Processed Aloe vera gel ameliorates cyclophosphamide-induced immunotoxicity

Abstract

The effects of processed Aloe vera gel (PAG) on cyclophosphamide (CP)-induced immunotoxicity were examined in mice. Intraperitoneal injection of CP significantly reduced the total number of lymphocytes and erythrocytes in the blood. Oral administration of PAG quickly restored CP-induced lymphopenia and erythropenia in a dose-dependent manner. The reversal of CP-induced hematotoxicity by PAG was mediated by the functional preservation of Peyer's patch cells. Peyer's patch cells isolated from CP-treated mice, which were administered PAG, produced higher levels of T helper 1 cytokines and colony-stimulating factors (CSF) in response to concanavalin A stimulation as compared with those isolated from CP-treated control mice. PAG-derived polysaccharides directly activated Peyer's patch cells isolated from normal mice to produce cytokines including interleukin (IL)-6, IL-12, interferon-γ, granulocyte-CSF, and granulocyte-macrophage-CSF. The cytokines produced by polysaccharide-stimulated Peyer's patch cells had potent proliferation-inducing activity on mouse bone marrow cells. In addition, oral administration of PAG restored IgA secretion in the intestine after CP treatment. These results indicated that PAG could be an effective immunomodulator and that it could prevent CP-induced immunotoxic side effects.

Figures

Figure 1

Comparison of the molecular sizes of the polysaccharides in native Aloe vera gel (A) and in PAG (B).

Figure 2

Oral administration of PAG prevents and restores CP-induced lymphopenia and erythropenia. Mice (n = 10) were orally administered 200 or 400 mg/kg/day PAG for 19 days. Immunosuppression was induced by intraperitoneal (i.p.) injection of CP (25 mg/kg/day) for three consecutive days starting on the fourth day after PAG administration. The changes in the total numbers of leukocytes (A); lymphocytes (B); and erythrocytes (C) in the blood were examined on the indicated days. * indicates p < 0.05 and ** indicates p < 0.01.

Figure 3

Oral administration of PAG preserves the cytokine-producing capability of Peyer’s patch cells. Peyer’s patch cells were isolated from CP-treated mice that were administered PAG and were then stimulated with Con A for 4 days. Cytokine levels in the cell culture supernatants were measured by using enzyme-linked immunosorbent assays (ELISA). * indicates p < 0.05 and ** indicates p < 0.01.

Figure 4

Aloe polysaccharides induce hematopoietic cytokine production by Peyer’s patch cells. Peyer’s patch cells isolated from control mice were stimulated with Aloe polysaccharides for 3 days. The cytokine levels in the culture supernatants were determined by using ELISA. ** indicates p < 0.01, compared to PAG-untreated group.

Figure 5

Effects of cytokines produced by Peyer’s patch cells stimulated with the Aloe polysaccharides on the proliferation of bone marrow cells. Peyer’s patch cells isolated from control mice were stimulated with 100 μg/mL of polysaccharides for 3 days. The indicated amounts of the cytokine-containing cell culture supernatants (v/v %) were added to cultures of mouse bone marrow cells. ** indicates p < 0.01, compared to culture supernatant-untreated group.

Figure 6

Effect of oral administration of PAG on CP-suppressed IgA production in the intestine. Fresh feces from mice from each group were collected on days 3, 7, 11, 15, and 19. The feces were freeze-dried, weighed, and dissolved in phosphate-buffered saline containing protease inhibitors. Total IgA levels in fecal extracts were assessed by using an ELISA. * indicates p < 0.05 and ** indicates p < 0.01.