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Published in: Chinese Medicine 1/2010

Open Access 01-12-2010 | Research

Preventive effects of Flos Perariae (Gehua) water extract and its active ingredient puerarin in rodent alcoholism models

Authors: Zaijun Zhang, Sha Li, Jie Jiang, Pei Yu, Jing Liang, Yuqiang Wang

Published in: Chinese Medicine | Issue 1/2010

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Abstract

Background

Radix Puerariae is used in Chinese medicine to treat alcohol addiction and intoxication. The present study investigates the effects of Flos puerariae lobatae water extract (FPE) and its active ingredient puerarin on alcoholism using rodent models.

Methods

Alcoholic animals were given FPE or puerarin by oral intubation prior or after alcohol treatment. The loss of righting reflex (LORR) assay was used to evaluate sedative/hypnotic effects. Changes of gama-aminobutyric acid type A receptor (GABAAR) subunits induced by alcohol treatment in hippocampus were measured with western blot. In alcoholic mice, body weight gain was monitored throughout the experiments. Alcohol dehydrogenase (ADH) levels in liver were measured.

Results

FPE and puerarin pretreatment significantly prolonged the time of LORR induced by diazepam in acute alcoholic rat. Puerarin increased expression of gama-aminobutyric acid type A receptor alpha1 subunit and decreased expression of alpha4 subunit. In chronic alcoholic mice, puerarin pretreatment significantly increased body weight and liver ADH activity in a dose-dependent manner. Puerarin pretreatment, but not post-treatment, can reverse the changes of gama-aminobutyric acid type A receptor subunit expression and increase ADH activity in alcoholism models.

Conclusion

The present study demonstrates that FPE and its active ingredient puerarin have preventive effects on alcoholism related disorders.
Appendix
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Literature
1.
go back to reference Bayard M, McIntyre J, Hill KR, Woodside J: Alcohol withdrawal syndrome. Am Fam Physician. 2004, 69: 1443-1450.PubMed Bayard M, McIntyre J, Hill KR, Woodside J: Alcohol withdrawal syndrome. Am Fam Physician. 2004, 69: 1443-1450.PubMed
2.
go back to reference Trevisan LA, Boutros N, Petrakis IL, Krystal JH: Complications of alcohol withdrawal: pathophysiological insights. Alcohol Health Res World. 1998, 22: 61-66.PubMed Trevisan LA, Boutros N, Petrakis IL, Krystal JH: Complications of alcohol withdrawal: pathophysiological insights. Alcohol Health Res World. 1998, 22: 61-66.PubMed
3.
go back to reference Brower KJ, Aldrich MS, Robinson EA, Zucker RA, Greden JF: Insomnia, self-medication, and relapse to alcoholism. Am J Psychiatry. 2001, 158: 399-404. 10.1176/appi.ajp.158.3.399.PubMedCentralCrossRefPubMed Brower KJ, Aldrich MS, Robinson EA, Zucker RA, Greden JF: Insomnia, self-medication, and relapse to alcoholism. Am J Psychiatry. 2001, 158: 399-404. 10.1176/appi.ajp.158.3.399.PubMedCentralCrossRefPubMed
4.
go back to reference Booth BM, Blow FC: The kindling hypothesis: further evidence from a U.S. national study of alcoholic men. Alcohol Alcohol. 1993, 28: 593-598.PubMed Booth BM, Blow FC: The kindling hypothesis: further evidence from a U.S. national study of alcoholic men. Alcohol Alcohol. 1993, 28: 593-598.PubMed
5.
go back to reference Becker HC, Hale RL: Repeated episodes of ethanol withdrawal potentiate the severity of subsequent withdrawal seizures: an animal model of alcohol withdrawal "kindling". Alcohol Clin Exp Res. 1993, 17: 94-98. 10.1111/j.1530-0277.1993.tb00731.x.CrossRefPubMed Becker HC, Hale RL: Repeated episodes of ethanol withdrawal potentiate the severity of subsequent withdrawal seizures: an animal model of alcohol withdrawal "kindling". Alcohol Clin Exp Res. 1993, 17: 94-98. 10.1111/j.1530-0277.1993.tb00731.x.CrossRefPubMed
6.
go back to reference Veatch LM, Gonzalez LP: Repeated ethanol withdrawal produces site-dependent increases in EEG spiking. Alcohol Clin Exp Res. 1996, 20: 262-267. 10.1111/j.1530-0277.1996.tb01638.x.CrossRefPubMed Veatch LM, Gonzalez LP: Repeated ethanol withdrawal produces site-dependent increases in EEG spiking. Alcohol Clin Exp Res. 1996, 20: 262-267. 10.1111/j.1530-0277.1996.tb01638.x.CrossRefPubMed
7.
go back to reference Haranaka R, Okada N, Kosoto H, Ohwada S, Hasegawa R, Nakagawa S, Kobayashi M: Effects of wu-ling-san on alcohol metabolism and alcoholic liver. J Tradit Chin Med. 1985, 5: 171-178.PubMed Haranaka R, Okada N, Kosoto H, Ohwada S, Hasegawa R, Nakagawa S, Kobayashi M: Effects of wu-ling-san on alcohol metabolism and alcoholic liver. J Tradit Chin Med. 1985, 5: 171-178.PubMed
8.
go back to reference Xu BJ, Zheng YN, Sung CK: Natural medicines for alcoholism treatment: a review. Drug Alcohol Rev. 2005, 24: 525-536. 10.1080/09595230500293795.CrossRefPubMed Xu BJ, Zheng YN, Sung CK: Natural medicines for alcoholism treatment: a review. Drug Alcohol Rev. 2005, 24: 525-536. 10.1080/09595230500293795.CrossRefPubMed
9.
go back to reference Keung WM, Vallee BL: Kudzu root: an ancient Chinese source of modern antidipsotropic agents. Phytochemistry. 1998, 47: 499-506. 10.1016/S0031-9422(97)00723-1.CrossRefPubMed Keung WM, Vallee BL: Kudzu root: an ancient Chinese source of modern antidipsotropic agents. Phytochemistry. 1998, 47: 499-506. 10.1016/S0031-9422(97)00723-1.CrossRefPubMed
10.
go back to reference Lukas SE, Penetar D, Berko J, Vicens L, Palmer C, Mallya G, Macklin EA, Lee DY: An extract of the Chinese herbal root kudzu reduces alcohol drinking by heavy drinkers in a naturalistic setting. Alcohol Clin Exp Res. 2005, 29: 756-762. 10.1097/01.ALC.0000163499.64347.92.CrossRefPubMed Lukas SE, Penetar D, Berko J, Vicens L, Palmer C, Mallya G, Macklin EA, Lee DY: An extract of the Chinese herbal root kudzu reduces alcohol drinking by heavy drinkers in a naturalistic setting. Alcohol Clin Exp Res. 2005, 29: 756-762. 10.1097/01.ALC.0000163499.64347.92.CrossRefPubMed
11.
go back to reference Overstreet DH, Keung WM, Rezvani AH, Massi M, Lee DY: Herbal remedies for alcoholism: promises and possible pitfalls. Alcohol Clin Exp Res. 2003, 27: 177-185. 10.1097/01.ALC.0000051022.26489.CF.CrossRefPubMed Overstreet DH, Keung WM, Rezvani AH, Massi M, Lee DY: Herbal remedies for alcoholism: promises and possible pitfalls. Alcohol Clin Exp Res. 2003, 27: 177-185. 10.1097/01.ALC.0000051022.26489.CF.CrossRefPubMed
12.
go back to reference Heyman GM, Keung WM, Vallee BL: Daidzin decreases ethanol consumption in rats. Alcohol Clin Exp Res. 1996, 20: 1083-1087. 10.1111/j.1530-0277.1996.tb01950.x.CrossRefPubMed Heyman GM, Keung WM, Vallee BL: Daidzin decreases ethanol consumption in rats. Alcohol Clin Exp Res. 1996, 20: 1083-1087. 10.1111/j.1530-0277.1996.tb01950.x.CrossRefPubMed
13.
go back to reference Rooke N, Li DJ, Li J, Keung WM: The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin. J Med Chem. 2000, 43: 4169-4179. 10.1021/jm990614i.CrossRefPubMed Rooke N, Li DJ, Li J, Keung WM: The mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway: a potential site of action of daidzin. J Med Chem. 2000, 43: 4169-4179. 10.1021/jm990614i.CrossRefPubMed
14.
go back to reference Benlhabib E, Baker JI, Keyler DE, Singh AK: Kudzu root extract suppresses voluntary alcohol intake and alcohol withdrawal symptoms in P rats receiving free access to water and alcohol. J Med Food. 2004, 7: 168-179. 10.1089/1096620041224210.CrossRefPubMed Benlhabib E, Baker JI, Keyler DE, Singh AK: Kudzu root extract suppresses voluntary alcohol intake and alcohol withdrawal symptoms in P rats receiving free access to water and alcohol. J Med Food. 2004, 7: 168-179. 10.1089/1096620041224210.CrossRefPubMed
15.
go back to reference Ariwodola OJ, Crowder TL, Grant KA, Daunais JB, Friedman DP, Weiner JL: Ethanol modulation of excitatory and inhibitory synaptic transmission in rat and monkey dentate granule neurons. Alcohol Clin Exp Res. 2003, 27: 1632-1639. 10.1097/01.ALC.0000089956.43262.17.CrossRefPubMed Ariwodola OJ, Crowder TL, Grant KA, Daunais JB, Friedman DP, Weiner JL: Ethanol modulation of excitatory and inhibitory synaptic transmission in rat and monkey dentate granule neurons. Alcohol Clin Exp Res. 2003, 27: 1632-1639. 10.1097/01.ALC.0000089956.43262.17.CrossRefPubMed
16.
go back to reference Aroor AR, Shukla SD: MAP kinase signaling in diverse effects of ethanol. Life Sci. 2004, 74: 2339-2364. 10.1016/j.lfs.2003.11.001.CrossRefPubMed Aroor AR, Shukla SD: MAP kinase signaling in diverse effects of ethanol. Life Sci. 2004, 74: 2339-2364. 10.1016/j.lfs.2003.11.001.CrossRefPubMed
17.
go back to reference Cagetti E, Liang J, Spigelman I, Olsen RW: Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol. 2003, 63: 53-64. 10.1124/mol.63.1.53.CrossRefPubMed Cagetti E, Liang J, Spigelman I, Olsen RW: Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol. 2003, 63: 53-64. 10.1124/mol.63.1.53.CrossRefPubMed
18.
go back to reference Liang J, Cagetti E, Olsen RW, Spigelman I: Altered pharmacology of synaptic and extrasynaptic GABAA receptors on CA1 hippocampal neurons is consistent with subunit changes in a model of alcohol withdrawal and dependence. J Pharmacol Exp Ther. 2004, 310: 1234-1245. 10.1124/jpet.104.067983.CrossRefPubMed Liang J, Cagetti E, Olsen RW, Spigelman I: Altered pharmacology of synaptic and extrasynaptic GABAA receptors on CA1 hippocampal neurons is consistent with subunit changes in a model of alcohol withdrawal and dependence. J Pharmacol Exp Ther. 2004, 310: 1234-1245. 10.1124/jpet.104.067983.CrossRefPubMed
19.
go back to reference Liang J, Zhang N, Cagetti E, Houser CR, Olsen RW, Spigelman I: Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptors. J Neurosci. 2006, 26: 1749-1758. 10.1523/JNEUROSCI.4702-05.2006.CrossRefPubMed Liang J, Zhang N, Cagetti E, Houser CR, Olsen RW, Spigelman I: Chronic intermittent ethanol-induced switch of ethanol actions from extrasynaptic to synaptic hippocampal GABAA receptors. J Neurosci. 2006, 26: 1749-1758. 10.1523/JNEUROSCI.4702-05.2006.CrossRefPubMed
20.
go back to reference Edenberg HJ, Xuei X, Chen HJ, Tian H, Wetherill LF, Dick DM, Almasy L, Bierut L, Bucholz KK, Goate A: Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis. Hum Mol Genet. 2006, 15: 1539-1549. 10.1093/hmg/ddl073.CrossRefPubMed Edenberg HJ, Xuei X, Chen HJ, Tian H, Wetherill LF, Dick DM, Almasy L, Bierut L, Bucholz KK, Goate A: Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis. Hum Mol Genet. 2006, 15: 1539-1549. 10.1093/hmg/ddl073.CrossRefPubMed
21.
go back to reference Institute of Materia Medica CAoMS: Zhong Yao Zhi. 1995, Beijing Institute of Materia Medica CAoMS: Zhong Yao Zhi. 1995, Beijing
22.
go back to reference Boehm SL, Ponomarev I, Jennings AW, Whiting PJ, Rosahl TW, Garrett EM, Blednov YA, Harris RA: gamma-Aminobutyric acid A receptor subunit mutant mice: new perspectives on alcohol actions. Biochem Pharmacol. 2004, 68: 1581-1602. 10.1016/j.bcp.2004.07.023.CrossRefPubMed Boehm SL, Ponomarev I, Jennings AW, Whiting PJ, Rosahl TW, Garrett EM, Blednov YA, Harris RA: gamma-Aminobutyric acid A receptor subunit mutant mice: new perspectives on alcohol actions. Biochem Pharmacol. 2004, 68: 1581-1602. 10.1016/j.bcp.2004.07.023.CrossRefPubMed
23.
go back to reference Liang J, Suryanarayanan A, Abriam A, Snyder B, Olsen RW, Spigelman I: Mechanisms of reversible GABAA receptor plasticity after ethanol intoxication. J Neurosci. 2007, 27: 12367-12377. 10.1523/JNEUROSCI.2786-07.2007.CrossRefPubMed Liang J, Suryanarayanan A, Abriam A, Snyder B, Olsen RW, Spigelman I: Mechanisms of reversible GABAA receptor plasticity after ethanol intoxication. J Neurosci. 2007, 27: 12367-12377. 10.1523/JNEUROSCI.2786-07.2007.CrossRefPubMed
24.
go back to reference Liang JH, Chen F, Krstew E, Cowen MS, Carroll FY, Crawford D, Beart PM, Lawrence AJ: The GABA(B) receptor allosteric modulator CGP7930, like baclofen, reduces operant self-administration of ethanol in alcohol-preferring rats. Neuropharmacology. 2006, 50: 632-639. 10.1016/j.neuropharm.2005.11.011.CrossRefPubMed Liang JH, Chen F, Krstew E, Cowen MS, Carroll FY, Crawford D, Beart PM, Lawrence AJ: The GABA(B) receptor allosteric modulator CGP7930, like baclofen, reduces operant self-administration of ethanol in alcohol-preferring rats. Neuropharmacology. 2006, 50: 632-639. 10.1016/j.neuropharm.2005.11.011.CrossRefPubMed
25.
go back to reference McGregor NR: Pueraria lobata (Kudzu root) hangover remedies and acetaldehyde-associated neoplasm risk. Alcohol. 2007, 41: 469-478. 10.1016/j.alcohol.2007.07.009.CrossRefPubMed McGregor NR: Pueraria lobata (Kudzu root) hangover remedies and acetaldehyde-associated neoplasm risk. Alcohol. 2007, 41: 469-478. 10.1016/j.alcohol.2007.07.009.CrossRefPubMed
26.
go back to reference Zhang JF, Lu YX, Qiu XX, Fang Y: Relationship between alcohol drinking and alcohol-related health problems. Biomed Environ Sci. 2004, 17: 196-202.PubMed Zhang JF, Lu YX, Qiu XX, Fang Y: Relationship between alcohol drinking and alcohol-related health problems. Biomed Environ Sci. 2004, 17: 196-202.PubMed
27.
go back to reference Lin RC, Li TK: Effects of isoflavones on alcohol pharmacokinetics and alcohol-drinking behavior in rats. Am J Clin Nutr. 1998, 68: 1512S-1515S.PubMed Lin RC, Li TK: Effects of isoflavones on alcohol pharmacokinetics and alcohol-drinking behavior in rats. Am J Clin Nutr. 1998, 68: 1512S-1515S.PubMed
28.
go back to reference Overstreet DH, Lee YW, Rezvani AH, Pei YH, Criswell HE, Janowsky DS: Suppression of alcohol intake after administration of the Chinese herbal medicine, NPI-028, and its derivatives. Alcohol Clin Exp Res. 1996, 20: 221-227. 10.1111/j.1530-0277.1996.tb01633.x.CrossRefPubMed Overstreet DH, Lee YW, Rezvani AH, Pei YH, Criswell HE, Janowsky DS: Suppression of alcohol intake after administration of the Chinese herbal medicine, NPI-028, and its derivatives. Alcohol Clin Exp Res. 1996, 20: 221-227. 10.1111/j.1530-0277.1996.tb01633.x.CrossRefPubMed
29.
go back to reference Keung WM, Vallee BL: Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase. Proc Natl Acad Sci USA. 1993, 90: 1247-1251. 10.1073/pnas.90.4.1247.PubMedCentralCrossRefPubMed Keung WM, Vallee BL: Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase. Proc Natl Acad Sci USA. 1993, 90: 1247-1251. 10.1073/pnas.90.4.1247.PubMedCentralCrossRefPubMed
30.
go back to reference Keung WM: Biochemical studies of a new class of alcohol dehydrogenase inhibitors from Radix puerariae. Alcohol Clin Exp Res. 1993, 17: 1254-1260. 10.1111/j.1530-0277.1993.tb05238.x.CrossRefPubMed Keung WM: Biochemical studies of a new class of alcohol dehydrogenase inhibitors from Radix puerariae. Alcohol Clin Exp Res. 1993, 17: 1254-1260. 10.1111/j.1530-0277.1993.tb05238.x.CrossRefPubMed
31.
go back to reference Keung WM, Lazo O, Kunze L, Vallee BL: Daidzin suppresses ethanol consumption by Syrian golden hamsters without blocking acetaldehyde metabolism. Proc Natl Acad Sci USA. 1995, 92: 8990-8993. 10.1073/pnas.92.19.8990.PubMedCentralCrossRefPubMed Keung WM, Lazo O, Kunze L, Vallee BL: Daidzin suppresses ethanol consumption by Syrian golden hamsters without blocking acetaldehyde metabolism. Proc Natl Acad Sci USA. 1995, 92: 8990-8993. 10.1073/pnas.92.19.8990.PubMedCentralCrossRefPubMed
32.
go back to reference Fernandez-Sola J, Preedy VR, Lang CH, Gonzalez-Reimers E, Arno M, Lin JC, Wiseman H, Zhou S, Emery PW, Nakahara T: Molecular and cellular events in alcohol-induced muscle disease. Alcohol Clin Exp Res. 2007, 31: 1953-1962. 10.1111/j.1530-0277.2007.00530.x.CrossRefPubMed Fernandez-Sola J, Preedy VR, Lang CH, Gonzalez-Reimers E, Arno M, Lin JC, Wiseman H, Zhou S, Emery PW, Nakahara T: Molecular and cellular events in alcohol-induced muscle disease. Alcohol Clin Exp Res. 2007, 31: 1953-1962. 10.1111/j.1530-0277.2007.00530.x.CrossRefPubMed
33.
go back to reference Singal AK, Anand BS: Mechanisms of synergy between alcohol and hepatitis C virus. J Clin Gastroenterol. 2007, 41: 761-772. 10.1097/MCG.0b013e3180381584.CrossRefPubMed Singal AK, Anand BS: Mechanisms of synergy between alcohol and hepatitis C virus. J Clin Gastroenterol. 2007, 41: 761-772. 10.1097/MCG.0b013e3180381584.CrossRefPubMed
34.
go back to reference Song BJ, Moon KH, Olsson NU, Salem N: Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids. J Hepatol. 2008, 49: 262-273. 10.1016/j.jhep.2008.04.023.PubMedCentralCrossRefPubMed Song BJ, Moon KH, Olsson NU, Salem N: Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain polyunsaturated fatty acids. J Hepatol. 2008, 49: 262-273. 10.1016/j.jhep.2008.04.023.PubMedCentralCrossRefPubMed
35.
go back to reference Sancho-Tello M, Muriach M, Barcia J, Bosch-Morell F, Genoves JM, Johnsen-Soriano S, Romero B, Almansa I, Diaz-Llopis M, Garcia-Delpech S: Chronic alcohol feeding induces biochemical, histological, and functional alterations in rat retina. Alcohol Alcohol. 2008, 43: 254-260.CrossRefPubMed Sancho-Tello M, Muriach M, Barcia J, Bosch-Morell F, Genoves JM, Johnsen-Soriano S, Romero B, Almansa I, Diaz-Llopis M, Garcia-Delpech S: Chronic alcohol feeding induces biochemical, histological, and functional alterations in rat retina. Alcohol Alcohol. 2008, 43: 254-260.CrossRefPubMed
36.
go back to reference Warnakulasuriya S, Parkkila S, Nagao T, Preedy VR, Pasanen M, Koivisto H, Niemela O: Demonstration of ethanol-induced protein adducts in oral leukoplakia (pre-cancer) and cancer. J Oral Pathol Med. 2008, 37: 157-165. 10.1111/j.1600-0714.2007.00605.x.CrossRefPubMed Warnakulasuriya S, Parkkila S, Nagao T, Preedy VR, Pasanen M, Koivisto H, Niemela O: Demonstration of ethanol-induced protein adducts in oral leukoplakia (pre-cancer) and cancer. J Oral Pathol Med. 2008, 37: 157-165. 10.1111/j.1600-0714.2007.00605.x.CrossRefPubMed
37.
go back to reference Li Y, Walker DW, King MA: Peroxide mediates ethanol-induced cytotoxicity in PC12 cells. Free Radic Biol Med. 2001, 30: 389-392. 10.1016/S0891-5849(00)00484-6.CrossRefPubMed Li Y, Walker DW, King MA: Peroxide mediates ethanol-induced cytotoxicity in PC12 cells. Free Radic Biol Med. 2001, 30: 389-392. 10.1016/S0891-5849(00)00484-6.CrossRefPubMed
38.
go back to reference Lockhart B, Jones C, Cuisinier C, Villain N, Peyroulan D, Lestage P: Inhibition of L-homocysteic acid and buthionine sulphoximine-mediated neurotoxicity in rat embryonic neuronal cultures with alpha-lipoic acid enantiomers. Brain Res. 2000, 855: 292-297. 10.1016/S0006-8993(99)02372-0.CrossRefPubMed Lockhart B, Jones C, Cuisinier C, Villain N, Peyroulan D, Lestage P: Inhibition of L-homocysteic acid and buthionine sulphoximine-mediated neurotoxicity in rat embryonic neuronal cultures with alpha-lipoic acid enantiomers. Brain Res. 2000, 855: 292-297. 10.1016/S0006-8993(99)02372-0.CrossRefPubMed
39.
go back to reference Cao X, Tian Y, Zhang T, Li X, Ito Y: Separation and purification of isoflavones from Pueraria lobata by high-speed counter-current chromatography. J Chromatogr A. 1999, 855: 709-713. 10.1016/S0021-9673(99)00715-3.CrossRefPubMed Cao X, Tian Y, Zhang T, Li X, Ito Y: Separation and purification of isoflavones from Pueraria lobata by high-speed counter-current chromatography. J Chromatogr A. 1999, 855: 709-713. 10.1016/S0021-9673(99)00715-3.CrossRefPubMed
Metadata
Title
Preventive effects of Flos Perariae (Gehua) water extract and its active ingredient puerarin in rodent alcoholism models
Authors
Zaijun Zhang
Sha Li
Jie Jiang
Pei Yu
Jing Liang
Yuqiang Wang
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2010
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/1749-8546-5-36

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