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传统药物宫劲丹在强迫应激小鼠运动模型中可改善慢性疲劳。

The traditional drug Gongjin-Dan ameliorates chronic fatigue in a forced-stress mouse exercise model.

作者信息

Hong Sung-Shin, Lee Ji-Young, Lee Jin-Seok, Lee Hye-Won, Kim Hyeong-Geug, Lee Sam-Keun, Park Bong-Ki, Son Chang-Gue

机构信息

Korean Medical College of Daejeon University, 22-5 Yongwoon-dong, Dong-gu, Daejeon 301-724, Republic of Korea.

Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daeheung-dong, Jung-gu, Daejeon 301-704, Republic of Korea.

出版信息

J Ethnopharmacol. 2015 Jun 20;168:268-78. doi: 10.1016/j.jep.2015.04.001. Epub 2015 Apr 10.

DOI:10.1016/j.jep.2015.04.001
PMID:25865680
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Gongjin-Dan is a representative traditional Oriental medicine herbal drug that has been used to treat chronic fatigue symptoms for several hundred years. We evaluated the anti-fatigue effects of Gongjin-Dan and the underlying mechanisms in a chronic forced exercise mouse model.

METHODS AND MATERIALS

Balb/C male mice underwent an extreme treadmill-based running stress (1-h, 5 days/week), and daily oral administration of distilled water, Gongjin-Dan (100, 200, or 400 mg/kg), or ascorbic acid (100 mg/kg) for 28 days. The anti-fatigue effects of Gongjin-Dan were evaluated with behavioral tests (exercise tolerance and swimming tests), and the corresponding mechanisms were investigated based on oxidative stress and inflammatory cytokine and stress hormone levels in skeletal muscle, sera, and brain tissue.

RESULTS

Gongjin-Dan significantly increased exercise tolerance and latency times but reduced the number of electric shocks and immobilization time on the treadmill running and swimming tests, compared with the control group. Gongjin-Dan also significantly ameliorated alterations in oxidative stress-related biomarkers (reactive oxygen species and malondialdehyde), inflammatory cytokines (tumor necrosis factor-α, interleukin-1 beta, interleukin-6, and interferon-γ) and glycogen and L-lactate levels in skeletal muscle, compared with those in the control group. Moreover, Gongjin-Dan considerably normalized the forced running stress-induced changes in serum corticosterone and adrenaline levels, as well as brain serotonin level. These antioxidant and anti-stress effects of Gongjin-Dan were supported by the results of Western blotting (4-hydroxynonenal and heme oxygenase-1) and the gene expression levels (serotonin receptor and serotonin transporter).

CONCLUSION

These results support the clinical relevance of Gongjin-Dan regarding anti-chronic fatigue properties. The underlying mechanisms involve attenuation of oxidative and inflammatory reactions in muscle and regulation of the stress response through the hypothalmo-pituitary-adrenal axis.

摘要

民族药理学相关性

宫津丹是一种具有代表性的传统东方草药,数百年来一直用于治疗慢性疲劳症状。我们在慢性强迫运动小鼠模型中评估了宫津丹的抗疲劳作用及其潜在机制。

方法和材料

Balb/C雄性小鼠接受基于跑步机的极端跑步应激(每周5天,每天1小时),并每天口服蒸馏水、宫津丹(100、200或400mg/kg)或抗坏血酸(100mg/kg),持续28天。通过行为测试(运动耐力和游泳测试)评估宫津丹的抗疲劳作用,并基于骨骼肌、血清和脑组织中的氧化应激、炎性细胞因子和应激激素水平研究相应机制。

结果

与对照组相比,宫津丹显著提高了运动耐力和潜伏期,但减少了跑步机跑步和游泳测试中的电击次数和固定时间。与对照组相比,宫津丹还显著改善了骨骼肌中氧化应激相关生物标志物(活性氧和丙二醛)、炎性细胞因子(肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6和干扰素-γ)以及糖原和L-乳酸水平的变化。此外,宫津丹使强迫跑步应激引起的血清皮质酮和肾上腺素水平以及脑血清素水平的变化显著恢复正常。蛋白质印迹法(4-羟基壬烯醛和血红素加氧酶-1)和基因表达水平(血清素受体和血清素转运体)的结果支持了宫津丹的这些抗氧化和抗应激作用。

结论

这些结果支持了宫津丹在抗慢性疲劳特性方面的临床相关性。其潜在机制包括减轻肌肉中的氧化和炎症反应以及通过下丘脑-垂体-肾上腺轴调节应激反应。

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