人参联合咖啡因对大鼠的抗疲劳作用及机制探讨

Anti-fatigue effects and mechanism of ginseng combined with caffeine in rats

目的评估人参联合咖啡因对大鼠的抗疲劳作用及机制。方法将SD大鼠随机分为空白组、模型组、人参组(60 mg·kg^(-1))、咖啡因组(3.0 mg·kg^(-1))、配伍组(30 mg·kg^(-1)+1.5mg·kg^(-1)),建立大鼠负重游泳疲劳模型,每日给药1次,连续给药21 d;采用负重游泳实验评价药物抗疲劳作用;采用两成分组合效应系数(two components combination index,TCCI)方法评估人参配伍咖啡因抗疲劳协同增效作用;比色法检测各组大鼠的尿素氮(BUN)、乳酸(LD)和肝/肌糖原水平;酶联免疫吸附法检测各组大鼠白细胞介素6(IL-6)、白细胞介素1β(IL-1β)和C反应蛋白(CRP)水平;使用网络药理学初步探讨人参联合咖啡因抗疲劳的可能作用机制。结果人参联合咖啡因TCCI值在0.17~0.61,两者联用显示明显的协同增效作用;与模型组相比,各给药组可不同程度地延长大鼠负重游泳时间,提高肝脏/骨骼肌组织中糖原含量,下调血清中尿素氮水平,降低炎症因子水平;通过网络药理学分析发现,其主要通过PI3K-Akt和MAPK等通路发挥抗疲劳功效。结论人参联合咖啡因可显著降低糖原分解和乳酸等代谢物积累,改善模型大鼠的疲劳症状。

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.