Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways
Abstract
Ruo-ming WU1, Yan-yan SUN1, Ting-ting ZHOU2, Zhi-yuan ZHU2, Jing-jing ZHUANG1, Xuan TANG2, Jing CHEN2, *, Li-hong HU2, *, Xu SHEN1, 2, *
1School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; 2Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Aim: Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan found in traditional Chinese herbs, has been determined to exhibit a variety of pharmacological activities, including anti-tumor, anti-inflammation, neuroprotection, and endurance enhancement. In the present study, we investigated the antioxidation and anti-fatigue effects of arctigenin in rats.
Methods: Rat L6 skeletal muscle cell line was exposed to H2O2 (700 μmol/L), and ROS level was assayed using DCFH-DA as a probe. Male SD rats were injected with arctigenin (15 mg·kg-1·d-1, ip) for 6 weeks, and then the weight-loaded forced swimming test (WFST) was performed to evaluate their endurance. The levels of antioxidant-related genes in L6 cells and the skeletal muscles of rats were analyzed using real-time RT-PCR and Western blotting.
Results: Incubation of L6 cells with arctigenin (1, 5, and 20 μmol/L) dose-dependently decreased the H2O2-induced ROS production. WFST results demonstrated that chronic administration of arctigenin significantly enhanced the endurance of rats. Furthermore, molecular biology studies on L6 cells and skeletal muscles of the rats showed that arctigenin effectively increased the expression of the antioxidant-related genes, including superoxide dismutase (SOD), glutathione reductase (Gsr), glutathione peroxidase (GPX1), thioredoxin (Txn) and uncoupling protein 2 (UCP2), through regulation of two potential antioxidant pathways: AMPK/PGC-1α/PPARα in mitochondria and AMPK/p53/Nrf2 in the cell nucleus.
Conclusion: Arctigenin efficiently enhances rat swimming endurance by elevation of the antioxidant capacity of the skeletal muscles, which has thereby highlighted the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases.
Keywords: arctigenin; skeletal muscle; weight-loaded forced swimming test; fatigue; physical endurance; ROS; antioxidant; AMPK; PPARα; Nrf2
This work was supported by the National Natural Science Foundation of China (No 81220108025 and 81373461) and the Science and Technology Commission of Shanghai Municipality (12431900300).
* To whom correspondence should be addressed.
E-mail xshen@mail.shcnc.ac.cn (Xu SHE); jingNchen@mail.shcnc.ac.cn (Jing CHEN); lhhu@simm.ac.cn (Li-hong HU)
Received 2014-02-11 Accepted 2014-06-09
Keywords:
1School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; 2Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Aim: Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan found in traditional Chinese herbs, has been determined to exhibit a variety of pharmacological activities, including anti-tumor, anti-inflammation, neuroprotection, and endurance enhancement. In the present study, we investigated the antioxidation and anti-fatigue effects of arctigenin in rats.
Methods: Rat L6 skeletal muscle cell line was exposed to H2O2 (700 μmol/L), and ROS level was assayed using DCFH-DA as a probe. Male SD rats were injected with arctigenin (15 mg·kg-1·d-1, ip) for 6 weeks, and then the weight-loaded forced swimming test (WFST) was performed to evaluate their endurance. The levels of antioxidant-related genes in L6 cells and the skeletal muscles of rats were analyzed using real-time RT-PCR and Western blotting.
Results: Incubation of L6 cells with arctigenin (1, 5, and 20 μmol/L) dose-dependently decreased the H2O2-induced ROS production. WFST results demonstrated that chronic administration of arctigenin significantly enhanced the endurance of rats. Furthermore, molecular biology studies on L6 cells and skeletal muscles of the rats showed that arctigenin effectively increased the expression of the antioxidant-related genes, including superoxide dismutase (SOD), glutathione reductase (Gsr), glutathione peroxidase (GPX1), thioredoxin (Txn) and uncoupling protein 2 (UCP2), through regulation of two potential antioxidant pathways: AMPK/PGC-1α/PPARα in mitochondria and AMPK/p53/Nrf2 in the cell nucleus.
Conclusion: Arctigenin efficiently enhances rat swimming endurance by elevation of the antioxidant capacity of the skeletal muscles, which has thereby highlighted the potential of this natural product as an antioxidant in the treatment of fatigue and related diseases.
Keywords: arctigenin; skeletal muscle; weight-loaded forced swimming test; fatigue; physical endurance; ROS; antioxidant; AMPK; PPARα; Nrf2
This work was supported by the National Natural Science Foundation of China (No 81220108025 and 81373461) and the Science and Technology Commission of Shanghai Municipality (12431900300).
* To whom correspondence should be addressed.
E-mail xshen@mail.shcnc.ac.cn (Xu SHE); jingNchen@mail.shcnc.ac.cn (Jing CHEN); lhhu@simm.ac.cn (Li-hong HU)
Received 2014-02-11 Accepted 2014-06-09