A review of traditional Japanese medicines and their potential mechanism of action

Current Pharmaceutical Design

Volumn 18, Issue 31, 2012, Pages 4839-4853

  Uezono, Yasuhito ^a   Miyano, Kanako ^a   Sudo, Yuka ^a   Suzuki, Masami ^a   Shiraishi, Seiji ^a   Terawaki, Kiyoshi ^a  

^a NATIONAL CANCER CENTER RESEARCH INSTITUTE   (Japan)

Author keywords

Ghrelin; GPCR; Herbal medicine; Kampo medicine; Rikkunshito

Indexed keywords

BAKUMONDOUTO; BU ZHONG YI QI TANG; CYCLIC AMP DEPENDENT PROTEIN KINASE; DAIKENCHUTO; G PROTEIN COUPLED RECEPTOR; GHRELIN; GHRELIN RECEPTOR; GOSHAJINKIGAN; GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATE; KAMISHOYOSAN; KAMPO; KEISHI BUKURYO GAN; LEPTIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PHOSPHODIESTERASE III; PLANT MEDICINAL PRODUCT; PROTEIN KINASE C; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RIKKUNSHITO; SAIBOKUTO; SAIREITO; SEROTONIN 2B RECEPTOR; SEROTONIN 2C RECEPTOR; SHAKUYAKUKANZOTO; SHOUSEIRYUTO; UNCLASSIFIED DRUG; VANILLOID RECEPTOR 1; YOKUKANSAN;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ACUTE GASTROENTERITIS; ALLERGIC RHINITIS; ALZHEIMER DISEASE; ANOREXIA; ANTINOCICEPTION; ANXIETY DISORDER; ANXIETY NEUROSIS; ASTHMA; BEHAVIOR DISORDER; BRONCHITIS; CONCENTRATION (PARAMETERS); CONFORMATIONAL TRANSITION; COUGHING; CYTOKINE PRODUCTION; DIARRHEA; DIFFUSE LEWY BODY DISEASE; DOSE RESPONSE; DRUG INDUCED DISEASE; DRUG MECHANISM; DYSPEPSIA; EDEMA; ENDOMETRITIS; ENZYME ACTIVATION; ENZYME INHIBITION; GASTRITIS; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL MOTILITY DISORDER; HALLUCINATION; HIGH THROUGHPUT SCREENING; HOT FLUSH; HUMAN; INSOMNIA; LEG PAIN; LIGAND BINDING; LOW BACK PAIN; MENOPAUSAL SYNDROME; MENTAL DISEASE; MUSCLE CRAMP; MYALGIA; NAUSEA AND VOMITING; NONHUMAN; PARESTHESIA; POSTOPERATIVE ILEUS; PRESCRIPTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; REVIEW; RHINITIS; SENILE DEMENTIA; SIGNAL TRANSDUCTION; STOMACH PAIN; TRADITIONAL JAPANESE MEDICINE; TRADITIONAL MEDICINE;

ANIMALS; DRUGS, CHINESE HERBAL; G-PROTEIN-COUPLED RECEPTOR KINASES; GHRELIN; HUMANS; MEDICINE, KAMPO; PLANT EXTRACTS; PLANT PREPARATIONS; PROTEIN KINASE INHIBITORS; RECEPTORS, GHRELIN; SIGNAL TRANSDUCTION;

EID: 84866371526     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212803216924     Document Type: Review

References (123)

1. Yu F, Takahashi T, Moriya J, et al. Traditional Chinese medicine and Kampo: a review from the distant past for the future. J Int Med Res 2006; 34:231-239.
2. Mizukami K, Asada T, Kinoshita T, et al. A randomized cross-over study of a traditional Japanese medicine (kampo), yokukansan, in the treatment of the behavioural and psychological symptoms of dementia. Int J Neuropsychopharmacol 2009; 12:191-199.
3. Takeda H, Sadakane C, Hattori T, et al. Rikkunshito, an herbal medicine, suppresses cisplatin-induced anorexia in rats via 5-HT2 receptor antagonism. Gastroenterology 2008; 134:2004-2013.
4. Hattori T. Rikkunshito and ghrelin. Int J Pept 2010; P2: 283549.
5. Agnati LF, Guidolin D, Leo G, et al. Possible new targets for GPCR modulation: allosteric interactions, plasma membrane domains, intercellular transfer and epigenetic mechanisms. J Recep Signal Trans Res 2011; 31:315-331.
6. Klabunde T, Hessler G. Drug design strategies for targeting Gprotein-coupled receptors. Chembiochem 2002; 3:928-944.
7. CSR Report. TSUMURA Corporate Social Responsibility Report 2011:1-54.
8. Satoh K, Hashimoto K, Hayakawa T, et al. Mechanism of atropineresistant contraction induced by Dai-kenchu-to in guinea pig ileum. Jpn J Pharmacol 2001; 86:32-37.
9. Arakawa T, Higuchi K, Fujiwara Y, et al. Gastroprotection by Liu- Jun-Zi-Tang (TJ-43): possible mediation of nitric oxide but not prostaglandins or sulfhydryls. Drugs Exp Clin Res 1999; 25:207-210.
10. Kido T, Nakai Y, Kase Y, et al. Effects of rikkunshi-to, a traditional Japanese medicine, on the delay of gastric emptying induced by N(G)-nitro-L-arginine. J Pharmacol Sci 2005; 98:161-167.
11. Kawakami Z, Ikarashi Y, Kase Y. Isoliquiritigenin is a novel NMDA receptor antagonist in kampo medicine yokukansan. Cell Mol Neurobiol 2011; 31:1203-1212.
12. Egashira N, Nogami A, Iwasaki K, et al. Yokukansan Enhances Pentobarbital-Induced Sleep in Socially Isolated Mice: Possible Involvement of GABA(A) - Benzodiazepine Receptor Complex. J Pharmacol Sci 2011; 116:316-320.
13. Foord SM. Receptor classification: post genome. Curr Opin Pharmacol 2002; 2:561-566.
14. Kristiansen K. Molecular mechanisms of ligand binding, signaling, and regulation within the superfamily of G-protein-coupled receptors: molecular modeling and mutagenesis approaches to receptor structure and function. Pharmacol Ther 2004; 103:21-80.
15. Bourne HR, Sanders DA, McCormick F. The GTPase superfamily: conserved structure and molecular mechanism. Nature 1991; 349:117-127.
16. Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol 2002; 3:639-650.
17. Lefkowitz RJ, Shenoy SK. Transduction of receptor signals by beta-arrestins. Science 2005; 308:512-517.
18. Bylund DB, Toews ML. Radioligand binding methods: practical guide and tips. Am J Physiol 1993; 265:L421-L429.
19. Milligan G. Principles: extending the utility of [35S]GTP gamma S binding assays. Trends Pharmacol Sci 2003; 24:87-90.
20. Harrison C, Traynor JR. The [35S]GTPgammaS binding assay: approaches and applications in pharmacology. Life Sci 2003; 74:489-508.
21. Emkey R, Rankl NB. Screening G protein-coupled receptors: measurement of intracellular calcium using the fluorometric imaging plate reader. Methods Mol Biol 2009; 565:145-158.
22. Itoh T, Yamakawa J, Mai M, Yamaguchi N, Kanda T. The effect of the herbal medicine dai-kenchu-to on post-operative ileus. J Int Med Res 2002; 30:428-432.
23. Ohya T, Usui Y, Arii S, Iwai T, Susumu T. Effect of dai-kenchu-to on obstructive bowel disease in children. Am J Chin Med 2003; 31:129-135.
24. Kono T, Kanematsu T, Kitajima M. Exodus of Kampo, traditional Japanese medicine, from the complementary and alternative medicines: is it time yet? Surgery 2009; 146:837-840.
25. Fukuda H, Chen C, Mantyh C, Ludwig K, Pappas TN, Takahashi T. The herbal medicine, Dai-Kenchu-to, accelerates delayed gastrointestinal transit after the operation in rats. J Surg Res 2006; 131:290-295.
26. Tokita Y, Yuzurihara M, Sakaguchi M, Satoh K, Kase Y. The pharmacological effects of Daikenchuto, a traditional herbal medicine, on delayed gastrointestinal transit in rat postoperative ileus. J Pharmacol Sci 2007; 104:303-310.
27. Tokita Y, Satoh K, Sakaguchi M, et al. The preventive effect of Daikenchuto on postoperative adhesion-induced intestinal obstruction in rats. Inflammopharmacology 2007; 15:65-66.
28. Satoh K, Kase Y, Yuzurihara M, Mizoguchi K, Kurauchi K, Ishige A. Effect of Dai-kenchu-to (Da-Jian-Zhong-Tang) on the delayed intestinal propulsion induced by chlorpromazine in mice. J Ethnopharmacol 2003; 86:37-44.
29. Satoh K, Hayakawa T, Kase Y, et al. Mechanisms for contractile effect of Dai-kenchu-to in isolated guinea pig ileum. Dig Dis Sci 2001; 46:250-256.
30. Jin XL, Shibata C, Naito H, et al. Intraduodenal and intrajejunal administration of the herbal medicine, dai-kenchu-tou, stimulates small intestinal motility via cholinergic receptors in conscious dogs. Dig Dis Sci 2001; 46:1171-1176.
31. Nagano T, Itoh H, Takeyama M. Effect of Dai-kenchu-to on levels of 3 brain-gut peptides (motilin, gastrin and somatostatin) in human plasma. Biol Pharm Bull 1999; 22:1131-1133.
32. Nagano T, Itoh H, Takeyama M. Effects of Dai-kenchu-to on levels of 5-hydroxytryptamine (serotonin) and vasoactive intestinal peptides in human plasma. Biol Pharm Bull 2000; 23:352-353.
33. Sato Y, Katagiri F, Inoue S, Itoh H, Takeyama M. Dai-kenchu-to raises levels of calcitonin gene-related peptide and substance P in human plasma. Biol Pharm Bull 2004; 27:1875-1877.
34. Sato Y, Inoue S, Katagiri F, Itoh H, Takeyama M. Effects of pirenzepine on Dai-kenchu-to-induced elevation of the plasma neuropeptide levels in humans. Biol Pharm Bull 2006; 29:166-171.
35. Murata P, Kase Y, Ishige A, Sasaki H, Kurosawa S, Nakamura T. The herbal medicine Dai-kenchu-to and one of its active components [6]-shogaol increase intestinal blood flow in rats. Life Sci 2002; 70:2061-2070.
36. Kono T, Koseki T, Chiba S, et al. Colonic vascular conductance increased by Daikenchuto via calcitonin gene-related peptide and receptor-activity modifying protein 1. J Surg Res 2008; 150:78-84.
37. Kono T, Kaneko A, Hira Y, et al. Anti-colitis and -adhesion effects of daikenchuto via endogenous adrenomedullin enhancement in Crohn's disease mouse model. J Crohns Colitis 2010; 4:161-170.
38. Foord SM, Marshall FH. RAMPs: accessory proteins for seven transmembrane domain receptors. Trends Pharmacol Sci 1999; 20:184-187.
39. McLatchie LM, Fraser NJ, Main MJ, et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 1998; 393:333-339.
40. Iwasaki K, Maruyama M, Tomita N, et al. Effects of the traditional Chinese herbal medicine Yi-Gan San for cholinesterase inhibitorresistant visual hallucinations and neuropsychiatric symptoms in patients with dementia with Lewy bodies. J Clin Psychiatry 2005; 66:1612-1613.
41. Monji A, Takita M, Samejima T, et al. Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33:308-311.
42. Ikarashi Y, Iizuka S, Imamura S, et al. Effects of yokukansan, a traditional Japanese medicine, on memory disturbance and behavioral and psychological symptoms of dementia in thiaminedeficient rats. Biol Pharm Bull 2009; 32:1701-1709.
43. Iizuka S, Kawakami Z, Imamura S, et al. Electron-microscopic examination of effects of yokukansan, a traditional Japanese medicine, on degeneration of cerebral cells in thiamine-deficient rats. Neuropathology 2010; 30: 524-536.
44. Tamano H, Kan F, Oku N, Takeda A. Ameliorative effect of Yokukansan on social isolation-induced aggressive behavior of zinc-deficient young mice. Brain Res Bull 2010; 83:351-355.
45. Sekiguchi K, Yamaguchi T, Tabuchi M, Ikarashi Y, Kase Y. Effects of yokukansan, a traditional Japanese medicine, on aggressiveness induced by intracerebroventricular injection of amyloid beta protein into mice. Phytother Res 2009; 23:1175-1181.
46. Sekiguchi K, Imamura S, Yamaguchi T, et al. Effects of yokukansan and donepezil on learning disturbance and aggressiveness induced by intracerebroventricular injection of amyloid OE_ protein in mice. Phytother Res 2011; 25:501-507.
47. Tabuchi M, Yamaguchi T, Iizuka S, Imamura S, Ikarashi Y, Kase Y. Ameliorative effects of yokukansan, a traditional Japanese medicine, on learning and non-cognitive disturbances in the Tg2576 mouse model of Alzheimer's disease. J Ethnopharmacol 2009; 122:157-162.
48. Kanno H, Sekiguchi K, Yamaguchi T, et al. Effect of yokukansan, a traditional Japanese medicine, on social and aggressive behaviour of para-chloroamphetamine-injected rats. J Pharm Pharmacol 2009; 61:1249-1256.
49. Terawaki K, Ikarashi Y, Sekiguchi K, Nakai Y, Kase Y. Partial agonistic effect of yokukansan on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells. J Ethnopharmacol 2010; 127:306-312.
50. Ueda T, Ugawa S, Ishida Y, Shimada S. Geissoschizine methyl ether has third-generation antipsychotic-like actions at the dopamine and serotonin receptors. Eur J Pharmacol 2011; 671:79-86.
51. Egashira N, Iwasaki K, Ishibashi A, et al. Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32:1516-1520.
52. Yamada M, Hayashida M, Zhao Q, et al. Ameliorative effects of yokukansan on learning and memory deficits in olfactory bulbectomized mice. J Ethnopharmacol 2011; 135:737-746.
53. Suzuki Y, Goto K, Ishige A, Komatsu Y, Kamei J. Antinociceptive effect of Gosha-jinki-gan, a Kampo medicine, in streptozotocininduceddiabetic mice. Jpn J Pharmacol 1999; 79:169-175.
54. Gotoh A, Goto K, Sengoku A, et al. Inhibition mechanism of Gosha-jinki-gan on the micturition reflex in rats. J Pharmacol Sci 2004; 96:115-123.
55. Isohama Y, Kurita K, Kai H, Takahama K, Miyata T. Bakumondoto (Mai-Men-Dong-Tang) increases β1-adrenergic receptor mRNA expression in rat alveolar type 2 cells. J Tradit Med 2001; 18:8-14.
56. Tamaoki J, Chiyotani A, Takeyama K, Kanemura T, Sakai N, Konno K. Potentiation of beta-adrenergic function by saiboku-to and bakumondo-to in canine bronchial smooth muscle. Jpn J Pharmacol 1993; 62:155-159.
57. Omiya Y, Suzuki Y, Yuzurihara M, et al. Antinociceptive effect of shakuyakukanzoto, a Kampo medicine, in diabetic mice. J Pharmacol Sci 2005; 99:373-380.
58. Das AK, Mizuguchi H, Kodama M, et al. Sho-seiryu-to suppresses histamine signaling at the transcriptional level in TDI-sensitized nasal allergy model rats. Allergol Int 2009; 58:81-88.
59. Sakaguchi M, Mase A, Iizuka A, et al. Further pharmacological study on Sho-seiryu-to as an antiallergic. Methods Find Exp Clin Pharmacol 1997; 19:707-713.
60. Ikarashi Y, Yuzurihara M, Sakakibara I, Takahashi A, Ishimaru H, Maruyama Y. Effects of an oriental herbal medicine, "Saiboku-to", and its constituent herbs on Compound 48/80-induced histamine release from peritoneal mast cells in rats. Phytomedicine 2001; 8:8-15.
61. Kobayashi I, Hamasaki Y, Sato R, et al. Saiboku-To, a herbal extract mixture, selectively inhibits 5-lipoxygenase activity in leukotriene synthesis in rat basophilic leukemia-1 cells. J Ethnopharmacol 1995; 48:33-41.
62. Nakamura T, Kuriyama M, Kosuge E, Ishihara K, Ito K. Effects of saiboku-to (TJ-96) on the production of platelet-activating factor in human neutrophils. Ann N Y Acad Sci 1993; 685:572-579.
63. Noguchi M, Ikarashi Y, Yuzurihara M, et al. Effects of the Japanese herbal medicine Keishi-bukuryo-gan and 17beta-estradiol on calcitonin gene-related peptide-induced elevation of skin temperature in ovariectomized rats. J Endocrinol 2003; 176:359-366.
64. Arai M, Matsumura T, Tsuchiya N, et al. Rikkunshito improves the symptoms in patients with functional dyspepsia, accompanied by an increase in the level of plasma ghrelin. Hepatogastroenterology 2012; 59:62-66.
65. Ohno T, Yanai M, Ando H, et al. Rikkunshito, a traditional Japanese medicine, suppresses cisplatin-induced anorexia in humans. Clin Exp Gastroenterol 2011; 4:291-296.
66. Tominaga K, Iwakiri R, Fujimoto K, et al. Rikkunshito improves symptoms in PPI-refractory GERD patients: a prospective, randomized, multicenter trial in Japan. J Gastroenterol 2011; 47:284-292
67. Yakabi K, Sadakane C, Noguchi M, et al. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia. Endocrinology 2010; 151:3773-3782.
68. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402:656-660.
69. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev 2005; 85:495-522.
70. Chen CY, Asakawa A, Fujimiya M, Lee SD, Inui A. Ghrelin gene products and the regulation of food intake and gut motility. Pharmacol Rev 2009; 61:430-481.
71. Smith RG, Van der Ploeg LH, Howard AD, et al. Peptidomimetic regulation of growth hormone secretion. Endocr Rev 1997; 18:621-645.
72. Fujitsuka N, Asakawa A, Hayashi M, et al. Selective serotonin reuptake inhibitors modify physiological gastrointestinal motor activities via 5-HT2c receptor and acyl ghrelin. Biol Psychiatry 2009; 65:748-759.
73. Pytliak M, Vargova V, Mechirova V, Felsoci M. Serotonin receptors - from molecular biology to clinical applications. Physiol Res 2011; 60:15-25.
74. De Vry J, Schreiber R. Effects of selected serotonin 5-HT(1) and 5- HT(2) receptor agonists on feeding behavior: possible mechanisms of action. Neurosci Biobehav Rev 2000; 24:341-353.
75. Nonogaki K, Nozue K, Oka Y. Hyperphagia alters expression of hypothalamic 5-HT2C and 5-HT1B receptor genes and plasma desacyl ghrelin levels in Ay mice. Endocrinology 2006; 147:5893-5900.
76. Nonogaki K. Ghrelin and feedback systems. Vitam Horm 2008; 77:149-170.
77. Taniguchi H, Ariga H, Zheng J, et al. Endogenous ghrelin and 5- HT regulate interdigestive gastrointestinal contractions in conscious rats. Am J Physiol Gastrointest Liver Physiol 2008; 295:G403-G411.
78. Fujitsuka N, Asakawa A, Uezono Y, et al. Potentiation of ghrelin signaling attenuates cancer anorexia'Äìcachexia and prolongs survival. Trans Psychiatry 2011; 1:1-10.
79. Kohno D, Gao HZ, Muroya S, Kikuyama S, Yada T. Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes 2003; 52:948-956.
80. Kohno D, Nakata M, Maekawa F, et al. Leptin suppresses ghrelininduced activation of neuropeptide Y neurons in the arcuate nucleus via phosphatidylinositol 3-kinase-and phosphodiesterase 3-mediated pathway. Endocrinology 2007; 148:2251-2263.
81. Sadakane C, Muto S, Nakagawa K, et al. 10-Gingerol, a component of rikkunshito, improves cisplatin-induced anorexia by inhibiting acylated ghrelin degradation. Biochem Biophys Res Commun 2011; 412:506-511.
82. Zhao AZ, Bornfeldt KE, Beavo JA. Leptin inhibits insulin secretion by activation of phosphodiesterase 3B. J Clin Invest 1998; 102:869-873.
83. Zhao AZ, Shinohara MM, Huang D, et al. Leptin induces insulinlike signaling that antagonizes cAMP elevation by glucagon in hepatocytes. J Biol Chem 2000; 275:11348-11354.
84. Yan C, Miller CL, Abe J. Regulation of phosphodiesterase 3 and inducible cAMP early repressor in the heart. Circ Res 2007; 100:489-501.
85. Takeda H, Muto S, Hattori T, et al. Rikkunshito ameliorates theaging-associated decrease in ghrelin receptor reactivity via phosphodiesterase III inhibition. Endocrinology 2010; 151:244-252.
86. Giaever I, Keese CR. Monitoring fibroblast behavior in tissue culture with an applied electric field. Proc Natl Acad Sci U S A 1984; 81:3761-3764.
87. Giaever I, Keese CR. Micromotion of mammalian cells measured electrically. Proc Natl Acad Sci USA 1991; 88:7896-7900.
88. Tiruppathi C, Malik AB, Del Vecchio PJ, Keese CR, Giaever I. Electrical method for detection of endothelial cell shape change in real time: assessment of endothelial barrier function. Proc Natl Acad Sci USA 1992; 89:7919-7923.
89. Giaever I, Keese CR. A morphological biosensor for mammalian cells. Nature 1993; 366:591-592.
90. Zhu J, Wang X, Xu X, Abassi YA. Dynamic and label-free monitoring of natural killer cell cytotoxic activity using electroniccell sensor arrays. J Immunol Methods 2006; 309:25-33.
91. Fang Y, Li G, Ferrie AM. Non-invasive optical biosensor for assaying endogenous G protein-coupled receptors in adherent cells. J Pharmacol Toxicol Methods 2007; 55:314-322.
92. Peters MF, Vaillancourt F, Heroux M, Valiquette M, Scott CW. Comparing label-free biosensors for pharmacological screening with cell-based functional assays. Assay Drug Dev Technol 2010; 8:219-227.
93. Leung G, Tang H, McGuinness R, Verdonk E, Michelotti M, Liu V. Cellular dielectric spectroscopy: A label-free technology for drug discovery. J Lab Autom 2005; 10:258-269.
94. Ciambrone GJ, Liu VF, Lin DC, McGuinness RP, Leung GK, Pitchford S. Cellular dielectric spectroscopy: a powerful new approach to label-free cellular analysis. J Biomol Screen 2004; 9:467-480.
95. Peters MF, Knappenberger KS, Wilkins D, et al. Evaluation of cellular dielectric spectroscopy, a whole-cell, label-free technology for drug discovery on Gi-coupled GPCRs. J Biomol Screen 2007; 12:312-319.
96. McGuinness RP, Proctor JM, Gallant DL, et al. Enhanced selectivity screening of GPCR ligands using a label-free cell based assay technology. Comb Chem High Throughput Screen 2009; 12:812-823.
97. Mori K, Kido T, Daikuhara H, et al. Effect of Hochu-ekki-to (TJ- 41), a Japanese herbal medicine, on the survival of mice infected with influenza virus. Antiviral Res 1999; 44:103-111.
98. Li T, Tamada K, Abe K, et al. The restoration of the antitumor T cell response from stress-induced suppression using a traditional Chinese herbal medicine Hochu-ekki-to (TJ-41:Bu-Zhong-Yi-Qi- Tang). Immunopharmacology 1999; 43:11-21.
99. Kurose I, Miura S, Fukumura D, Suzuki H, Tsuchiya M, Ishii H. Inhibitions of platelet-activating factor production and granulocyte oxidative activation by Rikkunshi-To in the process of gastric mucosal injury . Pathophysiology 1995; 2:153-159.
100. Tamaki K, Otaka M, Shibuya T, et al. Traditional harbel medicine, Rikkunshito, induced HSP60 and enhances cytoprotection of small intestinal mucosal cell as a nontoxic chaperone inducer. Evid-Based Comp Alter Med 2012:1-7.
101. Ono K, Saito K, Saeki T, Iwasaki A, Arakawa Y. Gastritis.Experimental study on inhibitory effect of acid secretion with Chinese medicine. Prog Med 1993; 13:2832-2835.
102. Takeda A, Tamano H, Itoh H, Oku N. Attenuation of abnormal glutamate release in zinc deficiency by zinc and Yokukansan. Neurochem Int 2008; 53:230-235.
103. Kawakami Z, Kanno H, Ueki T, et al. Neuroprotective effects of yokukansan, a traditional Japanese medicine, on glutamatemediated excitotoxicity in cultured cells. Neuroscience 2009; 159:1397-1407.
104. Mizowaki M, Toriizuka K, Hanawa T. Anxiolytic effect of Kami- Shoyo-San (TJ-24) in mice: possible mediation of neurosteroid synthesis. Life Sci 2001; 69:2167-2177.
105. Suzuki Y, Goto K, Ishige A, Komatsu Y, Kamei J. Effects of gosha-jinki-gan, a kampo medicine, on peripheral tissue blood flow in streptozotocin-induced diabetic rats. Methods Find Exp Clin Pharmacol 1998; 20:321-328.
106. Hattori T, Maruyama H, Nishimura H, et al. Effects of Saireito, a Japanese herbal medicine, on edema via antagonistic actions against aldosterone in anti-GBM nephritic rats. Clin Exp Nephrol 2006; 10:13-18.
107. Kaneko T, Chiba H, Horie N, et al. Inhibition of prostaglandin E2 production by flavone and its related compounds. In Vivo 2010; 24:55-58.
108. Kaneko T, Chiba H, Horie N, et al. Effect of Scutellariae radix ingredients on prostaglandin E(2) production and COX-2 expression by LPS-activated macrophage. In Vivo 2009; 23:577-581.
109. Iwai I, Suda T, Tozawa F, et al. Stimulatory effect of Saireito on proopiomelanocortin gene expression in the rat anterior pituitary gland. Neurosci Lett 1993; 157:37-40.
110. Sato Y, Akao T, He JX, et al. Glycycoumarin from Glycyrrhizae Radix acts as a potent antispasmodic through inhibition of phosphodiesterase 3. J Ethnopharmacol 2006; 105:409-414.
111. Ikeda Y, Kaneko A, Yamamoto M, Ishige A, Sasaki H. Possible involvement of suppression of Th2 differentiation in the antiallergic effect of Sho-seiryu-to in mice. Jpn J Pharmacol 2002; 90:328-336.
112. Tanaka A, Ohashi Y, Kakinoki Y, et al. The herbal medicine shoseiryu-to inhibits allergen-induced synthesis of tumour necrosis factor alpha by peripheral blood mononuclear cells in patients with perennial allergic rhinitis. Acta Otolaryngol Suppl 1998; 538:118-125.
113. Ikeda K, Wu DZ, Ishigaki M, Sunose H, Takasaka T. Inhibitory effects of sho-seiryu-to on acetylcholine-induced responses in nasal gland acinar cells. Am J Chin Med 1994; 22:191-196.
114. Tohda Y, Haraguchi R, Kubo H, Muraki M, Fukuoka M, Nakajima S. Effects of saiboku-to on the survival of human eosinophils. Methods Find Exp Clin Pharmacol 1999; 21:327-330.
115. Tamaoki J, Kondo M, Chiyotani A, Takemura H, Konno K. Effect of saiboku-to, an antiasthmatic herbal medicine, on nitric oxide generation from cultured canine airway epithelial cells. Jpn J Pharmacol 1995; 69:29-35.
116. Sakamoto S, Kudo H, Kawasaki T, et al. Effects of a Chinese herbal medicine, keishi-bukuryo-gan, on the gonadal system of rats. J Ethnopharmacol 1988; 23:151-158.
117. Mori T, Sakamoto S, Matsuda M, et al. Suppression of spontaneous development of uterine adenomyosis and mammary hyperplastic alveolar nodules by Chinese herbal medicines in mice. Am J Chin Med 1993; 21:263-268.
118. Kito Y, Suzuki H. Effects of Dai-kenchu-to on spontaneous activity in the mouse small intestine. J Smooth Muscle Res 2006; 42:189-201.
119. Kono T, Omiya Y, Hira Y, et al. Daikenchuto (TU-100) ameliorates colon microvascular dysfunction via endogenous adrenomedullin in Crohn's disease rat model. J Gastroenterol 2011; 46:1187-196.
120. Nyunt AK, Takeuchi Y, Yokomuro K, Miyanaga Y. Comparative studies on the antiallergic effects of kampo medicines used for the therapy of respiratory diseases. Arerugi 1995; 44:503-512.
121. Homma M, Minami M, Taniguchi C, et al. Inhibitory effects of lignans and flavonoids in saiboku-to, a herbal medicine for bronchial asthma, on the release of leukotrienes from human polymorphonuclear leukocytes. Planta Med 2000; 66:88-91.
122. Kobayashi I, Hamasaki Y, Yamamoto S, et al. [Inhibitory effects of saiboku-to and compornent herbs on the production of peptide leukotrienes (LTs) and LTB4]. Arerugi 1996; 45:577-583.
123. Yakabi K, Kurosawa S, Tamai M, et al. Rikkunshito and 5-HT2C receptor antagonist improve cisplatin-induced anorexia via hypothalamic ghrelin interaction. Regul Pept 2010; 161:97-105.