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

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• 作者：Hyun Jung Kim^a ; ^b ; Sun Young Park^a ; Dae Geon Kim^a ; So-Hae Park^c ; Heeseob Lee^c ; Dae Youn Hwang^d ; Myeong Ho Jung^a ; ^b ; Ki-Tae Ha^b ; ^e ; Byung Joo Kim^a ; ^b ; ^{vision@pusan.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Roots of Liriope Platyphylla Wang Et tang ; Interstitial cells of Cajal ; Pacemaker potentials ; Gastrointestinal tract ; Motility
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：26 May 2016
• 年：2016
• 卷：184
• 期：Complete
• 页码：144-153
• 全文大小：2088 K

文摘

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 GDP_βS 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 Ca²⁺free solution or thapsigargin (a Ca²⁺-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 (0.01–1 g/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 Ca²⁺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.