1. Uncaria Tomentosa (Cat’s Claw) Improves Quality of Life in Patients With Advanced Solid Tumors J Altern Complement Med , 21 (1), 22-30 Jan 2015
Authors Larissa Carvalho Lopes de Paula  1 Fernando FonsecaFabio PerazzoFelipe Melo CruzDaniel CuberoDamila Cristina TrufelliSuelen Patrícia Dos Santos MartinsPatrícia Xavier SantiEliana Araújo da SilvaAuro Del Giglio
Affiliation 1 1 Department of Hematology and Oncology, School of Medicine, ABC Foundation, Brazilian Institute for Cancer Control , São Paulo, Brazil . PMID: 25495394 DOI: 10.1089/acm.2014.0127
Objective: Cat’s claw (Uncaria tomentosa) is a native Amazon plant that exhibits anti-inflammatory and antitumor properties. We wanted to assess its activity for symptom management of terminal cancer patients.
Methods: This prospective phase II study assessed the effects of a 100-mg dose of a dry extract of U. tomentosa three times per day in patients with advanced solid tumors who had no further therapeutic options and a life expectancy of at least 2 months. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) and Functional Assessment of Chronic Illness Therapy – Fatigue questionnaires were used to assess the participants’ quality of life, the Hospital Anxiety and Depression Scale questionnaire was used to assess anxiety and depression, and the Pittsburgh Sleep Quality Index was used to assess sleep quality. In addition, several biochemical and inflammatory parameters were analyzed. Results: Fifty-one volunteers were recruited. Their median age was 64 (range, 33-85) years, and 47% of patients were female. More than 65% of patients had scores on the Karnofsky Performance Scale of 80% or less. Treatment improved the patients’ overall quality of life (p=0.0411) and social functioning (p=0.0341), as assessed by the EORTC QLQ C-30, and reduced fatigue (p=0.0496) according to the Chalder Fatigue Questionnaire. None of the biochemical or inflammatory parameters assessed (interleukin-1 and -6, C-reactive protein, tumor necrosis factor-α, erythrocyte sedimentation rate, and α-1-acid glycoprotein) changed significantly. No tumor response was detected according to the Response Evaluation Criteria In Solid Tumors; however, the disease stabilized for more than 8 months in four participants. The medication was well tolerated by most patients. Conclusion: Use of cat’s claw might be beneficial in patients with advanced cancer by improving their quality of life and reducing fatigue. The mechanism of action does not seem to be related to the anti-inflammatory properties of this plant. Cited by 2 PMC articles Publication types Clinical Trial, Phase II MeSH terms Adult Aged Aged, 80 and over Antineoplastic Agents / adverse effects Antineoplastic Agents / therapeutic use Cat’s Claw / chemistry Disease-Free Survival Female Humans Male Middle Aged Neoplasms / drug therapy Phytotherapy Plant Extracts / adverse effects Plant Extracts / therapeutic use Quality of Life Substances Antineoplastic Agents Plant Extracts Full-text links Atypon
2. Mitraphylline Inhibits Lipopolysaccharide-Mediated Activation of Primary Human Neutrophils Phytomedicine , 23 (2), 141-8 2016 Feb 15 Authors Sergio Montserrat-de la Paz  1 Angeles Fernandez-Arche  2 Rocío de la Puerta  2 Ana M Quilez  2 Francisco J G Muriana  3 Maria Dolores Garcia-Gimenez  2 Beatriz Bermudez  4 Affiliations 1 Department of Pharmacology, School of Pharmacy, University of Seville, 41012, Seville, Spain ; Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, Seville, Spain. 2 Department of Pharmacology, School of Pharmacy, University of Seville, 41012, Seville, Spain. 3 Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, Seville, Spain. 4 Department of Pharmacology, School of Pharmacy, University of Seville, 41012, Seville, Spain . Electronic address: PMID: 26926175 DOI: 10.1016/j.phymed.2015.12.015 Abstract
Background: Mitraphylline (MTP) is the major pentacyclic oxindolic alkaloid presented in Uncaria tomentosa. It has traditionally been used to treat disorders including arthritis, heart disease, cancer, and other inflammatory diseases. However, the specific role of MTP is still not clear, with more comprehensivestudies, our understanding of this ancient herbal medicine will continue growing.
Hypothesis/purpose: Some studies provided its ability to inhibit proinflamatory cytokines, such as TNF-α, through NF-κB-dependent mechanism. TNF-α primes neutrophils and modulates phagocytic and oxidative burst activities in inflammatory processes. Since, neutrophils represent the most abundant pool of leukocytes in human blood and play a crucial role in inflammation, we aimed to determine the ability of MTP to modulate neutrophil activation and differentially regulate inflammatory-related cytokines. Methods: To determine the mechanism of action of MTP, we investigated the effects on LPS-activated human primary neutrophils responses including activation surface markers by FACS and the expression of inflammatory cytokines, measured by real time PCR and ELISA.
Results: Treatment with MTP reduced the LPS-dependent activation effects. Activated neutrophils (CD16(+)CD62L(-)) diminished after MTP administration. Moreover, proinflamatory cytokines (TNF-α, IL-6 or IL-8) expression and secretion were concomitantly reduced, similar to basal control conditions.
Conclusion: Taken together, our results demonstrate that MTP is able to elicit an anti-inflammatory response that modulates neutrophil activation contributing to the attenuation of inflammatory episodes. Further studies are need to characterize the mechanism by which MTP can affect this pathway that could provide a means to develop MTP as new candidate for inflammatory disease therapies.
Keywords: Alkaloids; Inflammation; Lipopolysaccharide; Mitraphylline; Neutrophils; Uncaria tomentosa.
Copyright © 2016 Elsevier GmbH. All rights reserved.
Cited by 4 PMC articles Publication types Research Support, Non-U.S. Gov’t MeSH terms Anti-Inflammatory Agents / pharmacology Cat’s Claw / chemistry Cytokines / metabolism Humans Indole Alkaloids / pharmacology Interleukin-6 / metabolism Interleukin-8 / metabolism Lipopolysaccharides NF-kappa B / metabolism Neutrophils / cytology Neutrophils / drug effects Oxindoles Plant Bark / chemistry Tumor Necrosis Factor-alpha / metabolism Substances Anti-Inflammatory Agents CXCL8 protein, human Cytokines IL6 protein, human Indole Alkaloids Interleukin-6 Interleukin-8 Lipopolysaccharides NF-kappa B Oxindoles Tumor Necrosis Factor-alpha mitraphylline Full-text links Elsevier Science
3. Hepatoprotective Activity of Uncaria Tomentosa Extract Against Sub-Chronic Exposure to Fipronil in Male Rats Environ Sci Pollut Res Int , 26 (1), 199-207 Jan 2019
Authors Rania Abdelrahman Elgawish  1 Heba M A Abdelrazek  2 Shimaa A A Ismail  3 Naglaa M Loutfy  4 Mohamed T A Soliman  5
Affiliations 1 Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt. 2 Department of Physiology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt. 3 Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt. 4 Department of Plant Protection, Faculty of Agriculture, Suez Canal University, Ismailia, 41522, Egypt. 5 Department of Clinical Pathology, College of Applied Medical Sciences, Bisha University, Bisha, Kingdom of Saudi Arabia. PMID: 30387063 DOI: 10.1007/s11356-018-3615-5
Abstract The effects of fipronil (FPN) on the liver of rats were studied. Rats (n = 6) were treated with 9.7 mg/kg (1/10 of FPN LD50), and other rats (n = 6) received 120 mg/kg of 10% Uncaria tomentosa extract, while a mixture of 9.7 mg/kg FPN and 120 mg/kg of 10% Uncaria tomentosa extract were administered orally to the rats (n = 6) daily for 6 weeks. Body, hepatic weights, liver enzymes, and lipid profile were determined. Hepatic activities of MDA, TNO, TAC, TNF-α, and IL-6 in liver homogenate were measured. Immunohistochemistry of NF-kB and liver histopathology were performed. Fipronil-treated rats had a significant (P = 0.02) lower weight gain. Moreover, relative liver weight was significantly (P = 0.003) increased in FPN-treated rats. Rats administrated with FPN exhibited a significantly (P = 0.02) higher liver enzymes and promoted levels of MDA, TNO, TNF-α, and IL-6 (P < 0.0001) than that in the other groups. Immunostaining of NF-κB was increased (P < 0.0001) in FPN-treated rats. Interestingly, Uncaria tomentosa alone or with FPN decreased the liver immunostaining of NF-κB. In conclusion, FPN produced liver injury through lipid peroxidation and stimulation of NF-κB. However, Uncaria tomentosa combated the oxidative stress and liver damage induced by FPN via inhibition of NF-κB.
Keywords: Fipronil; MDA; NF-κB; Rats; Uncaria tomentosa. Cited by 1 PMC article 40 references MeSH terms Animals Antioxidants / metabolism Antioxidants / pharmacology Antioxidants / therapeutic use Cat’s Claw / chemistry Cell Line Chemical and Drug Induced Liver Injury / metabolism Chemical and Drug Induced Liver Injury / prevention & control Environmental Pollutants / adverse effects Insecticides / adverse effects Interleukin-6 / metabolism Lipid Peroxidation / drug effects Liver / drug effects Liver / metabolism Liver / pathology Male Malondialdehyde / metabolism NF-kappa B / metabolism Oxidative Stress / drug effects Phytotherapy Plant Extracts / pharmacology Plant Extracts / therapeutic use Protective Agents / pharmacology Protective Agents / therapeutic use Pyrazoles / adverse effects Rats, Wistar Tumor Necrosis Factor-alpha / antagonists & inhibitors Substances Antioxidants Environmental Pollutants Insecticides Interleukin-6 NF-kappa B Plant Extracts Protective Agents Pyrazoles Tumor Necrosis Factor-alpha Malondialdehyde fipronil Full-text links Springer
Immunomodulation of Uncaria Tomentosa Over Dendritic Cells, il-12 and Profile TH1/TH2/TH17 in Breast Cancer Rev Peru Med Exp Salud Publica , 32 (4), 643-51 Oct 2015 [Article in Spanish]
Authors César Núñez  1 Iván Lozada-Requena  1 Tíndara Ysmodes  1 Daniel Zegarra  1 Fatima Saldaña  1 José Aguilar1
Affiliation 1 Laboratorio de Inmunología, Departamento de Ciencias Celulares y Moleculares, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru. PMID: 26732910
Objetives. This study aimed to research the in vitro immunomodulatory effects of an Uncaria tomentosa hydroalcoholic extract standardized (5.03%, pentacyclic oxindole alkaloids) (UT-POA) on the immunophenotype of dendritic cells (DC) subsets, Th1, Th2, Th17 and IL-12 cytokines from patients with stage II breast cancer (BCII) and healthy women (H).
Materials and methods: Blood of 11 H and 7 BCII was obtained, PBMC were isolated and cultured for 2h with/without various concentrations of UT-POA and stimulated or not with LPS for 24h. PBMC were labeled with specific antibodies for DC and in the supernatant we measured Th1/Th2/Th17 cytokines, both by flow cytometry. Furthermore IL-12 was measured by ELISA.
Results: UT-POA did not alter DC or accessory molecules expression in BCII. However, H exhibited a decrease in the percentage of mDC (myeloid DC) and an increase in HLA-DR and CD86 expression at 1000 μg/mL. IL-12 secretion was modified only in the H group, increasing p70 subunit and decreasing p40 subunit. UT-POA increased Th1 (IFN-γ and IL-2), Th2 (IL-4) and Th17 (IL-17) secretion in both groups.
Conclusions: UT-POA increased the production of cytokines related with anti-tumoral response at concentrations of 500-1000 μg/mL. This positive effect should be evaluated not only systemically but also in the tumor microenvironment in further studies. UT-POA may be a useful phytochemical in chemoprevention and in the alternative use in cancer therapies. MeSH terms Breast Neoplasms / drug therapy Breast Neoplasms / immunology Cat’s Claw Dendritic Cells Female Humans Immunomodulation Interleukin-12 Leukocytes, Mononuclear Plant Extracts / therapeutic use Substances Plant Extracts Interleukin-12 Full-text links Scientific Electronic Library Online
5. Uncaria tomentosa (Willd. Ex Schult.) DC (Rubiaceae) Sensitizes THP-1 Cells to Radiation-induced Cell Death Pharmacognosy Res , 9 (3), 221-229 Jul-Sep 2017 Authors Lisa Allen  1   2 Alison Buckner  1   2 Carly A Buckner  1   2 Pablo Cano  2 Robert M Lafrenie  1   2   3   4
Affiliations 1 Program in Biomolecular Science, Laurentian University, Sudbury, ON P3E 2C6, Canada. 2 Health Sciences North, Sudbury, ON P3E 5J1, Canada. 3 Division of Medical Science, Northern Ontario School of Medicine, Sudbury, ON P3E 2C6, Canada. 4 Health Sciences North Research Institute, Sudbury, ON, P3E 5J1, Canada. PMID: 28827961 PMCID: PMC5541476 DOI: 10.4103/pr.pr_83_16
Background: Uncaria tomentosa (Willd. ex Schult.) DC (Rubiaceae), known as Cat’s Claw or Uña de gato, is a traditionally used medicinal plant native to Peru. Some studies have shown that U. tomentosa can act as an antiapoptotic agent and enhance DNA repair in chemotherapy-treated cells although others have shown that U. tomentosa enhanced apoptosis.
Objective: To determine if treatment with U. tomentosa can significantly enhance cell death in THP-1 cells exposed to ionizing radiation.
Materials and methods: THP-1 monocyte-like cells were treated with ethanolic extracts of U. tomentosa in the presence or absence of bacterial lipopolysaccharide and then exposed to ionizing radiation. Cell proliferation was assessed by MTT and clonogenic assays and the effects on cell cycle measured by flow cytometry and immunoblotting. Changes in cell signaling were determined by immunoblotting and cytokine ELISA and activation of apoptosis measured by caspase activation and DNA fragmentation analysis. Results: Treatment of THP-1 cells with U. tomentosa had a small effect on cell proliferation. However, when the U. tomentosa-pretreated cells were also subjected to 5-9 Gy ionizing radiation, they showed a significant decrease in cell proliferation and increased cellular apoptosis as measured by DNA fragmentation and caspase activation. Treatment with U. tomentosa also decreased the expression of Cyclin E and Cyclin B, key regulators of normal cell cycle progression, and decreased the phosphorylation of various stress-activated, cell survival proteins including p38, ERK, and SAP/JNK kinase. Conclusions: These results suggest that U. tomentosa could be useful in enhancing cell death following anticancer therapies including ionizing radiation.
Summary: Treatment of THP-1 cells with Uncaria tomentosa increases their susceptibility to X-rays. The combination of Uncaria tomentosa and X-ray exposure strongly inhibits cell signaling and promotes apoptosis.
Abbreviations Used: LPS: Lipopolysaccharide, TNF: Tumor necrosis factor: IL-1, Interleukin-1: SDS: Sodium dodecylsulphate, TBS: Tris-buffered saline.
Keywords: Cell signaling; Uncaria tomentosa; X-rays; cell survival; cytokine; monocyte. Conflict of interest statement There are no conflicts of interest.
50 references 7 figures
Full-text links Medknow Publications and Media Pvt Ltd Free PMC article
6. Uncaria Tomentosa Alkaloidal Fraction Reduces Paracellular Permeability, IL-8 and NS1 Production on Human Microvascular Endothelial Cells Infected With Dengue Virus
Nat Prod Commun , 8 (11), 1547-50 Nov 2013
Authors Raimundo Sousa Lima-Junior  1 Cintia da Silva Mello  2 Antonio Carlos Siani  3 Ligia M Marino Valente  4 Claire Fernandes Kubelka  2
Affiliations 1Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Av. Brasil 4365, 21040-360, Rio de Janeiro, RJ, Brazil. 2Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Av. Brasil 4365, 21040-360, Rio de Janeiro, RJ, Brazil. 3lnstituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, Av. Brasil 4365, 21040-360, Rio de Janeiro, RJ, Brazil. 4Instituto de Química, Universidade Federal do Rio de Janeiro, Av. Athos da Silveira Ramos 149, C.T., Bl.A, 21941-909, Rio de Janeiro, RJ, Brazil. PMID: 24427938
Abstract: Dengue is the major Arbovirus in the world, annually causing morbidity and death. Severe dengue is associated with changes in the endothelial barrier function due to the production of inflammatory mediators by immune cells and by the endothelium. Dengue virus (DENV) replicates efficiently in human endothelial cells in vitro and elicits immune responses resulting in endothelial permeability. Uncaria tomentosa (Willd.) DC.(Rubiaceae), known as cat’s claw, has been used in folk medicine for the treatment of a wide-array of symptoms, and several scientific studies reported its antiviral, immunomodulatory, anti-inflammatory and antioxidant properties. Here we infected a human lineage of dermal microvascular endothelial cells (HMEC-1) with DENV-2 and treated it with an alkaloidal fraction from U. tomentosa bark (AFUT). We showed antiviral and immunomodulatory activities of U. tomentosa by determining the NS1 antigen and IL-8 in supernatant of DENV-2 infected HMEC-1. Furthermore, by measurement of transendothelial electrical resistance (TEER) we demonstrated, for the first time, that a plant derivative contributed to the reduction of paracellular permeability in DENV-2 infected HMEC-1. We also showed that IL-8 contributed significantly to the induction of permeability. Although further investigations should be conducted before a new drug can be suggested, our in vitro data support evidence that AFUT could be potentially useful in developing a treatment for severe dengue.
Cited by 2 PMC articles Publication types Research Support, Non-U.S. Gov’t MeSH terms Alkaloids / pharmacology Cat’s Claw / chemistry Cells, Cultured Dengue Virus / drug effects Endothelial Cells / immunology Endothelial Cells / virology Humans Interleukin-8 / biosynthesis Permeability Plant Bark / chemistry Viral Nonstructural Proteins / biosynthesis Substances Alkaloids Interleukin-8 NS1 protein, Dengue virus type 2 Viral Nonstructural Proteins
7. The Potency of Immunomodulatory Herbs May Be Primarily Dependent Upon Macrophage Activation J Med Food , 10 (1), 73-9 Mar 2007 Authors S N Groom  1 T JohnsP R Oldfield Affiliation 1 Department of Nutrition, McGill University, Montreal, Quebec, Canada. PMID: 17472470 DOI: 10.1089/jmf.2006.233 Abstract: Standardized extracts of Echinacea, cat’s claw, and saw palmetto were each evaluated for ability to activate macrophage and natural killer cells, in vitro, using two independent measures of activation for each immune cell population. A standard series of exposure concentrations were tested for each herbal extract in a panel of four assays that evaluated macrophage phagocytosis, macrophage synthesis of interleukin-12, natural killer (NK) cell cytocidal activity (synthesis of granzyme B), and NK cell synthesis of interferon-gamma. Macrophage phagocytosis was stimulated by all three herbs tested: saw palmetto (up to 2.3-fold, P < .05), Echinacea (up to 3.6-fold, P < .01), and cat’s claw (up to 4.7-fold, P < .01). Additionally, NK cell synthesis of interferon-gamma was stimulated by saw palmetto (up to 6.3-fold, P < .01) and Echinacea (up to 8.1 fold, P < .01) but not by exposure to cat’s claw. None of the three herbs stimulated macrophage synthesis of interleukin-12 or NK cell synthesis of granzyme B. Comparison of the in vitro data with our earlier observations that cat’s claw and Echinacea (but not saw palmetto) were each effective in reducing B16/F10 lung tumor colony formation in C57BL/6J mice suggests macrophage activation is the primary means by which these herbs modulate the immune system. Thus, macrophage activation (phagocytosis) may provide a potentially higher throughput method to identify herbal extracts with in vivo stimulatory effects. Cited by 2 PMC articles Publication types Research Support, Non-U.S. Gov’t MeSH terms Cat’s Claw / chemistry Cell Line Echinacea / chemistry Granzymes / biosynthesis Humans Immunologic Factors / pharmacology Interferon-gamma / biosynthesis Interleukin-12 / biosynthesis Killer Cells, Natural / drug effects Killer Cells, Natural / immunology Macrophage Activation / drug effects Macrophages / drug effects Macrophages / immunology Phagocytosis / drug effects Phytotherapy Plant Extracts / pharmacology Serenoa / chemistry Substances Immunologic Factors Plant Extracts Interleukin-12 Interferon-gamma Granzymes Full-text links Atypon
8. Effect of a Herbal-Leucine Mix on the IL-1β-induced Cartilage Degradation and Inflammatory Gene Expression in Human Chondrocytes BMC Complement Altern Med , 11, 66 2011 Aug 19
Authors Nahid Akhtar  1 Mark Js MillerTariq M Haqqi
Affiliation 1 Department of Medicine/Rheumatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio 44109, USA. PMID: 21854562 PMCID: PMC3176482 DOI: 10.1186/1472-6882-11-66 Abstract Background: Conventional treatments for the articular diseases are often effective for symptom relief, but can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favorable influence on the course of the disease. 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.
Methods: Primary OA chondrocytes or OA cartilage explants were pretreated with Herbal-Leucine mixture (HLM, 1-10 μg/ml) and then stimulated with IL-1β (5 ng/ml). Effect of HLM on IL-1β-induced gene expression of iNOS, MMP-9, MMP-13, ACAN and COL2A1 was verified by real time-PCR. Estimation of NO and GAG release in culture supernatant was done using commercially available kits.
Results: HLM tested in these in vitro studies was found to be an effective anti-inflammatory agent, as evidenced by strong inhibition of iNOS, MMP-9 and MMP-13 expression and NO production in IL-1β-stimulated OA chondrocytes (p < 0.05). Supporting these gene expression results, IL-1β-induced cartilage matrix breakdown, as evidenced by GAG release from cartilage explants, was also significantly blocked (p < 0.05). Moreover, in the presence of herbal-Leucine mixture (HLM) up-regulation of ACAN and COL2A1 expression in IL-1β-stimulated OA chondrocytes was also noted (p < 0.05). The inhibitory effects of HLM were mediated by inhibiting the activation of nuclear factor (NF)-kB in human OA chondrocytes in presence of IL-1β.
Conclusion: 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. Cited by 16 PMC articles 49 references 6 figures Publication types Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t MeSH terms Boswellia / chemistry Cartilage, Articular / drug effects Cartilage, Articular / immunology Cat’s Claw / chemistry Cells, Cultured Chondrocytes / drug effects Chondrocytes / immunology Female Gene Expression Regulation / drug effects Humans Interleukin-1beta / adverse effects Interleukin-1beta / immunology Lepidium / chemistry Leucine / pharmacology Male Middle Aged Osteoarthritis / chemically induced Osteoarthritis / drug therapy Osteoarthritis / genetics Osteoarthritis / immunology Plant Extracts / pharmacology Substances Interleukin-1beta Plant Extracts Leucine Grant support R01 AT-003267/AT/NCCIH NIH HHS/United States R01-AT-005520/AT/NCCIH NIH HHS/United States R21-AT504615/AT/NCCIH NIH HHS/United States Full-text links BioMed Central Free PMC article
9. Treatment of THP-1 Cells With Uncaria Tomentosa Extracts Differentially Regulates the Expression if IL-1beta and TNF-alpha J Ethnopharmacol , 109 (2), 312-7 2007 Jan 19 Authors Lisa Allen-Hall  1 Pablo CanoJohn T ArnasonRosario RojasOlga LockRobert M Lafrenie
Affiliation: 1Regional Cancer Program, Sudbury Regional Hospital, Sudbury, Ont, Canada. PMID: 16959454 DOI: 10.1016/j.jep.2006.07.039
Abstract: Uncaria tomentosa, commonly known as cat’s claw, is a medicinal plant native to Peru, which has been used for decades in the treatment of various inflammatory disorders. Uncaria tomentosa can be used as an antioxidant, has anti-apoptotic properties, and can enhance DNA repair, however it is best know for its anti-inflammatory properties. Treatment with Uncaria tomentosa extracts inhibits the production of the pro-inflammatory cytokine, TNF-alpha, which is a critical mediator of the immune response. In this paper, we showed that treatment of THP-1 monocyte-like cells with Uncaria tomentosa extracts inhibited the MAP kinase signaling pathway and altered cytokine expression. Using ELISA assays, we showed that treatment with Uncaria tomentosa extracts augmented LPS-dependent expression of IL-1beta by 2.4-fold, while inhibiting the LPS-dependent expression of TNF-alpha by 5.5-fold. We also showed that treatment of LPS-stimulated THP-1 cells with Uncaria tomentosa extracts blocked ERK1/2 and MEK1/2 phosphorylation in a dose-dependent manner. These data demonstrate that treatment of THP-1 cells with Uncaria tomentosa extracts has opposite effects on IL-1beta and TNF-alpha secretion, and that these changes may involve effects on the MAP kinase pathway. Cited by 12 PMC articles MeSH terms Cat’s Claw / chemistry Cell Death / drug effects Cell Line Cell Survival / drug effects Humans Interleukin-1beta / metabolism Lipopolysaccharides / pharmacology MAP Kinase Signaling System / drug effects Monocytes / cytology Monocytes / drug effects Monocytes / metabolism Plant Extracts / chemistry Plant Extracts / pharmacology Plants, Medicinal Tumor Necrosis Factor-alpha / metabolism Substances Interleukin-1beta Lipopolysaccharides Plant Extracts Tumor Necrosis Factor-alpha Full-text links Elsevier Science
10. Anti-inflammatory Activity of Mitraphylline Isolated From Uncaria Tomentosa Bark J Ethnopharmacol , 143 (3), 801-4 2012 Oct 11 Authors R Rojas-Duran  1 G González-AspajoC Ruiz-MartelG BourdyV H Doroteo-OrtegaJ Alban-CastilloG RobertP AubergerE Deharo
Affiliation 1 Unidad de Investigación en Productos Naturales, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, SMP, Lima, Peru. PMID: 22846434 DOI: 10.1016/j.jep.2012.07.015 Abstract
Ethnopharmacological relevance: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) is widely used by populations living in South America to treat many ailments associated with inflammatory disorders. Mitraphylline was shown to be the major pentacyclic oxindolic alkaloid present in the bark chloroformic extract of this plant. Its activity against cytokines involved in inflammation process was tested in a murine model in vivo.
Materials and methods: Mice received mitraphylline once a day for 3 days at 30 mg/kg/day by oral route. Then, they were subjected to bacterial lipopolysaccharide (LPS) endotoxin (15 mg/kg) and the LPS-induced production of 16 different cytokines was determined by Elisa multiplex. Control group received dexamethasone orally at 2mg/kg/day. Toxicity on K565 cells and murine peritoneal macrophages, in vitro, at doses up to 100 μM was monitored by XTT-colorimetric assay.
Results and conclusions: For the first time mitraphylline was tested in vivo against a large range of cytokines that play a crucial role in inflammation. Mitraphylline inhibited around 50% of the release of interleukins 1α, 1β, 17, and TNF-α. This activity was similar to dexamethasone. It also reduced almost 40% of the production of interleukin 4 (IL-4) while the corticoid did not. Lastly it did not show any toxicity on K565 cells nor murine macrophages at doses up to 100 μM. Copyright © 2012. Published by Elsevier Ireland Ltd. Cited by 12 PMC articles Publication types Research Support, Non-U.S. Gov’t MeSH terms Animals Anti-Inflammatory Agents / pharmacology Cat’s Claw Cell Survival / drug effects Cells, Cultured Cytokines / blood Female Indole Alkaloids / pharmacology Lipopolysaccharides Macrophages, Peritoneal / drug effects Mice Mice, Inbred BALB C Oxindoles Plant Bark / chemistry Substances Anti-Inflammatory Agents Cytokines Indole Alkaloids Lipopolysaccharides Oxindoles mitraphylline Full-text links Elsevier Science
11. The Chrondoprotective Actions of a Natural Product Are Associated With the Activation of IGF-1 Production by Human Chondrocytes Despite the Presence of IL-1beta BMC Complement Altern Med , 6, 13 2006 Apr 7
Authors Mark J S Miller  1 Salahuddin AhmedPaul BobrowskiTariq M Haqqi Affiliation 1Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA. PMID: 16603065 PMCID: PMC1456997 DOI: 10.1186/1472-6882-6-13 Abstract
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. Cited by 9 PMC articles 66 references 5 figures Publication types Research Support, N.I.H., Extramural MeSH terms Cells, Cultured / drug effects Chondrocytes / drug effects Chondrocytes / metabolism Dose-Response Relationship, Drug Gene Expression / drug effects Glycosaminoglycans / metabolism Humans Insulin-Like Growth Factor I / biosynthesis Insulin-Like Growth Factor I / genetics Interleukin-1 / metabolism Interleukin-1beta Lepidium Nitric Oxide / biosynthesis Peptide Fragments / metabolism Plant Extracts / pharmacology Recombinant Proteins Uncaria Substances Glycosaminoglycans Interleukin-1 Interleukin-1beta Peptide Fragments Plant Extracts RN 180 RNI 249 Recombinant Proteins reparagen interleukin-1beta (163-171) Nitric Oxide Insulin-Like Growth Factor I Grant support R43 AG024733/AG/NIA NIH HHS/United States R43 AG024733-01/AG/NIA NIH HHS/United States Full-text links BioMed Central Free PMC article

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