Effects of the roots of Liriope Platyphylla Wang Et tang on gastrointestinal motility function

Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Materials and 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.

Conclusion: 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.

Keywords: Gastrointestinal tract; Interstitial cells of Cajal; Motility; Pacemaker potentials; Roots of Liriope Platyphylla Wang Et tang.