Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations
Abstract
:1. Introduction
2. Results
2.1. Effect of Ginsenoside Rg5 on Gene Expression Profiles in the Murine Hippocampal Neuronal Cell Line HT22
2.2. Effect of Ginsenoside Rg5 on Signaling Canonical Pathways
2.2.1. Neurotransmitters and Nervous System Signaling
The Neuroinflammation Signaling Pathway
The cAMP/CREB Signaling Pathway in Neurons
2.2.2. Cellular Immune Response, Cellular stress and Injury Signaling
Senescence
Eukaryotic Translation Initiation Factor EIF2 Signaling
2.2.3. Nuclear Receptors Signaling and Transcriptional Regulators Signaling
Estrogen Receptors Signaling
Sirtuin Signaling Pathway
2.2.4. Apoptosis and Cancer Signaling
Death Receptor Signaling
Tumor Microenvironment Pathway
The Programmed Cell Death Receptor PD-1 Cancer Immunotherapy Pathway
2.3. Effect of Ginsenoside Rg5 on Metabolic Pathways
2.4. Predicted Effects of Ginsenoside Rg5
2.4.1. Molecular and Cellular Functions
2.4.2. Physiological Functions
2.4.3. Diseases and Disorders
3. Discussion
4. Materials and Methods
4.1. mRNA Microarray Hybridization
4.2. Ingenuity Pathway Analysis (IPA)
4.3. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sample Name | Rg5 Concentration | Molecules of Rg5 per Cells, Ratio | Number of Deregulated Genes | Number of Deregulated Genes Unique Only in Selected Conc. | Fold Changes of the Only Gene, Ca6, Which is Deregulated in All Conc. |
---|---|---|---|---|---|
S2 | 10−4 M | 1 2 × 1011 | 1670 | 1215 | 731 |
S3 | 10−6 M | 1 2 × 109 | 280 | 120 | −306 |
S4 | 10−9 M | 1 2 × 106 | 328 | 122 | −286 |
S5 | 10−12 M | 1 2 × 103 | 380 | 163 | −274 |
S6 | 10−15 M | 1 2 | 471 | 252 | −281 |
S7 | 10−17 M | 2:102 | 343 | 159 | −293 |
S8 | 10−18 M | 2:103 | 422 | 178 | −313 |
Concentration of Rg5, M | 10−4 | 10−6 | 10−9 | 10−12 | 10−15 | 10−17 | 10−18 | |
---|---|---|---|---|---|---|---|---|
No. of matching genes | 23 | 5 | 2 | 6 | 5 | 4 | 8 | |
Amyloid-β plaque accumulation | disease | + | 0 | − | − | 0 | + | − |
Astrogliosis | disease | + | − | + | + | + | + | − |
Aβ formation/generation | disease | + | − | + | + | + | + | + |
Blood-brain barrier disruption | disease | + | − | +/− | + | + | + | − |
Major depression | disease | + | − | + | + | + | + | − |
Oxidative stress | disease | + | − | − | + | − | + | − |
Neuron’s damage | disease | + | − | + | + | + | + | − |
Neuron’s survival | process | − | − | + | + | + | + | + |
Neuron’s apoptosis | process | + | 0 | − | − + | + | + | + − |
Th1 cell recruitment | process | − | + | − | − | − | − | + |
T cell recruitment | process | + | 0 | − | + | + | + | − |
GABAergic neuron density | process | + | − | + | + | + | + | − |
Amyloid-β precursor protein | protein | + | 0 | − | − | 0 | + | − |
Concentration of Rg5, M | 10−4 | 10−6 | 10−9 | 10−12 | 10−15 | 10−17 | 10−18 | |
---|---|---|---|---|---|---|---|---|
No. of matching genes | 43 | 10 | 5 | 8 | 9 | 3 | 8 | |
Cell division cycle | function | − | + | + | + | + | + | + |
Cellular senescence | function | + | − | − | − | − | − | − |
Concentration of Rg5, M | 10−4 | 10−6 | 10−9 | 10−12 | 10−15 | 10−17 | 10−18 | |
---|---|---|---|---|---|---|---|---|
No. of matching genes | 32 | 3 | 8 | 5 | 9 | 8 | 9 | |
Cardio-protection | disease | + | 0 | − | − | − | − | − |
ER stress response | function | + | 0 | − | − | − | − | − |
Uptake of D-glucose | function | − | 0 | + | + | + | + | + |
Vascularization | function | − | 0 | − | − | 0 | 0 | + |
Assembly of stress granule | function | − | 0 | − | − | 0 | 0 | − |
Translation/protein elongation | function | − | − | − | − | + | − | − |
Concentration of Rg5, M | 10−4 | 10−6 | 10−9 | 10−12 | 10−15 | 10−17 | 10−18 | |
---|---|---|---|---|---|---|---|---|
No. of matching genes | 56 | 5 | 13 | 8 | 10 | 1 | 11 | |
Atrophy of muscle | disease | + | + | − | − | − | 0 | + |
Breast cancer cell line tumorigenesis | disease | 0 | − | + | 0 | − | 0 | + |
Metastasis | disease | + | 0 | − | 0 | − | 0 | 0 |
Oxidative stress | disease | + | 0 | 0 | 0 | 0 | 0 | + |
Tumor cell proliferation | disease | 0 | − | + | 0 | − | 0 | +0 |
Angiogenesis | function | 0 | − | + | + | − | 0 | + |
Apoptosis | function | + | + | − | − | − | 0 | + |
Cell proliferation | function | − | − | + | 0 | − | 0 | + |
Coronary vessel relaxation | function | − | 0 | − | + | 0 | 0 | + |
Neuroprotection | function | + | − | + | + | + | + | + |
Survival of cells | function | + | − | + | + | + | + | 0 |
Synapse maturation | function | − | + | + | − | − | 0 | + |
Concentration of Rg5, M | 10−4 | 10−6 | 10−9 | 10−12 | 10−15 | 10−17 | 10−18 | |
---|---|---|---|---|---|---|---|---|
No. of matching genes | 8 | 0 | 0 | 5 | 5 | 2 | 2 | |
Apoptosis | function | − | 0 | 0 | − | − | − | − |
Cell shrinkage | function | − | 0 | 0 | − | − | − | + |
Chromatin condensation | function | − | 0 | 0 | − | − | − | − |
DNA fragmentation | function | − | 0 | 0 | − | − | − | − |
DNA repair | function | + | 0 | 0 | + | + | + | + |
Concentration of Rg5, M | 10−4 | 10−6 | 10−9 | 10−12 | 10−15 | 10−17 | 10−18 | |
---|---|---|---|---|---|---|---|---|
No. of matching genes | 29 | 5 | 2 | 4 | 7 | 4 | 5 | |
Apoptosis of tumor cells | Disease | − + | ++ | 0 | − − | − − | − + | − + |
Viability of tumor cells | function | + | − | 0 | + | + | + | + |
Survival of tumor cells | disease | + | − | 0 | + | + | + | + |
Proliferation of tumor cells | disease | − | − | 0 | + | + | + | + |
Metastasis | disease | + | − | 0 | + | + | + | + |
Tumor cell invasion | disease | − | − | 0 | + | + | + | + |
Concentration Rg5, M | 10−4 | 10−6 | 10−9 | 10−12 | 10−15 | 10−17 | 10−18 | |
---|---|---|---|---|---|---|---|---|
No. of matching genes | 9 | 4 | 1 | 2 | 6 | 1 | 3 | |
Cancer cell proliferation | disease | + | − | − | 0 | + | + | + |
T-cell exhaustion | disease | + | + | 0 | − | − | 0 | + |
Effector function of T cells | function | − | − | 0 | + | + | 0 | − |
T-cell apoptosis | function | − | + | 0 | 0 | − | − | + |
T-cell proliferation | function | − | − | 0 | + | + | 0 | 0 |
T-cell activation | function | − | − | 0 | + | + | 0 | − |
Tr1 cell specialization | function | + | + | 0 | − | − | 0 | + |
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Panossian, A.; Abdelfatah, S.; Efferth, T. Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations. Pharmaceuticals 2021, 14, 999. https://doi.org/10.3390/ph14100999
Panossian A, Abdelfatah S, Efferth T. Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations. Pharmaceuticals. 2021; 14(10):999. https://doi.org/10.3390/ph14100999
Chicago/Turabian StylePanossian, Alexander, Sara Abdelfatah, and Thomas Efferth. 2021. "Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations" Pharmaceuticals 14, no. 10: 999. https://doi.org/10.3390/ph14100999
APA StylePanossian, A., Abdelfatah, S., & Efferth, T. (2021). Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations. Pharmaceuticals, 14(10), 999. https://doi.org/10.3390/ph14100999