Ginseng Purified Dry Extract, BST204, Improved Cancer Chemotherapy-Related Fatigue and Toxicity in Mice

Abstract

Cancer related fatigue (CRF) is one of the most common side effects of cancer and its treatments. A large proportion of cancer patients experience cancer-related physical and central fatigue so new strategies are needed for treatment and improved survival of these patients. BST204 was prepared by incubating crude ginseng extract with ginsenoside-β-glucosidase. The purpose of the present study was to examine the effects of BST204, mixture of ginsenosides on 5-fluorouracil (5-FU)-induced CRF, the glycogen synthesis, and biochemical parameters in mice. The mice were randomly divided into the following groups: the naïve normal (normal), the HT-29 cell inoculated (xenograft), xenograft and 5-FU treated (control), xenograft + 5-FU + BST204-treated (100 and 200 mg/kg) (BST204), and xenograft + 5-FU + modafinil (13 mg/kg) treated group (modafinil). Running wheel activity and forced swimming test were used for evaluation of CRF. Muscle glycogen, serum inflammatory cytokines, aspartic aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE), white blood cell (WBC), neutrophil (NEUT), red blood cell (RBC), and hemoglobin (HGB) were measured. Treatment with BST204 significantly increased the running wheel activity and forced swimming time compared to the control group. Consistent with the behavioral data, BST204 markedly increased muscle glycogen activity and concentrations of WBC, NEUT, RBC, and HGB. Also, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), AST, ALT, and CRE levels in the serum were significantly reduced in the BST204-treated group compared to the control group. This result suggests that BST204 may improve chemotherapy-related fatigue and adverse toxic side effects.

Figure 1

Figure 2

Voluntary running wheel activity during three days recorded before drug treatment as a baseline value (a), the 13th day (b), and the 27th day after drug treatment (c). Each value represents the mean ± S.E.M. ^# P < 0.05, ^## P < 0.01, and ^### P < 0.001 compared to the normal and ^* P < 0.05, ^** P < 0.01 compared to the control group. Naïve normal (normal); HT-29 cell inoculated + saline treated group (xenograft). Xenograft + 5-FU + vehicle treated group (control); xenograft + 5-FU + BST204-treated group (BST204). Xenograft + 5-FU + modafinil treated group (modafinil).

Figure 3

The effects of BST204 and modafinil with 5-FU treatment on forced swimming test. Each value represents the mean ± S.E.M. ^# P < 0.05, ^## P < 0.01, and ^### P < 0.001 compared to the normal and ^** P < 0.01, ^*** P < 0.001, compared to the control group. Naïve normal (normal); HT-29 cell inoculated + saline treated group (xenograft). Xenograft + 5-FU + vehicle treated group (control); xenograft + 5-FU + BST204-treated group (BST204). Xenograft + 5-FU + modafinil treated group (modafinil).

Figure 4

The effects of BST204 and modafinil with 5-FU treatment on glycogen synthesis (a), TNF-α (b), and IL-6 (c). Each value represents the mean ± S.E.M. ^# P < 0.05, ^## P < 0.01, and ^### P < 0.001 compared to the normal and ^* P < 0.05, ^** P < 0.01, and ^*** P < 0.001 compared to the control group. Naïve normal (normal); HT-29 cell inoculated + saline treated group (xenograft). Xenograft + 5-FU + vehicle treated group (control); xenograft + 5-FU + BST204-treated group (BST204). Xenograft + 5-FU + modafinil treated group (modafinil).

Figure 5

The effects of BST204 and modafinil with 5-FU treatment on AST (a), ALT (b), and Cre (c). Each value represents the mean ± S.E.M. ^# P < 0.05, ^## P < 0.01, and ^### P < 0.001 compared to the normal and ^* P < 0.05, ^** P < 0.01 compared to the control group. Naïve normal (normal); HT-29 cell inoculated + saline treated group (xenograft). Xenograft + 5-FU + vehicle treated group (control); xenograft + 5-FU + BST204-treated group (BST204). Xenograft + 5-FU + modafinil treated group (modafinil).

Figure 6

The effects of BST204 and modafinil with 5-FU treatment on WBC (a), NEUT (b), RBC (c), and Hgb (d). Each value represents the mean ± S.E.M. ^# P < 0.05, ^## P < 0.01, and ^### P < 0.001 compared to the normal and ^* P < 0.05, ^** P < 0.01, and ^*** P < 0.001 compared to the control group. Naïve normal (normal); HT-29 cell inoculated + saline treated group (xenograft). Xenograft + 5-FU + vehicle treated group (control); xenograft + 5-FU + BST204-treated group (BST204). Xenograft + 5-FU + modafinil treated group (modafinil).

Figure 7

The effects of BST204 and modafinil with 5-FU treatment on tumor size. Each value represents the mean ± S.E.M. ^# P < 0.05, ^## P < 0.01, and ^### P < 0.001 compared to the normal and ^* P < 0.05, ^** P < 0.01, and ^*** P < 0.001 compared to the control group. Naïve normal (normal); HT-29 cell inoculated + saline treated group (xenograft). Xenograft + 5-FU + vehicle treated group (control); xenograft + 5-FU + BST204-treated group (BST204). Xenograft + 5-FU + modafinil treated group (modafinil).