Abstract: Objective To evaluate the anti-fatigue effect and mechanism of ginseng extract combined with caffeine in rats. Methods The two components combination index was used to evaluate the synergistic effect of ginseng and caffeine in combating fatigue. SD rats were randomly divided into the control group, model group, ginseng group (60 mg·kg^-1), caffeine group (3 mg·kg^-1), and combined group (30 mg·kg^-1+1.5 mg·kg^-1). A rat fatigue model was established via weight bearing swimming, and the drugs were administered once daily for 21 consecutive days. The anti-fatigue effect was evaluated by weight bearing swimming experiments. Colorimetry was used to detect the levels of urea nitrogen (BUN), lactic acid (LD), and liver/skeletal muscle glycogen in each group of rats. Enzyme linked immunosorbent assay (ELISA) was adopted to detect the levels of interleukin 6 (IL-6), interleukin 1β (IL-1β), and C-reactive protein (CRP) while network pharmacology was used to explore the possible mechanism of anti-fatigue effect of ginseng extract combined with caffeine. Results The TCCI of ginseng and caffeine was calculated to be 0.17~0.61, indicating a synergistic anti-fatigue effect. Compared with the model group, each drug administration group prolonged the weight bearing swimming time of rats to varying degrees, increased the content of glycogen in liver/skeletal muscle tissues, decreased the level of BUN in serum, and reduced the level of inflammatory cytokines. Network pharmacology analysis found that the anti-fatigue effects were exerted through such pathways as PI3K-Akt and MAPK signaling pathway. Conclusion Ginseng extract combined with caffeine could significantly decrease the accumulation of metabolic products such as lactic acid, reduce the breakdown of glycogen, and improve fatigue symptoms of model rats.

Key words: ginseng, caffeine, anti-fatigue, two components combination index, colorimetry, enzyme linked immunosorbent assay, network pharmacology, rats