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

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

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