Yoo-Jin Jeon1, Jin-Seok Lee2, Yong-Rae Cho3, Sung-Bae Lee4, Won-Young Kim5, Seong-Soo Roh6, Jin-Yong Joung7, Hwa-Dong Lee8, Sung-Ok Moon9, Jung-Hyo Cho10, Chang-Gue Son11. 1. Liver & Immunology Research Center, Doonsan Oriental Hospital, 75, Daedeok-daero 176 Street, Seo-gu, Daejeon, 35235, Republic of Korea. Electronic address: jyj940916@naver.com. 2. Liver & Immunology Research Center, Doonsan Oriental Hospital, 75, Daedeok-daero 176 Street, Seo-gu, Daejeon, 35235, Republic of Korea. Electronic address: Neptune@dju.ac.kr. 3. Liver & Immunology Research Center, Doonsan Oriental Hospital, 75, Daedeok-daero 176 Street, Seo-gu, Daejeon, 35235, Republic of Korea. Electronic address: dragonac@naver.com. 4. Liver & Immunology Research Center, Doonsan Oriental Hospital, 75, Daedeok-daero 176 Street, Seo-gu, Daejeon, 35235, Republic of Korea. Electronic address: sky161300@naver.com. 5. Liver & Immunology Research Center, Doonsan Oriental Hospital, 75, Daedeok-daero 176 Street, Seo-gu, Daejeon, 35235, Republic of Korea. Electronic address: godunga3@naver.com. 6. Department of Herbology, College of Korean Medicine, DaeguHaany University, 136 Shinchendong-ro, Suseong-gu, Daegu, 42158, Republic of Korea. Electronic address: ddede@dhu.ac.kr. 7. Liver & Immunology Research Center, Doonsan Oriental Hospital, 75, Daedeok-daero 176 Street, Seo-gu, Daejeon, 35235, Republic of Korea. Electronic address: bluetxt1@gmail.com. 8. Office of Strategic Planning, National Development Institute of Korean Medicine (NIKOM), 94, Hwarang-ro(Gapje-dong), Gyengsan-si, Republic of Korea. Electronic address: lee00003@hanmail.net. 9. Korean Medicine R&D Team 2, Korea Medicine Development, National Development Institute of Korean Medicine (NIKOM), 94, Hwarang-ro(Gapje-dong), Gyengsan-si, Republic of Korea. Electronic address: somoon@nikom.or.kr. 10. Liver & Immunology Research Center, Doonsan Oriental Hospital, 75, Daedeok-daero 176 Street, Seo-gu, Daejeon, 35235, Republic of Korea. Electronic address: choajoa@dju.ac.kr. 11. Liver & Immunology Research Center, Doonsan Oriental Hospital, 75, Daedeok-daero 176 Street, Seo-gu, Daejeon, 35235, Republic of Korea. Electronic address: ckson@dju.ac.kr.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Banha-sasim-tang (BST; Hange-shashin-to in Kampo medicine; Banxia xiexin tang in traditional Chinese medicine) is a traditional Chinese harbal medicine that has been commonly used for gastrointestinal disorders. AIM OF THE STUDY: To investigate the pharmacological effects of BST, a standardized herbal drug, on main symptoms of functional dyspepsia including delayed gastric emptying, and underlying mechanisms of action in mouse model. METHODS AND MATERIALS: Balb/C mice were pretreated with BST (25, 50, 100 mg/kg, po) or mosapride (3 mg/kg, po) for 3 days, and then treated with loperamide (10 mg/kg, ip) after 19 h fasting. A solution of 0.05% phenol red (500 μL) or 5% charcoal diet (200 μL) was orally administered, followed by scarifying and assessment of gastric emptying or gastro-intestinal motility. C-kit (immunofluorescence), nNOS (western blot) and gastric contraction-related gene expression were examined in stomach tissue. RESULTS: The loperamide injection substantially delayed gastric emptying, while the BST pretreatment significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of stomach-retained phenol red (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The BST pretreatment significantly tempered the loperamide-induced inactivation of c-kit and nNOS (p < 0.05 or 0.01) as well as the contraction-related gene expression, such as the 5HT4 receptor (5HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK). The BST pretreatment also significantly attenuated the alterations in gastro-intestinal motility (p < 0.01). CONCLUSION: Our results are the first evidence of the prokinetic agent effects of Banha-sasim-tang in a loperamide-induced FD animal model. The underlying mechanisms of action may involve the modulation of peristalsis via activation of the interstitial cells of Cajal and the smooth muscle cells in the stomach.
ETHNOPHARMACOLOGICAL RELEVANCE: Banha-sasim-tang (BST; Hange-shashin-to in Kampo medicine; Banxia xiexin tang in traditional Chinese medicine) is a traditional Chinese harbal medicine that has been commonly used for gastrointestinal disorders. AIM OF THE STUDY: To investigate the pharmacological effects of BST, a standardized herbal drug, on main symptoms of functional dyspepsia including delayed gastric emptying, and underlying mechanisms of action in mouse model. METHODS AND MATERIALS: Balb/C mice were pretreated with BST (25, 50, 100 mg/kg, po) or mosapride (3 mg/kg, po) for 3 days, and then treated with loperamide (10 mg/kg, ip) after 19 h fasting. A solution of 0.05% phenol red (500 μL) or 5% charcoal diet (200 μL) was orally administered, followed by scarifying and assessment of gastric emptying or gastro-intestinal motility. C-kit (immunofluorescence), nNOS (western blot) and gastric contraction-related gene expression were examined in stomach tissue. RESULTS: The loperamide injection substantially delayed gastric emptying, while the BST pretreatment significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of stomach-retained phenol red (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The BST pretreatment significantly tempered the loperamide-induced inactivation of c-kit and nNOS (p < 0.05 or 0.01) as well as the contraction-related gene expression, such as the 5HT4 receptor (5HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK). The BST pretreatment also significantly attenuated the alterations in gastro-intestinal motility (p < 0.01). CONCLUSION: Our results are the first evidence of the prokinetic agent effects of Banha-sasim-tang in a loperamide-induced FD animal model. The underlying mechanisms of action may involve the modulation of peristalsis via activation of the interstitial cells of Cajal and the smooth muscle cells in the stomach.