Effect of the Chinese Medicine YangZheng XiaoJi on Reducing Fatigue in Mice with Orthotopic Transplantation of Colon Cancer

Abstract

Background: Fatigue is a common, distressing, and persistent symptom for patients with malignant tumor including colorectal cancer (CRC). Although studies of cancer-related fatigue (CRF) have sprung out in recent years, the pathophysiological mechanisms that induce CRF remain unclear, and effective therapeutic interventions have yet to be established.

Methods: To investigate the effect of the traditional Chinese medicine YangZheng XiaoJi (YZXJ) on CRF, we constructed orthotopic colon cancer mice, randomly divided into YZXJ group and control (NS) group. Physical or mental fatigue was respectively assessed by swimming exhaustion time or suspension tail resting time. At the end of the experiment, serum was collected to measure the expression level of inflammatory factors by ELISA and feces to microbiota changes by 16s rDNA, and hepatic glycogen content was detected via the anthrone method.

Result: The nutritional status of the YZXJ group was better than that of the control group, and there was no statistical difference in tumor weight. The swimming exhaustion times of YZXJ group and control group were (162.80 ± 14.67) s and (117.60 ± 13.42, P < 0.05) s, respectively; the suspension tail resting time of YZXJ group was shorter than that of the control group (49.85 ± 4.56) s and (68.83 ± 7.26) s, P < 0.05)). Serum levels of IL-1β and IL-6 in YZXJ group were significantly lower than the control group (P < 0.05). Liver glycogen in YZXJ group was (5.18 ± 3.11) mg/g liver tissue, which was significantly higher than that in control group (2.95 ± 2.06) mg/g liver tissue (P < 0.05). At phylum level, increased abundance of Bacteroidetes, Verrucomicrobia, Actinobacteria, and Cyanobacteria and decreased Proteobacteria in YZXJ group emerged as the top differences between the two groups, and the Firmicutes/Bacteroidetes ratio was decreased in YZXJ group compared to the control group. At genus level, the abundance of Parabacteroides, unidentified Saprospiraceae, and Elizabethkingia which all belong to phylum Bacteroidetes were increased, while Arcobacter, Marinobacter, Alkanindiges, Sulfuricurvum, Haliangium, and Thiobacillus in phylum Proteobacteria were decreased after YZXJ intervention. YZXJ can also increase Pirellula, Microbacterium, and Alpinimonas and decrease Rubrobacter and Iamia.

Conclusion: YZXJ may reduce the physical and mental fatigue caused by colorectal cancer by inhibiting inflammatory reaction, promoting hepatic glycogen synthesis, and changing the composition of intestinal microbiota.

Figure 1

General condition of the two groups. (a) Tumor weight comparison of NS and YZXJ groups. No statistically significant difference was observed between the two groups. (b) Colon cancer orthotopic transplantation in BALB/c mice. (c) Appearance and activity. NS group had rougher, lusterless hair, more apathetic condition, and lower movement than YZXJ group. (d) Average daily food intake of each mouse weighted every 4 days. (e) Average weight of each mouse weighted every week. ∗ Weight without in situ tumor.

Figure 2

Comparison of fatigue state. (a) Physical fatigue exhaustive swimming time of NS and YZXJ group tested after 10-day intervention. (b) Immobile time in tail suspension test of NS and YZXJ group tested after 14-day intervention. ∗ P<0.05.

Figure 3

Concentration of inflammatory factors and hepatic glycogen. (a) Fatigue-related inflammatory factors in YZXJ group were generally lower than NS group, particularly for IL-1β and IL-6. (b) The level of liver glycogen in the two groups, reflexing the advantage energy reserve capacity in YZXJ treated mice. ∗ P<0.05.

Figure 4

Comparison of α and β diversity. (a, b) Two indicators of α diversity detected in NS and YZXJ group. Chao 1 is represented as the bacteria abundance, and Simpson index reflects the bacteria diversity. (c) Unifrac distance of β diversity is used to calculate the distance between samples by using the evolutionary information and further constructing weighted Unifrac distance through OTUs abundance information. (d) Intergroups difference was greater than intragroup difference, but the difference was not statistically significant (P=0.117).

Figure 5

Alteration of fecal microbiota due to the intervention of YZXJ. (a) Cumulative column chart of relative species abundance in phylum level. (b) Top differences of fecal microbiota shifts in genus level.