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. 2022 May 19;11(10):1348.
doi: 10.3390/plants11101348.

Prediction of the Medicinal Mechanisms of Pinellia ternata Breitenbach, a Traditional Medicine for Gastrointestinal Motility Disorders, through Network Pharmacology

Na Ri Choi  1 , Jongwon Park  2 , Seok-Jae Ko  2   3 , Jeong Nam Kim  1 , Woogyun Choi  1 , Jae-Woo Park  2   3 , Byung Joo Kim  1
Affiliations

Prediction of the Medicinal Mechanisms of Pinellia ternata Breitenbach, a Traditional Medicine for Gastrointestinal Motility Disorders, through Network Pharmacology

Na Ri Choi et al. Plants (Basel). .

Abstract

Pinellia ternata Breitenbach (PTB) is a widely used herbal medicine in China, Japan, and South Korea. It has antiemetic, anti-inflammatory, antitussive, and sedative properties. The raw material is toxic, but can be made safer using alum solution or by boiling it for a long time. In addition, PTB seems to be effective for gastrointestinal motility disorders (GMDs), but this is yet to be conclusively proven. Herein, PTB compounds, targets, and related diseases were investigated using the traditional Chinese medical systems pharmacology database and an analysis platform. Information on target genes was confirmed using the UniProt database. Using Cytoscape 3.8.2, a network was established and GMD-related genes were searched using the Cytoscape stringApp. The effects of the PTB extract on the pacemaker potential of interstitial cells of Cajal and GMD mouse models were investigated. In total, 12 compounds were found to target 13 GMD-related genes. In animal experiments, PTB was found to better regulate pacemaker potential in vitro and inhibit GMD signs compared to control groups in vivo. Animal studies showed that the mechanism underlying the effects of PTB is closely related to gastrointestinal motility. The results obtained demonstrated that PTB offers a potential means to treat GMDs, and we suggested that the medicinal mechanism of GMDs can be explained by the relationship between 12 major components of PTB, including oleic acid, and 13 GMD-related genes.

Keywords: Pinellia ternata Breitenbach; gastrointestinal motility disorders; network-based systems pharmacological; traditional medicine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic of the study protocol for network pharmacology exploration. ADME: absorption, distribution, metabolism, and excretion.
Figure 2
Figure 2
Compound–target network of Pinellia ternate Breitenbach. The size of the node depends on the number of connected edges. The compounds are expressed as red square nodes, and the targets are expressed as blue round nodes.
Figure 3
Figure 3
Venn diagram of the interactions between active compounds and gastrointestinal (GI) disease-related compounds in Pinellia ternate Breitenbach.
Figure 4
Figure 4
Network of gastrointestinal motility disorder-related genes and Pinellia ternate Breitenbach-targeting genes. The 13 genes included in both “genes related to gastrointestinal motility disorder” and “Pinellia ternate Breitenbach-target genes” are collected in the center.
Figure 5
Figure 5
Network of compounds of Pinellia ternate Breitenbach and gastrointestinal (GI) motility disorder-related genes.
Figure 6
Figure 6
Effects of PTB extract on pacemaker potential of interstitial cells of Cajal (ICCs). (A–D) PTB extract depolarized the ICC pacemaker potentials. (E,F) The changes in pacemaker potential and amplitude induced by PTB extract are summarized. Means ± SEs. **** p < 0.0001. PTB: Pinellia ternate Breitenbach. CTRL: control.
Figure 7
Figure 7
Effects of Ca2+ on PTB extract-induced pacemaker potential depolarization. (A) For external Ca2+-free solution, PTB extract did not result in depolarization. (B) With thapsigargin, PTB extract also did not result in depolarization. (C,D) Depolarization and amplitude responses to PTB extract are summarized. Means ± SEs. **** p < 0.0001. PTB: Pinellia ternate Breitenbach. CTRL: control.
Figure 8
Figure 8
Effects of muscarinic and 5-HT receptor antagonists on PTB extract-induced pacemaker potential depolarization. (A) Pre-treatment with 4-DAMP inhibited PTB extract-induced effects. (B) Pre-treatment with methoctramine had no effects on PTB extract-induced effects. (C,E) Pre-treatment with Y25130 or SB269970 inhibited PTB extract-induced effects. (D) Pre-treatment with RS39604 had no effects on PTB extract-induced effects. (F,G) Depolarization and amplitude responses to PTB extract are summarized. Means ± SEs. **** p < 0.0001. PTB: Pinellia ternate Breitenbach. CTRL: control. Metho.: methoctramine.
Figure 9
Figure 9
Effects of PTB extract on the intestinal transit rate (ITR) in normal and gastrointestinal motility disorder (GMD) mice. (A) PTB extract increased the ITR. (B) The ITR was recovered by PTB extract in GMD mice. Means ± SEs. * p < 0.05. *** p < 0.001. **** p < 0.0001. PTB: Pinellia ternate Breitenbach. CTRL: control.
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