Phytosubstances – focus on cat’s claw

There is a substantial amount current research on cat’s claw (uncaria tomentosa, in Spanish Uña de Gato), a herb imported from the Peruvian Amazon.  This blog entry documents some of the properties of this remarkable substance and a number of recent research findings regarding it.

Cat’s claw is a tall woody vine “indigenous to the Amazon rainforest, with its habitat being restricted primarily to the tropical areas of South and Central America.  — There are two species of Cat’s Claw, Uncaria tomentosa and Uncaria guianensis, each having different properties and uses. The two are frequently confused but U. tomentosa is the more heavily researched for medicinal use^[2] and immune modulation, while U. guianensis may be more useful for osteoarthritis.^[3] U. tomentosa is further divided into two chemotypes with different properties and active compounds, a fact ignored by most manufacturers^[4(ref).”  There is also a species Uncaria rhynchophylla used in traditional Chinese medicine..

Indigenous use of cat’s claw

From a tropical plant database site:  “Both South American Uncaria species are used by the indigenous peoples of the Amazon rainforest in very similar ways and have long histories of use. Cat’s claw (U. tomentosa) has been used medicinally by the Aguaruna, Asháninka, Cashibo, Conibo, and Shipibo tribes of Peru for at least 2,000 years. The Asháninka Indian tribe in central Peru has the longest recorded history of use of the plant. They are also the largest commercial source of cat’s claw from Peru today. The Asháninka use cat’s claw to treat asthma, inflammations of the urinary tract, arthritis, rheumatism, and bone pain; to recover from childbirth; as a kidney cleanser; to cure deep wounds; to control inflammation and gastric ulcers; and for cancer. Indigenous tribes in Piura use cat’s claw to treat tumors, inflammations, rheumatism, and gastric ulcers. Other Peruvian indigenous tribes use cat’s claw to treat diabetes, urinary tract cancer in women, hemorrhages, menstrual irregularity, cirrhosis, fevers, abscesses, gastritis, rheumatism, tumors, and inflammations as well as for internal cleansing and to “normalize the body.” Reportedly, cat’s claw has also been used as a contraceptive by several different tribes of Peru (but only in very large dosages). Dr. Fernando Cabieses, M.D., a noted authority on Peruvian medicinal plants, explains that the Asháninka boil 5 to 6 kg (about 12 pounds) of the root in water until it is reduced to little more than 1 cup. This decoction is then taken 1 cup daily during the period of menstruation for three consecutive months; this supposedly causes sterility for three to four years. — Cat’s claw has been used in Peru and Europe since the early 1990s as an adjunctive treatment for cancer and AIDS as well as for other diseases that target the immune system. In herbal medicine today, cat’s claw is employed around the world for many different conditions, including immune disorders, gastritis, ulcers, cancer, arthritis, rheumatism, rheumatic disorders, neuralgias, chronic inflammation of all kinds, and such viral diseases as herpes zoster (shingles). Dr. Brent Davis, D.C. has written several articles on cat’s claw and refers to it as the “opener of the way” for its ability to cleanse the entire intestinal tract and its effectiveness in treating stomach and bowel disorders (such as Crohn’s disease, leaky bowel syndrome, ulcers, gastritis, diverticulitis, and other inflammatory conditions of the bowel, stomach, and intestines). Dr. Julian Whitaker, M.D. reports using cat’s claw for its immune-stimulating effects, for cancer, to help prevent strokes and heart attacks, to reduce blood clots, and for diverticulitis and irritable bowel syndrome(ref).”

“The indigenous peoples of South and Central America have used U. tomentosa for medicinal purposes for two thousand years or more. It is often added to Ayahuasca. Researchers have investigated the use of the plant by the Asháninka tribe of Peru, who use the plant as a general health tonic, contraceptive, anti-inflammatory agent for the gastrointestinal tract, and as a treatment for diarrhea, rheumatic disorders, acne, diabetes, cancer and diseases of the urinary tract.^[12] In Brazilian traditional medicine it is used against dengue to reduce inflammation ^[13] (ref).”

Cat’s claw as a dietary supplement

Once discovered by the West, anectdotal enthusiasm for supplementation with cat’s claw grew rapidly.  Written in 1996: “– there is evidence that Cat’s Claw can help, at least in some cases, people suffering from tumors and growths, arthritis, bursitis, gout, fibromyalgia, asthma, hay fever, allergies, chemical and environmental sensitivities, multiple sclerosis, shingles, canker sores, chronic fatigue and depression, candidiasis, parasites, dysbiosis, Crohn’s disease, ulcers, gastritis, hemorrhoids and inflammatory bowel, prostate problems, diabetes, hypoglycemia, PMS and menstrual irregularities, circulatory problems and various viral and bacterial infections, including secondary infections in AIDS patients. There have also been reports of Cat’s Claw’s effectiveness in reducing the side effects of both radiation and chemotherapy when used in conjunction with conventional cancer treatments. Will all this stand up to scientific scrutiny? I believe that in time it will; however, we will have to wait until the appropriate clinical trials have been completed. For now, at least, Cat’s Claw seems to be virtually non-toxic and safe to use up to as much as 20 grams per day for several weeks to several months at a time. This is the amount generally used by the indigenous people of Peru, who boil inner bark and/or root in a liter of water for 30 minutes, then consume this decoction throughout the day for a variety of illnesses(ref).” 

Use of cat’s claw as a herbal supplement has been significant By 1997, over 50 dietary supplement manufacturers offered cat’s claw products in the United States. “Some ingredients appear to act as anti-inflammatory, antioxidant and anticancer agents.^[7] As a herbal treatment, Cat’s Claw is used to treat intestinal ailments such as Crohn’s disease, gastric ulcers and tumors, parasites, colitis, gastritis, diverticulitis and leaky bowel syndrome, while manufacturers claim that U. tomentosa can also be used in the treatment of AIDS in combination with AZT, the treatment and prevention of arthritis and rheumatism, diabetes, PMS, chronic fatigue syndrome, prostate conditions,^[8] immune modulation,^[9]Lyme disease^[10] and systemic lupus erythematosus.^[11] A 2005 review of the scholarly literature on Cat’s Claw indicates there is supporting evidence toward its use in treating cancer, inflammation, viral infection and vascular conditions, and for its use as an immunostimulant, antioxidant, antibacterial and CNS-related agent.^[7] (ref).”

What is cat’s claw?

Exactly what is a cat’s claw product or extract depends on the species and mode of extraction.  The substance is chemically very complicated consisting of multiple bioactive compounds Again, from a tropical plant database site: “Cat’s claw has several groups of plant chemicals that account for much of the plant’s actions and uses. First and most studied is a group of oxidole alkaloids that has been documented with immune-stimulant and antileukemic properties. Another group of chemicals called quinovic acid glycosides have documented anti-inflammatory and antiviral actions. Antioxidant chemicals (tannins, catechins and procyanidins) as well as plant sterols (beta-sitosterol, stigmasterol, and campesterol) account for the plant’s anti-inflammatory properties. A class of compounds known as carboxyl alkyl esters found in cat’s claw has been documented with immunostimulant, anti-inflammatory, anticancerous, and cell-repairing properties. — Cat’s claw contains ajmalicine, akuammigine, campesterol, catechin, carboxyl alkyl esters, chlorogenic acid, cinchonain, corynantheine, corynoxeine, daucosterol, epicatechin, harman, hirsuteine, hirsutine, iso-pteropodine, loganic acid, lyaloside, mitraphylline, oleanolic acid, palmitoleic acid, procyanidins, pteropodine, quinovic acid glycosides, rhynchophylline, rutin, sitosterols, speciophylline, stigmasterol, strictosidines, uncarine A thru F, and vaccenic acid.”

Research related to cat’s claw

While clinical evidence for the efficacy of cat’s claw for all of the mentioned health issues may or may not be eventually forthcoming, the herb has come under increasing Western research scrutiny.  A search for uncaria tormentose in pubmed.org retrieves 102 research publications, with more than 12 of these being published in the last year alone.  The publications cited below are exemplary.

Biological activities of cat’s claw

Ungaria tormentosa is a powerful anti-inflammatory, working through inhibition of the expression of NF-kappaB.

The 2010 publication Uncaria tomentosa acts as a potent TNF-alpha inhibitor through NF-kappaBreports: “AIM OF THE STUDY: Uncaria tomentosa, commonly known as Cat’s Claw or Uña 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.”  Inhibition of the expression of NF-kappaB is an important strategy for pro[er neurogenesis and for control of inflammatory processes and cancers and is a property of a number of other phytosubstances discussed in my treatise.  See the discussion there in the segment on Increase in aberrant NF-kappaB signaling.

Uncaria tormentosa extract can modulate the immune system so as to increase the number of T helper lymphocytes and B lymphocytes and stimulates lymphocyte viability.. 

The 2011 publication Uncaria tomentosa aqueous-ethanol extract triggers an immunomodulation toward a Th2 cytokine profile reports: “The present work used in vivo immunotoxic and in vitro immunomodulatory experiments to investigate the effects of a pentacyclic oxindole alkaloid extract from U. tomentosa bark on lymphocyte phenotype, Th1/Th2 cytokine production, cellular proliferation and cytotoxicity. For the in vivo immunotoxicity testing, BALB/c male mice were treated once a day with 125, 500 or 1250 mg/kg of U. tomentosa extract for 28 days. For the in vitro protocol, lymphocytes were cultured with 10-500 μg/mg of the extract for 48 h. The extract increased the cellularity of splenic white pulp and the thymic medulla and increased the number of T helper lymphocytes and B lymphocytes. Also, a large stimulatory effect on lymphocyte viability was observed. However, mitogen-induced T lymphocyte proliferation was significantly inhibited at higher concentrations of U. tomentosa extract. Furthermore, an immunological polarization toward a Th2 cytokine profile was observed. These results suggest that the U. tomentosa aqueous-ethanol extract was not immunotoxic to mice and was able to modulate distinct patterns of the immune system in a dose-dependent manner.”

Uncaria tormentosa appears to inhibit the Wnt pathway.

The 2011 publication Inhibitory mechanisms of two Uncaria tomentosa extracts affecting the Wnt-signaling pathway reports “Although recent studies have reported anti-inflammatory and anti-proliferative properties of different alkaloids extracted from this plant, the underlying molecular mechanisms of these effects have not been elucidated yet. Our study investigates the inhibitory mechanisms of Uncaria tomentosa extracts on the Wnt-signaling pathway, a central regulator of development and tissue homoeostasis. A modified cell-based luciferase assay for screening inhibitors of the Wnt-pathway was used for analysis. Three cancer cell lines displaying different levels of aberrant Wnt-signaling activity were transfected with Wnt-signaling responsive Tcf-reporter plasmids and treated with increasing concentrations of two Uncaria tomentosa bark extracts. Wnt-signaling activity was assessed by luciferase activity and by expression of Wnt-responsive target genes. We show that both, an aqueous and an alkaloid-enriched extract specifically inhibit Wnt-signaling activity in HeLa, HCT116 and SW480 cancer cells resulting in reduced expression of the Wnt-target gene: c-Myc. The alkaloid-enriched extract (B/S(rt)) was found to be more effective than the aqueous extract (B/W(37)). The strongest effect was observed in SW480 cells, displaying the highest endogenous Wnt-signaling activity. Downregulation of Wnt-signaling by a dominant negative-TCF-4 variant in non-cancer cells rendered the cells insensitive towards treatment with B/S(rt). B/Srt was less toxic in non-cancer cells than in cancer cells. Our data suggest that the broad spectrum of pharmacological action of Uncaria tomentosa involves inhibition of the Wnt-signaling pathway, downstream of beta-Catenin activity.”  There have been numerous mentions of the Wnt pathway in this blog and its roles in development and aging, for example (ref)(ref)(ref).

Therapeutic applications of cat’s claw

Uncaria tormentosa could possibly be the basis for a therapy for protecting against cartilage loss in arthritis and osteoarthritis.

This issue has been studied for some time.  The 2001 publication Efficacy and safety of freeze-dried cat’s claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis., a study involving 45 patients, reports: ‘The purpose of this investigation was to evaluate 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-inflammatory actions of Uncaria guianensis and Uncaria tomentosa in vitro.  Forty-five patients with osteoarthritis 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 alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) free radical scavenging method. Inhibition of TNFalpha and prostaglandin E2 (PGE2) production was determined in RAW 264.7 cells by ELISA. – RESULTS:  Cat’s claw had no deleterious effects on blood or liver function or other significant side-effects compared to placebo. Pain associated with activity, medical and patient assessment scores were all significantly reduced, with benefits occurring within the first week of therapy. Knee pain at rest or at night, and knee circumference were not significantly reduced by cat’s claw during this brief trial. In vitro tests indicated that U guianensis and U. tomentosa were equivalent at quenching DPPH radicals (EC50, 13.6-21.7 microg/ml) as well as inhibiting TNFalpha production. However, the latter action was registered at much lower concentrations (EC50, 10.2-10.9 ng/ml). Cat’s claw (10 microg/ml) had no effect on basal PGE2 production, but reduced LPS-induced PGE2 release (P < 0.05), but at higher concentrations than that required for TNFalpha inhibition.  CONCLUSION: Cat’s claw is an effective treatment for osteoarthritis. The species, U guianensis and U tomentosa are equiactive. They are effective antioxidants, but their anti-inflammatory properties may result from their ability to inhibit TNFalpha and to a lesser extent PGE2 production.”

The 2004 publication Effect of hypoxia and reoxygenation on gene expression and response to interleukin-1 in cultured articular chondrocytes reports:  “BACKGROUND: Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat’s claw (Uncaria guianensis, vincaria), is a well-described inhibitor of NF-kappaB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality.  METHODS: Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1beta.  RESULTS: RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P < 0.05). As expected, IL-1beta exposure completely silenced IGF-1 production by chondrocytes. However, in the presence of IL-1beta both RNI 249 and vincaria protected IGF-1 production in an additive manner (P < 0.01) with the combination restoring chondrocyte IGF-1 production to normal levels. Cartilage NO production was dramatically enhanced by IL-1beta. Both vincaria and RNI 249 partially attenuated NO production in an additive manner (p < 0.05). IL-1beta – induced degradation of cartilage matrix was quantified as glycosaminoglycan release. Individually RNI 249 or vincaria, prevented this catabolic action of IL-1beta.  CONCLUSION: The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1beta, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases.”

A 2007 publication Cat’s claw: an Amazonian vine decreases inflammation in osteoarthritis reports: “The mechanism of cat’s claw appears to be as an inhibitor of TNFalpha and antioxidant. Understanding the processes in osteoarthritis may facilitate and clarify the potential role of cat’s claw as a complementary therapy to assist in the reduction of pro-inflammatory mediators and effectors.”

The 2010 publicationAntioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis concludes, based on analysis of 16 separate studies: “Three studies support cat’s claw alone or in combination for OA, and two studies support omega-3 fatty acids for the treatment of RA. We cannot recommend use of vitamin E alone; vitamins A, C, and E in combination; ginger; turmeric; or Zyflamend (New Chapter, Brattleboro, Vermont) for the treatment of OA or RA or omega-3 fatty acids for OA.”

The 2011 publication Effect of a Herbal-Leucine mix on the IL-1β-induced cartilage degradation and inflammatory gene expression in human chondrocytes reports “The objective of this study was to investigate the anti-inflammatory/chondroprotective potential of a Herbal and amino acid mixture containing extract of the Uncaria tomentosa, Boswellia spp., Lepidium meyenii and L-Leucine on the IL-1β-induced production of nitric oxide (NO), glycosaminoglycan (GAG), matrix metalloproteinases (MMPs), aggrecan (ACAN) and type II collagen (COL2A1) in human OA chondrocytes and OA cartilage explants. – “  The conclusion is “Our data suggests that HLM could be chondroprotective and anti-inflammatory agent in arthritis, switching chondrocyte gene expression from catabolic direction towards anabolic and regenerative, and consequently this approach may be potentially useful as a new adjunct therapeutic/preventive agent for OA or injury recovery.”  How much of the impact is due only to uncaria tormentosa is not reported.

Uncaria tormentosa can be renoprotective in the case of acute ischemic kidney injury.

At least this appears to be the case in rats.  The 2011 publication [Uncaria tomentosa and acute ischemic kidney injury in rats] reports: “The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat’s claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities.”

Ungaria tormentosa extract can protect against the experimental induction of diabetes and increases the number of regulatory T cells.

The 2011 publication Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both? relates: “In this study we investigated the immunomodulatory potential of Uncaria tomentosa (UT) aqueous-ethanol extract on the progression of immune-mediated diabetes. — MATERIALS AND METHODS: C57BL/6 male mice were injected with MLDS (40mg/kg) and orally treated with UT at 10-400mg/kg during 21 days. Control groups received MLDS alone or the respective dilution vehicle. Pancreatic mononuclear infiltrate and β-cell insulin content were analyzed by HE and immunohistochemical staining, respectively, and measured by digital morphometry. Lymphocyte immunophenotyping and cytokine production were determined by flow cytometry analysis. — RESULTS: Treating the animals with 50-400mg/kg of UT caused a significant reduction in the glycemic levels, as well as in the incidence of diabetes. The morphometric analysis of insulitis revealed a clear protective effect. Animals treated with UT at 400mg/kg presented a higher number of intact islets and a significant inhibition of destructive insulitis. Furthermore, a significant protection against the loss of insulin-secreting presented β-cells was achieved, as observed by a careful immunohistochemical evaluation. The phenotypic analysis indicated that the groups treated with higher doses (100-400mg/kg) presented CD4(+) and CD8(+) T-cell values similar to those observed in healthy animals. These same higher doses also increased the number of CD4(+)CD25(+)Foxp3(+) regulatory T-cells. Moreover, the extract modulated the production of Th1 and Th2, with increased levels of IL-4 and IL-5. — CONCLUSIONS: The extract was effective to prevent the progression of immune-mediated diabetes by distinct pathways.” 

Treatment with ungaria tormentosa may accelerate recovery of sensorineural functioning after hearing injury due to excessive noise.

The August 2011 publication Carboxy alkyl esters of Uncaria tomentosa augment recovery of sensorineural functions following noise injury relates “This study tested the hypothesis that hydrophilic chemotypes of the medicinal vine Uncaria tomentosa (UT) would facilitate recovery of sensorineural functions following exposure to a damaging level of noise. The particular chemotypes investigated were carboxy alkyl esters (CAE) which are known to exhibit multifunctional cytoprotective properties that include: enhanced cellular DNA repair, antioxidation and anti-inflammation. Long-Evans rats were divided into four treatment groups: vehicle-control, noise-only, CAE-only and CAE+noise. The noise exposure was an 8kHz octave band of noise at 105dB SPL for 4h. Outer hair cell (OHC) function was measured with the cubic 2f(1)-f(2) distortion product otoacoustic emissions (DPOAE) at the start of the study (baseline) and at time-points that corresponded to 1day, 1week and 4weeks post-noise exposure to determine within-group effects. Compound action potentials to puretone stimuli were recorded from the VIIIth craniofacial nerve at 4weeks post-noise exposure to determine between-group effects. Additionally, cytocochleograms were constructed for each row of OHCs from each group. Noise exposure produced significant sensorineural impairments. However, CAE treatment facilitated almost complete recovery of OHC function and limited the magnitude of cell loss. The loss of neural sensitivity to puretone stimuli was inhibited with CAE treatment. Therefore, it appears that the multifunctional cytoprotective capacity of CAE from UT may generalize to otoprotection from acoustic over-exposure.”

Uncaria rhynchophylla appears to function as an anticonvulsive for the control of epileptic seizures.

Uncaria rhynchophylla is the Chinese version of cat’s claw. The 2012 publication Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression reports “Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABA_A) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus, — UR, a Chinese herb, has been used for anticonvulsive effects and the treatment of epileptic seizures. The alkaloid component of UR is composed of rhynchophylline, isorhynchophylline, corynoxeine, hirsutine, and hirsuteine. UR can also protect hippocampal neurons from cell death. The cell death and apoptosis-related genes such as c-jun, bax, and p53 were attenuated when hippocampal neurons were pretreated with the alkaloid component of UR [32]. Our previous study demonstrated that the alkaloid component of UR can ameliorate KA-induced lipid peroxide in vitro and in animal behavior, such as wet dog shakes, paw tremors, and facial myoclonia [29].”

Ungaria tormentosa contains alkaloids that appear to inhibit the replication of several cancer cell lines including medullary thyroid carcinoma, sarcoma and breast cancer.

The 2009 publicationAntiproliferative and pro-apoptotic effects of Uncaria tomentosa in human medullary thyroid carcinoma cells reports: Medullary thyroid carcinoma (MTC), a rare calcitonin-producing tumor, is derived from parafollicular C-cells of the thyroid and is characterized by constitutive Bcl-2 overexpression. The tumor is relatively insensitive to radiation therapy as well as conventional chemotherapy. To date, the only curative treatment is the early and complete surgical removal of all neoplastic tissue. In this study, the antiproliferative and pro-apoptotic effects of fractions obtained from Uncaria tomentosa (Willd.) DC, commonly known as uña de gato or cat’s claw were investigated. Cell growth of MTC cells as well as enzymatic activity of mitochondrial dehydrogenase was markedly inhibited after treatment with different fractions of the plant. Furthermore, there was an increase in the expressions of caspase-3 and -7 and poly(ADP-ribose) polymerase (PARP) fraction, while bcl-2 overexpression remained constant. In particular, the alkaloids isopterpodine and pteropodine of U. tomentosa exhibited a significant pro-apoptotic effect on MTC cells, whereas the alkaloid-poor fraction inhibited cell proliferation but did not show any pro-apoptotic effects. These promising results indicate the growth-restraining and apoptotic potential of plant extracts against neuroendocrine tumors, which may add to existing therapies for cancer.”

The 2010 publication Cytotoxic effect of the pentacyclic oxindole alkaloid mitraphylline isolated from Uncaria tomentosa bark on human Ewing’s sarcoma and breast cancer cell lines reports “Preparations from Uncaria tomentosa, a South American Rubiaceae, have been used in the Peruvian traditional medicine for the treatment of infective, inflammatory and tumoral processes. In this study, the pentacyclic oxindole alkaloid mitraphylline was isolated from the dried inner bark of this plant species, and its structure elucidated by analysis of NMR spectroscopic data. Mitraphylline was differentially identified from its stereoisomeric pair isomitraphylline by (15)N-NMR. Its antiproliferative and cytotoxic effects have been tested on human Ewing’s sarcoma MHH-ES-1 and breast cancer MT-3 cell lines, using cyclophosphamide and vincristine as reference controls. A Coulter counter was used to determine viable cell numbers, followed by the application of the tetrazolium compound MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] an inner salt. A colorimetric method was employed to evaluate cell viability in this cytotoxic assay. Micromolar concentrations of mitraphylline (5 microM to 40 microM) inhibited the growth of both cell lines in a dose-dependent manner. The IC (50) +/- SE values were 17.15 +/- 0.82 microM for MHH-ES-1 and 11.80 +/- 1.03 microM for MT-3 for 30 hours, smaller than those obtained for the reference compounds. This action suggests that the pentacyclic oxindole alkaloid mitraphylline might be a new promising agent in the treatment of both human sarcoma and breast cancer.”

The 2010 publicationAntitumoral and antioxidant effects of a hydroalcoholic extract of cat’s claw (Uncaria tomentosa) (Willd. Ex Roem. & Schult) in an in vivo carcinosarcoma model reports: “The present work intended to study the antitumoral and antioxidant effects of Uncaria tomentosa (UT) hydroalcoholic extract in the Walker-256 cancer model. — Walker-256 cells were subcutaneously inoculated in the pelvic limb of male Wistar rats. — UT hydroalcoholic extract successfully reduced the tumor growth. In addition, treatment with UT reduced the activity of AST, which had been increased as a result of tumor inoculation, thus attempting to return it to normal levels. UT did not reverse the increase of LDH and GGT plasma levels, although all doses were remarkably effective in reducing urea plasma levels. An important in vitro free radical-scavenging activity was detected at various concentrations of UT extract (1-300 microg mL(-1)). –This data represent an in vivo demonstration of both antitumoral and antioxidant effects of UT hydroalcoholic extract. The antineoplastic activity may result, partially at least, from the ability of UT to regulate redox and metabolism homeostasis.”

The 2010 publication Anticancer activity of the Uncaria tomentosa (Willd.) DC. preparations with different oxindole alkaloid composition states “Further animal studies on mice bearing Lewis lung carcinoma showed significant inhibition of tumor growth by B/W(37) administered for 21 days at daily doses of 5 and 0.5 mg (p=0.0009).”

The 2011 publication Mixtures of Uncaria and Tabebuia extracts are potentially chemopreventive in CBA/Ca mice: a long-term experiment reports: “A long-term experimental animal model was developed by our research group for the evaluation of potential chemopreventive effects. The inhibitory effects of agents on carcinogen (7,12-dimethylbenz[a]anthracene (DMBA) induced molecular epidemiological biomarkers, in this case the expression of key onco/suppressor genes were investigated. — According to the examined gene expression patterns in this long-term experiment the chemopreventive effect of CoD™ tea consumption could be confirmed.”

Uncaria tormentosa can contribute to skin DNA repair.

Commercially-sponsored research has been focused on investigating whether incorporating cat’s claw water extract in skin lotions and sunscreen could contribute to skin DNA repair.  The 2006 publication A water soluble extract from Uncaria tomentosa (Cat’s Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin reports “Cat’s Claw (Uncaria tomentosa) water extracts, essentially free of oxindole alkaloids, have been shown to possess a broad spectrum of biological activity including DNA repair enhancement and antiinflammatory properties. These two biological mechanisms are key molecular targets to develop treatments that protect skin exposed to ultraviolet light from the sun. Because C-Med-100, a Cat’s Claw water extract, is the only documented natural source of components that can up-regulate simultaneously both DNA repair and antiinflammation, its ability to modulate DNA repair in human skin organ cultures was undertaken. For this purpose skin cultures were treated with or without 5 mg/mL C-Med-100, irradiated with 0-100 mJ/cm2 UVB, and microscopically analysed for necrosis as well as the level of pyrimidine dimers using immunofluorescent TT-dimer antibody staining. The data clearly demonstrated that co-incubation with C-Med-100 reduced skin cell death from UV exposure, and this protection was accounted for by a concomitant increase in DNA repair. Based on these results, it was concluded that C-Med-100 was a natural plant extract worthy of further consideration as a sunscreen product.”

A Sweedish 2000 study Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa reported on DNA repair capabilities, toxicity and absence of side effects after treatment with ungaria tormentosa water extracts: “Female W/Fu rats were gavaged daily with a water-soluble extract (C-MED-100) of Uncaria tomentosa supplied commercially by CampaMed at the doses of 0, 5, 10, 20, 40 and 80 mg/kg for 8 consecutive weeks. Phytohemagglutinin (PHA) stimulated lymphocyte proliferation was significantly increased in splenocytes of rats treated at the doses of 40 and 80 mg/kg. White blood cells (WBC) from the C-MED-100 treatment groups of 40 and 80 mg/kg for 8 weeks or 160 mg/kg for 4 weeks were significantly elevated compared with controls (P < 0.05). In a human volunteer study, C-MED-100 was given daily at 5 mg/kg for 6 consecutive weeks to four healthy adult males. No toxicity was observed and again, WBC were significantly elevated (P < 0.05) after supplement. Repair of DNA single strand breaks (SSB) and double strand breaks (DSB) 3 h after 12 Gy whole body irradiation of rats were also significantly improved in C-MED-100 treated animals (P < 0.05). The LD50 and MTD of a single oral dose of C-MED-100 in the rat were observed to be greater than 8 g/kg. Although the rats were treated daily with U. tomentosa extracts at the doses of 10-80 mg/kg for 8 weeks or 160 mg/kg for 4 weeks, no acute or chronic toxicity signs were observed symptomatically. In addition, no body weight, food consumption, organ weight and kidney, liver, spleen, and heart pathological changes were found to be associated with C-MED-100 treatment.”

Uncaria tormentosa might provide an effective therapy for Dengue fever.

The 2008 publication Immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue Virus-2 reported : “Uncaria tomentosa (Willd.) DC., a large woody vine native to the Amazon and Central American rainforests has been used medicinally by indigenous peoples since ancient times and has scientifically proven immunomodulating, anti-inflammatory, cytotoxic and antioxidant activities. Several inflammatory mediators that are implicated in vascular permeability and shock are produced after Dengue Virus (DENV) infection by monocytes, the primary targets for virus replication. Here we assessed the immunoregulatory and antiviral activities from U. tomentosa-derived samples, which were tested in an in vitro DENV infection model. DENV-2 infected human monocytes were incubated with U. tomentosa hydro-alcoholic extract or either its pentacyclic oxindole alkaloid-enriched or non-alkaloid fractions. The antiviral activity was determined by viral antigen (DENV-Ag) detection in monocytes by flow cytometry. Our results demonstrated an in vitro inhibitory activity by both extract and alkaloidal fraction, reducing DENV-Ag+ cell rates in treated monocytes. A multiple microbead immunoassay was applied for cytokine determination (TNF-alpha, IFN-alpha, IL-6 and IL-10) in infected monocyte culture supernatants. The alkaloidal fraction induced a strong immunomodulation: TNF-alpha and IFN-alpha levels were significantly decreased and there was a tendency towards IL-10 modulation. We conclude that the alkaloidal fraction was the most effective in reducing monocyte infection rates and cytokine levels. The antiviral and immunomodulating in vitro effects from U. tomentosa pentacyclic oxindole alkaloids displayed novel properties regarding therapeutic procedures in Dengue Fever and might be further investigated as a promising candidate for clinical application.”

Cat’s claw extract could provide a promising alternative for treating endometriosis.

The 2011 publication Experimental endometriosis reduction in rats treated with Uncaria tomentosa (cat’s claw) extract reports “Cat’s claw extract appears to be a promising alternative for treating endometriosis.”

There is test-tube evidence that uncaria tormentosa is an effective antimicrobial substance against oral microbes including enterobacteriaceae and staphylococcus.

See In vitro antimicrobial activity of phytotherapic Uncaria tomentosa against endodontic pathogens (2010) and Antimicrobial activity of Uncaria tomentosa against oral human pathogens (2007).

Commentary

This has been only a sampler of research related to cat’s claw.  While the substance seems very promising, as is typical for herbal substances the studies are limited by their nature.  Practicing medical doctors normally do not read these kinds of research studies.  I could find no clinical trials searching either under cat’s claw or uncaria tormentosa.  So effectively, there is a powerful barrier where no matter how many promising research studies such as these there are, they do not ever lead to clinical medical use of cat’s claw.  Like resveratrol, curcumin, green tea and many other health-providing phyto substances, cat’s claw remains in the domain of dietary supplements where most medical practitioners will dismiss it as “unproven” or as a “fad substance.”  Of course, skepticism may be correct when it comes to a specific human illnesses.  But this state of limbo could be depriving millions of ill people from participating in the benefits cat’s claw could quite possibly produce for them.