The role of ghrelin in patients with functional dyspepsia and its potential clinical relevance (Review)
- Authors:
- Takakazu Yagi
- Akihiro Asakawa
- Hirotaka Ueda
- Shouichi Miyawaki
- Akio Inui
-
Affiliations: Department of Orthodontics and Dentofacial Orthopedics, Medical and Dental Hospital, Kagoshima University, Kagoshima 890-8544, Japan, Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan, Department of Orthodontics and Dentofacial Orthopedics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan - Published online on: June 14, 2013 https://doi.org/10.3892/ijmm.2013.1418
- Pages: 523-531
This article is mentioned in:
Abstract
Tack J, Talley NJ, Camilleri M, et al: Functional gastroduodenal disorders. Gastroenterology. 130:1466–1479. 2006. View Article : Google Scholar | |
Geeraerts B and Tack J: Functional dyspepsia: past, present, and future. J Gastroenterol. 43:251–255. 2008. View Article : Google Scholar : PubMed/NCBI | |
Tack J and Talley NJ: Gastroduodenal disorders. Am J Gastroenterol. 105:757–763. 2010. View Article : Google Scholar | |
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H and Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 402:656–660. 1999. View Article : Google Scholar : PubMed/NCBI | |
Matsumoto M, Kitajima Y, Iwanami T, et al: Structural similarity of ghrelin derivatives to peptidyl growth hormone secretagogues. Biochem Biophys Res Commun. 284:655–659. 2001. View Article : Google Scholar : PubMed/NCBI | |
Tanaka M, Hayashida Y, Iguchi T, Nakao N, Nakai N and Nakashima K: Organization of the mouse ghrelin gene and promoter: occurrence of a short noncoding first exon. Endocrinology. 142:3697–3700. 2001. View Article : Google Scholar : PubMed/NCBI | |
Hosoda H, Kojima M, Matsuo H and Kangawa K: Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun. 279:909–913. 2000. View Article : Google Scholar : PubMed/NCBI | |
Chen CY, Asakawa A, Fujimiya M, Lee SD and Inui A: Ghrelin gene products and the regulation of food intake and gut motility. Pharmacol Rev. 61:430–481. 2009. View Article : Google Scholar : PubMed/NCBI | |
Asakawa A, Inui A, Kaga T, et al: Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology. 120:337–345. 2001. View Article : Google Scholar : PubMed/NCBI | |
Nakazato M, Murakami N, Date Y, et al: A role for ghrelin in the central regulation of feeding. Nature. 409:194–198. 2001. View Article : Google Scholar : PubMed/NCBI | |
Wren AM, Small CJ, Ward HL, et al: The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 141:4325–4328. 2000. View Article : Google Scholar : PubMed/NCBI | |
Inui A: Ghrelin: an orexigenic and somatotrophic signal from the stomach. Nat Rev Neurosci. 2:551–560. 2001. View Article : Google Scholar : PubMed/NCBI | |
An W, Li Y, Xu G, et al: Modulation of ghrelin O-acyltransferase expression in pancreatic islets. Cell Physiol Biochem. 26:707–716. 2010. | |
Murray CD, Martin NM, Patterson M, et al: Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study. Gut. 54:1693–1698. 2005. View Article : Google Scholar : PubMed/NCBI | |
Tack J, Depoortere I, Bisschops R, Verbeke K, Janssens J and Peeters T: Influence of ghrelin on gastric emptying and meal-related symptoms in idiopathic gastroparesis. Aliment Pharmacol Ther. 22:847–853. 2005. View Article : Google Scholar : PubMed/NCBI | |
Tack J, Depoortere I, Bisschops R, et al: Influence of ghrelin on interdigestive gastrointestinal motility in humans. Gut. 55:327–333. 2006. View Article : Google Scholar : PubMed/NCBI | |
Mori M, Suzuki H, Masaoka T, et al: Intravenous ghrelin administration enhances gastric acid secretion - evaluation using wireless pH capsule. Aliment Pharmacol Ther. 24:96–103. 2006. View Article : Google Scholar | |
Masuda Y, Tanaka T, Inomata N, et al: Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun. 276:905–908. 2000. View Article : Google Scholar : PubMed/NCBI | |
Castaneda TR, Tong J, Datta R, Culler M and Tschop MH: Ghrelin in the regulation of body weight and metabolism. Front Neuroendocrinol. 31:44–60. 2010. View Article : Google Scholar : PubMed/NCBI | |
Fetissov SO, Laviano A, Kalra S and Inui A: Update on ghrelin. Int J Pept. 2010:9635012010. View Article : Google Scholar | |
Asakawa A, Inui A, Kaga T, et al: A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology. 74:143–147. 2001. View Article : Google Scholar : PubMed/NCBI | |
Hotta M, Ohwada R, Akamizu T, Shibasaki T, Takano K and Kangawa K: Ghrelin increases hunger and food intake in patients with restricting-type anorexia nervosa: a pilot study. Endocr J. 56:1119–1128. 2009. View Article : Google Scholar : PubMed/NCBI | |
Akamizu T, Iwakura H, Ariyasu H, et al: Effects of ghrelin treatment on patients undergoing total hip replacement for osteoarthritis: different outcomes from studies in patients with cardiac and pulmonary cachexia. J Am Geriatr Soc. 56:2363–2365. 2008. View Article : Google Scholar : PubMed/NCBI | |
Miki K, Maekura R, Nagaya N, et al: Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled trial. PloS One. 7:e357082012. View Article : Google Scholar | |
Akamizu T, Iwakura H, Ariyasu H, et al: Repeated administration of ghrelin to patients with functional dyspepsia: its effects on food intake and appetite. Eur J Endocrinol. 158:491–498. 2008. View Article : Google Scholar : PubMed/NCBI | |
Wo JM, Ejskjaer N, Hellstrom PM, et al: Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting - randomised clinical study subset data. Aliment Pharmacol Ther. 33:679–688. 2011. View Article : Google Scholar | |
Drossman DA and Dumitrascu DL: Rome III: New standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis. 15:237–241. 2006.PubMed/NCBI | |
Miwa H: Why dyspepsia can occur without organic disease: pathogenesis and management of functional dyspepsia. J Gastroenterol. 47:862–871. 2012. View Article : Google Scholar : PubMed/NCBI | |
Miwa H: Life style in persons with functional gastrointestinal disorders - large-scale internet survey of lifestyle in Japan. Neurogastroenterol Motil. 24:464–471. e2172012. View Article : Google Scholar : PubMed/NCBI | |
Norton GR, Norton PJ, Asmundson GJ, Thompson LA and Larsen DK: Neurotic butterflies in my stomach: the role of anxiety, anxiety sensitivity and depression in functional gastrointestinal disorders. J Psychosom Res. 47:233–240. 1999. View Article : Google Scholar : PubMed/NCBI | |
Khoo J, Rayner CK, Feinle-Bisset C, Jones KL and Horowitz M: Gastrointestinal hormonal dysfunction in gastroparesis and functional dyspepsia. Neurogastroenterol Motil. 22:1270–1278. 2010. View Article : Google Scholar : PubMed/NCBI | |
Quartero AO, de Wit NJ, Lodder AC, Numans ME, Smout AJ and Hoes AW: Disturbed solid-phase gastric emptying in functional dyspepsia: a meta-analysis. Dig Dis Sci. 43:2028–2033. 1998. View Article : Google Scholar : PubMed/NCBI | |
Geeraerts B, Van Oudenhove L, Fischler B, et al: Influence of abuse history on gastric sensorimotor function in functional dyspepsia. Neurogastroenterol Motil. 21:33–41. 2009. View Article : Google Scholar : PubMed/NCBI | |
Holtmann G, Siffert W, Haag S, et al: G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 126:971–979. 2004. View Article : Google Scholar : PubMed/NCBI | |
Toyoshima F, Oshima T, Nakajima S, et al: Serotonin transporter gene polymorphism may be associated with functional dyspepsia in a Japanese population. BMC Med Genet. 12:882011. View Article : Google Scholar : PubMed/NCBI | |
Mearin F, Perez-Oliveras M, Perello A, et al: Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak: one-year follow-up cohort study. Gastroenterology. 129:98–104. 2005.PubMed/NCBI | |
Drossman DA: The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 130:1377–1390. 2006. View Article : Google Scholar : PubMed/NCBI | |
Danesh J, Lawrence M, Murphy M, Roberts S and Collins R: Systematic review of the epidemiological evidence on Helicobacter pylori infection and nonulcer or uninvestigated dyspepsia. Arch Intern Med. 160:1192–1198. 2000.PubMed/NCBI | |
Kawamura A, Adachi K, Takashima T, et al: Prevalence of functional dyspepsia and its relationship with Helicobacter pylori infection in a Japanese population. J Gastroenterol Hepatol. 16:384–388. 2001. View Article : Google Scholar : PubMed/NCBI | |
Thumshirn M, Camilleri M, Saslow SB, Williams DE, Burton DD and Hanson RB: Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal function. Gut. 44:55–64. 1999. View Article : Google Scholar : PubMed/NCBI | |
Sarnelli G, Cuomo R, Janssens J and Tack J: Symptom patterns and pathophysiological mechanisms in dyspeptic patients with and without Helicobacter pylori. Dig Dis Sci. 48:2229–2236. 2003. View Article : Google Scholar : PubMed/NCBI | |
Savarino E, Zentilin P, Dulbecco P, Malesci A and Savarino V: The role of Acid in functional dyspepsia. Am J Gastroenterol. 106:1168–1169. 2011. View Article : Google Scholar : PubMed/NCBI | |
Jin X and Li YM: Systematic review and meta-analysis from Chinese literature: the association between Helicobacter pylori eradication and improvement of functional dyspepsia. Helicobacter. 12:541–546. 2007. View Article : Google Scholar : PubMed/NCBI | |
Moayyedi P, Soo S, Deeks J, et al: Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev. 2006:CD0020962006.PubMed/NCBI | |
Moayyedi P: Helicobacter pylori eradication for functional dyspepsia: what are we treating?: comment on ‘Helicobacter pylori eradication in functional dyspepsia’. Arch Intern Med. 171:1936–1937. 2011. View Article : Google Scholar | |
Suzuki H and Moayyedi P: Helicobacter pylori infection in functional dyspepsia. Nat Rev Gastroenterol Hepatol. 10:168–174. 2013. View Article : Google Scholar | |
Sugano K: Should we still subcategorize Helicobacter pylori-associated dyspepsia as functional disease? J Neurogastroenterol Motil. 17:366–371. 2011. View Article : Google Scholar : PubMed/NCBI | |
Tack J, Caenepeel P, Fischler B, Piessevaux H and Janssens J: Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology. 121:526–535. 2001. View Article : Google Scholar : PubMed/NCBI | |
Boeckxstaens GE, Rumessen JJ, de Wit L, Tytgat GN and Vanderwinden JM: Abnormal distribution of the interstitial cells of cajal in an adult patient with pseudo-obstruction and megaduodenum. Am J Gastroenterol. 97:2120–2126. 2002. View Article : Google Scholar : PubMed/NCBI | |
Rhee PL, Kim YH, Son HJ, et al: Evaluation of individual symptoms cannot predict presence of gastric hypersensitivity in functional dyspepsia. Dig Dis Sci. 45:1680–1684. 2000. View Article : Google Scholar : PubMed/NCBI | |
Chrousos GP: Regulation and dysregulation of the hypothalamic-pituitary-adrenal axis. The corticotropin-releasing hormone perspective. Endocrinol Metab Clin North Am. 21:833–858. 1992.PubMed/NCBI | |
Lamberts SW, Verleun T, Oosterom R, de Jong F and Hackeng WH: Corticotropin-releasing factor (ovine) and vasopressin exert a synergistic effect on adrenocorticotropin release in man. J Clin Endocrinol Metab. 58:298–303. 1984. View Article : Google Scholar : PubMed/NCBI | |
Vale W, Spiess J, Rivier C and Rivier J: Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science. 213:1394–1397. 1981. View Article : Google Scholar : PubMed/NCBI | |
Vaughan J, Donaldson C, Bittencourt J, et al: Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature. 378:287–292. 1995. View Article : Google Scholar : PubMed/NCBI | |
Bale TL and Vale WW: CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol. 44:525–557. 2004. View Article : Google Scholar : PubMed/NCBI | |
Ataka K, Kuge T, Fujino K, Takahashi T and Fujimiya M: Wood creosote prevents CRF-induced motility via 5-HT3 receptors in proximal and 5-HT4 receptors in distal colon in rats. Auton Neurosci. 133:136–145. 2007. View Article : Google Scholar : PubMed/NCBI | |
Martinez V, Rivier J, Wang L and Tache Y: Central injection of a new corticotropin-releasing factor (CRF) antagonist, astressin, blocks CRF- and stress-related alterations of gastric and colonic motor function. J Pharmacol Exp Ther. 280:754–760. 1997. | |
Tache Y, Martinez V, Million M and Wang L: Stress and the gastrointestinal tract III. Stress-related alterations of gut motor function: role of brain corticotropin-releasing factor receptors. Am J Physiol Gastrointest Liver Physiol. 280:G173–G177. 2001.PubMed/NCBI | |
O'Mahony SM, Marchesi JR, Scully P, et al: Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 65:263–267. 2009. View Article : Google Scholar : PubMed/NCBI | |
Brevet M, Kojima H, Asakawa A, et al: Chronic foot-shock stress potentiates the influx of bone marrow-derived microglia into hippocampus. J Neurosci Res. 88:1890–1897. 2010.PubMed/NCBI | |
Sengupta JN: Visceral pain: the neurophysiological mechanism. Handb Exp Pharmacol. 194:31–74. 2009. View Article : Google Scholar : PubMed/NCBI | |
Shindo T, Futagami S, Hiratsuka T, et al: Comparison of gastric emptying and plasma ghrelin levels in patients with functional dyspepsia and non-erosive reflux disease. Digestion. 79:65–72. 2009. View Article : Google Scholar : PubMed/NCBI | |
Lee KJ, Cha DY, Cheon SJ, Yeo M and Cho SW: Plasma ghrelin levels and their relationship with gastric emptying in patients with dysmotility-like functional dyspepsia. Digestion. 80:58–63. 2009. View Article : Google Scholar : PubMed/NCBI | |
Sarnelli G, Caenepeel P, Geypens B, Janssens J and Tack J: Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol. 98:783–788. 2003. View Article : Google Scholar : PubMed/NCBI | |
Asakawa A, Inui A, Ueno N, Makino S, Fujino MA and Kasuga M: Urocortin reduces food intake and gastric emptying in lean and ob/ob obese mice. Gastroenterology. 116:1287–1292. 1999. View Article : Google Scholar : PubMed/NCBI | |
Fujino K, Inui A, Asakawa A, Kihara N, Fujimura M and Fujimiya M: Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats. J Physiol. 550:227–240. 2003. View Article : Google Scholar : PubMed/NCBI | |
Fujimiya M, Itoh E, Kihara N, Yamamoto I, Fujimura M and Inui A: Neuropeptide Y induces fasted pattern of duodenal motility via Y(2) receptors in conscious fed rats. Am J Physiol Gastrointest Liver Physiol. 278:G32–G38. 2000.PubMed/NCBI | |
Fujimiya M, Asakawa A, Ataka K, Kato I and Inui A: Different effects of ghrelin, des-acyl ghrelin and obestatin on gastroduodenal motility in conscious rats. World J Gastroenterol. 14:6318–6326. 2008. View Article : Google Scholar : PubMed/NCBI | |
Peeters TL: Central and peripheral mechanisms by which ghrelin regulates gut motility. J Physiol Pharmacol. 54(Suppl 4): S95–S103. 2003.PubMed/NCBI | |
Venkova K and Greenwood-Van Meerveld B: Application of ghrelin to gastrointestinal diseases. Curr Opin Investig Drugs. 9:1103–1107. 2008.PubMed/NCBI | |
Asakawa A, Inui A, Fujimiya M, et al: Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut. 54:18–24. 2005. View Article : Google Scholar : PubMed/NCBI | |
Ariyasu H, Takaya K, Iwakura H, et al: Transgenic mice overexpressing des-acyl ghrelin show small phenotype. Endocrinology. 146:355–364. 2005. View Article : Google Scholar : PubMed/NCBI | |
Chen CY, Chao Y, Chang FY, Chien EJ, Lee SD and Doong ML: Intracisternal des-acyl ghrelin inhibits food intake and non-nutrient gastric emptying in conscious rats. Int J Mol Med. 16:695–699. 2005.PubMed/NCBI | |
Chen CY, Inui A, Asakawa A, et al: Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology. 129:8–25. 2005. View Article : Google Scholar : PubMed/NCBI | |
Inhoff T, Monnikes H, Noetzel S, et al: Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats. Peptides. 29:2159–2168. 2008. View Article : Google Scholar : PubMed/NCBI | |
Qader SS, Hakanson R, Rehfeld JF, Lundquist I and Salehi A: Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas. Regul Pept. 146:230–237. 2008. View Article : Google Scholar | |
Banks WA, Tschop M, Robinson SM and Heiman ML: Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther. 302:822–827. 2002. View Article : Google Scholar : PubMed/NCBI | |
Martinez V, Barquist E, Rivier J and Tache Y: Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF2 receptors. Am J Physiol. 274:G965–G970. 1998.PubMed/NCBI | |
Million M, Maillot C, Saunders P, Rivier J, Vale W and Tache Y: Human urocortin II, a new CRF-related peptide, displays selective CRF(2)-mediated action on gastric transit in rats. Am J Physiol Gastrointest Liver Physiol. 282:G34–G40. 2002. View Article : Google Scholar : PubMed/NCBI | |
Kihara N, Fujimura M, Yamamoto I, Itoh E, Inui A and Fujimiya M: Effects of central and peripheral urocortin on fed and fasted gastroduodenal motor activity in conscious rats. Am J Physiol Gastrointest Liver Physiol. 280:G406–G419. 2001.PubMed/NCBI | |
Zhang JV, Ren PG, Avsian-Kretchmer O, et al: Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science. 310:996–999. 2005. View Article : Google Scholar | |
Chartrel N, Alvear-Perez R, Leprince J, et al: Comment on ‘Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake’. Science. 315:7662007. | |
Holst B, Egerod KL, Schild E, et al: GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology. 148:13–20. 2007. View Article : Google Scholar : PubMed/NCBI | |
Tremblay F, Perreault M, Klaman LD, Tobin JF, Smith E and Gimeno RE: Normal food intake and body weight in mice lacking the G protein-coupled receptor GPR39. Endocrinology. 148:501–506. 2007. View Article : Google Scholar : PubMed/NCBI | |
Bassil AK, Haglund Y, Brown J, et al: Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract. Br J Pharmacol. 150:58–64. 2007. View Article : Google Scholar : PubMed/NCBI | |
Bresciani E, Rapetti D, Dona F, et al: Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat. J Endocrinol Invest. 29:RC16–RC18. 2006. View Article : Google Scholar : PubMed/NCBI | |
Ataka K, Inui A, Asakawa A, Kato I and Fujimiya M: Obestatin inhibits motor activity in the antrum and duodenum in the fed state of conscious rats. Am J Physiol Gastrointest Liver Physiol. 294:G1210–G1218. 2008. View Article : Google Scholar : PubMed/NCBI | |
Takamori K, Mizuta Y, Takeshima F, et al: Relation among plasma ghrelin level, gastric emptying, and psychologic condition in patients with functional dyspepsia. J Clin Gastroenterol. 41:477–483. 2007. View Article : Google Scholar : PubMed/NCBI | |
Nishizawa T, Suzuki H, Nomoto Y, et al: Enhanced plasma ghrelin levels in patients with functional dyspepsia. Aliment Pharmacol Ther. 24(Suppl 4): S104–S110. 2006. View Article : Google Scholar | |
Shinomiya T, Fukunaga M, Akamizu T, et al: Plasma acylated ghrelin levels correlate with subjective symptoms of functional dyspepsia in female patients. Scand J Gastroenterol. 40:648–653. 2005. View Article : Google Scholar : PubMed/NCBI | |
Kim YS, Lee JS, Lee TH, et al: Plasma levels of acylated ghrelin in patients with functional dyspepsia. World J Gastroenterol. 18:2231–2237. 2012. View Article : Google Scholar : PubMed/NCBI | |
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. 295:G403–G411. 2008. View Article : Google Scholar : PubMed/NCBI | |
Tack J, Janssen P, Masaoka T, Farre R and Van Oudenhove L: Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia. Clin Gastroenterol Hepatol. 10:1239–1245. 2012. View Article : Google Scholar : PubMed/NCBI | |
Seto Y, Yoshida N and Kaneko H: Effects of mosapride citrate, a 5-HT4-receptor agonist, on gastric distension-induced visceromotor response in conscious rats. J Pharmacol Sci. 116:47–53. 2011. View Article : Google Scholar : PubMed/NCBI | |
Lee JW, Sung KW, Lee OY, Lee SE and Sohn CI: The effects of 5-HT4 receptor agonist, mosapride citrate, on visceral hypersensitivity in a rat model. Dig Dis Sci. 57:1517–1524. 2012. View Article : Google Scholar : PubMed/NCBI | |
Fujitsuka N, Asakawa A, Amitani H, Hattori T and Inui A: Efficacy of ghrelin in cancer cachexia: clinical trials and a novel treatment by rikkunshito. Crit Rev Oncog. 17:277–284. 2012. View Article : Google Scholar : PubMed/NCBI | |
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. 59:62–66. 2012.PubMed/NCBI | |
Takeda H, Sadakane C, Hattori T, et al: Rikkunshito, an herbal medicine, suppresses cisplatin-induced anorexia in rats via 5-HT2 receptor antagonism. Gastroenterology. 134:2004–2013. 2008. View Article : Google Scholar : PubMed/NCBI | |
Matsumura T, Arai M, Yonemitsu Y, et al: The traditional Japanese medicine Rikkunshito increases the plasma level of ghrelin in humans and mice. J Gastroenterol. 45:300–307. 2010. View Article : Google Scholar : PubMed/NCBI |