Uncaria Tomentosa Research Articles

Contraceptive effect of Uncaria tomentosa (cat's claw) in rats with experimental endometriosis

Evaluate the histological changes in parenchyma's epithelial layer of the uterus and ovarian of rats with induced endometriosis, treated with Uncaria tomentosa extract. 29 rats with experimental endometriosis, were selected and divided in three groups: The uncaria group received 32 mg/ml of Uncaria tomentosa extract, 1 ml administered daily and the placebo group received 1 ml of saline 0.9% per day, during for 14 days (both groups); the leuprolide group received leuprolide acetate 1mg/kg body weight applied single subcutaneous dose. In the 15th day of treatment the uterine horn and ovaries were removed for histopathological analysis. The uncaria group presented nine samples (90%) with immature ovarian follicles, whereas the placebo group did not present any case and in the leuprolide group there were eight rats (88%) with the same change. The placebo group showed mature corpus luteum in all animals, occurring less frequent in uncaria (10%) and leuprolide (22%) groups. The uterine epithelium showed weak proliferative in nine (90%) samples of the uncaria group, in two (20%) animals in the placebo group and seven (77.8%) rats in the leuprolide group. The findings suggest that Uncaria tomentosa has contraceptive effect.

Structural and ultrastructural study of Capsicum annuum leaves after treatment with Uncaria tomentosa bark extracts

<p>The influence of an <em>Uncaria tomentosa </em>extract on the development of <em>Capsicum </em>plants grown in green-house conditions was examined. The effect of the treatment was investigated with microscopic techniques (light and electron microscope) in leaves from three levels of control plants and plants after treatment with the extract added to the soil in doses of 0.4 and 16 mg/ml (200 ml per pot/plant). In control leaves, changes typical of the subsequent phases of normal development were observed: nuclear chromatin became slightly condensed, plastoglobuli of chloroplasts increased in number and size, intragranal thylakoids were somewhat dilatated. In addition to such commonly occurring changes, some symptoms typical of pepper were observed in the ontogenesis of the examined plant: an increased number of spherical electron-dense deposits in vacuoles, an increased number of peroxisomes, the occurrence of numerous paracrystalline structures in chloroplasts of mature leaves, and, starting in mature leaves, expulsion of plastoglobuli from chloroplasts.</p><p>After the treatment, most of those changes, leading to ageing, occurred much earlier and were more distinct. Chloroplasts, already in the youngest examined leaves, showed dilatation of intergranal thylakoids, which intensified with aging of the leaves and degradation of grana in the oldest leaves. Starch grains decreased in size and number and plastoglobuli became large. Vesiculation of ground cytoplasm in all leaves was stronger than in the control. No paracrystalline structures in chloroplasts or expulsion of plastoglobuli were observed. Another unusual phenomenon was the disappearance of spherical electron-dense deposits in the central vacuoles of cells.</p><p>Those observations suggested that <em>U. tomentosa </em>extract enhanced the natural ontogenesis of <em>Capsicum annuum </em>leaves, by accelerating and enhancing the typical characteristics of ageing, and, additionally, it changed the structure and physiology of cells.</p>

Antigenotoxicity, Cytotoxicity, and Apoptosis Induction by Apigenin, Bisabolol, and Protocatechuic Acid

Medicinal plants represent an important resource in new drug research. Antioxidant properties of plants can help to scavenge reactive oxygen species. The objective of this work was to evaluate the genotoxic, antigenotoxic, tumoricidal, and apoptotic effect of some major phenols (apigenin, bisabolol, and protocatechuic acid) from two medicinal plants, Matricaria chamomilla and Uncaria tomentosa. The wing spot test of Drosophila melanogaster was used to evaluate the genotoxicity and antigenotoxicity of the three phenols. The human model of HL-60 leukemia cells was used for the assessment of the cytotoxic effect, growth, and cellular viability. The apoptotic effect was evaluated using a DNA fragmentation assay based on the formation of internucleosomal units. Protocatechuic acid (0.25 and 1 mM), apigenin (0.46 and 1.85 mM), and bisabolol (0.56 and 2.24 mM) did not exhibit any genotoxic effect. The three phenols showed an antigenotoxic effect against the hydrogen peroxide effect and also exhibited tumoricidal activity. Apigenin (2.24-35.96 mM) showed a lower 50% inhibitory concentration (0.75 and 3.87 mM for the trypan blue test and WST-8 colorimetric assay, respectively) than bisabolol and protocatechuic acid. These phenolics also induced apoptosis in HL-60 leukemia cells. This study suggests that the antioxidant activity of Chamomilla and Uncaria could be partially responsible of their beneficial activity.

Inhibitory mechanisms of two Uncaria tomentosa extracts affecting the Wnt-signaling pathway

Uncaria tomentosa ("uña de gato"; "cat's claw"), a woody vine native to the Amazon rainforest, is commonly used in South American traditional medicine to treat a broad spectrum of diseases. 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.

Experimental endometriosis reduction in rats treated with Uncaria tomentosa (cat's claw) extract

ObjectiveThe aim of this study was to analyze the macroscopic and histological changes that occur in experimental endometriosis after treatment with Uncaria tomentosa. Study designExperimental endometriosis was induced in twenty-five female Wistar rats. After three weeks, 24 animals developed grade III experimental endometriosis and were divided into two groups. Group “U” received U. tomentosa extract orally (32mg/day), and group “C” (control group) received a 0.9% sodium chloride solution orally (1ml/100g of body weight/day). Both groups were treated with gavage for 14 days. At the surgical intervention and after the animal was euthanized, the implant volume was calculated with the following formula: [4π (length/2)×(width/2)×(height/2)/3]. The autotransplants were removed, dyed with hematoxylin–eosin, and analyzed by light microscopy. The Mann–Whitney test was used for the independent samples, and the Wilcoxon test analyzed the related samples, with a significance level of 5%. ResultsThe difference between the initial average volumes of the autotransplants was not significant between the groups (p=0.18). However, the final average volumes were significantly different between the groups (p=0.001). There was a significant increase (p=0.01) between the initial and final average volumes in the control group, and treatment with the U. tomentosa caused a marked reduction in the growth over time (p=0.009). Histologically, in the experimental group (n=10) six rats had a well-preserved epithelial layer, three had mildly preserved epithelium, and one had poorly preserved epithelium. The epithelial layer occasionally presented sporadic epithelial cells. The control group (n=12) presented seven cases (58.3%) of well-preserved epithelial cells and five cases (41.7%) of mildly preserved epithelial cells. ConclusionsCat's claw extract appears to be a promising alternative for treating endometriosis.

Anticancer activity of the Uncaria tomentosa (Willd.) DC. preparations with different oxindole alkaloid composition

The activity of Uncaria tomentosa preparations on cancer cells was studied using in vitro and in vivo models. IC (50) values were calculated for preparations with different quantitative and qualitative oxindole alkaloid composition: B/W(37) --bark extracted in water at 37 °C, B/W(b)--bark extracted in boiling water, B/50E(37) --bark extracted in 50% ethanol at 37 °C, B/E(b)--bark extracted in boiling 96% ethanol, B/96E(37) --bark extracted in 96% ethanol at 37 °C and B/SRT--bark extracted in water and dichloromethane. Generally, the results obtained showed a high correlation between the total oxindole alkaloid content (from 0.43% to 50.40% d.m.) and the antiproliferative activity of the preparations (IC(50) from >1000 μg/ml to 23.57 μg/ml). B/96E(37) and B/SRT were the most cytotoxic preparations, whereas the lowest toxicity was observed for B/W(37). B/96E(37) were shown to be active against Lewis lung carcinoma (LL/2) [IC(50) =25.06 μg/ml], cervical carcinoma (KB) [IC(50) =35.69 μg/ml] and colon adenocarcinoma (SW707) [IC(50) =49.06 μg/ml]. B/SRT was especially effective in inhibiting proliferation of cervical carcinoma (KB) [IC(50) =23.57 μg/ml], breast carcinoma (MCF-7) [IC(50) =29.86 μg/ml] and lung carcinoma (A-549) [IC(50) =40.03 μg/ml]. 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). There were no significant changes in the cell cycles of tumor cells with the exception of cell decrease at the G₂/M phase after the administration of B/96E(37) at a daily dose of 0.5 mg and the G(1)/G(0) cells cycle arrest demonstrated after the B/SRT therapy at a daily-dose of 0.05 mg. All tested preparations were non-toxic and well tolerated.

ChemInform Abstract: Two New 19-Hydroxyursolic Acid-Type Triterpenes from Peruvian “Una de Gato” (Uncaria tomentosa).

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

Antitumoral and antioxidant effects of a hydroalcoholic extract of cat's claw ( Uncaria tomentosa) (Willd. Ex Roem. & Schult) in an in vivo carcinosarcoma model

Aim of the study The present work intended to study the antitumoral and antioxidant effects of Uncaria tomentosa (UT) hydroalcoholic extract in the Walker-256 cancer model. Methods and materials Walker-256 cells were subcutaneously inoculated in the pelvic limb of male Wistar rats. Daily gavage with UT extract (10, 50 or 100 mg kg −1, Groups UT) or saline solution (Control, Group C) was subsequently initiated, until 14 days afterwards. For some parameters, a group of healthy rats (Baseline, Group B) was added. At the end of treatment the following parameters were evaluated: (a) tumor volume and mass; (b) plasmatic concentration of urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) and lactate dehydrogenase (LDH); (c) hepatic and tumoral activity of catalase (CAT) and superoxide dismutase (SOD), as well as the rate of lipid peroxidation (LPO) and gluthatione (GSH); and (d) hepatic glutathione-S-transferase (GST) activity. The reactivity of UT extract with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) was assessed in parallel. Results 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 μg mL −1). Treatment also resulted in increased CAT activity in liver, while decreasing it in tumor tissue. SOD activity was reduced in liver as well as in tumor, compared to Group C. No statistical significance concerning ALT, GST, LPO or GSH were observed. Conclusions 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.

Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.

The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E.

In vitro antimicrobial activity of phytotherapic Uncaria tomentosa against endodontic pathogens

The aim of this study was to evaluate the antimicrobial activity of Uncaria tomentosa (Willd.) DC (cat's claw) against Enterococcus faecalis, Staphylococcus aureus, and Candida albicans. Suspensions with 10(8) cells/ml of each microorganism were plated in triplicate on Mueller-Hinton agar. Wells in the agar were made and filled with 2% chlorhexidine (CHX) gel, 2% cat's claw (CC) gel, 2% CHX+CC, and 1% hydroxyethylcellulose (NAT) gel. Inhibition halos were measured after 24 h at 37°C and differences were analyzed using one-way ANOVA. The mean diameter of the microbial growth inhibition zones of 2% CHX+CC against the tested microbial strains ranged from 21.7 to 33.5 mm. This was the most effective substance against E. faecalis and C. albicans, followed by CHX and CC. Against S. aureus, CHX+CC, CHX, and CC showed similar antimicrobial activity (P > 0.05). The results indicate that all the investigated compounds had antimicrobial activity against microorganisms frequently found in infected root-filled teeth.

Uncaria tomentosa acts as a potent TNF-α inhibitor through NF-κB

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-α while augmenting the production of IL-1β. Since TNF-α and IL-1β are usually regulated similarly and share a number of common promoter elements, including NF-κB 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-κB 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-κB and AP-1 components. In addition, treatment with Uncaria tomentosa enhanced cell death when NF-κB was inhibited. The ability of Uncaria tomentosa to inhibit TNF-α production was diminished when NF-κB activation was prevented by drugs that mask NF-κB subunit nuclear localization signals, while IL-1β expression was unchanged. Conclusions These results demonstrate that Uncaria tomentosa is able to elicit a response via an NF-κB-dependent mechanism. Further studies to characterize the mechanism by which Uncaria tomentosa can affect this pathway could provide a means to develop anti-TNF-α therapies.

Cytotoxic Effect of the Pentacyclic Oxindole Alkaloid Mitraphylline Isolated fromUncaria tomentosaBark on Human Ewing's Sarcoma and Breast Cancer Cell Lines

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.

Synthesis and biological evaluation of quinic acid derivatives as anti-inflammatory agents

Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. cat’s claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB). Herein, we describe the synthesis and biological testing of novel QA derivatives. Inhibition of NF-κB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-κB response element. A549-NF-κB cells were stimulated with TNF-α (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at the carboxylic acid position yielded potent inhibitors of NF-κB. A variety of modifications to the amide substitution were tolerated with the N-propyl amide derivative being the most potent. Further examination of the SAR demonstrated that acetylation of the hydroxyl groups reduced NF-κB inhibitory activity. QA amide derivatives lacked anti-oxidant activity and were found to be neither anti-proliferative nor cytotoxic at concentrations up to 100 μM. In conclusion, we have discovered a novel series of non-toxic QA amides that potently inhibit NF-κB, despite their lack of anti-oxidant activity. Mechanistic studies and pre-clinical efficacy studies in various inflammatory animal models are on-going.

Antioxidant and antimicrobial properties of Malaysian Uncaria longiflora var. pteropoda

Uncaria is a genus of woody climbers from the Rubiaceae family which can be found in many parts of the world. Many Uncaria species are used as traditional medicine for the treatment of cancer and other diseases. The most popular and extensively studied species is the Peruvian medicinal plant Uncaria tomentosa known as Cat's Claw which has been marketed in the form of various medicinal products [1]. In Malaysia, the plants of the genus are generally known as „gambir“ or „kekait“ and are used to treat various diseases including diarrhea, dysentery and rheumatism [2]. However, not much has been reported on their biological activities. In this study, the methanolic extracts of a local Uncaria species, U. longiflora var. pteropoda (Miq.) Ridsdale was evaluated for its antioxidant, radical-scavenging and antimicrobial potential. The leaves and stems extracts exhibited stronger antioxidant potential than vitamin E and quercetin (>90% inhibition) and showed strong radical-scavenging properties with IC50 values of 8–10µg/ml, comparable to vitamin C. In the antimicrobial assay, both leaves and stems extracts displayed good inhibition against Gram-positive bacteria and were found to inhibit Candida albicans with MIC values of <1.0µg/ml, comparable to cyclohexamide. Phytochemical screening of the extract and TLC screening of fractions revealed the presence of flavonoids, alkaloids and tannins. This study provides evidence for the antioxidant and antimicrobial properties of U. longiflora. However, further studies are required to identify compounds responsible for these activities.

Efecto de un extracto hidroalcohólico de Uncaria tomentosa (uña de gato) sobre la población de células dendríticas y sus moléculas HLA-DR y CD86 ante el estimulo con lipopolisacáridos

Objective. To determine the effect of an hydro-alcoholic extract of cats claw Uncaria tomentosa (uG) over lipopolysaccharides - treated dendritic cells (DC) and HLA-DR and CD86 molecules expression of peripheral blood samples obtained from healthy individuals. Materials and methods. Peripheral blood samples were collected from healthy individuals. Peripheral Blood Mononuclear Cells (PBMC) were isolated by centrifugation over density gradient, pre-treated with and without the addition of uG, and then stimulated for 24 h with lipopolysaccharides (LPS), then the cells were labelled with specific fluorescent monoclonal antibodies to HLA-DR, Linage type 1 (Lin1), CD11c and CD86 and prepared for flow. Results. Compared to PBMC with LPS but without uG group, we found a decrease of myeloid DC (mDC) percentage (p<0.05) and a tendency to increase plasmacytoid DC (pDC) percentage, both in a dose-dependent manner. There was a decrease in media fluorescence intensity (MfI) of HLA-DR in DCp between 500 and 1000 µg/mL of CC (p<0,001), but we found a increase in MfI of CD86 at all concentrations (p<0,05). There was no effect of uG over MfI of the HLA-DR or CD86 expression in mDC. Conclusions. uG showed a tendency to increase pDC percentage and decreased mDC percentage. uG did not affect the expression of CD86 and HLA-DR from mDC. This study demonstrates that uG promotes activation/differentiation of pDC, which has a demonstrated involvement in the adaptive immune response mechanisms.

Avaliação clínica e laboratorial do gel da Uncaria tomentosa (Unha de Gato) sobre candidose oral

Na odontologia, a fitoterapia já vem sendo utilizada com sucesso há vários anos. Trata-se de um meio terapêutico que apresenta como vantagem sobre as medicações alopáticas o fato de apresentar reações adversas mínimas. A Uncaria tomentosa é uma planta indígena da floresta Amazônica e de outras áreas tropicais da América do Sul e Central. Tem aplicação no tratamento de diversas patologias, entre elas a candidose. Este trabalho avalia clínico e laboratorialmente a ação do gel da Uncaria tomentosa em pacientes portadores de candidose na cavidade oral. Foram selecionados 20 pacientes que apresentaram clínico e laboratorialmente infecção pelo Candida. Os mesmos foram divididos em 2 grupos. O grupo-teste (Uncaria tomentosa/Imuno-Max Gel), composto por 10 pacientes, foi orientado a utilizar o gel da Uncaria tomentosa, sobre as lesões na cavidade oral, 3x ao dia por um período de 14 dias. O grupo-controle (Miconazol/Daktarin Gel) utilizou a medicação da mesma forma prescrita para o grupo-teste. Após o período de tratamento, os pacientes retornaram para nova avaliação clínica e laboratorial. A Uncaria tomentosa mostrou ser um fitofármaco promissor na odontologia, apresentando vantagem sobre o miconazol de não ter provocado reações adversas nos pacientes, uma vez que, 40% dos pacientes do grupo-controle, apresentaram reações indesejáveis.

Oxidative stress induces alkaloid production in Uncaria tomentosa root and cell cultures in bioreactors

AbstractThe effect of oxidative stress on indole alkaloids accumulation by cell suspensions and root cultures of Uncaria tomentosa in bioreactors was investigated. Hydrogen peroxide (H2O2, 200 μM) added to U. tomentosa cell suspension cultures in shaken flasks induced the production of monoterpenoid oxindole alkaloids (MOA) up to 40.0 μg/L. In a stirred tank bioreactor, MOA were enhanced by exogenous H2O2 (200 μM) from no detection up to 59.3 μg/L. Root cultures grew linearly in shaken flasks with a μ=0.045 days−1 and maximum biomass of 12.08±1.24 g DW/L (at day 30). Roots accumulated 3α‐dihydrocadambine (DHC) 2354.3±244.8 μg/g DW (at day 40) and MOA 348.2±32.1 μg/g DW (at day 18). Exogenous addition of H2O2 had a differential effect on DHC and MOA production in shaken flasks. At 200 μM H2O2, MOA were enhanced by 56% and DHC by 30%; while addition of 800 and 1000 μM H2O2, reduced by 30–40% DHC accumulation without change in MOA. Root cultures in the airlift reactor produced extracellular H2O2 with a characteristic biphasic profile after changing aeration. Maximum MOA was 9.06 mg/L at day 60 while at this time roots reached ca. 1 mg/L of DHC. Intracellular H2O2 in root cultures growing in the bioreactor was 0.87 μmol/g DW compared to 0.26 μmol/g DW of shaken flasks cultures. These results were in agreement with a higher activity of the antioxidant enzymes superoxide dismutase and peroxidase by 6‐ and 2‐times, respectively. U. tomentosa roots growing in the airlift bioreactor were exposed to an oxidative stress and their antioxidant system was active allowing them to produce oxindole alkaloids.

Pharmacology and therapeutic uses of cat’s claw

Cat’s claw, also known as the “life-giving vine of Peru,” “saventaro,” or “uña de gato,” is a thick woody vine indigenous to the Amazon rain forest and other tropical areas of South and Central America.1 It has been used as a sacred plant of healing for over 2000 years. The plant, described by its Spanish folk name “uña de gato,” has a hooklike thorn that grows largely along the vine in a leafy pattern that resembles the claws of a cat.1 There are several species of cat’s claw, but the two most common species used and marketed interchangeably for their various properties are Uncaria tomentosa and Uncaria guianensis.2,3U. tomentosa, evidently the preferred species because of its higher alkaloid content and the ease of standardization, is the focus of this article. U. tomentosa may be contaminated with other Uncaria species, including Uncaria rhynchophylla, which has been used in Chinese herbal preparations. In some European countries (e.g., Germany, Austria), cat’s claw can only be dispensed with a prescription. Currently, cat’s claw is widely used and is one of the top herbal remedies sold in the United States, despite a lack of high-quality human evidence supporting its benefits. Its popularity in the alternative medicine market might be partly because of its proposed abilities to strengthen the immune system, inhibit inflammation, inhibit tumor growth, and suppress viral replication.4 Despite the alleged medical benefits associated with cat’s claw use, relatively few scientific studies have been conducted to establish the safety and efficacy of this plant.

Antigenotoxic, Antioxidant and Lymphocyte Induction Effects Produced by Pteropodine

Pteropodine is a heterohimbine-type oxindole alkaloid specifically isolated from 'Cat's claw' (Uncaria tomentosa), a plant that has shown cytostatic, anti-inflammatory and antimutagenic properties and is used in traditional medicine to cure a number of diseases. In this report, we studied the ability of pteropodine to decrease the rate of sister-chromatid exchanges and micronucleated polychromatic erythrocytes in mice administered doxorubicin. We also determined its capacity to induce lymphocyte production in mice as well as its free radical scavenging potential by applying the DPPH assay. We found pteropodine (100-600 mg/kg) to significantly decrease the frequency of sister-chromatid exchanges and micronucleated polychromatic erythrocytes in mice administered with 10 mg/kg of doxorubicin. Furthermore, we determined that pteropodine partially corrected bone marrow cytotoxicity induced by doxorubicin, as it showed an improvement in the rate of polychromatic erythrocytes. Besides, 600 mg/kg of pteropodine increased 25.8% of the production of lymphocytes over the control value along a 96-hr assay, and it exhibited a strong capacity to trap the DPPH-free radical (98.26% with 250 microg/ml). Our results establish that pteropodine is an effective antimutagen in the model used, and suggest that pteropodine deserves further research in the area of cell protective potential and its mechanism of action.

Plant extracts with anti-inflammatory properties—A new approach for characterization of their bioactive compounds and establishment of structure–antioxidant activity relationships

Geranium robertianum L. (Geraniacea) and Uncaria tomentosa (Willd.) DC. (Rubiaceae) plant extracts, frequently used in traditional medicine for treatment of inflammatory and cancer diseases, were studied to identify potential bioactive compounds that may justify their therapeutic use and their underlying mechanisms of action. Since some of the pharmacological properties of these plant extracts may be linked to their antioxidant potential, the antioxidant activity, in relation to free radical scavenging, was measured by the ABTS/HRP and DPPH assays, presenting U. tomentosa the higher activity. The antioxidant activity was also evaluated by scavenging of HOCl, the major strong oxidant produced by neutrophils and a potent pro-inflammatory agent. U. tomentosa was found to be a better protector against HOCl, which may justify its effectiveness against inflammatory diseases. SPE/LC-DAD was used for separation/purification purposes and ESI-MS/MS for identification/characterization of the major non-volatile components, mainly flavonoids and phenolic acids. The ESI-MS/MS methodology proposed can be used as a model procedure for identification/characterization of unknowns without the prerequisite for standard compounds analysis. The ESI-MS/MS data obtained were consistent with the antioxidant activity results and structure–activity relationships for the compounds identified were discussed.