Functional protein-protein interaction networks regulated by 6-gingerol targeting stomach and small intestine

Ginger is widely used as a spice and traditional Chinese medicine achieving warming interior for dispelling cold during its long time clinical observations and practices. However, its mechanism is still obscure. In this study, interior is restricted to stomach and small intestine. 6-gingerol, ginger's quality control and main bio-active chemical compound, is chosen to represent ginger. Started with biomarkers reported in literatures. Functional protein-protein interactions (FPPI) from biomarkers to proteins expressed in stomach and small intestine were filtered out. These FPPIs form networks regulated by 6-gingerol targeting interior. Further enrichment analysis highlighted biological processes concentrated on metabolic regulations for more energy generation, metal ion transmembrane transporter activity for better digest, more blood flow volume for nutrient and warmth, and cell cycle regulation to prevent canceration. Taken together, ginger's warming up interior for cold expelling is elaborated via bioinformatics analysis on 6-gingerol.

[1]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[2]  Qi Zhang,et al.  Assessment of anti-cancerous potential of 6-gingerol (Tongling White Ginger) and its synergy with drugs on human cervical adenocarcinoma cells. , 2017, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[3]  Damian Szklarczyk,et al.  STITCH 5: augmenting protein–chemical interaction networks with tissue and affinity data , 2015, Nucleic Acids Res..

[4]  Lin Zhou,et al.  Inhibitory effect 6-gingerol on adipogenesis through activation of the Wnt/β-catenin signaling pathway in 3T3-L1 adipocytes. , 2015, Toxicology in vitro : an international journal published in association with BIBRA.

[5]  M. Caplan,et al.  Residues of the Fourth Transmembrane Segments of the Na,K-ATPase and the Gastric H,K-ATPase Contribute to Cation Selectivity* , 2000, The Journal of Biological Chemistry.

[6]  I-Min Liu,et al.  [6]-gingerol dampens hepatic steatosis and inflammation in experimental nonalcoholic steatohepatitis. , 2015, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[7]  Tanya Z. Berardini,et al.  The Gene Ontology (GO) Cellular Component Ontology: integration with SAO (Subcellular Anatomy Ontology) and other recent developments , 2013, J. Biomed. Semant..

[8]  Yun Yang,et al.  Triptolide targets on MYC towards testis may induce male reproductive toxicity , 2016, 2016 IEEE International Conference on Bioinformatics and Biomedicine (BIBM).

[9]  E. Soniya,et al.  [6]-Gingerol Induces Caspase-Dependent Apoptosis and Prevents PMA-Induced Proliferation in Colon Cancer Cells by Inhibiting MAPK/AP-1 Signaling , 2014, PloS one.

[10]  Davide Heller,et al.  STRING v10: protein–protein interaction networks, integrated over the tree of life , 2014, Nucleic Acids Res..

[11]  Chunhua Yang,et al.  Absorption, Metabolic Stability, and Pharmacokinetics of Ginger Phytochemicals , 2017, Molecules.

[12]  Zhi-Jun Duan,et al.  Effect of gingerol on colonic motility via inhibition of calcium channel currents in rats. , 2015, World journal of gastroenterology.

[13]  R. Webb,et al.  RhoA/Rho-kinase, vascular changes, and hypertension , 2001, Current hypertension reports.

[14]  Min-Sook Kang,et al.  6-Shogaol and 6-gingerol, the pungent of ginger, inhibit TNF-alpha mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes. , 2008, Biochemical and biophysical research communications.

[15]  I Kimura,et al.  Suppression of spontaneous calcium spikes and contraction in isolated portal veins of mice by gingerols and chemically related compounds. , 1988, Japanese journal of pharmacology.

[16]  Graham W. Horgan,et al.  Ginger phytochemicals mitigate the obesogenic effects of a high-fat diet in mice: a proteomic and biomarker network analysis. , 2011, Molecular nutrition & food research.

[17]  Xin Yang,et al.  6-Gingerol inhibits osteosarcoma cell proliferation through apoptosis and AMPK activation , 2015, Tumor Biology.

[18]  L. Rashed,et al.  Effect of 6-gingerol on AMPK- NF-κB axis in high fat diet fed rats. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[19]  I-Min Liu,et al.  6-Gingerol Protects against Nutritional Steatohepatitis by Regulating Key Genes Related to Inflammation and Lipid Metabolism , 2015, Nutrients.

[20]  Durga Prasad Mishra,et al.  Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-Gingerol in cervical cancer cells , 2015, Oncotarget.

[21]  Michael K. Gilson,et al.  BindingDB in 2015: A public database for medicinal chemistry, computational chemistry and systems pharmacology , 2015, Nucleic Acids Res..

[22]  Nami Kim,et al.  [6]‐Gingerol Affects Glucose Metabolism by Dual Regulation via the AMPKα2‐Mediated AS160–Rab5 Pathway and AMPK‐Mediated Insulin Sensitizing Effects , 2015, Journal of cellular biochemistry.

[23]  Ming Xu,et al.  6‐Gingerol protects intestinal barrier from ischemia/reperfusion‐induced damage via inhibition of p38 MAPK to NF‐&kgr;B signalling , 2017, Pharmacological research.

[24]  Yo Tsuchiya,et al.  [6]-gingerol induces electrogenic sodium absorption in the rat colon via the capsaicin receptor TRPV1. , 2014, Journal of nutritional science and vitaminology.

[25]  V. S. Shubin,et al.  Ca2+ Ions Regulate Activity of Na+,Cl–(HCO3−)-ATPase in the Mucosa of Rabbit Small Intestine , 2015, Bulletin of Experimental Biology and Medicine.

[26]  John P. Overington,et al.  ChEMBL: a large-scale bioactivity database for drug discovery , 2011, Nucleic Acids Res..