Innovative Application of Medicinal Insects: Employing UHPLC-MS, Bioinformatics, In Silico Studies and In Vitro Experiments to Elucidate the Multi-Target Hemostatic Mechanism of Glenea cantor (Coleoptera: Cerambycidae) Charcoal-Based Medicine
Abstract
:1. Introduction
2. Results
2.1. In Vitro Coagulation Assay Results of GC-CM
2.2. UHPLC-MS Analysis
2.3. Active Components of GC-CM and Its Potential Targets Related to Hemostasis
2.4. The “Active Ingredient–Intersecting Target–Hemostasis” Network and Key Components of GC-CM
2.5. PPI Network
2.6. GO and KEGG Pathway Analysis of GC-CM with Hemostatic Intersection Targets
2.7. Verification with Molecular Docking
2.8. Verification with Molecular Dynamics Simulation
3. Discussion
4. Materials and Methods
4.1. Source of Glenea cantor
4.2. Reagents and Instruments
4.3. Experimental Animals
4.4. Preparation of GC-CM
4.5. In Vitro Coagulation Test
4.6. UHPLC-MS Analysis Conditions
4.6.1. UHPLC Conditions
4.6.2. Orbitrap Explorisrm™ 480 Mass Spectrometry Conditions
4.6.3. Data Analysis Process
4.7. Collection of Bioactive Components and Gene Targets of GC-CM
4.8. Collection of Potential Targets for Hemostasis
4.9. Construction of the “GC-CM Active Components–Intersection Targets–Hemostasis” Network
4.10. Construction of Protein–Protein Interaction (PPI) Network
4.11. Enrichment Analysis of GO and KEGG
4.12. Molecular Docking
4.13. Molecular Dynamics Simulation
4.14. Statistical Analysis Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
List of Abbreviations
GC-CM | Glenea cantor charcoal medicine |
APTT | activated partial thromboplastin time |
PT | prothrombin time |
DC | Degree Centrality |
BC | Betweenness Centrality |
CC | Closeness Centrality |
GO | Gene Ontology |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
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Groups | APTT (s) | PT (s) |
---|---|---|
blank control group | 31.97 ± 1.90 | 12.77 ± 0.73 |
GC-CM group | 24.93 ± 0.85 ** | 10.04 ± 0.70 ** |
positive control group | 22.86 ± 1.42 ** | 9.68 ± 0.83 ** |
No. | Name | Degree | BC | CC |
---|---|---|---|---|
1 | 1-monolinoleoyl-rac-glycerol | 23 | 0.15123 | 0.38356 |
2 | 2′,6′-dihydroxy 4′-methoxydihydrochalcone | 20 | 0.13134 | 0.38043 |
3 | 3-(4-formylaminobutyryl)pyridine | 13 | 0.08402 | 0.37333 |
4 | 6h-thieno [3,2-f][1,2,4]triazolo [4,3-a][1,4]diazepine-6-acetic acid, 4-(4-chlorophenyl)-2,3,9-trimethyl-, 1,1-dimethylethyl ester, (6r)- | 9 | 0.05643 | 0.36939 |
5 | 1,3-dicyclohexylurea | 7 | 0.04247 | 0.36745 |
6 | Arachidonoyl ethanolamide | 7 | 0.04247 | 0.36745 |
7 | Galiellalactone | 7 | 0.04247 | 0.36745 |
8 | Neoabietic acid | 7 | 0.04247 | 0.36745 |
9 | 1-(4-piperidinyl)-1,3-dihydro-2h-indol-2-one | 6 | 0.03546 | 0.36649 |
10 | 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol | 6 | 0.03546 | 0.36649 |
11 | 4-acetamidoantipyrin | 6 | 0.03546 | 0.36649 |
12 | alpha-ionone | 5 | 0.02842 | 0.36554 |
13 | (1r,5s)-8-methyl-8-azabicyclo [3.2.1]octan-3-amine | 5 | 0.02842 | 0.36554 |
14 | 10-hydroxydecanoate | 5 | 0.02842 | 0.36554 |
15 | Dibutyl adipate | 5 | 0.02842 | 0.36554 |
16 | Dodecanoic acid, 12-[[(cyclohexylamino)carbonyl]amino]- | 5 | 0.02842 | 0.36554 |
17 | L-Fucose | 5 | 0.02842 | 0.36554 |
18 | N-acetyl-5-hydroxytryptamine | 5 | 0.02842 | 0.36554 |
19 | Primaquine | 5 | 0.02842 | 0.36554 |
20 | Pro-leu | 5 | 0.02842 | 0.36554 |
Target | Description | UniProt | DC | BC | CC |
---|---|---|---|---|---|
SRC | Proto-oncogene tyrosine-protein kinase Src | P12931 | 26 | 275.73 | 0.01176 |
AKT1 | RAC-alpha serine/threonine-protein kinase | P31749 | 26 | 337.79 | 0.0119 |
PIK3R1 | Phosphatidylinositol 3-kinase regulatory subunit alpha | P27986 | 22 | 87.27 | 0.01087 |
MAPK1 | Mitogen-activated protein kinase 1 | P28482 | 22 | 138.64 | 0.01099 |
MAPK3 | Mitogen-activated protein kinase 3 | P27361 | 21 | 154.09 | 0.01124 |
PIK3CA | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform | P42336 | 21 | 72.93 | 0.01075 |
TP53 | Cellular tumor antigen p53 | P04637 | 21 | 218.78 | 0.01087 |
PTK2 | Focal adhesion kinase 1 | Q05397 | 20 | 103.93 | 0.01042 |
STAT3 | Signal transducer and activator of transcription 3 | P40763 | 19 | 190.94 | 0.01087 |
PIK3CD | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform | O00329 | 18 | 41.64 | 0.0101 |
PIK3CB | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform | P42338 | 18 | 41.64 | 0.0101 |
JUN | Transcription factor Jun | P05412 | 18 | 204.33 | 0.01075 |
EGFR | Epidermal growth factor receptor | P00533 | 17 | 97.91 | 0.0101 |
RAF1 | RAF proto-oncogene serine/threonine-protein kinase | P04049 | 15 | 43.79 | 0.00935 |
GRB2 | Growth factor receptor-bound protein 2 | P62993 | 14 | 83.64 | 0.00962 |
ESR1 | Estrogen receptor | P03372 | 14 | 34.25 | 0.0101 |
FYN | Tyrosine-protein kinase Fyn | P06241 | 14 | 81.66 | 0.00909 |
LYN | Tyrosine-protein kinase Lyn | P07948 | 14 | 35.55 | 0.00935 |
TNF | Tumor necrosis factor | P01375 | 14 | 285.73 | 0.01031 |
CASP3 | Caspase-3 | P42574 | 12 | 90.93 | 0.0098 |
HIF1A | Hypoxia-inducible factor 1-alpha | Q16665 | 12 | 101.36 | 0.00962 |
MTOR | Serine/threonine-protein kinase mTOR | P42345 | 11 | 43.51 | 0.00909 |
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Zhong, B.; Zhang, W.; Ming, L.; Fan, Q.; Zhang, L.; Lai, H.; Huang, G.; Liu, H.; Dong, Z. Innovative Application of Medicinal Insects: Employing UHPLC-MS, Bioinformatics, In Silico Studies and In Vitro Experiments to Elucidate the Multi-Target Hemostatic Mechanism of Glenea cantor (Coleoptera: Cerambycidae) Charcoal-Based Medicine. Pharmaceuticals 2025, 18, 479. https://doi.org/10.3390/ph18040479
Zhong B, Zhang W, Ming L, Fan Q, Zhang L, Lai H, Huang G, Liu H, Dong Z. Innovative Application of Medicinal Insects: Employing UHPLC-MS, Bioinformatics, In Silico Studies and In Vitro Experiments to Elucidate the Multi-Target Hemostatic Mechanism of Glenea cantor (Coleoptera: Cerambycidae) Charcoal-Based Medicine. Pharmaceuticals. 2025; 18(4):479. https://doi.org/10.3390/ph18040479
Chicago/Turabian StyleZhong, Bangyu, Wen Zhang, Liangshan Ming, Qimeng Fan, Lei Zhang, Hongyu Lai, Genwang Huang, Hongning Liu, and Zishu Dong. 2025. "Innovative Application of Medicinal Insects: Employing UHPLC-MS, Bioinformatics, In Silico Studies and In Vitro Experiments to Elucidate the Multi-Target Hemostatic Mechanism of Glenea cantor (Coleoptera: Cerambycidae) Charcoal-Based Medicine" Pharmaceuticals 18, no. 4: 479. https://doi.org/10.3390/ph18040479
APA StyleZhong, B., Zhang, W., Ming, L., Fan, Q., Zhang, L., Lai, H., Huang, G., Liu, H., & Dong, Z. (2025). Innovative Application of Medicinal Insects: Employing UHPLC-MS, Bioinformatics, In Silico Studies and In Vitro Experiments to Elucidate the Multi-Target Hemostatic Mechanism of Glenea cantor (Coleoptera: Cerambycidae) Charcoal-Based Medicine. Pharmaceuticals, 18(4), 479. https://doi.org/10.3390/ph18040479