Abstract: Objective To investigate the protective effect and mechanism of licorice and dried ginger decoction (LDGD) against cisplatin-induced cytotoxicity in macrophages. Methods The effects of different concentrations of cisplatin（1、2、3、4、6 μg·mL^-1）, LDGD (5、10、20 mg·mL^-1), the sequential administration and coadministration of cisplatin and LDGD on the cell viability of mouse macrophage RAW264.7 cells cultured in vitro were detected by MTT assay. The apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of RAW264.7 cells were analyzed by flow cytometry. Twenty-four male C57/BL6J mice were randomly divided into four groups (n=6): the control group, model group, cisplatin (4 mg·kg^-1) group and combination group (4 mg·kg^-1+LDGD 5 g·kg^-1). One day after inoculation with Lewis lung carcinoma (LLC), the mice in each group except those in the control group were given LDGD by intragastric administration for 20 days. The cisplatin group and the combination group were intraperitoneally injected with cisplatin every 3 days. The changes of tumor volume, body weight, visceral indexes, spleen T lymphocyte typing, immune factors of serum TNF-α, IL-6 and macrophage infiltration in tumor sections were determined after 21 days. Results Compared with the control group, cisplatin dose-dependently inhibited the cells' viability of RAW264.7 (P<0.01), while LDGD promoted the cell viability (P<0.01). LDGD could reduce the inhibitory effect of cisplatin on RAW264.7 cell viability (P<0.01). LDGD could reduce the apoptosis rate of RAW264.7 induced by cisplatin (P<0.01). Cisplatin induced an increase of ROS and a decrease of mitochondrial membrane potential (MMP) in RAW264.7 cells, but LDGD reversed the cisplatin - induced increase of ROS and the decrease of MMP (P<0.01). Both the cisplatin group and the combination group could significantly inhibit the growth of tumors, and cisplatin could lead to a significant increase in the liver indexes of mice, and a significant decrease in the indexes of body weight, kidneys, spleens and thymuses. Thymus indexes were restored to normal in the combination group, so were the organ indexes. LDGD could improve the levels of CD3⁺, CD4⁺ and CD8⁺ T lymphocytes in the spleen of mice following the use of cisplatin. LDGD increased macrophage infiltration in tumor tissues and TNF-α contents, but reduced IL-6 contents in mice serum. Conclusion LDGD inhibits cisplatin-induced apoptosis and reduces cisplatin-induced cytotoxicity in mouse macrophage RAW264.7 cells by reducing ROS production and stabilizing MMP. LDGD can mitigate the damage to the liver, kidney and immune organs caused by cisplatin, promote macrophage function, and improve the body's immunity.

Key words: cisplatin, licorice and dried ginger decoction, reactive oxygen species, mitochondrial membrane potential, apoptosis, Lewis lung carcinoma, macrophage cells, TNF-α, IL-6