{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:11:24Z","timestamp":1789398684631,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,9,23]],"date-time":"2017-09-23T00:00:00Z","timestamp":1506124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Heat stress conditions lead to neuroinflammation, neuronal death, and memory loss in animals. Coptidis Rhizoma (CR) exhibits potent fever-reducing effects and has been used as an important traditional medicinal herb for treating fever. However, to date, the effects of antipyretic CR on heat-induced brain damages have not been investigated. In this study, CR significantly reduced the elevation of ear and rectal temperatures after exposure to heat in mice. Additionally, CR attenuated hyperthermia-induced stress responses, such as release of cortisol into the blood, and upregulation of heat shock protein and c-Fos in the hypothalamus and hippocampus of mice. The administration of CR inhibited gliosis and neuronal loss induced by thermal stress in the hippocampal CA3 region. Treatment with CR also reduced the heat stress-induced expression of nuclear factor kappa \u03b2, tumor necrosis factor-\u03b1, and interleukin-1\u03b2 (IL-1\u03b2) in the hippocampus. Moreover, CR significantly decreased proinflammatory mediators such as IL-9 and IL-13 in the heat-stressed hypothalamus. Furthermore, CR attenuated cognitive dysfunction triggered by thermal stress. These results indicate that CR protects the brain against heat stress-mediated brain damage via amelioration of hyperthermia and neuroinflammation in mice, suggesting that fever-reducing CR can attenuate thermal stress-induced neuropathology.<\/jats:p>","DOI":"10.3390\/nu9101057","type":"journal-article","created":{"date-parts":[[2017,9,26]],"date-time":"2017-09-26T04:28:01Z","timestamp":1506400081000},"page":"1057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Coptidis Rhizoma Prevents Heat Stress-Induced Brain Damage and Cognitive Impairment in Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Minho","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Huh","sequence":"additional","affiliation":[{"name":"Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"},{"name":"Department of Herbal Pharmacology, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-850X","authenticated-orcid":false,"given":"Wonil","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deok-Sang","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Korean Gynecology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Formulae Pharmacology, School of Oriental Medicine, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam 13120, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"},{"name":"Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1093\/geronj\/39.5.547","article-title":"Body temperature responses of aged mice to ambient temperature and humidity stress","volume":"39","author":"Keir","year":"1984","journal-title":"J. Gerontol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1152\/jappl.1999.86.3.895","article-title":"The physiological strain index applied to heat-stressed rats","volume":"86","author":"Moran","year":"1999","journal-title":"J. Appl. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.2527\/jas.2011-3949","article-title":"Acute heat stress impairs performance parameters and induces mild intestinal enteritis in broiler chickens: Role of acute hypothalamic-pituitary-adrenal axis activation","volume":"90","author":"Rodrigues","year":"2012","journal-title":"J. Anim. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0896-6273(93)90192-T","article-title":"Expression of a mitogen-inducible cyclooxygenase in brain neurons: Regulation by synaptic activity and glucocorticoids","volume":"11","author":"Yamagata","year":"1993","journal-title":"Neuron"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s12974-015-0324-6","article-title":"Heat stress-induced memory impairment is associated with neuroinflammation in mice","volume":"12","author":"Lee","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.medengphy.2006.01.011","article-title":"An approach to estimate EEG power spectrum as an index of heat stress using backpropagation artificial neural network","volume":"29","author":"Sinha","year":"2007","journal-title":"Med. Eng. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/j.1600-0838.2010.01210.x","article-title":"Cognitive function in hot environments: A question of methodology","volume":"20","author":"Gaoua","year":"2010","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1080\/0265673021000054630","article-title":"Effects of heat stress on cognitive performance: The current state of knowledge","volume":"19","author":"Hancock","year":"2003","journal-title":"Int. J. Hyperth."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Rauf, A., Khan, R., Khan, H., Ullah, B., and Pervez, S. (2014). Antipyretic and antinociceptive potential of extract\/fractions of potentilla evestita and its isolated compound, acacetin. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-448"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Muhammad, N., Saeed, M., and Khan, H. (2012). Antipyretic, analgesic and anti-inflammatory activity of viola betonicifolia whole plant. BMC Complement. Altern. Med., 12.","DOI":"10.1186\/1472-6882-12-59"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hong, B.N., Do, M.H., Her, Y.R., Lee, Y.R., and Kang, T.H. (2015). The effects of panax ginseng and panax quinquefolius on thermoregulation in animal models. Evid. Based Complement. Altern. Med., 2015.","DOI":"10.1155\/2015\/748041"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.etap.2014.06.004","article-title":"Effects of ginsenoside RB1 on the stress-induced changes of BDNF and HSP70 expression in rat hippocampus","volume":"38","author":"Kim","year":"2014","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1746-4269-2-43","article-title":"Medicinal plants used by traditional healers in kancheepuram district of tamil nadu, india","volume":"2","author":"Muthu","year":"2006","journal-title":"J. Ethnobiol. Ethnomed."},{"key":"ref_14","unstructured":"Gao, X.M. (2007). Traditional Chinese Pharmacology, Traditional Chinese Medicine Press."},{"key":"ref_15","unstructured":"Jiangsu New Medical College (1986). Zhongyao Dacidian (Encyclopaedia of Chinese Traditional Medicine), The People\u2019s Publishing Company."},{"key":"ref_16","first-page":"1725","article-title":"Antifungal activity of rhizome coptidis and alpinia galangal against candida species","volume":"7","author":"Khodavandi","year":"2013","journal-title":"J. Pure Appl. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Huang, K.C. (1999). The Pharmacology of Chinese Herbs, CCRC Press Inc.","DOI":"10.4324\/9780367801892"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1142\/S0192415X11008671","article-title":"Metabolomic study of a rat fever model induced with 2,4-dinitrophenol and the therapeutic effects of a crude drug derived from coptis chinensis","volume":"39","author":"Liu","year":"2011","journal-title":"Am. J. Chin. Med."},{"key":"ref_19","first-page":"3813","article-title":"Effect of traditional chinese medicines with different properties on thermoregulation and temperature-sensitive transient receptor potentialion channel protein of rats with yeast-induced fever","volume":"39","author":"Wan","year":"2014","journal-title":"Zhongguo Zhongyao Zazhi China J. Chin. Mater. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jiang, J.F., Wang, Y.G., Hu, J., Lei, F., Kheir, M.M., Wang, X.P., Chai, Y.S., Yuan, Z.Y., Lu, X., and Xing, D.M. (2013). Novel effect of berberine on thermoregulation in mice model induced by hot and cold environmental stimulation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054234"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jep.2014.02.007","article-title":"Rheum palmatum L. and coptis chinensis Franch., exert antipyretic effect on yeast-induced pyrexia rats involving regulation of TRPV1 and TRPM8 expression","volume":"153","author":"Kong","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0304-3835(00)00496-1","article-title":"Anticachectic effects of Coptidis Rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6","volume":"158","author":"Iizuka","year":"2000","journal-title":"Cancer Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1007\/s11373-005-9003-4","article-title":"Acetaldehyde-induced interleukin-1beta and tumor necrosis factor-alpha production is inhibited by berberine through nuclear factor-kappab signaling pathway in HEPG2 cells","volume":"12","author":"Hsiang","year":"2005","journal-title":"J. Biomed. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.jep.2013.07.008","article-title":"Inhibitory effect of coptis chinensis on inflammation in lps-induced endotoxemia","volume":"149","author":"Choi","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bbrc.2014.04.121","article-title":"6-shogaol, an active constituent of ginger, attenuates neuroinflammation and cognitive deficits in animal models of dementia","volume":"449","author":"Moon","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.neuro.2013.10.004","article-title":"Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivo","volume":"40","author":"Kim","year":"2014","journal-title":"Neurotoxicology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1248\/bpb.26.701","article-title":"Dynamic responses to acute heat stress between 34 degrees C and 38.5 degrees C, and characteristics of heat stress response in mice","volume":"26","author":"Harikai","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1152\/jappl.1990.68.4.1337","article-title":"Thermal adjustments to nonexertional heat stress in mature and senescent fischer 344 rats","volume":"68","author":"Kregel","year":"1990","journal-title":"J. Appl. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1515\/JBCPP.1996.7.4.375","article-title":"Heat acclimation: Cardiovascular response to hot\/dry and hot\/wet heat loads in rats","volume":"7","author":"Moran","year":"1996","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1007\/s12192-014-0514-7","article-title":"Effects of heat stress on antioxidant defense system, inflammatory injury, and heat shock proteins of muscovy and pekin ducks: Evidence for differential thermal sensitivities","volume":"19","author":"Zeng","year":"2014","journal-title":"Cell. Stress Chaperones"},{"key":"ref_31","first-page":"177","article-title":"Effect of heat stress on physiological parameters and blood composition in polish merino rams","volume":"127","author":"Cwynar","year":"2014","journal-title":"Berl. Munch. Tierarztl. Wochenschr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3892\/br.2015.445","article-title":"Effect of acute heat stress on adrenocorticotropic hormone, cortisol, interleukin-2, interleukin-12 and apoptosis gene expression in rats","volume":"3","author":"Wang","year":"2015","journal-title":"Biomed. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11250-014-0692-4","article-title":"Hsp70 as a marker of heat and humidity stress in tarai buffalo","volume":"47","author":"Manjari","year":"2015","journal-title":"Trop. Anim. Health Prod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/nn.3159","article-title":"Neural circuitry engaged by prostaglandins during the sickness syndrome","volume":"15","author":"Saper","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6246","DOI":"10.1523\/JNEUROSCI.16-19-06246.1996","article-title":"Ventromedial preoptic prostaglandin E2 activates fever-producing autonomic pathways","volume":"16","author":"Scammell","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00281-012-0342-8","article-title":"Multifaceted roles of PGE2 in inflammation and cancer","volume":"35","author":"Nakanishi","year":"2013","journal-title":"Semin. Immunopathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"a001651","DOI":"10.1101\/cshperspect.a001651","article-title":"The nuclear factor nf-kappab pathway in inflammation","volume":"1","author":"Lawrence","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.jphysparis.2014.05.002","article-title":"Synaptic nf-kappa B pathway in neuronal plasticity and memory","volume":"108","author":"Salles","year":"2014","journal-title":"J. Physiol. Paris"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1007\/s11064-012-0708-2","article-title":"Neuroinflammation and synaptic loss","volume":"37","author":"Rao","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1113\/expphysiol.2005.030734","article-title":"Actions of tnf-alpha on glutamatergic synaptic transmission in the central nervous system","volume":"90","author":"Pickering","year":"2005","journal-title":"Exp. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/0031-9384(90)90025-Y","article-title":"Thermal biology of the laboratory rat","volume":"47","author":"Gordon","year":"1990","journal-title":"Physiol. Behav."},{"key":"ref_42","unstructured":"Carter, C.S., and DeVries, A.C. (1999). Stress and soothing: An endocrine perspective. Soothing and Stress, Psychology Press."},{"key":"ref_43","unstructured":"Akil, H., Campeau, S., Cullinan, W.E., Lechan, R.M., Toni, R., Watson, S.J., and Moore, R.Y. (1999). Neuroendocrine systems I: Overview-thyroid and adrenal axes. Fundamental Neuroscience, Elsevier."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.jaci.2013.09.007","article-title":"The biology of the glucocorticoid receptor: New signaling mechanisms in health and disease","volume":"132","author":"Oakley","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.beem.2013.10.008","article-title":"Determination of cortisol in serum, saliva and urine","volume":"27","author":"Turpeinen","year":"2013","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nrendo.2009.106","article-title":"Stress and disorders of the stress system","volume":"5","author":"Chrousos","year":"2009","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/qjmed\/93.6.323","article-title":"The stress response and the hypothalamic-pituitary-adrenal axis: From molecule to melancholia","volume":"93","author":"Shanahan","year":"2000","journal-title":"QJM"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.tem.2012.11.005","article-title":"The five RS of glucocorticoid action during inflammation: Ready, reinforce, repress, resolve, and restore","volume":"24","author":"Busillo","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.cell.2010.02.016","article-title":"Mechanisms underlying inflammation in neurodegeneration","volume":"140","author":"Glass","year":"2010","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1139\/Y09-028","article-title":"Chunghyuldan attenuates brain microglial inflammatory response","volume":"87","author":"Nam","year":"2009","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"296","DOI":"10.2183\/pjab.83.296","article-title":"Physiology and pathophysiology of prostanoid receptors","volume":"83","author":"Narumiya","year":"2007","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1177\/1535370213493705","article-title":"Heme oxygenase-1 aggravates heat stress-induced neuronal injury and decreases autophagy in cerebellar purkinje cells of rats","volume":"238","author":"Li","year":"2013","journal-title":"Exp. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1379\/1466-1268(2003)008<0395:SAOCDA>2.0.CO;2","article-title":"Spatial analysis of cell death and hsp70 induction in brain, thymus, and bone marrow of the hyperthermic rat","volume":"8","author":"Belay","year":"2003","journal-title":"Cell Stress Chaperones"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bbi.2010.10.015","article-title":"Immune modulation of learning, memory, neural plasticity and neurogenesis","volume":"25","author":"Yirmiya","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"138","DOI":"10.4088\/JCP.08m04666yel","article-title":"A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia","volume":"71","author":"Levkovitz","year":"2010","journal-title":"J. Clin. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s00702-010-0438-z","article-title":"Neuroinflammatory processes in alzheimer\u2019s disease","volume":"117","author":"Heneka","year":"2010","journal-title":"J. Neural Transm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/glia.20051","article-title":"Minocycline inhibits neuronal death and glial activation induced by beta-amyloid peptide in rat hippocampus","volume":"48","author":"Ryu","year":"2004","journal-title":"Glia"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jep.2006.04.023","article-title":"Evaluation of the anti-proliferative properties of selected psoriasis-treating chinese medicines on cultured hacat cells","volume":"108","author":"Tse","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"194896","DOI":"10.1155\/2010\/194896","article-title":"Rhizoma coptidis inhibits LPS-induced mcp-1\/CCL2 production in murine macrophages via an AP-1 and nfkappab-dependent pathway","volume":"2010","author":"Remppis","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.fct.2010.09.032","article-title":"Preventive effect of coptis chinensis and berberine on intestinal injury in rats challenged with lipopolysaccharides","volume":"49","author":"Zhang","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1248\/bpb.32.1433","article-title":"Anti-alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids","volume":"32","author":"Jung","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jep.2008.02.024","article-title":"Effects of San-Huang-Xie-Xin-Tang on U46619-induced increase in pulmonary arterial blood pressure","volume":"117","author":"Tsai","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_63","first-page":"142","article-title":"Computational pharmaceutical analysis of anti-alzheimer\u2019s chinese medicine Coptidis Rhizoma alkaloids","volume":"5","author":"Hong","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1080\/00140130210158419","article-title":"Effects of hot and cold temperature exposure on performance: A meta-analytic review","volume":"45","author":"Pilcher","year":"2002","journal-title":"Ergonomics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1007\/s12272-009-2006-3","article-title":"Kaempferol glycosides with antioxidant activity from brassica juncea","volume":"32","author":"Jung","year":"2009","journal-title":"Arch. Pharm. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1055\/s-0034-1383038","article-title":"Mechanisms of action of phytochemicals from medicinal herbs in the treatment of alzheimer\u2019s disease","volume":"80","author":"Kim","year":"2014","journal-title":"Planta Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"97","DOI":"10.5717\/jenb.2014.18.1.97","article-title":"Chronic exercise improves repeated restraint stress-induced anxiety and depression through 5HT1A receptor and camp signaling in hippocampus","volume":"18","author":"Kim","year":"2014","journal-title":"J. Exerc. Nutr. Biochem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jep.2014.06.004","article-title":"Coptis chinensis franch. Exhibits neuroprotective properties against oxidative stress in human neuroblastoma cells","volume":"155","author":"Friedemann","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_69","first-page":"43","article-title":"Treatment of dementia with herbs: A short review","volume":"164","author":"Tang","year":"2013","journal-title":"Clin. Ter."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/10\/1057\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:45:44Z","timestamp":1760208344000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/10\/1057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,23]]},"references-count":69,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10]]}},"alternative-id":["nu9101057"],"URL":"https:\/\/doi.org\/10.3390\/nu9101057","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,23]]}}}