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Effect of Naturally Occurring Triterpenoids Ursolic Acid and Glycyrrhizic Acid on the Cell-Mediated Immune Responses of Metastatic Tumor-Bearing Animals

Effect of terpenoids, ursolic acid and glycyrrhizic acid on the cell-mediated immune response was studied in metastatic tumor-bearing C57BL/6 mice. Intraperitoneal administration of ursolic acid and glycyrrhizic acid (50 μmoles/Kg body wt for 5 consecutive days) was found to produce increased natural killer cell activity (NK-activity) in metastatic tumor-bearing animals. In the glycyrrhizic acid- and ursolic acid-treated groups the peak activity was observed on the 4th day (60.2% and 43% cell lysis respectively). Whereas in control animals the maximum cell lysis was obtained only on 16th day (25% cell lysis). Administration of terpenoids clearly enhanced the antibody dependent cell mediated cytotoxicity (ADCC). In tumor-bearing control animals maximum cell lysis was obtained only on the 16th day (20% cell lysis). But in the case of glycyrrhizic acid- and ursolic acid-treated groups, the maximum lysis was obtained on the 12th day. and it was 47% and 32.5% cell lysis, respectively. Intraperitoneal administration of these 2 terpenoids was also found to enhance antibody-dependent complement-mediated cytotoxicity (ACC) in metastatic tumor-bearing animals. The elevated level of GM-CSF in tumor-alone treated control animals (37.9 ± 1.1 pg/ml) was reduced by the treatment with glycyrrhizic acid (20.3 pg/ml) and ursolic acid (22.5 pg/ml). The highly elevated level of IL-6 (370.1 pg/ml) in control animals was also reduced by the treatment of glycyrrhizic acid (313 pg/ml) and ursolic acid (299 pg/ml). The level of IL-2 was enhanced by the treatment with glycyrrhizic acid (37.9 pg/ml) and ursolic acid (35.9) compared to untreated tumor-bearing control animals (24.9 pg/ml).