{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T20:14:21Z","timestamp":1782504861278,"version":"3.54.5"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T00:00:00Z","timestamp":1588550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Science and Technology, Republic of Korea","award":["NRF-2018R1A2B6003332 and NRF-2018R1D1A3B07049191"],"award-info":[{"award-number":["NRF-2018R1A2B6003332 and NRF-2018R1D1A3B07049191"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The present study aimed to evaluate the anti-fatigue effects of Aralia continentalis kitagawa (AC) extract during exhaustive exercise of rats by forced swimming. Rats were subjected to forced swimming until exhausted after pre-treatment with AC extract for 21 days. Exhaustion time significantly increased in rats treated with AC extract. AC treatment also preserved blood homeostasis during fatigue due to exhaustive exercise. For fatigue-related serum biomarkers, AC extract significantly fail to decrease glucose and triglyceride (TG), but ameliorated increased lactate levels compared with levels in control rats. Metabolic acidosis, a major cause of fatigue, was effectively attenuated by AC extract, according to metabolic acidosis-related blood parameters. AC extract suppressed muscle injury and attenuated gastrocnemius muscle apoptotic responses due to exhaustive exercise. To investigate the mechanisms behind the AC extract anti-fatigue effect, we evaluated its effect on oxidative stress-related fatigue. We showed that pro-oxidants were inhibited, while antioxidants were preserved by AC extract treatment. Therefore, the anti-fatigue effect of AC extract was mediated by suppression of oxidative stress. Overall, the study demonstrated that AC extract effectively attenuates fatigue from exhaustive exercise through oxidative stress inhibition. AC extract, as an antioxidant, could be utilized as a therapeutic or preventive strategy against exhaustive exercise fatigue.<\/jats:p>","DOI":"10.3390\/antiox9050379","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T14:00:43Z","timestamp":1588600843000},"page":"379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Aralia continentalis kitagawa Extract Attenuates the Fatigue Induced by Exhaustive Exercise through Inhibition of Oxidative Stress"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7674-3690","authenticated-orcid":false,"given":"Dong Kwon","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8725-6639","authenticated-orcid":false,"given":"Sei-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Korea Basic Science Institute Jeonju Center, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-8117","authenticated-orcid":false,"given":"Gareeballah Osman","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9041-6565","authenticated-orcid":false,"given":"Shang-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Jeonbuk National University, Iksan 54596, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fncel.2018.00014","article-title":"Exercise-Induced Fatigue Impairs Bidirectional Corticostriatal Synaptic Plasticity","volume":"12","author":"Ma","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.phymed.2017.10.016","article-title":"Anti-inflammatory and anti-arthritic effects of the ethanolic extract of Aralia continentalis Kitag. In IL-1\u03b2-stimulated human fibroblast-like synoviocytes and rodent models of polyarthritis and nociception","volume":"38","author":"Hong","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/wcs.1222","article-title":"Stress and cognition","volume":"4","author":"Sandi","year":"2013","journal-title":"Wiley Interdiscip. Rev. Cogn. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E543","DOI":"10.1152\/ajpendo.00232.2016","article-title":"Liver glycogen metabolism during and after prolonged endurance-type exercise","volume":"311","author":"Gonzalez","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_5","first-page":"101","article-title":"Assessment of anaerobic endurance based on selected biochemical parameters in 400 M\/400 M hurdles male athletes","volume":"14","author":"Kaczmarczyk","year":"2016","journal-title":"Cent. Eur. J. Sport Sci. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2165\/00007256-200636040-00001","article-title":"Lactic acid and exercise performance: Culprit or friend?","volume":"36","author":"Cairns","year":"2006","journal-title":"Sports Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s12011-014-9983-x","article-title":"Relationships between blood Mg 2+ and energy metabolites\/enzymes after acute exhaustive swimming exercise in rats","volume":"161","author":"Rahman","year":"2014","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.foodchem.2010.06.007","article-title":"In vitro antioxidant activity and in vivo anti-fatigue effect of loach (Misgurnus anguillicaudatus) peptides prepared by papain digestion","volume":"124","author":"You","year":"2011","journal-title":"Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1249\/00005768-199302000-00010","article-title":"Exercise-induced oxidative stress","volume":"25","author":"Alessio","year":"1993","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17181","DOI":"10.18632\/oncotarget.24729","article-title":"Oxidative stress: Role of physical exercise and antioxidant nutraceuticals in adulthood and aging","volume":"9","author":"Simioni","year":"2018","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kawamura, T., and Muraoka, I. (2018). Exercise-Induced Oxidative Stress and the Effects of Antioxidant Intake from a Physiological Viewpoint. Antioxidants, 7.","DOI":"10.3390\/antiox7090119"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jep.2004.03.022","article-title":"Effect of medicinal plant extracts on forced swimming capacity in mice","volume":"93","author":"Jung","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.2174\/0929867324666170414164607","article-title":"Anti-fatigue effects of active ingredients from traditional Chinese medicine: A review","volume":"26","author":"Zhou","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.fct.2008.10.011","article-title":"Protective effect of the Aralia continentalis root extract against carbon tetrachloride-induced hepatotoxicity in mice","volume":"47","author":"Hwang","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1248\/cpb.39.405","article-title":"Analgesic principles from Aralia cordata Thunb","volume":"39","author":"Okuyama","year":"1991","journal-title":"Chem. Pharm. Bull."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jep.2010.02.010","article-title":"HY253, a novel decahydrofluorene analog, from Aralia continentalis, induces cell cycle arrest at the G1 phase and cytochrome c-mediated apoptosis in human lung cancer A549 cells","volume":"129","author":"Oh","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s12272-009-1909-3","article-title":"Anti-inflammatory activity of the constituents of the roots of Aralia continentalis","volume":"32","author":"Lim","year":"2009","journal-title":"Arch. Pharmacal. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1248\/bpb.26.1502","article-title":"Ethanol fraction of Aralia elata Seemann enhances antioxidant activity and lowers serum lipids in rats when administered with benzo (\u03b1) pyrene","volume":"26","author":"Chung","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.jep.2012.07.031","article-title":"Src and Syk are targeted to an anti-inflammatory ethanol extract of Aralia continentalis","volume":"143","author":"Yang","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.biopha.2017.02.085","article-title":"Effect of diterpenoid kaurenoic acid on genotoxicity and cell cycle progression in gastric cancer cell lines","volume":"89","author":"Cardoso","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0031-9422(00)00379-4","article-title":"Five saponins from the root bark of Aralia elata","volume":"56","author":"Song","year":"2001","journal-title":"Phytochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1248\/cpb.44.1915","article-title":"Bioactive saponins and glycosides. VI. Elatosides A and B, potent inhibitors of ethanol absorption, from the bark of Aralia elata SEEM. (Araliaceae): The structure-requirement in oleanolic acid glucuronide-saponins for the inhibitory activity","volume":"44","author":"Yoshikawa","year":"1996","journal-title":"Chem. Pharm. Bull."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lee, J.E., Sim, S.J., Jeong, W., Choi, C.W., Kim, N., Park, Y., Kim, M.J., Lee, D., and Hong, S.S. (2020). Diterpenoids and phenolic analogues from the roots of Aralia continentalis. J. Asian Nat. Prod. Res., 1\u20138.","DOI":"10.1080\/10286020.2020.1737859"},{"key":"ref_24","first-page":"20","article-title":"Isolation of Phenolics, Nucleosides, Sacchardies and an Alkaloid from the root of Aralia cordata","volume":"16","author":"Hyun","year":"2010","journal-title":"Netural. Product. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2147\/DDDT.S228751","article-title":"Protective Effects of Chlorogenic Acid on Cerebral Ischemia\/Reperfusion Injury Rats by Regulating Oxidative Stress-Related Nrf2 Pathway","volume":"14","author":"Liu","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.phymed.2010.11.010","article-title":"Inhibitory effects of kaurenoic acid from Aralia continentalis on LPS-induced inflammatory response in RAW264.7 macrophages","volume":"18","author":"Choi","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/ptr.1693","article-title":"Effects ofAralia continentalis on hyperalgesia with peripheral inflammation","volume":"19","author":"Park","year":"2005","journal-title":"Phytother. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/bmb\/ldm014","article-title":"Creatine kinase monitoring in sport medicine","volume":"81\u201382","author":"Brancaccio","year":"2007","journal-title":"Br. Med. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/cs0990001","article-title":"Fatigue in chronic disease","volume":"99","author":"Swain","year":"2000","journal-title":"Clin. Sci. Lond."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Finsterer, J. (2012). Biomarkers of peripheral muscle fatigue during exercise. BMC Musculoskelet. Disord., 13.","DOI":"10.1186\/1471-2474-13-218"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1097\/00002060-200211001-00007","article-title":"Exercise-induced muscle damage in humans","volume":"81","author":"Clarkson","year":"2002","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1248\/bpb.29.1423","article-title":"Effect of Aralia cordata extracts on cartilage protection and apoptosis inhibition","volume":"29","author":"Baek","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1211\/0022357056578","article-title":"Pharmacological comparison of the vasorelaxant action displayed by kaurenoic acid and pimaradienoic acid","volume":"57","author":"Tirapelli","year":"2005","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1055\/s-0030-1250177","article-title":"Inhibitory effect of human breast cancer cell proliferation via p21-mediated G1 cell cycle arrest by araliadiol isolated from Aralia cordata Thunb","volume":"77","author":"Cheng","year":"2011","journal-title":"Planta. Med."},{"key":"ref_35","first-page":"480","article-title":"Antioxidant properties of a series of extracts from medicinal plants","volume":"42","author":"Lozovskaia","year":"1997","journal-title":"Biofizika"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1016\/j.fct.2008.08.035","article-title":"Protective mechanisms of Aralia continentalis extract against tert-butyl hydroperoxide-induced hepatotoxicity: In vivo and in vitro studies","volume":"46","author":"Hwang","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"468","DOI":"10.3892\/br.2017.866","article-title":"Nigella sativa seed extract attenuates the fatigue induced by exhaustive swimming in rats","volume":"6","author":"Rahman","year":"2017","journal-title":"Biomed. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2165\/00007256-200939050-00005","article-title":"Exercise and fatigue","volume":"39","author":"Ament","year":"2009","journal-title":"Sports Med."},{"key":"ref_39","first-page":"361","article-title":"Skeletal muscle energy metabolism and fatigue during intense exercise in man","volume":"75","author":"Hultman","year":"1991","journal-title":"Sci. Prog."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1016\/j.yexcr.2010.05.019","article-title":"Skeletal muscle: Energy metabolism, fiber types, fatigue and adaptability","volume":"316","author":"Westerblad","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lima, F.D., Stamm, D.N., Della-Pace, I.D., Dobrachinski, F., de Carvalho, N.R., Royes, L.F., Soares, F.A., Rocha, J.B., Gonz\u00e1lez-Gallego, J., and Bresciani, G. (2013). Swimming training induces liver mitochondrial adaptations to oxidative stress in rats submitted to repeated exhaustive swimming bouts. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055668"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1046\/j.1365-201X.1996.199000.x","article-title":"Effects of training on potassium, calcium and hydrogen ion regulation in skeletal muscle and blood during exercise","volume":"156","author":"McKenna","year":"1996","journal-title":"Acta Physiol. Scand."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Xun, P., Wang, R., Mao, L., and He, K. (2017). Can Magnesium Enhance Exercise Performance?. Nutrients, 9.","DOI":"10.3390\/nu9090946"},{"key":"ref_44","first-page":"180","article-title":"Update on the relationship between magnesium and exercise","volume":"19","author":"Nielsen","year":"2006","journal-title":"Magnes. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1540\/jsmr1965.20.427","article-title":"Potassium-induced contraction in smooth muscle","volume":"20","author":"Karaki","year":"1984","journal-title":"J. Smooth Muscle Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/j.1469-7793.1997.687bm.x","article-title":"Sprint training enhances ionic regulation during intense exercise in men","volume":"501","author":"McKenna","year":"1997","journal-title":"J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jtemb.2019.01.006","article-title":"Reduction of hemoglobin, not iron, inhibited maturation of red blood cells in male rats exposed to high intensity endurance exercises","volume":"52","author":"Tang","year":"2019","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s40279-014-0282-7","article-title":"The role of oxidative, inflammatory and neuroendocrinological systems during exercise stress in athletes: Implications of antioxidant supplementation on physiological adaptation during intensified physical training","volume":"45","author":"Slattery","year":"2015","journal-title":"Sports Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1152\/physrev.00031.2007","article-title":"Exercise-induced oxidative stress: Cellular mechanisms and impact on muscle force production","volume":"88","author":"Powers","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sun, Y., Cui, D., Zhang, Z., Zhang, T., Shi, J., Jin, H., Ge, Z., and Ji, L. (2016). Attenuated oxidative stress following acute exhaustive swimming exercise was accompanied with modified gene expression profiles of apoptosis in the skeletal muscle of mice. Oxi. Med. Cell. Longev., 1\u20138.","DOI":"10.1155\/2016\/8381242"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"65","DOI":"10.4236\/ojmip.2012.23010","article-title":"The modulation of sirtuins and apoptotic proteins in rats after exhaustive exercise","volume":"2","author":"Marfe","year":"2012","journal-title":"Open J. Mol. Integr. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0278-5919(05)70166-6","article-title":"Antioxidants and exercise","volume":"18","author":"Powers","year":"1999","journal-title":"Clin. Sports Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1006\/abbi.1995.1125","article-title":"Glutathione depletion in rested and exercised mice: Biochemical consequence and adaptation","volume":"316","author":"Leeuwenburgh","year":"1995","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12367","DOI":"10.4238\/2015.October.16.3","article-title":"Effects of high intensity exhaustive exercise on SOD, MDA, and NO levels in rats with knee osteoarthritis","volume":"14","author":"Li","year":"2015","journal-title":"Genet. Mol. Res."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/5\/379\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:09:56Z","timestamp":1760364596000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/9\/5\/379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,4]]},"references-count":54,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["antiox9050379"],"URL":"https:\/\/doi.org\/10.3390\/antiox9050379","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,4]]}}}