Effect Of Rikkunshito Research Articles

Effects of the Japanese kampo medicine, Rikkunshito, on gastrointestinal motility functions

Background: Rikkunshito is known as a prokinetic agent for gastrointestinal (GI) diseases. Objectives: The objective was to find the effect of GI motility with Rikkunshito. Materials and Methods: The prokinetic effect of Rikkunshito was investigated by studying the gastric emptying (GE) and intestinal transit rate (ITR) or experimentally induced GI motility dysfunction (GMD). Results: The oral administration of Rikkunshito significantly increased GE and ITR and restored the delayed GE and ITR. Its effect was similar to that of conventional prokinetics, such as domperidone and mosapride. Moreover, we made the mouse GMD models, such as acetic acid or streptozotocin, and ITR had shown a great decrease. This decrease was recovered by Rikkunshito. Conclusion: Rikkunshito revealed its prokinetic effect through an increase of GE and ITR. We found a great possibility of Rikkunshito for the GI control drug.

Prophylactic effect of rikkunshito, an herbal medicine, for chemotherapy-induced nausea in thoracic cancer patients receiving carboplatin-based chemotherapy.

Rikkunshito has been shown to improve upper gastrointestinal symptoms and anorexia. The aim of this study was to evaluate whether rikkunshito improves chemotherapy-induced nausea in thoracic cancer patients receiving carboplatin (CBDCA)-based chemotherapy. A retrospective before-and-after comparison study was conducted in patients with thoracic cancer receiving the first cycle of CBDCA-based chemotherapy. Among 61 eligible patients, 34 received standard antiemetic therapy with a combination of 5-hydroxytryptamine-3 receptor antagonist and dexamethasone from September 2012 and June 2013 (standard group), while the other 27 received the standard antiemetic therapy plus oral rikkunshito from July 2013 and December 2014 (rikkunshito group). The rates of no nausea showed no significant difference between the standard and rikkunshito group (Overall phase: 64.7 % for standard group vs 74.1 % for rikkunshito group, p = 0.579). Subgroup analysis indicated that, in female patients, the rates of no nausea in rikkunshito groups was significantly higher than in standard group (overall phase: 44.4 % vs 100 %, p = 0.034). Rikkunshito did not demonstrate an additional prophylactic effect on standard antiemetic therapy for nausea in patients with thoracic cancer receiving CBDCA-based chemotherapy, but showed a prophylactic effect of nausea in female patients.

Tu1309 – Effect of Rikkunshito on Gastrointestinal Motility and Upper Gastrointestinal Symptoms - the First Study in a Belgian Functional Dyspepsia Population

Tu1309 – Effect of Rikkunshito on Gastrointestinal Motility and Upper Gastrointestinal Symptoms - the First Study in a Belgian Functional Dyspepsia Population

The Effect of Rikkunshito on Gastric Accommodation and Nutrient Volume Tolerance in Functional Dyspepsia

The Effect of Rikkunshito on Gastric Accommodation and Nutrient Volume Tolerance in Functional Dyspepsia

Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia.

Despite the similar phenotypes, including weight loss, reduction of food intake, and lower adiposity, associated with caloric restriction (CR) and cancer cachexia (CC), CC is a progressive wasting syndrome, while mild CR improves whole body metabolism. In the present study, we compared adipose metabolic changes in a novel rat model of CC, mild CR (70% of the food intake of control rats, which is similar to the food consumption of CC rats), and severe CR (30% of the food intake of controls). We show that CC and severe CR are associated with much smaller adipocytes with significantly lower mitochondrial DNA content; but, that mild CR is not. CC and both mild and severe CR similarly upregulated proteins involved in lipolysis. CC also downregulated proteins involved in fatty acid biosynthesis, but mild CR upregulated these. These findings suggest that CC might impair de novo fatty acid biosynthesis and reduce mitochondrial biogenesis, similar to severe CR. We also found that rikkunshito, a traditional Japanese herbal medicine, does not ameliorate the enhanced lipolysis and mitochondrial impairment, but rather, rescues de novo fatty acid biosynthesis, suggesting that rikkunshito administration might have partially similar effects to mild CR.

Influence of food on the gastric motor effect of the Kampo medicine rikkunshito in rat.

Rikkunshito, one of the Kampo medicines, is widely prescribed as a remedy for various upper gastrointestinal syndromes. The effect of rikkunshito is related to endogenous ghrelin and its active ingredient atractylodin enhances ghrelin receptor signaling. Kampo medicines are traditionally administered before or between meals; however, no definitive benefit of the timing of administration has been proven yet. To clarify the influence of food on the pharmacological action of rikkunshito, we investigated the gastric motor activity and pharmacokinetic profiles of atractylodin after the administration of rikkunshito in fasted and fed rats. Phase III-like contractions in the gastric antrum after an injection of ghrelin were measured using a strain gauge force transducer. Rikkunshito was administered to rats during fasting or after a nutrient test meal. Ghrelin was injected 30minutes later and gastric motility was evaluated. Furthermore, after rikkunshito administration, the pharmacokinetic profiles of atractylodin in the plasma and brain of fasted and free-fed rats were assessed. Rikkunshito administration potentiated ghrelin-induced phase III-like contractions under fasting conditions. This effect was attenuated in animals fed a test meal. Atractylodin was detected pharmacokinetically in the plasma and brain after rikkunshito administration in rats, and free-fed rats exhibited a decreased maximum concentration of plasma atractylodin and a delayed time to reach the maximum concentration. We show that the pharmacological action of rikkunshito is influenced by food in rats. The efficacy of rikkunshito may be associated with decreased absorption of its active ingredient atractylodin when food is in the stomach.

1473P - The effect of rikkunshito, a traditional Japanese herbal medicine, on food intake and plasma acylated ghrelin levels in lung cancer patients treated with platinum-based chemotherapy

1473P - The effect of rikkunshito, a traditional Japanese herbal medicine, on food intake and plasma acylated ghrelin levels in lung cancer patients treated with platinum-based chemotherapy

Gastric emptying and colonic transit in patients with Parkinson's disease. Effects of Rikkunshi-to on gastrointestinal dysfunction

s from The Japanese Journal: The Autonomic Nervous System #1 Heart rate variability in menopausal state. Analysis with short-time measurements at rest and after work load Yuka Goto, Hiroyuki Okuda, Yuko Nakamura, Mikiya Nakatsuka Kurashiki Daiichi Hospital Outpatient Kampo Clinic for Women, Okayama 710-0826, Japan Graduate School of Health Sciences, Okayama University, Okayama 700-8558, Japan The aim of this study was to compare heart rate variability (HRV) between women in pre-menopausal state and women in postmenopausal state, and to determine whether difference in age and estrogen-level could account for any difference in HRV between the two groups. 264 subjectswere analyzedwithoutmaking adjustments for age. In this study the post-menopausal state was characterized by amenorrhea of more than 12 months, an E2 value of 20 pg/ml in the blood, and an FSH blood level higher than 40 mlU/ml. We have found that in the post-menopausal state the value of VLF, LF, HF at rest, HR and LF/HF ratio atmaximum load, and VLF and LF after exercise, were significantly lower than in the pre-menopausal state. Subsequently, 36 subjects were analyzed after adjusting for age. The resultswere almost the same before and after adjustment for age. In conclusion, women in post-menopausal state, showed less fluctuation of autonomic nervous activity represented by HRV than women in pre-menopausal state. (The Autonomic Nervous System, 50: 293-299, 2013). doi:10.1016/j.autneu.2014.09.005 #2 Gastric emptying and colonic transit in patients with Parkinson's disease. Effects of Rikkunshi-to on gastrointestinal dysfunction Hirokazu Doi, Ryuji Sakakibara, Masahiko Kishi, Yohei Tsuyuzaki, Fuyuki Tateno, Shigekazu Hiraia, Tohru Masaka, Mitsutoshi Sato Pharmaceutical Unit, Sakura Medical Center, Toho University, Chiba 285-8741, Japan Neurology, Internal Medicine, Sakura Medical Center, Toho University, Chiba 285-8741, Japan Chemical Pharmacology, Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan Gastric motility impairment and constipation are common complications of Parkinson's disease. Degeneration of enteric nerves and ganglia is considered to be part of the pathogenesis of those autonomic dysfunctions. In this study, we evaluated the correlation between gastric emptying and colonic transit time in 56 Parkinson's disease patients. In addition, we investigated the effect of Rikkunshi-to, an extract of the dietary herbs commonly used for dyspepsia, in 9 patients. Gastric emptyingwas examined by the 13C-acetate breath test [the peak time of the 13C percentage-dose-excess curve (Tmax-13C)]. Colonic transit time (CTT) was examined after ingestion of a radio-opaque marker. In Parkinson's disease patients, Tmax-13C and CTT were markedly delayed when compared with the data from a normal group published in previous reports. Although therewas not significant correlation between Tmax-13C and CTT among these patients, the frequency of highly delayed gastric emptying (Tmax-13C ≧ 75 min) tended to be larger in patients with delayed CTT (CTT N 39 h). Rikkunshi-to was administered at the dose of 15 g/day to 9 patients, of whom 8 had delayed CTT and 4 had delayed gastric emptying. Tmax-13C and CTTweremeasured before and after the treatment. After three months of treatment, 7 of the 8 patients with delayed CTT had an improvement; the Tmax-13C test was improved in all the 4 patients with delayed gastric emptying. These results suggest that Rikkunshi-has beneficial effects in Parkinson's disease patientswith constipation and/orwith delayed gastric emptying. (The Autonomic Nervous System, 50: 300-305, 2013). doi:10.1016/j.autneu.2014.09.006 #3 Effects of pain caused by orthodontic tooth movement on autonomic nervous system Jun Oba, Naoto Hara, Yasue Kotegawa, Yukiko Miyazawa, Kazuo Mukuno, Hiroo Oda, Kazuichi Yoshida Department of Orthodontics, Kanagawa Dental University Yokohama Dental and Medical Clinic, Kanagawa 221-0835, Japan Department of Ophthalmology, Kanagawa Dental University, Yokohama Dental and Medical Clinic, Kanagawa 221-0835, Japan Department of Orthodontics, Kanagawa Dental University Hospital, Kanagawa 238-8580, Japan Department of Anesthesiology, Graduate School of Kanagawa Dental University, Kanagawa 238-8580, Japan In order to investigate the effects of pain caused by orthodontic tooth movement on the autonomic nervous system, we selected three healthy men and three healthy women (mean age: 30.3 ± 8.4 years) and inserted separating elastic strips between the upper right first molar and the adjacent tooth to induce pain due to the tooth movement, and we conducted our testing after 3, 6, 9 and 24 h. The degree of pain was Autonomic Neuroscience: Basic and Clinical 186 (2014) 95–98

Heart rate variability in menopausal state. Analysis with short-time measurements at rest and after work load

s from The Japanese Journal: The Autonomic Nervous System #1 Heart rate variability in menopausal state. Analysis with short-time measurements at rest and after work load Yuka Goto, Hiroyuki Okuda, Yuko Nakamura, Mikiya Nakatsuka Kurashiki Daiichi Hospital Outpatient Kampo Clinic for Women, Okayama 710-0826, Japan Graduate School of Health Sciences, Okayama University, Okayama 700-8558, Japan The aim of this study was to compare heart rate variability (HRV) between women in pre-menopausal state and women in postmenopausal state, and to determine whether difference in age and estrogen-level could account for any difference in HRV between the two groups. 264 subjectswere analyzedwithoutmaking adjustments for age. In this study the post-menopausal state was characterized by amenorrhea of more than 12 months, an E2 value of 20 pg/ml in the blood, and an FSH blood level higher than 40 mlU/ml. We have found that in the post-menopausal state the value of VLF, LF, HF at rest, HR and LF/HF ratio atmaximum load, and VLF and LF after exercise, were significantly lower than in the pre-menopausal state. Subsequently, 36 subjects were analyzed after adjusting for age. The resultswere almost the same before and after adjustment for age. In conclusion, women in post-menopausal state, showed less fluctuation of autonomic nervous activity represented by HRV than women in pre-menopausal state. (The Autonomic Nervous System, 50: 293-299, 2013). doi:10.1016/j.autneu.2014.09.005 #2 Gastric emptying and colonic transit in patients with Parkinson's disease. Effects of Rikkunshi-to on gastrointestinal dysfunction Hirokazu Doi, Ryuji Sakakibara, Masahiko Kishi, Yohei Tsuyuzaki, Fuyuki Tateno, Shigekazu Hiraia, Tohru Masaka, Mitsutoshi Sato Pharmaceutical Unit, Sakura Medical Center, Toho University, Chiba 285-8741, Japan Neurology, Internal Medicine, Sakura Medical Center, Toho University, Chiba 285-8741, Japan Chemical Pharmacology, Pharmaceutical Sciences, Toho University, Chiba 274-8510, Japan Gastric motility impairment and constipation are common complications of Parkinson's disease. Degeneration of enteric nerves and ganglia is considered to be part of the pathogenesis of those autonomic dysfunctions. In this study, we evaluated the correlation between gastric emptying and colonic transit time in 56 Parkinson's disease patients. In addition, we investigated the effect of Rikkunshi-to, an extract of the dietary herbs commonly used for dyspepsia, in 9 patients. Gastric emptyingwas examined by the 13C-acetate breath test [the peak time of the 13C percentage-dose-excess curve (Tmax-13C)]. Colonic transit time (CTT) was examined after ingestion of a radio-opaque marker. In Parkinson's disease patients, Tmax-13C and CTT were markedly delayed when compared with the data from a normal group published in previous reports. Although therewas not significant correlation between Tmax-13C and CTT among these patients, the frequency of highly delayed gastric emptying (Tmax-13C ≧ 75 min) tended to be larger in patients with delayed CTT (CTT N 39 h). Rikkunshi-to was administered at the dose of 15 g/day to 9 patients, of whom 8 had delayed CTT and 4 had delayed gastric emptying. Tmax-13C and CTTweremeasured before and after the treatment. After three months of treatment, 7 of the 8 patients with delayed CTT had an improvement; the Tmax-13C test was improved in all the 4 patients with delayed gastric emptying. These results suggest that Rikkunshi-has beneficial effects in Parkinson's disease patientswith constipation and/orwith delayed gastric emptying. (The Autonomic Nervous System, 50: 300-305, 2013). doi:10.1016/j.autneu.2014.09.006 #3 Effects of pain caused by orthodontic tooth movement on autonomic nervous system Jun Oba, Naoto Hara, Yasue Kotegawa, Yukiko Miyazawa, Kazuo Mukuno, Hiroo Oda, Kazuichi Yoshida Department of Orthodontics, Kanagawa Dental University Yokohama Dental and Medical Clinic, Kanagawa 221-0835, Japan Department of Ophthalmology, Kanagawa Dental University, Yokohama Dental and Medical Clinic, Kanagawa 221-0835, Japan Department of Orthodontics, Kanagawa Dental University Hospital, Kanagawa 238-8580, Japan Department of Anesthesiology, Graduate School of Kanagawa Dental University, Kanagawa 238-8580, Japan In order to investigate the effects of pain caused by orthodontic tooth movement on the autonomic nervous system, we selected three healthy men and three healthy women (mean age: 30.3 ± 8.4 years) and inserted separating elastic strips between the upper right first molar and the adjacent tooth to induce pain due to the tooth movement, and we conducted our testing after 3, 6, 9 and 24 h. The degree of pain was Autonomic Neuroscience: Basic and Clinical 186 (2014) 95–98

Tu1839 Improvement Effect of Rikkunshito Mediated by Serotonin 2B Receptor Antagonism in Inhibition of Gastric Accommodation

Tu1839 Improvement Effect of Rikkunshito Mediated by Serotonin 2B Receptor Antagonism in Inhibition of Gastric Accommodation

Tu1603 Prophylactic Effect of Rikkunshito on Body Weight Loss and Malnutrition Accompanied With Anorexia in Esophageal Cancer Patients After Esophagectomy

Tu1603 Prophylactic Effect of Rikkunshito on Body Weight Loss and Malnutrition Accompanied With Anorexia in Esophageal Cancer Patients After Esophagectomy

Effect of Rikkunshito on the expression of substance P and CGRP in dorsal root ganglion neurons and voluntary movement in rats with experimental reflux esophagitis

While there are reports that the herbal medicine rikkunshito (RKT) relieves upper gastrointestinal disease symptoms, the effect of RKT on primary afferent neurons is unknown. A model of reflux esophagitis (RE) was implemented using male Wistar rats aged 6-7 weeks. Ten days after surgery, the total area of esophageal mucosal erosion sites was determined. Th8-10 dorsal root ganglia (DRG) were dissected out and the expression of substance P (SP), calcitonin gene-related peptide (CGRP), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was determined in DRG using immunohistochemistry. RKT (0.6%/WV) or omeprazole (OME) (10 mg/kg) was administered for 10 days beginning on the day after surgery. Voluntary movement was measured with an infrared sensor for 22 h each day. RE rats showed esophageal mucosal erosion and significantly increased number of SP/CGRP- and p-ERK1/2-immunoreactive neurons in DRG. Treatment with OME improved the size of erosive lesions in the esophageal mucosa of RE rats, while RKT did not. Treatment with RKT or OME significantly reduced the expression of SP/CGRP and p-ERK1/2 in DRG, and significantly increased voluntary movement in RE rats. RKT inhibited the activation of ERK1/2 and decreased the expression of SP and CGRP in DRG of RE rats, which may be associated with the observed amelioration of voluntary movement.

Preventive effect of rikkunshito, traditional Japanese medicine, for chemotherapy-induced nausea and vomiting.

131 Background: Supportive therapies are being developed for chemotherapy-induced nausea and vomiting (CINV). Rikkunshito is a Kanpo medicine, which is a part of traditionally practiced Japanese-based ancient Chinese medicine. It has been reported to be effective against cisplatin-induced anorexia in rats. In the present study, we evaluated the preventive effect of Rikkunshito for CINV in patients receiving high-dose cisplatin. Methods: We selected subjects who received chemotherapy including cisplatin (≥60mg/m2) for gastric or esophageal cancer between April 2010 and August 2012 at our institution. We targeted 20 cases treated without a reduction in the anti-cancer medication in the second course and added 7.5g/day of Rikkunshito, orally administered for seven days, to their second course treatment regimen. All cases were treated with 5-HT3 receptor antagonist and steroid, and palonosetron for the prevention of CINV in their first and second courses. We evaluated the complete response (CR, defined as no emesis and no rescue medication) rate and other toxicity, according to CTCAE v4.0, of the first and second courses. Results: The median age of the patients was 63 years (range, 49–77 years). The chemotherapy regimens were cisplatin + 5-FU in 15 cases with esophageal cancer, cisplatin + S-1 in five cases with gastric cancer. Anorexia in the first course was grade 0/1/2 = 5/11/4, but had been mitigated in the second course to grade 0/1/2 = 12/6/2 (P = 0.042). CR rate was 75.0% in the first course (95% CI, 56.0%–94.0%) and by the second course had improved to 95.0% (95% CI, 85.4%–100%). And about the other major toxicity, there was no significant difference between first and second courses. Conclusions: These results suggest that Rikkunshito has the potential to improve CINV in patients receiving high-dose cisplatin.

Neurohormones, Rikkunshito and Hypothalamic Neurons Interactively Control Appetite and Anorexia

Ghrelin is the orexigenic peptide produced in the periphery, and its plasma level shows remarkable pre/postprandial changes. Ghrelin is considered a pivotal signal to the brain to stimulate feeding. Hence, characterizing the target neurons for ghrelin in the hypothalamic feeding center and the signaling cascade in the target neurons are essential for understanding the mechanisms regulating appetite. Anorexia and cachexia associated with gastric surgery, stress-related diseases, and use of anti-cancer drugs cause the health problems, markedly deteriorating the quality of life. The anorexia involves several neurotransmitters and neuropeptides in the hypothalamic feeding center, in which corticotropin-releasing hormone (CRH), urocortine, serotonin (5HT) and brain-derived neurotrophic factor (BDNF) play a pivotal role. A Japanese herbal medicine, rikkunshito, has been reported to ameliorate the anorexia by promoting the appetite. This review describes 1) the interaction of ghrelin with the orexigenic neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) and underlying signaling cascade in NPY neurons, 2) the anorectic pathway driven by BDNF-CRH/urocortine and 5HTCRH/ urocortine pathways, 3) the effect of rikkunshito on the interaction of ghrelin and NPY neurons in ARC, and 4) the effect of rikkunshito on the interaction of 5HT on CRH neurons in paraventricular nucleus (PVN).

Preventive effect of rikkunshito, traditional Japanese medicine, for chemotherapy-induced nausea and vomiting.

135 Background: Supportive therapies are being developed for chemotherapy-induced nausea and vomiting (CINV). Rikkunshito is a Kanpo medicine, which is a part of traditionally practiced Japanese-based ancient Chinese medicine. It has been reported to be effective against cisplatin-induced anorexia in rats. In the present study, we evaluated the preventive effect of rikkunshito for CINV in patients receiving high-dose cisplatin. Methods: We selected subjects who received chemotherapy including cisplatin (≥60mg/m2) for gastric or esophageal cancer between April 2008 and July 2011 at our institution. We targeted 26 cases treated without a reduction in the anti-cancer medication in the second course and added 7.5g/day of rikkunshito, orally administered for seven days, to their second course treatment regimen. All cases were treated with 5-HT3 receptor antagonist and steroid, and 12 cases were treated with palonosetron for the prevention of CINV in their first and second courses. We evaluated the complete response (CR, defined as no emesis and no rescue medication) rate and other toxicity, according to CTCAE v4.0, of the first and second courses. Results: The median age of the patients was 67 years (range, 49–77 years). There were nine cases of gastric cancer and 17 cases of esophageal cancer. The chemotherapy regimens were cisplatin + irinotecan in two cases, cisplatin + 5-FU in 15 cases, cisplatin + S-1 in seven cases and cisplatin + 5-FU + docetaxel in two cases. Six cases received concomitant radiation therapy. Anorexia in the first course was grade 0/1/2 = 4/12/10, but had been mitigated in the second course to grade 0/1/2 = 11/11/4 (P = 0.020). CR rate was 69.3% in the first course (95% CI, 51.6%–87.0%) and by the second course had improved to 88.5% (95% CI, 76.2%–100%) (P = 0.089). And about the other major toxicity, there was no significant difference between first and second courses. Conclusions: These results suggest that rikkunshito has the potential to improve CINV in patients receiving high-dose cisplatin.

Editorial: New drugs for Alzheimer's disease in Japan

Editorial: New drugs for Alzheimer's disease in Japan

Traditional Herbal Medicine, Rikkunshito, Induces HSP60 and Enhances Cytoprotection of Small Intestinal Mucosal Cells as a Nontoxic Chaperone Inducer

Increasing incidence of small intestinal ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs) has become a topic with recent advances of endoscopic technology. However, the pathogenesis and therapy are not fully understood. The aim of this study is to examine the effect of Rikkunshito (TJ-43), a traditional herbal medicine, on expression of HSP60 and cytoprotective ability in small intestinal cell line (IEC-6). Effect of TJ-43 on HSP60 expression in IEC-6 cells was evaluated by immunoblot analysis. The effect of TJ-43 on cytoprotective abilities of IEC-6 cells against hydrogen peroxide or indomethacin was studied by MTT assay, LDH-release assay, caspase-8 activity, and TUNEL. HSP60 was significantly induced by TJ-43. Cell necrosis and apoptosis were significantly suppressed in IEC-6 cells pretreated by TJ-43 with overexpression of HSP60. Our results suggested that HSP60 induced by TJ-43 might play an important role in protecting small intestinal epithelial cells from apoptosis and necrosis in vitro.

消化管の空腹期強収縮運動に及ぼす六君子湯の影響

消化管の空腹期強収縮運動に及ぼす六君子湯の影響