific species of TOA-free catís claw contains
considerable quantities of quinovic acid glycosides. These
compounds are what the latest generation of quinolone
antibiotics (such as Cipro) are based on. The natural compounds
provide safe and significant direct antimicrobial effects on
Three companies currently market the improved catís claw.
Allergy Research Group/Nutricology, which also distributes
artemisinin, can be reached at 800-545-9960 or
www.nutricology.com. Ask for Prima Una de Gato. Nutramedixís
product is called Samento Plus, and is available by calling
561-745-2917 or on the web site: www.nutramedix.com. Farmacopia
also carries the product (www.farmacopia.net or 800-896-1484). I
donít recommend any other commercially available catís claw at
this time because of the likelihood of TOA content.
Now we are
on a hunt for this "research conducted in Austria" by Klaus
Keplinger in the 1970s.
SAMENTO is a very rare form of the Peruvian medicinal plant
called Catís Claw - Uncaria tomentosa...
Unlike traditional Catís Claw products, SAMENTO does not contain
a group of chemical antagonists called tetracyclic oxindole
alkaloids (TOAs) that act upon the central nervous system and
greatly inhibit its effectiveness. SAMENTO contains a
standardized amount of pentacyclic oxindole alkaloids (POAs)
that act on the cellular immune system and demonstrate powerful
immune system modulating properties. According to research conducted in Austria,
traditional Catís Claw products may contain as much as 80% TOAs,
and as little as 1% TOAs can cause a 30% reduction in immune
system modulating properties that POAs provide. This may explain
why large dosages, at times far exceeding 20,000 mg per day, of
traditional Catís Claw containing TOAs are required to obtain
some results in treating the previously mentioned immune system
related conditions... The Austrian scientist Klaus Keplinger
discovered as early as in the 1970s that there was such a
TOA-free Catís Claw, but it is so rare in nature that Keplinger
managed to find in the Peruvian rainforest only separate
Research papers about TNF-alpha
article mentions a couple of other candidates, such as Tripterygium wilfordii Hook F.
Uncaria tomentosa acts as a
potent TNF-alpha inhibitor through NF-kappaB.
Ethnopharmacol. 2010 Feb 17;127(3):685-93. Epub 2009 Dec 6.
L, Arnason JT, Cano P, Lafrenie RM.
Laurentian University, Biomolecular Science, Sudbury Regional
Hospital, Sudbury, Ontario, Canada.
AIM OF THE STUDY: Uncaria tomentosa, commonly known as Cat's
Claw or UŮa de gato, is a medicinal plant that has been shown to
have effective anti-inflammatory activities. We have previously
shown that treatment of monocyte-like THP-1 cells with Uncaria tomentosa inhibits the
production of the pro-inflammatory cytokine TNF-alpha
while augmenting the production of IL-1beta. Since TNF-alpha and
IL-1beta are usually regulated similarly and share a number of
common promoter elements, including NF-kappaB and AP-1, the
ability of Uncaria tomentosa to differentially regulate these
inflammatory cytokines is of particular interest.
MATERIALS AND METHODS: To determine the mechanism of action of
Uncaria tomentosa, we investigated the effects of specific
inhibitors of NF-kappaB on cellular responses including
transcription factor activation using TransAM assays, the
expression of cytokines as measured by ELISA, and cell survival
as measured by changes in cell number following treatment.
RESULTS: Treatment with Uncaria tomentosa inhibited the
LPS-dependent activation of specific NF-kappaB and AP-1
components. In addition, treatment with Uncaria tomentosa
enhanced cell death when NF-kappaB was inhibited. The ability of
Uncaria tomentosa to inhibit TNF-alpha production was diminished
when NF-kappaB activation was prevented by drugs that mask
NF-kappaB subunit nuclear localization signals, while IL-1beta
expression was unchanged.
CONCLUSIONS: These results demonstrate that Uncaria tomentosa is
able to elicit a response via an NF-kappaB-dependent mechanism.
Further studies to characterize the mechanism by which Uncaria
tomentosa can affect this pathway could provide a means to
develop anti-TNF-alpha therapies.
Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
PMID: 19995599 [PubMed - indexed for MEDLINE]
Treatment of THP-1 cells with
Uncaria tomentosa extracts differentially regulates the
expression if IL-1beta and TNF-alpha.
Ethnopharmacol. 2007 Jan 19;109(2):312-7. Epub 2006 Aug 3.
Allen-Hall L, Cano P, Arnason JT, Rojas R, Lock O, Lafrenie RM.
Regional Cancer Program, Sudbury Regional Hospital, Sudbury,
Uncaria tomentosa, commonly known as cat's claw, is a medicinal
plant native to Peru, which has been used for decades in the
treatment of various inflammatory disorders. Uncaria tomentosa
can be used as an antioxidant, has anti-apoptotic properties,
and can enhance DNA repair, however it is best know for its
anti-inflammatory properties. Treatment
with Uncaria tomentosa extracts inhibits the production of the
pro-inflammatory cytokine, TNF-alpha, which is a
critical mediator of the immune response. In this paper, we
showed that treatment of THP-1 monocyte-like cells with Uncaria
tomentosa extracts inhibited the MAP kinase signaling pathway
and altered cytokine expression. Using ELISA assays, we showed
that treatment with Uncaria tomentosa extracts augmented
LPS-dependent expression of IL-1beta by 2.4-fold, while
inhibiting the LPS-dependent expression of TNF-alpha by
5.5-fold. We also showed that treatment of LPS-stimulated THP-1
cells with Uncaria tomentosa extracts blocked ERK1/2 and MEK1/2
phosphorylation in a dose-dependent manner. These data
demonstrate that treatment of THP-1 cells with Uncaria tomentosa
extracts has opposite effects on IL-1beta and TNF-alpha
secretion, and that these changes may involve effects on the MAP
PMID: 16959454 [PubMed - indexed for MEDLINE]
Modulation of cytokine
expression by traditional medicines: a review of herbal
Rev. 2006 Jun;11(2):128-50.
K, Burns J, Nichols D, Winters N, Ottersberg S, Tenborg M.
Clinical Division, Department of Herbal Medicine, Tai Sophia
Institute, 7750 Montpelier Road, Laurel, MD 20723, USA.
Modulation of cytokine secretion may offer novel approaches in
the treatment of a variety of diseases. One strategy in the
modulation of cytokine expression may be through the use of
herbal medicines. A class of herbal medicines, known as
immunomodulators, alters the activity of immune function through
the dynamic regulation of informational molecules such as
cytokines. This may offer an explanation of the effects of herbs
on the immune system and other tissues. For this informal
review, the authors surveyed the primary literature on medicinal
plants and their effects on cytokine expression, taking special
care to analyze research that utilized the multi-component
extracts equivalent to or similar to what are used in
traditional medicine, clinical phytotherapy, or in the
METHODOLOGY: MEDLINE, EBSCO, and BIOSIS were used to identify
research on botanical medicines, in whole or standardized form,
that act on cytokine activity through different models, i.e., in
vivo (human and animal), ex vivo, or in vitro.
RESULTS: Many medicinal plant extracts had effects on at least
one cytokine. The most
frequently studied cytokines were IL-1, IL-6, TNF, and IFN.
Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum,
Ananus comosus, Cissampelos sympodialis, Coriolus versicolor,
Curcuma longa, Echinacea purpurea, Grifola frondosa,
Harpagophytum procumbens, Panax ginseng, Polygala tenuifolia,
Poria cocos, Silybum marianum, Smilax glabra, Tinospora
cordifolia, Uncaria tomentosa,
and Withania somnifera demonstrate modulation of multiple
CONCLUSION: The in vitro and
in vivo research demonstrates that the reviewed botanical
medicines modulate the secretion of multiple cytokines.
The reported therapeutic success of these plants by traditional
cultures and modern clinicians may be partially due to their
effects on cytokines. Phytotherapy offers a potential
therapeutic modality for the treatment of many differing
conditions involving cytokines. Given the activity demonstrated
by many of the reviewed herbal medicines and the increasing
awareness of the broad-spectrum effects of cytokines on
autoimmune conditions and chronic degenerative processes,
further study of phytotherapy for cytokine-related diseases and
syndromes is warranted.
PMID: 16813462 [PubMed - indexed for MEDLINE]
Full text: http://www.ncbi.nlm.nih.gov/pubmed/16813462
Herbal medications commonly
used in the practice of rheumatology: mechanisms of action,
efficacy, and side effects.
Rheum. 2005 Jun;34(6):773-84.
AR, Sigal LH.
Massachusetts General Hospital, Department of Rheumatology,
OBJECTIVE: To review the literature on herbal preparations
commonly utilized in the treatment of rheumatic indications.
METHODS: Search of MEDLINE (PubMed) was performed using both the
scientific and the common names of herbs. Relevant articles in
English were collected from PubMed and reviewed.
RESULTS: This review summarizes the efficacy and toxicities of
herbal remedies used in complementary and alternative medical
(CAM) therapies for rheumatologic conditions, by elucidating the
immune pathways through which these preparations have
antiinflammatory and/or immunomodulatory activity and providing
a scientific basis for their efficacy. Gammalinolenic acid
suppresses inflammation by acting as a competitive inhibitor of
prostaglandin E2 and leukotrienes (LTs) and by reducing the
auto-induction of interleukin1alpha (IL-1alpha)-induced
pro-IL-1beta gene expression. It appears to be efficacious in
rheumatoid arthritis (RA) but not for Sjogrens disease. The
antiinflammatory actions of Harpagophytum procumbens is due to
its action on eicosanoid biosynthesis and it may have a role in
treating low back pain. While in vitro experiments with
Tanacetum parthenium found inhibition of the expression of
intercellular adhesion molecule-1, tumor necrosis factor alpha
(TNF-alpha), interferon-gamma, IkappaB kinase, and a decrease in
T-cell adhesion, to date human studies have not proven it useful
in the treatment of RA. Current experience with Tripterygium
wilfordii Hook F, Uncaria
tomentosa, finds them to be efficacious in the
treatment of RA, while Urtica diocia and willow bark extract are
effective for osteoarthritis. T. wilfordii Hook F extract
inhibits the production of cytokines and other mediators from
mononuclear phagocytes by blocking the up-regulation of a number
of proinflammatory genes, including TNF-alpha, cyclooxygenase 2
(COX-2), interferon-gamma, IL-2, prostaglandin, and iNOS. Uncaria tomentosa and Urtica diocia
both decrease the production of TNF-alpha. At present
there are no human studies on Ocimum spp. in rheumatic diseases.
The fixed oil appears to have antihistaminic, antiserotonin, and
antiprostaglandin activity. Zingiber officinale inhibits
TNF-alpha, prostaglandin, and leukotriene synthesis and at
present has limited efficacy in the treatment of osteoarthritis.
CONCLUSIONS: Investigation of the mechanism and potential uses
of CAM therapies is still in its infancy and many studies done
to date are scientifically flawed. Further systematic and
scientific inquiry into this topic is necessary to validate or
refute the clinical claims made for CAM therapies. An
understanding of the mechanism of action of CAM therapies allows
physicians to counsel effectively on their proper and improper
use, prevent adverse drug-drug interactions, and anticipate or
RELEVANCE: The use of CAM therapies is widespread among
patients, including those with rheumatic diseases. Herbal
medications are often utilized with little to no physician
guidance or knowledge. An appreciation of this information will
help physicians to counsel patients concerning the utility and
toxicities of CAM therapies. An understanding and elucidation of
the mechanisms by which CAM therapies may be efficacious can be
instrumental in discovering new molecular targets in the
treatment of diseases.
PMID: 15942912 [PubMed - indexed for MEDLINE]
Antioxidant properties of
proanthocyanidins of Uncaria tomentosa bark decoction: a
mechanism for anti-inflammatory activity.
Phytochemistry. 2005 Jan;66(1):89-98.
C, Dinis T, Batista MT.
Decoctions prepared from the bark of Uncaria tomentosa (cat's
claw) are widely used in the traditional Peruvian medicine for
the treatment of several diseases, in particular as a potent
anti-inflammatory agent. Therefore, the main purpose of this
study was to determine if the well-known anti-inflammatory
activity of cat's claw decoction was related with its reactivity
with the oxidant species generated in the inflammatory process
and to establish a relationship between such antioxidant ability
and its phenolic composition. We observed that the decoction
prepared according to the traditional Peruvian medicine
presented a potent radical scavenger activity, as suggested by
its high capacity to reduce the free radical
diphenylpicrylhydrazyl, and by its reaction with superoxide
anion, peroxyl and hydroxyl radicals as well as with the oxidant
species, hydrogen peroxide and hypochlorous acid. It also
protected membrane lipids against peroxidation induced by the
iron/ascorbate system, as evaluated by the formation of
thiobarbituric acid-reactive substances (TBARs). The decoction
phenolic profile was established by chromatographic analysis
(HPLC/DAD and TLC) revealing essentially the presence of
proanthocyanidins (oligomeric procyanidins) and phenolic acids,
mainly caffeic acid. Thus, our results provide evidence for an
antioxidant mechanism underlying the anti-inflammatory activity
of cat's claw and support some of the biological effects of
proanthocyanidins, more exactly its antioxidant and radical
PMID: 15649515 [PubMed]
Cat's claw inhibits TNFalpha
production and scavenges free radicals: role in
Biol Med. 2000 Jul 1;29(1):71-8.
M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti
AM, Miller MJ.
Department of Pediatrics and Center for Cardiovascular Sciences,
Albany Medical College, Albany, NY 12208, USA.
Cat's claw (Uncaria tomentosa) is a medicinal plant from the
Amazon River basin that is widely used for inflammatory
disorders and was previously described as an inhibitor of
NF-kappaB. Cat's claw was prepared as a decoction (water
extraction) of micropulverized bark with and without
concentration by freeze-drying. Murine macrophages (RAW 264.7
cells) were used in cytotoxicity assays (trypan blue exclusion)
in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl
(DPPH, 0.3 microM) and ultraviolet light (UV) light. TNFalpha
production was induced by lipopolysaccharide (LPS 0.5
microg/ml). Cat's claw was an effective scavenger of DPPH; the
EC(50) value for freeze-dried concentrates was significantly
less than micropulverized (18 vs. 150 microg/ml, p <.05).
Cat's claw (10 microg/ml freeze-dried) was fully protective
against DPPH and UV irradiation-induced cytotoxicity. LPS
increased TNFalpha media levels from 3 to 97 ng/ml. Cat's claw
suppressed TNFalpha production by approximately 65-85% (p
<.01) but at concentrations considerably lower than its
antioxidant activity: freeze-dried EC(50) = 1.2 ng/ml,
micropulverized EC(50) = 28 ng/ml. In conclusion, cat's claw is an effective
antioxidant, but perhaps more importantly a remarkably potent
inhibitor of TNFalpha production. The primary mechanism
for cat's claw anti-inflammatory actions appears to be
immunomodulation via suppression of TNFalpha synthesis.
PMID: 10962207 [PubMed]
One man's medicine is another man's poison... From NMSS
(National Multiple Sclerosis Society):
articl from the National MS Society was obtained from this site:
Potential Risks of Anti-Tumor
Necrosis Factor Therapy for People with MS
May 26, 2003-We have received a number of questions from people
about medications that block Tumor Necrosis Factor alpha (TNF
alpha). TNF, a substance that is part of the immune system,
plays a role in the inflammation that occurs in a variety of
autoimmune diseases. It has additional functions in the immune
system that are still unclear.1 While medications that block TNF
have been found to be useful in other autoimmune diseases, they
should not be used in the treatment of multiple sclerosis (MS)
because they may actually worsen the disease. Cases of new onset
multiple sclerosis, optic neuritis and other demyelinating
disorders have been associated with the use of some of these
agents.2 When this class of medications was tested on people who
already had MS, there was an increase in disease activity.3
Autoimmune Disease and Treatment
Medications called tumor necrosis factor antagonists or
anti-tumor necrosis factor agents, such as Enbrel(r)
(etanercept), Remicade(r) (infliximab), and a Humira(r)
(adalimubab), are used in the treatment of rheumatoid arthritis
and other autoimmune diseases, including psoriatic arthritis and
Drugs that inhibit TNF decrease the inflammation in these
diseases and have been shown to halt the progression of joint
destruction and reduce the signs and symptoms of both rheumatoid
and psoriatic arthritis. Enbrel(r) is now recommended as an
initial therapy for rheumatoid arthritis. It appears, however,
that drugs that inhibit TNF may also have a negative impact on
the immune system. Some patients have developed serious
infections, such as tuberculosis, while taking Enbrel(r).
Tumor necrosis factor and MS
Although TNF seems to be involved in the inflammation seen in
other autoimmune diseases, its precise role in MS is
controversial. When TNF was blocked in EAE, an animal model of
MS, severity of EAE was decreased. In humans, MS plaques and
cerebrospinal fluid have been shown to contain high levels of
TNF. However, anti-tumor necrosis factor medications have been
associated with an increase in exacerbations and a worsening of
symptoms in people who have MS.4 This may be because TNF alpha
antagonists cannot cross the blood brain barrier and work on the
cells in the central nervous system that are affected in MS,
whereas in rheumatoid arthritis and Crohn's disease, they can go
to work directly on the diseased cells in the joints and in the
bowel. Another explanation is that when TNF alpha antagonists
exert their effect outside the central nervous system, they
heighten the activity of a type of T cell involved in the
autoimmune response, precipitating further MS symptoms.
Although the causal relationship between TNF alpha antagonists
and either the onset or worsening of MS remains unclear, the
National MS Society advises against the use of TNF alpha
antagonists in people with MS. Patients who develop new
neurological symptoms while on any TNF alpha antagonist
medication should be seen by a neurologist and monitored with
1 Mohan, N., et al. "Demyelination Occurring During Anti-Tumor
Necrosis Factor Alpha Therapy for Inflammatory Arthritides."
Arthritis and Rheumatism; 44: no.12 (December 2001) 2862.
2 Immunex Corporation. "Enbrel(r) package insert." Seattle,
3 Robinson, W.H., Genovese, M.C., and Moreland, L.W.
Demyelinating and Neurologic Events Reported in Association With
Tumor Necrosis Factor Alpha Antagonism. Arthritis and
Rheumatism; 44: no. 9 (September, 2001) 1978.
4 Robinson, W.H. "Demyelinating and Neurologic Events..." 1978.
5 Mohan, N. et al. "Demyelination Occurring During Anti-Tumor
Necrosis Factor Therapy...) 2868.
that it is no longer on the NMSS
Home Preface Brain Failure Notes References
pg. 1 References pg. 2
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