Chemoprotective and Adjuvant Effects of Immunomodulator Ginsan in Cyclophosphamide-Treated Normal and Tumor Bearing Mice

Abstract

Ginsan is a polysaccharide extracted from Panax ginseng that is known to have multiple immunomodulatory effects. This study evaluates the chemoprotective effect of ginsan on normal mice and the adjuvant effect on tumor bearing mice in combination with cyclophosphamide (CP). Ginsan (100 mg/kg) was injected 24 h before or after a sublethal dose of a CP treatment. The mice pre-treated with ginsan all died within 10 days whereas up to 53 percent of the mice post-treated with ginsan increased survival to day 30 compared with only 10 percent in the CP alone treated group on day 30. The post-treatment of ginsan accelerated the recovery of the bone marrow cells and blood neutrophils by approximately 1.3- and 1.75-fold compared to CP treated control mice at 5 days after CP administration, respectively. These marked differences in activity between the pre- and post-treatment of ginsan with CP was clarified by examining the mRNA expression levels of several cytokines in spleen cells and the self-renewal potential of hematopoietic progenitor cells, CFU-s. The post-treatment with ginsan increased the mRNA expression levels of TNF-alpha, IL-1beta, IL-6, SCF, and GM-CSF with respect to that of the CP alone or ginsan pre-treated group. Similarly, the number of CFU-s was significantly higher in the mice post-treated with ginsan. The inhibition of tumor growth and survival elongation was also observed when ginsan was administered 24 h after the CP treatment. These results show that the post-treatment with ginsan had an immunomodulating and adjuvant effect in combination with CP, which indicates its wide applications in reducing the adverse effects of chemotherapy and improving the general conditions of patients.