In vitro Effects of Two Extracts and Two Pure Alkaloid Preparations of Uncaria tomentosa on Peripheral Blood Mononuclear Cells

C. Winkler; B. Wirleitner; K. Schroecksnadel; H. Schennach; E. Mur; D. Fuchs

doi:10.1055/s-2004-815536

Planta Medica, Inhaltsverzeichnis

Planta Med 2004; 70(3): 205-210
DOI: 10.1055/s-2004-815536

Original Paper

Pharmacology
© Georg Thieme Verlag Stuttgart · New York

In vitro Effects of Two Extracts and Two Pure Alkaloid Preparations of Uncaria tomentosa on Peripheral Blood Mononuclear Cells

C. Winkler¹ ^, ² , B. Wirleitner¹ , K. Schroecksnadel¹ , H. Schennach³ , E. Mur⁴ , D. Fuchs¹ ^, ²

¹Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Innsbruck, Austria
²Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria
³Central Institute of Blood Transfusion and Immunology, University Hospital, Innsbruck, Austria
⁴Department of Internal Medicine, University Hospital, Innsbruck, Austria

This work was supported by the Austrian Funds ”Zur Förderung der wissenschaftlichen Forschung”, project 14 154-Med and by the Austrian Federal Ministry of Social Affairs and Generations

Abstract

In the traditional Peruvian medicine, hot aqueous extracts of Uncaria tomentosa have been used for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. Some of the beneficial effects observed in patients suggest an immunomodulatory capacity of Uncaria tomentosa extracts. In this study, the effects of two extracts and two mixtures of tetracyclic and pentacyclic oxindole alkaloids of Uncaria tomentosa were investigated in freshly isolated human peripheral blood mononuclear cells (PBMC) stimulated with the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) in vitro. Neopterin production and tryptophan degradation were monitored in culture supernatants to determine the effects of the test substances on immunobiochemical pathways induced by interferon-γ. Compared to unstimulated cells PHA and Con A increased the production of neopterin and degradation of tryptophan (p < 0.01). HCl and ethanol extracts and mixtures of alkaloids of Uncaria tomentosa inhibited both effects in a dose-dependent manner, the lowest effective concentrations of the extracts were 500 - 1000 μg/mL and of the alkaloid mixtures 100 - 175 μg/mL (p < 0.05 and < 0.01). With the highest concentrations of extracts and mixtures complete suppression of mitogen-induced neopterin production and tryptophan degradation was observed. These data demonstrate that Uncaria tomentosa extracts and mixtures of alkaloids modulate the immunobiochemical pathways induced by interferon-γ. The findings imply a potential application of the extracts as immunoregulators and would be in line with observations in patients using these extracts.

Abbreviations

Con A:concanavalin A

EDTA:ethylenediaminetetraacetic acid, Titriplex III

IDO:indoleamine (2,3)-dioxygenase

IFN-γ:interferon-γ

kyn:kynurenine

MTT:3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide

PBMC:peripheral blood mononuclear cells

PHA:phytohaemagglutinin

POA:pentacyclic oxindole alkaloids

ROS:reactive oxygen species

TOA:tetracyclic oxindole alkaloids

trp:tryptophan

Key words

Uncaria tomentosa - Rubiaceae - immunomodulation - neopterin - tryptophan - indoleamine (2,3)-dioxygenase

Volltext

Referenzen

References

1 Obregon L E. Cat’s claw, genus Uncaria. Botanical, chemical and pharmacological studies of Uncaria tomentosa (Willd.) D.C. (Rubiaceae) and Uncaria guianensis (Aubl.) Gmel. Institute of American Phytotherapy 1995 Lima, Peru;
2 Keplinger K, Laus G, Wurm M, Dierich M P, Teppner H. Uncaria tomentosa (Willd.) DC - Ethnomedical use and new pharmaceutical, toxicological and botanical results. J Ethnopharmacol. 1999; 64 23-34
3 Wagner H. Kreutzkamp B, Jurcic K. Die Alkaloide von Uncaria tomentosa und ihre Phagozytose-steigernde Wirkung. Planta Med. 1985; 51 419-23
4 Wurm M, Kacani L, Laus G, Keplinger K, Dierich M P. Pentacyclic oxindole alkaloids from Uncaria tomentosa induce human endothelial cells to release a lymphocyte-proliferation-regulating factor. Planta Med. 1998; 64 701-4
5 Lemaire I, Assinewe V, Cano P, Awang D VC, Arnason J T. Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa (Uña de gato). J Ethnopharmacol. 1999; 64 109-15
6 Wagner H KM. Immunostimulants and Adaptogens form plants. In: Arnason J, Mata R, Romeo J. (eds.) Phytochemistry of Medicinal Plants. Record of Advanced Phytochemistry 1995 29: 1-18
7 Zvetkova E, Wirleitner B, Tram N T, Schennach H, Fuchs D. Aqueous extracts of Crinum latifolium (L.) and Camellia sinensis show immunomodulatory properties in human peripheral blood mononuclear cells. Intern Immunopharmacol. 2001; 1 2143-50
8 Neurauter G, Wirleitner B, Laich A, Schennach H, Weiss G, Fuchs D. Atorvastatin suppress IFN-γ-induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. Clin Exp Immunol. 2003; 131 264-7
9 Fuchs D, Weiss G, Wachter H. Neopterin, biochemistry and clinical use as a marker for cellular immune reactions. Int Arch Allergy Immunol. 1993; 101 1-6
10 Wirleitner B, Reider D, Ebner H. Monocyte-derived dendritic cells release neopterin. J Leukocyte Biol. 2002; 72 1148-53
11 Widner B, Ledochowski M, Fuchs D. Interferon-γ-induced tryptophan degradation: neuropsychiatric and immunological consequences. Curr Drug Metabol. 2000; 1 193-204
12 Fuchs D, Möller A A, Reibnegger G, Stöckle E, Werner E R, Wachter H. Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms. J Acquir Immune Defic Syndr. 1990; 3 873-6
13 Weiss G, Murr C, Zoller H. Modulation of neopterin formation and tryptophan degradation by Th1- and Th2-derived cytokines in human monocytic cell. Clin Exp Immunol. 1999; 116 435-40
14 Widner B, Werner E R, Schennach H, Wachter H, Fuchs D. Simultaneous measurement of serum tryptophan and kynurenine by HPLC. Clin Chem. 1997; 43 2424-6
15 Aguilar J L, Rojas P, Marcelo A, Plaza A, Bauer R, Reininger E, Klaas C, Merfort I. Anti-inflammatory activity of two different extracts of Uncaria tomentosa (Rubiaceae). J Ethnopharm. 2002; 81 271-6
16 Wurm M. Untersuchungen der immunologischen Wirkungsmechanismen der pentazyklischen Oxindolalkaloide aus Uncaria tomentosa . Sci. D. thesis University of Innsbruck, Austria; 1997
17 Sandoval M, Charbonnet R M, Okuhana N N, Roberts J, Krenova Z, Trentacosti A M, Miller M JS. Cat’s claw inhibits TNF-α production and scavenges free radicals: role in cytoprotection. Free Radical Biol Med. 2000; 29 71-8
18 Sandoval-Chacòn M, Thompson J H, Zhang X -J, Liu X, Mannick E E, Sadowska-Krowicka H, Charbonnet R M, Clark D A, Miller M JS. Anti-inflammatory actions of cat’s claw: the role of NF-κB. Aliment Pharmacol Ther. 1998; 12 1279-89
19 Gutteridge J M, Halliwell B. Free radicals and antioxidants in the year 2000. A historical look to the future. Ann NY Acad Sci. 2000; 899 136-47
20 Nathan C F. Peroxide and pteridine: a hypothesis on the regulation of macrophage antimicrobial activity by interferon gamma. Interferon. 1986; 7 125-43
21 Mur E, Hartig F, Eibl G, Schirmer M. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of Uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002; 29 678-81

Dietmar Fuchs

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