Abstract
This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT) brute hydroethanolic (BHE) extract with those of two fractions derived from it. These fractions are choroformic (CHCl3) and n-butanolic (BuOH), rich in pentacyclic oxindole alkaloids (POA) and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg−1) or its fractions (as per the yield of the fractioning process) or vehicle (Control) was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.
Highlights
Uncaria tomentosa is a vine native to the Peruvian Amazon Basin [1] that is biologically active especially as antiinflammatory, immunonomodulant and anti-oxidant agent
Compounds were revealed with UV254 light and H2SO4 solution in both fractions, but only the CHCl3 fraction provided a positive test with the Dragendorff alkaloid-specific reagent, indicating the presence of these compounds in its composition
The BuOH fraction was found to be constituted by a complex mixture of components, as shown in its high-performance liquid chromatography (HPLC) chromatogram (Figure 1A)
Summary
Uncaria tomentosa is a vine native to the Peruvian Amazon Basin [1] that is biologically active especially as antiinflammatory, immunonomodulant and anti-oxidant agent. For the last couple of decades, researchers have experimented several types and methods of extraction to observe a wide array of pharmacological properties, including limitation of the epithelial cell death in response to oxidant stress [2], amelioration of the oedema via inhibition of cyclooxygenase-1 and 22 [3], cytoprotection by means of free radical scavenging, reduction of oxidative stress and direct inhibition of the TNF-a production [4,5,6], to name a few Most of these researchers have attributed the biological effects of U. tomentosa to the pentacyclic oxindole alkaloids present in this plant. Albeit older, suggests that the anti-inflammatory properties of UT may be related to a synergic combination of compounds [7,15]
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