Anti-Inflammatory Activity of the Constituents from the Leaves of Perilla frutescens var. acuta
Abstract
:1. Introduction
2. Results
2.1. Isolation of the Compounds
2.2. In Silico Docking Simulation
2.3. Cell Viability
2.4. PPAR-α/δ/γ Transcriptional Activity
2.5. NF-κB Transcriptional Activity
2.6. NF-κB Target Gene Expression
3. Discussion
4. Materials and Methods
4.1. Plant Material
4.2. General Experimental Procedures
4.3. Extraction and Isolation
4.4. Molecular Docking
4.5. Cell Viability
4.6. PPAR and NF-κB Transcriptional Activity
4.7. NF-κB Target Gene Expression
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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Compound | Autodock Vina | Autodock 4 | Dock6 | |
---|---|---|---|---|
PPAR-α | EPA * | −6.7 | −7.8 | −35.5 |
1 | −7.2 | −13.2 | −41.5 | |
2 | −6.5 | −9.1 | −41.7 | |
3 | −8.6 | −9.7 | −43.0 | |
PPAR-δ | EPA | −7.8 | −7.4 | −41.0 |
1 | −9.7 | −14.7 | −58.1 | |
2 | −9.4 | −13.2 | −43.3 | |
3 | −8.3 | −9.3 | −41.5 | |
PPAR-γ | EPA | −6.8 | −8.1 | −37.2 |
1 | −5.8 | −9.7 | −57.1 | |
2 | −5.6 | −13.4 | −51.6 | |
3 | −7.6 | −8.9 | −40.1 |
Category | Feature | EPA | 1 | 2 | 3 |
---|---|---|---|---|---|
Physicochemical properties | Molecular weight | 302.22 | 638.11 | 622.12 | 360.08 |
Van der Waals (Volume) | 356.24 | 564.63 | 555.84 | 346.37 | |
Density | 0.85 | 1.13 | 1.12 | 1.03 | |
No. a of H-bond b acceptors | 2 | 18 | 17 | 8 | |
No. of H-bond donors | 1 | 10 | 9 | 5 | |
No. of rotatable bonds | 13 | 7 | 7 | 7 | |
No. of rings | 0 | 5 | 5 | 2 | |
No. of atoms in the biggest ring | 0 | 10 | 10 | 6 | |
Pure LogS (log mol/L) | −4.42 | −4.37 | −2.94 | −2.95 | |
LogP | 5.18 | −0.31 | 0.88 | 1.51 | |
Medicinal chemistry | SA score c | 3.04 | 4.88 | 4.74 | 2.90 |
MCE-18 | 0 | 127.46 | 123.92 | 30 | |
Lipinski rule | Accepted | Rejected | Rejected | Accepted | |
Pfizer rule | Rejected | Accepted | Accepted | Accepted | |
GSK rule | Rejected | Rejected | Rejected | Accepted | |
Absorption | Caco-2 cell permeability (log unit) | −5.08 | −6.90 | −6.94 | −5.80 |
MDCK cell permeability (cm/s) | 1.7 × 10−5 | 5.96 × 10−5 | 3.30 × 10−5 | 5.00 × 10−6 | |
F20% | 0.94 | 0.01 | 0.84 | 0.98 | |
Distribution | Plasma protein binding (%) | 100.70 | 83.34 | 81.14 | 92.41 |
Volume distribution (L/kg) | 0.26 | 0.61 | 0.50 | 0.36 | |
BBB penetration probability | 0.001 | 0.054 | 0.045 | 0.021 | |
Fu (The fraction unbound in plasma %) | 1.09 | 14.64 | 11.64 | 3.31 | |
Metabolism | CYP1A2-inhibition probability | 0.072 | 0.116 | 0.041 | 0.251 |
CYP1A2-substrate probability | 0.117 | 0.015 | 0.006 | 0.022 | |
CYP2C19-inhibition probability | 0.028 | 0.048 | 0.054 | 0.064 | |
CYP2C19-substrate probability | 0.050 | 0.034 | 0.030 | 0.034 | |
CYP2C9-inhibition probability | 0.116 | 0.004 | 0.004 | 0.481 | |
CYP2C9-substrate probability | 1.00 | 0.09 | 0.15 | 0.94 | |
Excretion | Clearance (mL/min/kg) | 1.77 | 1.10 | 1.04 | 9.52 |
Toxicity | Human hepatotoxicity probability | 0.92 | 0.14 | 0.25 | 0.59 |
Ames toxicity probability | 0.003 | 0.305 | 0.042 | 0.235 | |
Rat oral acute toxicity probability | 0 | 0.008 | 0.027 | 0.272 | |
Carcinogenicity probability | 0.105 | 0.037 | 0.109 | 0.536 | |
Respiratory toxicity probability | 0.535 | 0.014 | 0.012 | 0.034 | |
Toxicophore rules | Acute toxicity rule (alerts) | 0 | 0 | 0 | 0 |
Genotoxic carcinogenicity rule (alerts) | 0 | 0 | 0 | 1 | |
Non-genotoxic carcinogenicity rule (alerts) | 0 | 0 | 0 | 1 | |
SureChEMBL rule (alerts) | 0 | 0 | 0 | 0 |
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Youn, I.; Han, S.; Jung, H.J.; Noh, S.G.; Chung, H.Y.; Koo, Y.K.; Shin, S.; Seo, E.K. Anti-Inflammatory Activity of the Constituents from the Leaves of Perilla frutescens var. acuta. Pharmaceuticals 2023, 16, 1655. https://doi.org/10.3390/ph16121655
Youn I, Han S, Jung HJ, Noh SG, Chung HY, Koo YK, Shin S, Seo EK. Anti-Inflammatory Activity of the Constituents from the Leaves of Perilla frutescens var. acuta. Pharmaceuticals. 2023; 16(12):1655. https://doi.org/10.3390/ph16121655
Chicago/Turabian StyleYoun, Isoo, Sujin Han, Hee Jin Jung, Sang Gyun Noh, Hae Young Chung, Yean Kyoung Koo, Sunhye Shin, and Eun Kyoung Seo. 2023. "Anti-Inflammatory Activity of the Constituents from the Leaves of Perilla frutescens var. acuta" Pharmaceuticals 16, no. 12: 1655. https://doi.org/10.3390/ph16121655
APA StyleYoun, I., Han, S., Jung, H. J., Noh, S. G., Chung, H. Y., Koo, Y. K., Shin, S., & Seo, E. K. (2023). Anti-Inflammatory Activity of the Constituents from the Leaves of Perilla frutescens var. acuta. Pharmaceuticals, 16(12), 1655. https://doi.org/10.3390/ph16121655