An active ingredient of Cat’s Claw water extracts identification and efficacy of quinic acid.
Historic medicinal practice has defined Cat’s Claw, also known as Una de Gato or Uncaria tomentosa, as an effective treatment for several health disorders including chronic inflammation, gastrointestinal dysfunction such as ulcers, tumors and infections. The efficacy of Cat’s Claw was originally believed, as early as the 1960s, to be due to the presence of oxindole alkaloids. However, more recently water-soluble Cat’s Claw extracts were shown not to contain significant amounts of alkaloids (<0.05%), and yet still were shown to be very efficacious. Here we characterize the active ingredients of a water-soluble Cat’s Claw extract called C-Med-100 as inhibiting cell growth without cell death thus providing enhanced opportunities for DNA repair, and the consequences thereof, such as immune stimulation, anti-inflammation and cancer prevention. The active ingredients were chemically defined as quinic acid esters and could also be shown to be bioactive in vivo as quinic acid.
J Ethnopharmacol. 2005 Jan 15;96(3):577-84
Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC.
The antioxidant properties of aqueous and ethanolic extracts of the Uncaria tomentosa bark were evaluated. The analysis included trolox equivalent antioxidant capacity (TEAC), peroxyl radical-trapping capacity (PRTC), superoxide radical scavenging activity (SOD) and quantitation of total tannins (TT) and total phenolic compounds (TPC). The obtained results indicate high antioxidant capacity of the studied materials in comparison to the other extracts of fruits, vegetables, cereals and medicinal plants. Higher antioxidant activity and total phenolic compounds of the alcoholic preparations -- TEAC=0.57 mmol of Trolox/g, PRTC=0.52 mmol of Trolox/g and SOD=0.39 U/mg than of the aqueous preparation -- TEAC=0.34 mmol of Trolox/g, PRTC=0.19 mmol of Trolox/g and SOD=0.10 U/mg were observed. These results might suggest higher medical suitability of alcoholic extracts. However, the highly elevated level of tannins in alcoholic extracts may cause undesirable gastric effects.
J Ethnopharmacol. 2006 Mar 8;104(1-2):18-23
A water soluble extract from Uncaria tomentosa (Cat’s Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin.
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.
Phytother Res. 2006 Mar;20(3):178-83
Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators.
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 marketplace. 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 cytokines. 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.
Altern Med Rev. 2006 Jun;11(2):128-50
Innate immune recognition and suppression of tumors.
In this chapter, we first summarized the strong evidence that now supports the existence of an effective cancer immune surveillance process that prevents cancer development in both mice and humans. We then focused the remainder of the chapter on methods of tumor recognition that contribute to natural host immune suppression of tumors. In particular, NKG2D is a type II transmembrane-anchored glycoprotein expressed as a disulfide-linked homodimer on the surface of all mouse and human natural killer cells (NK cells). Stimulation of NK cell through NKG2D triggers cell-mediated cytotoxicity and in some cases induces production of cytokines. NKG2D binds to family of ligands with structural homology to major histocompatibility complex (MHC) class I, however, NKG2D ligands often display upregulated surface expression on stressed cells and are frequently overexpressed by tumors unlike conventional MHC class I molecules. Evidence clearly implicate that NKG2D recognition plays an important role in tumor immune surveillance.
Adv Cancer Res. 2006;95:293-322
Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells.
Natural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs. Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2 sublines with tetracycline-regulated expression of bcl-2, p16ink4A or constitutively expressing the cowpox virus protein crm-A were used for further studies of the apoptosis-inducing properties of these alkaloids. Neither overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced apoptosis. Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.
Br J Haematol. 2006 Mar;132(5):615-22
The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line.
Uncaria tomentosa, also known as “Una de gato”, is a Rubiaceae species widely used in South-American folk medicine for the treatment of cancer, arthritis, gastritis and epidemic diseases. Extracts of the plant have been shown to possess cytostatic and anti-inflammatory activity as well as mutagenic and antimutagenic properties. However, to date no studies have been carried out to verify the direct antitumor activity of the extracts. The present study investigates the effects of some extracts and their chromatographic fractions from the bark of U. tomentosa on the growth of a human breast cancer cell line (MCF7). Our data indicated that, in addition to the antimutagenic activity, U. tomentosa extracts and fractions exert a direct antiproliferative activity on MCF7. The bioassay-directed fractionation from barks and leaves resulted in the isolation of two active fractions, which displayed an IC50 of 10 mg/ml and 20 mg/ml, respectively and an antiproliferative effect, with about 90% of inhibition at a concentration of 100 mg/ml.
Anticancer Res. 2001 Jul-Aug;21(4A):2457-61
DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study.
The Uncaria tomentosa water extracts (C-Med-100) have been shown to enhance DNA repair, mitogenic response and leukocyte recovery after chemotherapy-induced DNA damage in vivo. In this study, the effect of C-Med-100 supplement was evaluated in a human volunteer study. Twelve apparently healthy adults working in the same environment were randomly assigned into 3 groups with age and gender matched. One group was daily supplemented with a 250 mg tablet containing an aqueous extract of Uncaria tomentosa of C-Med-100, and another group with a 350 mg tablet, for 8 consecutive weeks. DNA repair after induction of DNA damage by a standard dose of hydrogen peroxide was measured 3 times before supplement and 3 times after the supplement for the last 3 weeks of the 8 week-supplement period. There were no drug-related toxic responses to C-Med-100 supplement when judged in terms of clinical symptoms, serum clinical chemistry, whole blood analysis and leukocyte differential counts. There was a statistically significant decrease of DNA damage and a concomitant increase of DNA repair in the supplement groups (250 and 350 mg/day) when compared with non-supplemented controls (p < 0.05). There was also an increased tendency of PHA induced lymphocyte proliferation in the treatment groups. Taken together, this trial has confirmed the earlier results obtained in the rat model when estimating DNA repair enhancement by C-Med-100.
Phytomedicine. 2001 Jul;8(4):275-82
An extract of Uncaria tomentosa inhibiting cell division and NF-kappa B activity without inducing cell death.
Previous reports have demonstrated that extracts of the plant Uncaria tomentosa inhibit tumor cell proliferation and inflammatory responses. We have confirmed that C-Med 100, a hot water extract of this plant, inhibits tumor cell proliferation albeit with variable efficiency. We extend these findings by showing that this extract also inhibits proliferation of normal mouse T and B lymphocytes and that the inhibition is not caused by toxicity or by induction of apoptosis. Further, the extract did not interfere with IL-2 production nor IL-2 receptor signaling. Since there was no discrete cell cycle block in C-Med 100-treated cells, we propose that retarded cell cycle progression caused the inhibition of proliferation. Collectively, these data suggested interference with a common pathway controlling cell growth and cell cycle progression. Indeed, we provide direct evidence that C-Med 100 inhibits nuclear factor kappa B (NF-kappa B) activity and propose that this at least partially causes the inhibition of proliferation.
Int Immunopharmacol. 2003 Dec;3(13-14):1889-900
Efficacy and safety of freeze-dried cat’s claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis.
AIM: 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. MATERIALS AND METHODS: 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.
Inflamm Res. 2001 Sep;50(9):442-8