Rutin, a flavonoid and principal component of Saussurea involucrata, attenuates physical fatigue in a forced swimming mouse model
Journal
International Journal of Medical Sciences
Journal Volume
11
Journal Issue
5
Pages
528-537
Date Issued
2014
Author(s)
Abstract
This study investigated the antifatigue effects of rutin, a flavonoid extracted from the ethyl acetate extract of S. involucrata. Mice were subjected to a weight-loaded forced swim test (WFST) on alternate days for 3 wk. Rutin was administered orally to the mice for 7 days in dosages of 15, 30, and 60 mg/kg body weight, and several biomarkers of physical fatigue were evaluated: swimming time, change in body weight, lipid peroxidation, lactic acid (LA), glycogen, and the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). On Day 7, the rutin-treated mice had a 3-fold longer exhaustive swimming time than the control mice, as well as significantly reduced blood LA concentrations. The 15, 30, and 60 mg/kg body weight ru- tin-supplemented groups displayed 11.2%, 22.5%, and 37.7% reduced malondialdehyde (MDA) concentrations, respectively, in brain and muscle tissues compared with the control exercised group. Our results indicated that the administration of rutin protected the mice against the de- pletion of SOD and GPx activities significantly. Following 7 days of rutin treatment, we sacrificed the mice and analyzed their soleus muscle and brain for peroxisome proliferator-activated re- ceptor-α coactivator (PGC-1α) and sirtuin 1 (SIRT1) mRNA expression. We observed that rutin treatment increased PGC-1α and SIRT1 mRNA and protein expression. The changes in these markers of mitochondrial biogenesis were associated with increased maximal endurance capacity. The application of 2D gel electrophoresis to analyze the rutin-responsive protein profiles in the WFST mouse brain further revealed the upregulation of the CB1 cannabinoid receptor-interacting protein 1, myelin basic protein, Rho GDP dissociation inhibitor (GDI) alpha, and TPI, indicating that rutin might inhibit anxiety through the upregulation of the expression of anxiety-associated proteins. Western blot analysis of MAPK expression further confirmed the antianxiety effects of rutin. Our study results thus indicate that rutin treatment ameliorates the various impairments associated with physical fatigue. ? Ivyspring International Publisher.
Other Subjects
cannabinoid 1 receptor; cannabinoid 1 receptor interacting protein 1; glutathione peroxidase; glycogen; lactic acid; malonaldehyde; messenger RNA; mitogen activated protein kinase; mitogen activated protein kinase kinase 4; mitogen activated protein kinase kinase 7; mitogen activated protein kinase p38; myelin basic protein; peroxisome proliferator activated receptor gamma coactivator 1alpha; protein; protein TPI; Rho guanine nucleotide dissociation inhibitor 1; rutoside; sirtuin 1; superoxide dismutase; unclassified drug; antioxidant; glutathione peroxidase; rutoside; superoxide dismutase; animal experiment; animal model; animal tissue; anxiety; article; biogenesis; brain tissue; concentration response; controlled study; disease association; drug dose comparison; drug mechanism; endurance; enzyme activity; fatigue; forced swim test; gene expression; lactate blood level; lipid peroxidation; male; mitochondrion; mouse; muscle tissue; nonhuman; nucleotide sequence; protein depletion; protein expression; Saussurea; Saussurea involucrata; soleus muscle; swimming; tranquilizing activity; treatment duration; two dimensional gel electrophoresis; upregulation; weight change; Western blotting; animal; biosynthesis; body weight; chemistry; drug effects; fatigue; human; metabolism; pathology; Animals; Antioxidants; Body Weight; Fatigue; Glutathione Peroxidase; Humans; Lipid Peroxidation; Mice; Physical Conditioning, Animal; Rutin; Saussurea; Superoxide Dismutase; Swimming
Type
journal article