Network Pharmacological Analysis and Experimental Validation of the Effect of Smilacis Glabrae Rhixoma on Gastrointestinal Motility Disorder
Abstract
:1. Introduction
2. Results
2.1. Information of 390 Targets Derived through Correlation Investigation between Compounds and Targets
2.2. Seventeen Active Compounds Achieved the Criteria for Absorption, Distribution, Metabolism, and Excretion Parameters Applied
2.3. Thirty-Nine Compounds Related to Gastrointestinal (GI) Disease Were Identified in SGR
2.4. Seventeen GI-Disease-Related Compounds in SGR Were Associated with GMD
2.5. The Network of GMD-Related Genes and Compounds for Identification of Interesting Molecules
2.6. Effects of SGR Extract on Pacemaker Activity on Interstitial Cells of Cajal (ICC) in Murine Small Intestine
2.7. Effects of SGR Extract on Delayed Gastric Emptying
2.8. Effects of SGR Extract on Intestinal Transit Rate (ITR) in Normal Mice
2.9. Effects of SGR Extract on ITR in Mice Regarding Gastrointestinal Motility Dysfunction
3. Discussion
4. Materials and Methods
4.1. Network Pharmacology Analysis by SGR
4.1.1. Classification of the Compound of SGR
4.1.2. Analysis of Target
4.1.3. Analysis of Network
4.1.4. Active Compound Screening
4.2. Animal Validation
4.2.1. SGR
4.2.2. Animal Experiments
4.2.3. Preparation of ICC and Electrophysiological Experiments
4.2.4. Gastric Weight and Gastric Emptying by Phenol Red
4.2.5. Intestinal Transit Rate Evaluation
4.2.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Molecule Name | Structure | MW * | OB (%) * | Caco-2 * | DL * |
---|---|---|---|---|---|
(-)-taxifolin | 304.27 | 60.51 | −0.24 | 0.27 | |
(2R,3R)-2-(3,5-dihydroxyphenyl)-3,5,7-trihydroxychroman-4-one | 304.27 | 63.17 | −0.34 | 0.27 | |
2H-3,9a-Methano-1-benzoxepin-9-methanol, octahydro-2,2,5a-trimethyl-, (3R-(3alpha,5aalpha,9alpha,9aalpha))- | 238.41 | 98.38 | 1.01 | 0.14 | |
4,7-Dihydroxy-5-methoxyl-6-methyl-8-formyl-flavan | 314.36 | 37.03 | 0.48 | 0.28 | |
beta-sitosterol | 414.79 | 36.91 | 1.32 | 0.75 | |
cis-Dihydroquercetin | 304.27 | 66.44 | −0.34 | 0.27 | |
Dihydroresveratrol | 230.28 | 87.27 | 0.81 | 0.11 | |
diosgenin | 414.69 | 80.88 | 0.82 | 0.81 | |
EIC | 280.5 | 41.9 | 1.16 | 0.14 | |
Enhydrin | 464.51 | 40.56 | −0.36 | 0.74 | |
Methyllinolenate | 292.51 | 46.15 | 1.48 | 0.17 | |
naringenin | 272.27 | 59.29 | 0.28 | 0.21 | |
oleic acid | 282.52 | 33.13 | 1.17 | 0.14 | |
quercetin | 302.25 | 46.43 | 0.05 | 0.28 | |
sitosterol | 414.79 | 36.91 | 1.32 | 0.75 | |
Stigmasterol | 412.77 | 43.83 | 1.44 | 0.76 | |
taxifolin | 304.27 | 57.84 | −0.23 | 0.27 |
Molecule Name | Target Name | Disease Name |
---|---|---|
(-)-epicatechin | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Interleukin-6 | * Gastrointestinal motility disorders | |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Transcription factor AP-1 | * Gastrointestinal motility disorders | |
Tumor necrosis factor | * Gastrointestinal motility disorders | |
Crohns’s Disease, unspecified | ||
(-)-taxifolin | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
(2R,3R)-2-(3,5-dihydroxyphenyl)-3,5,7-trihydroxychroman-4-one | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
(2S,3R)-3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-4-one | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
(L)-alpha-Terpineol | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Sodium channel protein type 5 subunit alpha | * Gastrointestinal motility disorders | |
(R)-linalool | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Sodium channel protein type 5 subunit alpha | * Gastrointestinal motility disorders | |
3-O-caffeoylshikimic acid | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
4,7-Dihydroxy-5-methoxyl-6-methyl-8-formyl-flavan | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz-Jeghers syndrome | ||
Sodium channel protein type 5 subunit alpha | * Gastrointestinal motility disorders | |
Aromadedrin | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
astilbin | Interleukin-10 | * Gastrointestinal motility disorders |
Tumor necrosis factor | * Gastrointestinal motility disorders | |
Crohns’s Disease, unspecified | ||
beta-sitosterol | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Mu-type opioid receptor | * Gastrointestinal motility disorders | |
Diarrhea | ||
Opioid-induced bowel dysfunction | ||
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz-Jeghers syndrome | ||
Sodium channel protein type 5 subunit alpha | * Gastrointestinal motility disorders | |
Sodium-dependent serotonin transporter | * Gastrointestinal motility disorders | |
Transcription factor AP-1 | * Gastrointestinal motility disorders | |
cis-Dihydroquercetin | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
delta-amorphene | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Dihydroresveratrol | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
diosgenin | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Vascular endothelial growth factor A | Colorectal Neoplasms | |
EIC | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Transient receptor potential cation channel subfamily V member 1 | * Gastrointestinal motility disorders | |
engeletin | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
FER | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Leukotriene A-4 hydrolase | Esophageal cancer | |
Nitric oxide synthase, endothelial | Colon cancer | |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
HMF | Acetylcholinesterase | * Gastrointestinal motility disorders |
Dipeptidyl peptidase IV | * Gastrointestinal motility disorders | |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
isoengelitin | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Istidina | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
L-Bornyl acetate | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Methyllinolenate | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
myristic acid | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
naringenin | Glutathione S-transferase P | Colorectal Neoplasms |
Gastrointestinal Neoplasms | ||
Rectal Neoplasms | ||
Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) | |
Peroxisome proliferator-activated receptor gamma | Crohns’s Disease, unspecified | |
Inflammatory Bowel Disease | ||
Ulcerative colitis | ||
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
n-butyl-β-D-fructopyronoside | Nitric oxide synthase, brain | * Gastrointestinal motility disorders |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
n-butyl-β-D-fructoufranoside | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
NCA | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
nonane | Tumor necrosis factor | * Gastrointestinal motility disorders |
Crohns’s Disease, unspecified | ||
oleic acid | Cholecystokinin | * Gastrointestinal motility disorders |
Glucagon | * Gastrointestinal motility disorders | |
Insulin | * Gastrointestinal motility disorders | |
Myeloperoxidase | * Gastrointestinal motility disorders | |
Peptide YY | * Gastrointestinal motility disorders | |
Peroxisome proliferator-activated receptor gamma | Crohns’s Disease, unspecified | |
Inflammatory Bowel Disease | ||
Ulcerative colitis | ||
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
palmitic acid | Interleukin-10 | * Gastrointestinal motility disorders |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Tumor necrosis factor | * Gastrointestinal motility disorders | |
Crohns’s Disease, unspecified | ||
quercetin | Acetylcholinesterase | * Gastrointestinal motility disorders |
Arachidonate 5-lipoxygenase | Gastrointestinal cancers | |
Inflammatory Bowel Disease | ||
Ulcerative colitis | ||
Cytochrome P450 1A2 | Colorectal Neoplasms | |
Dipeptidyl peptidase IV | * Gastrointestinal motility disorders | |
Epidermal growth factor receptor | Colorectal cancer | |
Glutathione S-transferase P | Colorectal Neoplasms | |
Gastrointestinal Neoplasms | ||
Rectal Neoplasms | ||
Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) | |
Interleukin-1 beta | * Gastrointestinal motility disorders | |
Interleukin-10 | * Gastrointestinal motility disorders | |
Interleukin-6 | * Gastrointestinal motility disorders | |
Interleukin-8 | * Gastrointestinal motility disorders | |
Myeloperoxidase | * Gastrointestinal motility disorders | |
Nitric oxide synthase, endothelial | Colon cancer | |
Ornithine decarboxylase | Hereditary Polyposis Syndromes | |
Peroxisome proliferator-activated receptor gamma | Crohns’s Disease, unspecified | |
Inflammatory Bowel Disease | ||
Ulcerative colitis | ||
Pro-epidermal growth factor | Colorectal Neoplasms | |
Rectal Neoplasms | ||
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz-Jeghers syndrome | ||
Proto-oncogene c-Fos | * Gastrointestinal motility disorders | |
Sodium channel protein type 5 subunit alpha | * Gastrointestinal motility disorders | |
Thrombomodulin | Radiation enteropathy | |
Transcription factor AP-1 | * Gastrointestinal motility disorders | |
Tumor necrosis factor | * Gastrointestinal motility disorders | |
Crohns’s Disease, unspecified | ||
Vascular endothelial growth factor A | Colorectal Neoplasms | |
resveratrol | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Interleukin-1 beta | * Gastrointestinal motility disorders | |
Interleukin-10 | * Gastrointestinal motility disorders | |
Interleukin-6 | * Gastrointestinal motility disorders | |
Interleukin-8 | * Gastrointestinal motility disorders | |
Mitogen-activated protein kinase 8 | Crohns’s Disease, unspecified | |
Myeloperoxidase | * Gastrointestinal motility disorders | |
Nitric oxide synthase, endothelial | Colon cancer | |
Ornithine decarboxylase | Hereditary Polyposis Syndromes | |
Peroxisome proliferator-activated receptor gamma | Crohns’s Disease, unspecified | |
Inflammatory Bowel Disease | ||
Ulcerative colitis | ||
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Proto-oncogene c-Fos | * Gastrointestinal motility disorders | |
Transcription factor AP-1 | * Gastrointestinal motility disorders | |
Tumor necrosis factor | * Gastrointestinal motility disorders | |
Crohns’s Disease, unspecified | ||
Vascular endothelial growth factor A | Colorectal Neoplasms | |
Sitogluside | 5-hydroxytryptamine receptor 3A | * Gastrointestinal motility disorders |
Diarrhea | ||
Irritable bowel syndrome | ||
Postoperative nausea and vomiting | ||
Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) | |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Sodium channel protein type 5 subunit alpha | * Gastrointestinal motility disorders | |
SKM | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
stearic acid | Prostaglandin G/H synthase 2 | Adenomatous polyposis |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Stigmasterol | Leukotriene A-4 hydrolase | Esophageal cancer |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome | ||
Sodium channel protein type 5 subunit alpha | * Gastrointestinal motility disorders | |
succinic acid | Nitric oxide synthase, brain | * Gastrointestinal motility disorders |
taxifolin | Heat shock protein HSP 90 | Gastrointestinal Stromal Tumors (GIST) |
Prostaglandin G/H synthase 2 | Adenomatous polyposis | |
Colorectal cancer | ||
Oropharyngeal squamous cell carcinoma | ||
Peutz–Jeghers syndrome |
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Share and Cite
Choi, N.-R.; Lee, K.; Seo, M.; Ko, S.-J.; Choi, W.-G.; Kim, S.-C.; Kim, J.; Park, J.-W.; Kim, B.-J. Network Pharmacological Analysis and Experimental Validation of the Effect of Smilacis Glabrae Rhixoma on Gastrointestinal Motility Disorder. Plants 2023, 12, 1509. https://doi.org/10.3390/plants12071509
Choi N-R, Lee K, Seo M, Ko S-J, Choi W-G, Kim S-C, Kim J, Park J-W, Kim B-J. Network Pharmacological Analysis and Experimental Validation of the Effect of Smilacis Glabrae Rhixoma on Gastrointestinal Motility Disorder. Plants. 2023; 12(7):1509. https://doi.org/10.3390/plants12071509
Chicago/Turabian StyleChoi, Na-Ri, Kangwook Lee, Mujin Seo, Seok-Jae Ko, Woo-Gyun Choi, Sang-Chan Kim, Jinsung Kim, Jae-Woo Park, and Byung-Joo Kim. 2023. "Network Pharmacological Analysis and Experimental Validation of the Effect of Smilacis Glabrae Rhixoma on Gastrointestinal Motility Disorder" Plants 12, no. 7: 1509. https://doi.org/10.3390/plants12071509