title: Effects of the roots of Liriope Platyphylla Wang Et tang on gastrointestinal motility function.
abstract: BACKGROUND
  Liriope platyphylla Wang et Tang continues to be used in Korea as a traditional medicine for the treatment of gastrointestinal (GI) disorders related to constipation and abnormal GI motility.
  
  
  OBJECTIVE
  Because GI disorders, especially GI motility dysfunctions, are major lifelong problems, the authors investigated the effects of a water extract of the roots of L. platyphylla Wang et Tang (LPE) on the pacemaker potentials (PPTs) of interstitial cells of Cajal (ICCs) and on GI motility in male ICR mice.
  
  
  METHODS
  Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record PPTs generated by cultured ICCs in vitro. In vivo effects of LPE on GI motility were investigated by measuring intestinal transit rates (ITRs) of Evans blue in normal mice and in acetic acid (AA) and streptozotocin (STZ)-induced diabetic mouse models of GI motility dysfunction.
  
  
  RESULTS
  LPE dose-dependently depolarized PPTs in ICCs. Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) did not block LPE-induced PPT depolarization. However, pretreatment with 4-DAMP (a muscarinic M3 receptor antagonist) blocked LPE-induced PPT depolarization. In addition, treatment with LY294002 (a phosphoinositide 3-kinase (PI3K) inhibitor) also blocked LPE-induced PPT depolarization. Intracellular GDPβS inhibited LPE-induced PPT depolarization, and LPE-induced PPT depolarization was found to occur in a phospholipase C (PLC)- and a protein kinase C (PKC)-dependent manner. Pretreatment with Ca(2+)free solution or thapsigargin (a Ca(2+)-ATPase inhibitor in endoplasmic reticulum) abolished PPTs, and under these conditions, LPE did not depolarize ICC PPTs. In normal mice, ITRs were significantly and dose-dependently increased by LPE (0.01-1g/kg administered intragastrically (i.g.)). In addition, LPE (i.g.) significantly recovered GI motility dysfunctions in both animal models.
  
  
  CONCLUSIONS
  LPE dose-dependently depolarizes ICC PPTs through M3 receptors via external and internal Ca(2+)regulation and via G protein-, PI3K-, PLC- and PKC- dependent pathways in vitro. Also, in vivo, LPE increased ITRs in treatment naïve mice and our two mouse models of GI dysfunction. Therefore, this study shows that LPE offers a basis for the development of a prokinetic agent that prevents or alleviates GI motility dysfunctions.
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea; Healthy Aging Korean Medical Research Center, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Dae Geon
authors.initials: DG
authors.lastname: Kim
authors.affiliation: College of Human Ecology, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: So-Hae
authors.initials: SH
authors.lastname: Park
authors.affiliation: College of Human Ecology, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Heeseob
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 627-706, Republic of Korea.
authors.forename: Dae Youn
authors.initials: DY
authors.lastname: Hwang
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea; Healthy Aging Korean Medical Research Center, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Jung
authors.affiliation: Healthy Aging Korean Medical Research Center, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea; Division of Applied Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea; Healthy Aging Korean Medical Research Center, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea. Electronic address: vision@pusan.ac.kr.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D019342:Acetic Acid; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D019204:GTP-Binding Proteins / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D056885:Interstitial Cells of Cajal / Q000187:drug effects* / Q000502:physiology; D007421:Intestine, Small / Q000166:cytology / Q000502:physiology; D031424:Liriope Plant; D008297:Male; D008813:Mice, Inbred ICR; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D011493:Protein Kinase C / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology
chemical_list: D010936:Plant Extracts; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D019342:Acetic Acid
keywords: Gastrointestinal tract; Interstitial cells of Cajal; Motility; Pacemaker potentials; Roots of Liriope Platyphylla Wang Et tang