An Integrative Approach to Investigate the Mode of Action of (−)-Dendroparishiol in Bacterial Meningitis: Computer-Aided Estimation of Biological Activity and Network Pharmacology
Abstract
:1. Introduction
2. Results and Discussion
2.1. Profiles of Estimated Biological Activity of (−)-Dendroparishiol
2.2. Cytotoxicity Profile of (−)-Dendroparishiol in BV-2 Microglial Cells
2.3. Effects of (−)-Dendroparishiol on Pro-Inflammatory Mediators in LPS-Stimulated BV-2 Cells
2.4. Molecular Docking to Determine the Interaction of (−)-Dendroparishiol with Proinflammatory Enzymes
2.5. Network Pharmacology Analysis of the Role of (−)-Dendroparishiol in Bacterial Meningitis
3. Materials and Methods
3.1. Materials and Chemicals
3.2. Prediction of Biological Activity of (−)-Dendroparishiol
3.3. In Vitro Cell-Based Assay
3.3.1. Extraction and Isolation of (−)-Dendroparishiol from Dendrobium parishii
3.3.2. BV-2 Cell Culture
3.3.3. Evaluation of Cytotoxic Effects of (−)-Dendroparishiol
3.3.4. Hoechst 33342/PI Dual Staining Assay
3.3.5. Anti-Inflammatory Effects of (−)-Dendroparishiol on LPS-Stimulated BV-2 Cells
3.3.6. Nitrite Concentration Analysis Using Griess Reagent
3.3.7. Determination of IL-6 and TNF-α Levels Using ELISA
3.3.8. Western Blot Analysis
3.4. Molecular Docking
3.5. Network Pharmacology Analysis
3.5.1. Identification of (−)-Dendroparishiol-Target Genes
3.5.2. Identification of Bacterial Meningitis-Target Genes
3.5.3. Construction of Protein–Protein Interaction (PPI) Network
3.5.4. GO Enrichment and Pathway Analysis
3.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
DP | Dendrobium parishii |
NF-κB | Nuclear factor kappa |
IL-1β | Interleukin-1beta |
IL-6 | Interleukin-6 |
IL-1 | Interleukin-1 |
TNF-α | Tumor necrosis factor alpha |
NO | Nitric oxide |
iNOS | Inducible nitric oxide synthase |
COX-2 | Cyclooxygenase-2 |
LPS | Lipopolysaccharide |
SOD | Superoxide dismutase |
GPx | Glutathione peroxidase |
CAT | Catalase |
MTT | 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide |
MMPs | Matrix metalloproteinases |
ROS | Reactive oxygen species |
JAK2 | Janus kinase 2 |
PGE-2 | Prostaglandin E2 |
BMG | Bacterial meningitis |
DMSO | Dimethyl sulfoxide |
ELISA | Enzyme-linked immunosorbent assay |
PPI | Protein–protein interactions |
MCC | Maximal clique centrality |
GO | Gene Ontology |
KEGG | Kyoto Encyclopedia of Genes and Genomes |
FDR | False discovery rate |
SDS-PAGE | Sodium dodecyl sulfate-polyacrylamide gels |
TBST | Tris Buffered Saline with 0.1% Tween 20 |
PDB | Protein data bank |
DMEM | Dulbecco’s modified Eagle’s medium |
FBS | Fetal bovine serum |
PBS | Phosphate buffered saline |
PI | Propidium iodide |
NED | N-1-Napthylenediamine dihydrochloride |
BCA | Bicinchoninic acid |
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Pa | Pi | Activity |
---|---|---|
0.806 | 0.008 | JAK2 expression inhibitor |
0.620 | 0.004 | NOS2 expression inhibitor |
0.437 | 0.041 | MMP9 expression inhibitor |
0.335 | 0.010 | Nitric oxide antagonist |
0.405 | 0.093 | Anti-inflammatory |
0.333 | 0.083 | TNF expression inhibitor |
0.285 | 0.048 | Non-steroidal anti-inflammatory agent |
0.213 | 0.024 | Transcription factor NF kappa B inhibitor |
0.187 | 0.020 | Lipoxygenase inhibitor |
0.172 | 0.014 | Cytokine release inhibitor |
0.175 | 0.040 | Leukotriene synthesis inhibitor |
0.145 | 0.055 | Interleukin 4 antagonist |
0.107 | 0.023 | 5-Lipoxygenase inhibitor |
0.210 | 0.129 | Phospholipase C inhibitor |
0.158 | 0.095 | Nitric oxide scavenger |
0.111 | 0.076 | Cyclooxygenase inhibitor |
0.076 | 0.072 | Cyclooxygenase 2 inhibitor |
Protein Targets | Ligands | ∆G (kcal/mol) | Interacting Residues | |||||||
---|---|---|---|---|---|---|---|---|---|---|
H-Bond | C-H Bond | Pi-Sulfur | Pi-Anion | Pi-Pi | Amide-Pi | Pi-Sigma | Hydrophobic | |||
COX-2 | (−)-dendroparishiol | −11.24 | SER353 MET522 | PHE518 | MET522 | - | TYR355 TRP387 | - | VAL349 VAL523 ALA527 | VAL116 TYR348 LEU352 TYR385 ALA516 LEU531 |
Rofecoxib | −10.70 | ILE517 PHE518 | ARG513 ALA527 | MET522 | - | - | GLY526 | VAL523 | VAL349 LEU352 | |
iNOS | (−)-dendroparishiol | −7.09 | ILE265 TYR347 ALA351 TRP372 | GLY371 GLU377 ASP382 | - | GLU377 | - | - | - | ARG199 CYS200 PRO350 VAL352 MET374 |
AR-C95791 | −6.62 | TYR347 | PHE369 | - | - | - | - | VAL352 | TRP346 PRO350 |
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Limcharoen, T.; Dasuni Wasana, P.W.; Hasriadi; Angsuwattana, P.; Muangnoi, C.; Warinhomhoun, S.; Ongtanasup, T.; Sritularak, B.; Vajragupta, O.; Rojsitthisak, P.; et al. An Integrative Approach to Investigate the Mode of Action of (−)-Dendroparishiol in Bacterial Meningitis: Computer-Aided Estimation of Biological Activity and Network Pharmacology. Int. J. Mol. Sci. 2023, 24, 8072. https://doi.org/10.3390/ijms24098072
Limcharoen T, Dasuni Wasana PW, Hasriadi, Angsuwattana P, Muangnoi C, Warinhomhoun S, Ongtanasup T, Sritularak B, Vajragupta O, Rojsitthisak P, et al. An Integrative Approach to Investigate the Mode of Action of (−)-Dendroparishiol in Bacterial Meningitis: Computer-Aided Estimation of Biological Activity and Network Pharmacology. International Journal of Molecular Sciences. 2023; 24(9):8072. https://doi.org/10.3390/ijms24098072
Chicago/Turabian StyleLimcharoen, Thanchanok, Peththa Wadu Dasuni Wasana, Hasriadi, Pornpoom Angsuwattana, Chawanphat Muangnoi, Sakan Warinhomhoun, Tassanee Ongtanasup, Boonchoo Sritularak, Opa Vajragupta, Pornchai Rojsitthisak, and et al. 2023. "An Integrative Approach to Investigate the Mode of Action of (−)-Dendroparishiol in Bacterial Meningitis: Computer-Aided Estimation of Biological Activity and Network Pharmacology" International Journal of Molecular Sciences 24, no. 9: 8072. https://doi.org/10.3390/ijms24098072