The Effects of Chunghyul-Dan, an Agent of Korean Medicine, on a Mouse Model of Traumatic Brain Injury
This article is part of Special Issue:
Won-Woo Choi,
Kyungjin Lee,
Beom-Joon Lee,
Seong-Uk Park,
Jung-Mi Park,
Chang-Nam Ko,
Youngmin Bu,
Won-Woo Choi
Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorKyungjin Lee
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorBeom-Joon Lee
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorSeong-Uk Park
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorJung-Mi Park
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorChang-Nam Ko
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorCorresponding Author
Youngmin Bu
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorWon-Woo Choi,
Kyungjin Lee,
Beom-Joon Lee,
Seong-Uk Park,
Jung-Mi Park,
Chang-Nam Ko,
Youngmin Bu,
Won-Woo Choi
Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorKyungjin Lee
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorBeom-Joon Lee
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorSeong-Uk Park
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorJung-Mi Park
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorChang-Nam Ko
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorCorresponding Author
Youngmin Bu
College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea khu.ac.kr
Search for more papers by this authorAcademic Editor: Krishnadas Nandakumar
Abstract
Chunghyul-Dan (CHD) is the first choice agent for the prevention and treatment of stroke at the Kyung Hee Medical Hospital. To date, CHD has been reported to have beneficial effects on brain disease in animals and humans, along with antioxidative and anti-inflammatory effects. The aim of this study was to evaluate the pharmacological effects of CHD on a traumatic brain injury (TBI) mouse model to explore the possibility of CHD use in patients with TBI. The TBI mouse model was induced using the controlled cortical impact method. CHD was orally administered twice a day for 5 d after TBI induction; mice were assessed for brain damage, brain edema, blood-brain barrier (BBB) damage, motor deficits, and cognitive impairment. Treatment with CHD reduced brain damage seen on histological examination and improved motor and cognitive functions. However, CHD did not reduce brain edema and BBB damage. In conclusion, CHD could be a candidate agent in the treatment of patients with TBI. Further studies are needed to assess the exact mechanisms of the effects during the acute-subacute phase and pharmacological activity during the chronic-convalescent phase of TBI.
References
- 1 Schmidt O. I., Heyde C. E., Ertel W., and Stahel P. F., Closed head injury—an inflammatory disease?, Brain Research Reviews. (2005) 48, no. 2, 388–399, https://doi.org/10.1016/j.brainresrev.2004.12.028, 2-s2.0-17844383934.
- 2 Rosenfeld J. V., Maas A. I., Bragge P., Morganti-Kossmann M. C., Manley G. T., and Gruen R. L., Early management of severe traumatic brain injury, The Lancet. (2012) 380, no. 9847, 1088–1098, 2-s2.0-84866522685, https://doi.org/10.1016/S0140-6736(12)60864-2.
- 3 Loane D. J. and Faden A. I., Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies, Trends in Pharmacological Sciences. (2010) 31, no. 12, 596–604, https://doi.org/10.1016/j.tips.2010.09.005, 2-s2.0-78449310195.
- 4 Marklund N. and Hillered L., Animal modelling of traumatic brain injury in preclinical drug development: Where do we go from here?, British Journal of Pharmacology. (2011) 164, no. 4, 1207–1229, 2-s2.0-80053317403, https://doi.org/10.1111/j.1476-5381.2010.01163.x.
- 5 Wang W., Li H., Yu J., Hong M., Zhou J., Zhu L., Wang Y., Luo M., Xia Z., Yang Z.-J., Tang T., Ren P., Huang X., and Wang J., Protective Effects of Chinese Herbal Medicine Rhizoma drynariae in Rats After Traumatic Brain Injury and Identification of Active Compound, Molecular Neurobiology. (2016) 53, no. 7, 4809–4820, 2-s2.0-84940706026, https://doi.org/10.1007/s12035-015-9385-x.
- 6 Quintard H., Lorivel T., Gandin C., Lazdunski M., and Heurteaux C., MLC901, a Traditional Chinese Medicine induces neuroprotective and neuroregenerative benefits after traumatic brain injury in rats, Neuroscience. (2014) 277, 72–86, 2-s2.0-84904717534, https://doi.org/10.1016/j.neuroscience.2014.06.047.
- 7 Zhu K. J. and Sun J. N., Study on effect and mechanism of cinnabaris and realgar in promoting awake of endotoxin-induced brain injury rat applied with angong niuhuang wan, China Journal of Chinese Materia Medica. (2014) 39, no. 20, 4007–4012, 2-s2.0-84929035755.
- 8 Yang S.-T., Lin J.-W., Chiu B.-Y., Hsu Y.-C., Chang C.-P., and Chang C.-K., Astragaloside improves outcomes of traumatic brain injury in rats by reducing microglia activation, American Journal of Chinese Medicine. (2014) 42, no. 6, 1357–1370, 2-s2.0-84929298712, https://doi.org/10.1142/S0192415X14500852.
- 9 Tsai M.-C., Chang C.-P., Peng S.-W., Jhuang K.-S., Fang Y.-H., Lin M.-T., and Tsao T. C.-Y., Therapeutic efficacy of Neuro AiD (MLC 601), a traditional Chinese medicine, in experimental traumatic brain injury, Journal of NeuroImmune Pharmacology. (2015) 10, no. 1, 45–54, https://doi.org/10.1007/s11481-014-9570-0.
- 10 Cho K., Ji N., Jung W., Park S., Moon S., and et al, Chunghyul-dan for the prevention of stroke progression in silent brain infarction, Journal of Korean Oriental Medicine. (2005) 26, no. 2, 77–84.
- 11 Cho K., Noh K., Jung W., Park S., Moon S., Park J., Ko C., Kim Y., and Bae H., A preliminary study on the inhibitory effect of Chunghyul-dan on stroke recurrence in patients with small vessel disease, Neurological Research. (2008) 30, no. 6, 655–658, 2-s2.0-47749152950, https://doi.org/10.1179/174313208X305382.
- 12 Kim Y.-S., Jung E.-A., Shin J. E., Chang J. C., Yang H. K. et al., Daio-Orengedokuto inhibits HMG-CoA reductase and pancreatic lipase, Biological and Pharmaceutical Bulletin. (2002) 25, no. 11, 1442–1445, https://doi.org/10.1248/bpb.25.1442, 2-s2.0-10844284757.
- 13 Cho K. H., Kang H. S., Jung W. S., Park S. U., and Moon S. K., Efficacy and safety of Chunghyul-dan (Qingwie-dan) in patients with hypercholesterolemia, The American Journal of Chinese Medicine. (2005) 33, no. 2, 241–248, https://doi.org/10.1142/s0192415x05002898, 2-s2.0-18744412136.
- 14 Park S., Jung W., Moon S., Ko C., Cho K., Kim Y., Bae H., and Chi S., Chunghyuldan activates NOS mRNA expression and suppresses VCAM-1 mRNA expression in human endothelial cells, Canadian Journal of Physiology and Pharmacology. (2005) 83, no. 12, 1101–1108, 2-s2.0-33646011257, https://doi.org/10.1139/y05-106.
- 15 Cho K. H., Kim Y. S., Bae H. S., Moon S. K., Jung W. S. et al., Inhibitory effect of Chunghyuldan in prostaglandin E2 and nitric oxide biosynthesis of lipopolysaccharide-induced RAW 264.7 cells, Biological and Pharmaceutical Bulletin. (2004) 27, no. 11, 1810–1813, https://doi.org/10.1248/bpb.27.1810, 2-s2.0-21144439044.
- 16 Wee S. S., Shin Y. W., Bae E. A., and Kim D. H., Effect of chunghyuldan in chronic oxazolone-induced mouse dermatitis, Biological and Pharmaceutical Bulletin. (2005) 28, no. 6, 1079–1082, https://doi.org/10.1248/bpb.28.1079, 2-s2.0-21144432105.
- 17 Kim H. G., Kim J.-Y., Whang W.-W., and Oh M. S., Neuroprotective effect of chunghyuldan from amyloid beta oligomer induced neuroinflammation in vitro and in vivo, Canadian Journal of Physiology and Pharmacology. (2014) 92, no. 6, 429–437, 2-s2.0-84907997390, https://doi.org/10.1139/cjpp-2013-0229.
- 18 Ko C.-N., Park I.-S., Park S.-U., Jung W.-S., Moon S.-K., Park J.-M., Kang C., and Cho K.-H., Neuroprotective effect of Chunghyuldan (Qing Xue Dan) on hypoxia-reoxygenation induced damage of neuroblastoma 2a cell lines, Chinese Journal of Integrative Medicine. (2013) 19, no. 12, 940–944, https://doi.org/10.1007/s11655-013-1657-6, 2-s2.0-84890939905.
- 19 Yun S. P., Jung W. S., Park S. U., Moon S. K., Ko C. N., Cho K. H., Kim Y. S., and Bae H. S., Anti-hypertensive effect of Chunghyul-dan (Qingxue-dan) on stroke patients with essential hypertension, American Journal of Chinese Medicine. (2005) 33, no. 3, 357–364, https://doi.org/10.1142/s0192415x05002977, 2-s2.0-21344474380.
- 20 Park S. U., Jung W. S., Moon S. K., Ko C. N., Cho K. H., Kim Y. S., and Bae H. S., Chunghyul-Dan (Qingxie-dan) improves arterial stiffness in patients with increased baPWV, The American Journal of Chinese Medicine. (2006) 34, no. 4, 553–563, https://doi.org/10.1142/s0192415x06004090, 2-s2.0-33749486871.
- 21 Onyszchuk G., Al-Hafez B., He Y.-Y., Bilgen M., Berman N. E. J., and Brooks W. M., A mouse model of sensorimotor controlled cortical impact: Characterization using longitudinal magnetic resonance imaging, behavioral assessments and histology, Journal of Neuroscience Methods. (2007) 160, no. 2, 187–196, 2-s2.0-33846907115, https://doi.org/10.1016/j.jneumeth.2006.09.007.
- 22 Homsi S., Federico F., Croci N., Palmier B., Plotkine M., Marchand-Leroux C., and Jafarian-Tehrani M., Minocycline effects on cerebral edema: Relations with inflammatory and oxidative stress markers following traumatic brain injury in mice, Brain Research. (2009) 1291, 122–132, 2-s2.0-69249208444, https://doi.org/10.1016/j.brainres.2009.07.031.
- 23 Goldstein L. B. and Davis J. N., Beam-walking in rats: studies towards developing an animal model of functional recovery after brain injury, Journal of Neuroscience Methods. (1990) 31, no. 2, 101–107, 2-s2.0-0025044655, https://doi.org/10.1016/0165-0270(90)90154-8.
- 24 Messier C., Object recognition in mice: Improvement of memory by glucose, Neurobiology of Learning and Memory. (1997) 67, no. 2, 172–175, 2-s2.0-0031103406, https://doi.org/10.1006/nlme.1996.3755.
- 25 Matthew C. B., Sils I. V., and Bastille A. M., Tissue-specific extravasation of albumin-bound Evans blue in hypothermic and rewarmed rats, Canadian Journal of Physiology and Pharmacology. (2002) 80, no. 3, 233–243, 2-s2.0-0036205023, https://doi.org/10.1139/y02-044.
- 26 Xiong Y., Mahmood A., and Chopp M., Animal models of traumatic brain injury, Nature Reviews Neuroscience. (2013) 14, no. 2, 128–142, 2-s2.0-84872528255, https://doi.org/10.1038/nrn3407.
- 27 Kim H. G., Ju M. S., Kim D. H., Hong J., Cho S. H. et al., Protective effects of Chunghyuldan against ROS-mediated neuronal cell death in models of Parkinson′s disease, Basic and Clinical Pharmacology and Toxicology. (2010) 107, no. 6, 958–964.
- 28 Kim G., Kim J., Chung S., Cho S., Oh M. et al., The protective effect of Chunghyul-dan(Qingxuedan) against 6-hydroxydopamine Induced neurotoxicity, Journal of Oriental Neuropsychiatry. (2009) 20, no. 1, 21–42.
- 29 Oshima N., Narukawa Y., Hada N., and Kiuchi F., Quantitative analysis of anti-inflammatory activity of orengedokuto: importance of combination of flavonoids in inhibition of PGE2 production in mouse macrophage-like cell line J774.1, Journal of Natural Medicines. (2013) 67, no. 2, 281–288, https://doi.org/10.1007/s11418-012-0679-2, 2-s2.0-84882855093.
- 30 Kong X. Y., Kong W., Miao G. X., Zhao S. M., Chen M., Zheng X. Y., and Bai J. T., Pretreatment with scutellaria baicalensis stem-leaf total flavonoid protects against cerebral ischemia/ reperfusion injury in hippocampal neurons, Neural Regeneration Research. (2014) 9, no. 23, 2066–2073, 2-s2.0-84921793588, https://doi.org/10.4103/1673-5374.147933.
- 31 Shang Y., Miao G., Zhao H., Guo K., Cheng J., Zhang S., Zhang X., Cai Z., and Miao H., Mechanisms underlying attenuation of apoptosis of cortical neurons in the hypoxic brain by flavonoids from the stems and leaves of Scutellaria baicalensis Georgi, Neural Regeneration Research. (2014) 9, no. 17, 1592–1598, https://doi.org/10.4103/1673-5374.141784.
- 32 Zhang Q., Qian Z., Pan L., Li H., and Zhu H., Hypoxia-inducible factor 1 mediates the anti-apoptosis of berberine in neurons during hypoxia/ischemia, Acta Physiologica Hungarica. (2012) 99, no. 3, 311–323, 2-s2.0-84866528539, https://doi.org/10.1556/APhysiol.99.2012.3.8.
- 33 Hughes R. H., Silva V. A., Ahmed I., Shreiber D. I., and MorrisonB.III, Neuroprotection by genipin against reactive oxygen and reactive nitrogen species-mediated injury in organotypic hippocampal slice cultures, Brain Research. (2014) 1543, 308–314, https://doi.org/10.1016/j.brainres.2013.11.020, 2-s2.0-84891739835.
- 34 Park Y.-K., Chung Y. S., Kim Y. S., Kwon O.-Y., and Joh T. H., Inhibition of gene expression and production of iNOS and TNF-α in LPS-stimulated microglia by methanol extract of Phellodendri cortex, International Immunopharmacology. (2007) 7, no. 7, 955–962, 2-s2.0-34247889983, https://doi.org/10.1016/j.intimp.2006.03.018.
- 35 Li F., Li W., Li X., Li F., Zhang L., Wang B., Huang G., Guo X., Wan L., Liu Y., Zhang S., Kang S., and Ma J., Geniposide attenuates inflammatory response by suppressing P2Y14 receptor and downstream ERK1/2 signaling pathway in oxygen and glucose deprivation-induced brain microvascular endothelial cells, Journal of Ethnopharmacology. (2016) 185, 77–86, 2-s2.0-84962313110, https://doi.org/10.1016/j.jep.2016.03.025.
- 36 Chen Y., Zhang Y., Li L., and Hölscher C., Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson′s disease, European Journal of Pharmacology. (2015) 768, 21–27, 2-s2.0-84947574098, https://doi.org/10.1016/j.ejphar.2015.09.029.
- 37 Lu K., Zhang C., Wu W., Zhou M., Tang Y. et al., Rhubarb extract has a protective role against radiation-induced brain injury and neuronal cell apoptosis, Molecular Medicine Reports. (2015) 12, no. 2, 2689–2694, https://doi.org/10.3892/mmr.2015.3693.
- 38 Hamm R. J., White-Gbadebo D. M., Lyeth B. G., Jenkins L. W., and Hayes R. L., The effect of age on motor and cognitive deficits after traumatic brain injury in rats, Neurosurgery. (1992) 31, no. 6, 1072–1078, 2-s2.0-0026476043, https://doi.org/10.1227/00006123-199212000-00013.
- 39 Lyeth B. G., Ji Yao Jiang, and Liu S., Behavioral protection by moderate hypothermia initiated after experimental traumatic brain injury, Journal of Neurotrauma. (1993) 10, no. 1, 57–64, 2-s2.0-0027319790, https://doi.org/10.1089/neu.1993.10.57.
- 40 Wood N. I., Sopesen B. V., Roberts J. C., Pambakian P., Rothaul A. L., Hunter A. J., and Hamilton T. C., Motor dysfunction in a photothrombotic focal ischaemia model, Behavioural Brain Research. (1996) 78, no. 2, 113–120, 2-s2.0-0030221645, https://doi.org/10.1016/0166-4328(95)00237-5.
- 41 Singleton R. H., Yan H. Q., Fellows-Mayle W., and Dixon C. E., Resveratrol attenuates behavioral impairments and reduces cortical and hippocampal loss in a rat controlled cortical impact model of traumatic brain injury, Journal of Neurotrauma. (2010) 27, no. 6, 1091–1099, 2-s2.0-77953956124, https://doi.org/10.1089/neu.2010.1291.
- 42 Tsenter J., Beni-Adani L., Assaf Y., Alexandrovich A. G., Trembovler V., and Shohami E., Dynamic changes in the recovery after traumatic brain injury in mice: Effect of injury severity on T2-weighted MRI abnormalities, and motor and cognitive functions, Journal of Neurotrauma. (2008) 25, no. 4, 324–333, 2-s2.0-41449108080, https://doi.org/10.1089/neu.2007.0452.
- 43 Shin S. S. and Dixon C. E., Alterations in cholinergic pathways and therapeutic strategies targeting cholinergic system after traumatic brain injury, Journal of Neurotrauma. (2015) 32, no. 19, 1429–1440, 2-s2.0-84942430914, https://doi.org/10.1089/neu.2014.3445.
- 44 Ennaceur A. and Delacour J., A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data, Behavioural Brain Research. (1988) 31, no. 1, 47–59, https://doi.org/10.1016/0166-4328(88)90157-x, 2-s2.0-0023691166.
- 45 Antunes M. and Biala G., The novel object recognition memory: neurobiology, test procedure, and its modifications, Cognitive Processing. (2012) 13, no. 2, 93–110, https://doi.org/10.1007/s10339-011-0430-z, 2-s2.0-84860889573.
- 46 Baratz R., Tweedie D., Wang J.-Y., Rubovitch V., Luo W., Hoffer B. J., Greig N. H., and Pick C. G., Transiently lowering tumor necrosis factor-alpha synthesis ameliorates neuronal cell loss and cognitive impairments induced by minimal traumatic brain injury in mice, Journal of Neuroinflammation. (2015) 12, article 45, https://doi.org/10.1186/s12974-015-0237-4.
- 47 Bye N., Habgood M. D., Callaway J. K., Malakooti N., Potter A., Kossmann T., and Morganti-Kossmann M. C., Transient neuroprotection by minocycline following traumatic brain injury is associated with attenuated microglial activation but no changes in cell apoptosis or neutrophil infiltration, Experimental Neurology. (2007) 204, no. 1, 220–233, 2-s2.0-33847261481, https://doi.org/10.1016/j.expneurol.2006.10.013.
- 48 Choi J. G., Moon M., Kim H. G., Mook-Jung I., Chung S. Y., Kang T. H., Kim S. Y., Lee E. H., and Oh M. S., Gami-Chunghyuldan ameliorates memory impairment and neurodegeneration induced by intrahippocampal Aβ1-42 oligomer injection, Neurobiology of Learning and Memory. (2011) 96, no. 2, 306–314, 2-s2.0-79960841704, https://doi.org/10.1016/j.nlm.2011.06.004.
- 49 Shang Y. Z., Zhang H., Cheng J. J., Miao H., Liu Y. P. et al., Flavonoids from scutellaria baicalensis georgi are effective to treat cerebral ischemia/reperfusion, Neural Regeneration Research. (2013) 8, no. 6, 514–522, https://doi.org/10.3969/j.issn.1673-5374.2013.06.004, 2-s2.0-84890844755.
- 50 Zhu F. and Qian C., Berberine chloride can ameliorate the spatial memory impairment and increase the expression of interleukin-1beta and inducible nitric oxide synthase in the rat model of Alzheimer′s disease, BMC Neuroscience. (2006) 7, no. 1, https://doi.org/10.1186/1471-2202-7-78, 2-s2.0-33845602246.
- 51 Lee B., Sur B., Shim I., Lee H., and Hahm D. H., Phellodendron amurense and its major alkaloid compound, berberine ameliorates scopolamine-induced neuronal impairment and memory dysfunction in rats, The Korean Journal of Physiology and Pharmacology. (2012) 16, no. 2, 79–89, https://doi.org/10.4196/kjpp.2012.16.2.79, 2-s2.0-84861035259.
- 52 Nam Y. and Lee D., Ameliorating effect of Zhizi (Fructus Gardeniae) extract and its glycosides on scopolamine-induced memory impairment, Journal of Traditional Chinese Medicine. (2013) 33, no. 2, 223–227, 2-s2.0-84879187067, https://doi.org/10.1016/S0254-6272(13)60129-6.
- 53 Arvin K. L., Han B. H., Du Y., Lin S.-Z., Paul S. M., and Holtzman D. M., Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury, Annals of Neurology. (2002) 52, no. 1, 54–61, 2-s2.0-0036289498, https://doi.org/10.1002/ana.10242.
- 54 Du Y., Ma Z., Lin S., Dodel R. C., Gao F., Bales K. R., Triarhou L. C., Chernet E., Perry K. W., Nelson D. L. G., Luecke S., Phebus L. A., Bymaster F. P., and Paul S. M., Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson′s disease, Proceedings of the National Academy of Sciences of the United States of America. (2001) 98, no. 25, 14669–14674, https://doi.org/10.1073/pnas.251341998, 2-s2.0-0035807904.
- 55 Reagan-Shaw S., Nihal M., and Ahmad N., Dose translation from animal to human studies revisited, The FASEB Journal. (2008) 22, no. 3, 659–661, https://doi.org/10.1096/fj.07-9574LSF, 2-s2.0-40449086665.
