Uncaria Tomentosa Research Articles

New oleanan-type triterpene and cincholic acid glycosides from Peruvian "Uña de Gato" (Uncaria tomentosa).

A new oleanan-type triterpene and three new cincholic acid glycosides were isolated from Peruvian "Una de Gato" (Cat's claw, plant of origin: Uncaria tomentosa), a traditional herbal medicine in Peru. Their structures were determined by spectroscopic analysis.

Developmental and ultrastructural effect of Uncaria tomentosa (Willd.) DC extract on the paprika Capsicum annuum L.

The effect of liana ( Uncaria tomentosa L.) extract on paprika (Capsicum annuum L.) cv. Koźlak. development, leaf ultrastructure and yielding were studied under greenhouse conditions. Uncaria extract was supplied before flowering of plants by two manners: to the soil or leaves. It is shown that the effect of Uncaria extract on paprika was dependent on the concentration and the way of supply of the preparation to plant. In the case of extract supply to the soil, distinct growth inhibition of plants and ultrastructural manifestations of senescence were observed. Simultaneously, acceleration of flowering and fruiting were noticed. The phenomena mentioned above caused the lower yield of paprika fruits compared to the control. In the case of extract supply to leaves, high acceleration of flowering and fruits maturation of paprika were observed. Spraying of leaves with Uncaria extract resulted in an increase of fruits yield compared to the control.

An extract of Uncaria tomentosa inhibiting cell division and NF-κB 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 κB (NF-κB) activity and propose that this at least partially causes the inhibition of proliferation.

Two new nor-triterpene glycosides from peruvian "Uña de Gato" (Uncaria tomentosa).

Two new 27-nor-triterpene glycosides, tomentosides A (1) and B (2), were isolated from Peruvian "Uña de Gato" (cat's claw, plant of origin: Uncaria tomentosa), a traditional herbal medicine in Peru. Their structures were determined by spectroscopic analysis and chemical interconversions. This is the first report of naturally occurring pyroquinovic acid glycosides.

Fatty Acid Compositions of Lipids in Cat's Claw (Uncaria tomentosa) and Maca (Lepidium meyenii)

Cat's Claw and Maca, both imported from Peru, were fractionated. The compositions of the total lipid fractions and fatty acids composing the lipid fractions were investigated. The five major fatty acids commonly detected in Cat's Claw and Maca were C16 : 0, C18 : 0, C18 : 1 n 9, C18 : 2 n 6 and C18 : 3 n3. The lipid fractions obtained from Cat's Claw were primarily composed of these five fatty acids, with, in addition to C14 : 0 and C20 : 0. The lipid fractions obtained from Maca were primarily composed of these five fatty acids plus C18 : 1 n7. A specific relationship between C18 : 1 n 9 and C 18 : 1 n 7 was seen in the TL and NL fractions derived from Maca. The percentage of C18 : 3 n 3 was also high in the fractions extracted from Maca.The n 6 /n 3 ratio and S. A. /UnS. A. (Saturated fatty acids/Unsaturated fatty acids) ratio were high in all the lipid fractions obtained from Cat's Claw but low in the fractions derived from Maca.

X‐Ray Crystal Structure Analysis of Oxindole Alkaloids

AbstractThe single‐crystal X‐ray structures of speciophylline, mitraphylline, and rhynchophylline, oxindole alkaloids from the Peruvian climbing vine Uncaria tomentosa (Rubiaceae), were determined. The three compounds show N⋅⋅⋅HN hydrogen bonding, which has not been observed in the crystal structures of the related alkaloids pteropodine and isopteropodine. In the tetracyclic alkaloid rhynchophylline, the side chain is rotated out of the ring plane into a position perpendicular to it. This is in contrast to the situation of the pentacyclic analogue mitraphylline, which possesses a conformationally rigid tricyclic core. This conformational difference possibly causes the competitive antagonism of these two types of alkaloids.

Biosynthesis of sterols and triterpenes in cell suspension cultures of Uncaria tomentosa.

Pectin administered to Uncaria tomentosa cell suspension cultures, was found to increase the production of triterpene acids (ursolic and oleanolic acid), however, neither growth nor sterol accumulation were affected. Cell cultures showed that pectin treatment caused a rapid threefold increase in the activities of enzymes involved in the biosynthesis of C(5) and C(30 )isoprenoid, such as isopentenyl diphosphate isomerase and squalene synthase. The activity of a farnesyl diphosphatase, which could divert the flux of farnesyl diphosphate to farnesol, was two times lower in elicited than in control cells. Elicited cells also transformed more rapidly a higher percentage of [5-(3)H]mevalonic acid into triterpene acids. Interestingly, addition of terbinafine, an inhibitor of squalene epoxidase, to elicited cell cultures inhibited sterol accumulation while triterpene production was not inhibited. These results suggest that in U. tomentosa cells, both the previously mentioned enzymes and those involved in squalene 2,3-oxide formation play an important regulatory role in the biosynthesis of sterols and triterpenes.

Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content.

Cat's claw is an herbal medicine from the Amazon that is used widely to treat inflammatory disorders. The purpose of this study was to characterize the antioxidative and antiinflammatory properties of cat's claw, Uncaria tomentosa (UT) and Uncaria guianensis (UG). Alkaloids and flavanols were determined using reversed-phase HPLC; scavenging of 1,1-diphenyl-2-picrilhydrazyl (DPPH), hydroxyl radicals, and lipid peroxidation by spectrophotometry; and TNFalpha production by ELISA. Anti-inflammatory activity was assessed in vitro by inhibition of TNFalpha and nitrite production from RAW 264.7 cells exposed to LPS (50 ng/ml) and in vivo using the indomethacin-induced gastritis model. Apoptosis was assessed using the TUNEL technique and TNFalpha mRNA by in situ RT-PCR. In each of the antioxidant assays tested, UG was more potent than UT (P < 0.01). The total oxindole and pentacyclic alkaloid content of UT was 35-fold > UG. The IC50 value for inhibition of TNFalpha production was significantly (P < 0.01) higher for UT (14.1 ng/ml) vs UG (9.5 ng/ml), yet at concentrations that were considerable lower than that required for antioxidant activity. Non-alkaloid HPLC fractions from UT decreased LPS-induced TNFalpha and nitrite production in RAW 264.7 cells (P < 0.01) at a concentration range comparable to the parent botanical. Oral pretreatment for 3 d with UT protected against indomethacin-induced gastritis, and prevented TNFalpha mRNA expression and apoptosis. These results indicate that while both species of cat's claw provide effective antioxidant and anti-inflammatory activities, U. guianensis is more potent. In conclusion, the presence of oxindole or pentacyclic alkaloids did not influence the antioxidant and anti-inflammatory properties of cat's claw.

Synthesis and absolute configuration of a new 3,4-dihydro-beta-carboline-type alkaloid, 3,4-dehydro-5(S)-5-carboxystrictosidine, isolated from Peruvian Uña de Gato (Uncaria tomentosa).

The structure including the absolute configuration of a new glucoalkaloid, 3,4-dehydro-5(S)-5-carboxystrictosidine, isolated from Peruvian Uña de Gato (Cat's Claw, original plant: Uncaria tomentosa), was confirmed by synthesis starting from secologanin and L-tryptophan.

Improved method for the determination of oxindole alkaloids in Uncaria tomentosa by high performance liquid chromatography.

This Paper describes an improved HPLC method for the determination of pentacyclic oxindole alkaloids in Uncaria tomentosa (Cat's Claw). Six of the isomeric compounds could be baseline separated at room temperature within less than 30 min by using 3 microm C-18 column material and a mobile phase consisting of 10 mM phosphate buffer at pH 7.0 and acetonitrile. At a wavelength of 245 nm all standard compounds could be detected at concentrations as low as 0.63 microg/ml. Different samples of U. tomentosa bark and market products containing Cat's Claw were extracted with a modified procedure ensuring the integrity of the alkaloids and analyzed successfully. The results indicated accuracy and consistency of the new method, and showed variations in the total alkaloid content in products from 0.156 to 0.962%.

Alkaloid Screening of Herbarium Samples of Rubiaceae from Panama

In an effort to study plants of the Rubiaceae from Panama, 299 herbarium samples, representing 133 species, were subjected to alkaloid screening. From this total, 234 samples (78%) afforded a positive test for alkaloids, and 99 samples (33%) gave a positive reaction for indole alkaloids; 109 species (82%) contain alkaloids and 58 (44%) produce indole alkaloids. This is the first time that 102 (94%) and 52 (90%) species are reported as alkaloid and indole alkaloid bearing, respectively. The results of 10 out of 15 species, that is 67%, corroborate earlier studies. The richest indole alkaloid species were: Hamelia patens, Hamelia xerocarpa, Hoffmannia morii, Hoffmannia unguis-canceris, Deppea grandiflora, Elaeagia nitidifolia, Rondeletia secunda, Simira maxonii, Uncaria tomentosa, Gonzalagunia rosea, Isertia haenkeana, Isertia laevis, Posoqueria latifolia and Cinchona pubescens.

Cat’s claw inhibits TNFα production and scavenges free radicals: role in cytoprotection

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-κB. 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 μM) and ultraviolet light (UV) light. TNFα production was induced by lipopolysaccharide (LPS 0.5 μg/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 μg/ml, p < .05). Cat’s claw (10 μg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFα media levels from 3 to 97 ng/ml. Cat’s claw suppressed TNFα 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 TNFα production. The primary mechanism for cat’s claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFα synthesis.

An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures.

Serial dilutions of 21 commercial ethanolic herbal extracts and tinctures, and 13 related pure plant compounds have been analyzed for their in vitro cytochrome P450 3A4 (CYP3A4) inhibitory capability via a fluorometric microtitre plate assay. Roughly 75% of the commercial products and 50% of the pure compounds showed significant inhibition of CYP3A4 metabolite formation. For each herbal product and pure compound exhibiting dose-dependency, the inhibition values were used to generate median inhibitory concentration (IC50) curves using linear regression. Among the commercial extracts, Hydrastis canadensis (goldenseal), Hypericum perforatum (St. John's wort), and Uncaria tomentosa (cat's claw) had the lowest IC50 values at < 1% full strength, followed by Echinacea angustifolia roots, Trifolium pratense (wild cherry), Matricaria chamomilla (chamomile), and Glycyrrhiza glabra (licorice), which had IC50 values ranging from 1%-2% of full strength. Dillapiol, hypericin, and naringenin had the lowest IC50 values among the pure plant compounds at < 0.5 mM; dillapiol was the most potent inhibitor at 23.3 times the concentration of the positive CYP3A4 inhibitor ketoconazole. Utilizing high-throughput screening methodologies for assessing CYP3A4 inhibition by natural products has important implications for predicting the likelihood of potential herbal-drug interactions, as well as determining candidates for further in-depth analyses.

Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa.

The Uncaria tomentosa water extracts (C-Med-100) depleted of indole alkaloids (< 0.05%, w/w) have been shown to induce apoptosis and inhibit proliferation in tumor cells in vitro and to enhance DNA repair, mitogenic response and white blood cells in vivo. In this study, the effect of C-Med-100 in the treatment of chemically induced leukopenia was evaluated in a rat model. W/Fu rats were treated first with doxorubicin (DXR) 2 mg/kg x 3 (i.p. injection at 24 hour-intervals) to induce leukopenia. Twenty-four hours after the last DXR treatment, the rats were daily gavaged with C-Med-100 for 16 consecutive days. As a positive control, Neupogen, a granulocyte colony stimulator was also administered by subcutaneous injection at a dose of 5 and 10 microg/ml for 10 consecutive days. The results showed that both C-Med-100 and Neupogen treatment groups recovered significantly sooner (p < 0.05 by Duncan test) than DXR group. However, the recovery by C-Med-100 treatment was a more natural process than Neupogen because all fractions of white blood cells were proportionally increased while Neupogen mainly elevated the neutrophil cells. These results were also confirmed by microscopic examination of the blood smears. The mechanism of the C-Med-100 effect on WBC is not known but other data showing enhanced effects on DNA repair and immune cell proliferative response support a general immune enhancement.

A CONCERTED APPROACH TOUÑA DE GATODEVELOPMENT IN PERU

Uncaria tomentosa and U. guianensis appear to hold a potential to become an important export commodity and a source of income for small farmers in the tropical forest belt of the country. Both species have been important in traditional healing in many South American countries. They contain about sixty substances that are being tested widely for possible medical treatments. Uncaria tomentosa has been traded from Peru since 1994 until it reached a peak export of 726 t in 1996. Despite the general discourse on the potential of species, such as these Uncaria spp., the many stakeholders with some interest in these species do not co-ordinate their activities sufficiently to enhance sustained income for the country and the rural poor. At the national level, there has been pressure on the government to implement legislation to prohibit the sales of the raw material of these species, in order to capture larger shares of benefits for the national economy. Initially false conservation arguments were used to stop collection from the wild, as there is sufficient evidence to argue that at current harvesting levels there is no threat to the two species. Regional government agencies have promoted the production of the two species without having a clear picture of future market development, allowing the possibility that much of the future production cannot be sold. Both actions may possibly negatively affect the benefits that accrue to local collectors or producers

A new gluco indole alkaloid, 3, 4-dehydro-5-carboxystrictosidine, from Peruvian Uña de Gato (Uncaria tomentosa).

A new gluco indole alkaloid, 3,4-dehydro-5-carboxystrictosidine, was obtained from Peruvian Uña de Gato (Cat's Claw, original plant: Uncaria tomentosa) together with two known gluco indole alkaloids. This compound was the first example of isolation of a gluco monoterpenoid indole alkaloid having a 3,4-dihydro-beta-carboline ring system from nature. A characteristic feature of the compound was the quick replacement of the methylene hydrogens on C-14 with deuterium that was observed when it was dissolved in CD3OD. We demonstrated a similar proton-deuterium exchange on a model compound, 1-methyl-3,4-dihydro-gamma-carboline, in CD3OD solution.

Two New 19-Hydroxyursolic Acid-type Triterpenes from Peruvian ‘Uña de Gato’ (Uncaria tomentosa)

Two new triterpenes having a 19-hydroxyursolic acid skeleton were isolated from ‘Uña de Gato’ (Uncaria tomentosa), a traditional herbal medicine in Peru. Their structures were determined by spectroscopic analyses and chemical conversion.

Uncaria tomentosa (Willd.) D.C.: cat's claw, uña de gato, or savéntaro.

Recently, Uncaria tomentosa (Willd.) D.C. has become known as a healing plant with an ethnomedicinal background. There have been several reports on its constituents, in particular, oxindole alkaloids. It was found that 2 chemotypes of Uncaria tomentosa with different alkaloid patterns occur in nature. The roots of one type contain pentacyclic oxindoles and the other contains tetracyclic oxindoles. This difference should be considered when the plant is to be used for medicinal applications. Tetracyclic oxindole alkaloids act on the central nervous system, whereas pentacyclic oxindole alkaloids affect the cellular immune system. Recent studies have shown that the tetracyclic alkaloids exert antagonistic effects on the action of the pentacyclic alkaloids. Mixtures of these 2 types of drugs are therefore unsuitable for medicinal uses.

Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa (Uña de Gato)

Two extracts of different collections of the traditional medicine uña de gato ( Uncaria tomentosa) from Peru were characterized by High Pressure Liquid Chromatography as containing approximately 6 mg/g total oxindole content prior to studies with alveolar macrophages. The plant preparations greatly stimulated IL-1 and IL-6 production by rat macrophages in a dose dependent manner in the range of 0.025–0.1 mg/ml. They were also able to enhance IL-1 and -6 in lipopolysaccharide-stimulated macrophages. The results suggest a strong immunostimulant action of this plant.

Antiinflammatory actions of cat's claw: the role of NF-kappaB.

Uncaria tomentosa is a vine commonly known as cat's claw or 'uña de gato' (UG) and is used in traditional Peruvian medicine for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. The aim of this study was to determine the proposed anti-inflammatory properties of cat's claw. Specifically: (i) does a bark extract of cat's claw protect against oxidant-induced stress in vitro, and (ii) to determine if UG modifies transcriptionally regulated events. Cell death was determined in two cell lines, RAW 264.7 and HT29 in response to peroxynitrite (PN, 300 microM). Gene expression of inducible nitric oxide synthase (iNOS) in HT29 cells, direct effects on nitric oxide and peroxynitrite levels, and activation of NF-kappaB in RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation was induced in rats with indomethacin (7.5 mg/kg), with UG administered orally in the drinking water (5 mg/mL). The administration of UG (100 microg/mL) attenuated (P < 0.05) peroxynitrite-induced apoptosis in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat's claw inhibited lipopolysaccharide-induced iNOS gene expression, nitrite formation, cell death and inhibited the activation of NF-kappaB. Cat's claw markedly attenuated indomethacin-enteritis as evident by reduced myeloperoxidase activity, morphometric damage and liver metallothionein expression. Cat's claw protects cells against oxidative stress and negated the activation of NF-kappaB. These studies provide a mechanistic evidence for the widely held belief that cat's claw is an effective anti-inflammatory agent.