Inhibition of Human Kallikrein 5 Protease by Triterpenoids from Natural Sources
Abstract
:1. Introduction
2. Results
2.1. Triterpenoids Inhibit KLK5 Protease Activity
2.2. Ursolic Acid and Tumulosic Acid Decreased LL-37 Production in Epidermal Keratinocytes
2.3. Pharmacokinetics of Triterpenoids in Rat after Oral Administration of JHT
3. Discussion
3.1. New Findings and Enzyme Selectivity
3.2. Structure–Activity Relationship
3.3. Effect of Proteolytic Activity on LL-37 Production
3.4. Potential of Triterpenoids as Internal Drugs
3.5. Summary: Possible Effects of Triterpenoids on Dermatoses
4. Materials and Methods
4.1. Tested Triterpenoids and Reference Regents
4.2. Measurements of Each Enzymatic Activity
4.3. Detection of LL-37 by Immunoprecipitation
4.4. Cell Growth Test
4.5. Pharmacokinetic Analysis of Triterpenoids in Rats
4.6. Statistical Analysis
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Not available. |
Structure | Compound | Anti-KLK5 Activity % Inhibition |
---|---|---|
Pentacyclic triterpenoid | ||
1 Ursolic acid | 54.6 ± 1.3 | |
2 Oleanolic acid | 51.6 ± 1.8 | |
3 Polygalacic acid | 5.5 ± 2.3 | |
4 Platycodigenin | 8.8 ± 2.0 | |
5 Platycodin D | −6.0 ± 2.9 | |
6 Betulinic acid | 5.5 ± 2.5 | |
7 18β-Glycyrrhetinic acid | 16.0 ± 1.2 | |
8 Saikosaponin a | 4.3 ± 0.7 | |
9 Saikosaponin c | 4.1 ± 1.6 | |
10 Saikosaponin d | −10.4 ± 3.5 | |
11 Saikosaponin b1 | 39.6 ± 1.6 | |
12 Saikosaponin b2 | 21.1 ± 1.4 | |
13 Saikogenin A | 24.3 ± 2.6 | |
14 Saikogenin D | −1.5 ± 3.6 | |
Tetracyclic triterpenoid | ||
15 Dehydrotumulosic acid | −46.2 ± 2.7 | |
16 Dehydropachymic acid | 33.9 ± 3.7 | |
17 Eburicoic acid | −51.0 ± 3.0 | |
18 Tumulosic acid | 36.0 ± 1.9 | |
19 Pachymic acid | 56.2 ± 1.5 | |
Reference | ||
Dexamethasone | −1.8 ± 2.8 | |
Leupeptin hemisulfate | 96.9 ± 0.1 |
Ursolic Acid | Tumulosic Acid | |||
---|---|---|---|---|
IC50 (μM) | Inhibition % at 100 μM | IC50 (μM) | Inhibition % at 100 μM | |
Kallikrein 5 | 5.8 | 74.5 ± 0.2 | 14.8 | 58.7 ± 0.2 |
Kallikrein 7 | >100 | 38.4 ± 1.6 | >100 | 19.5 ± 1.5 |
Trypsin | 14.8 | 76.9 ± 3.5 | 45.3 | 73.2 ± 1.6 |
Chymotrypsin C | >100 | 35.3 ± 2.9 | >100 | 4.1 ± 5.2 |
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Matsubara, Y.; Matsumoto, T.; Koseki, J.; Kaneko, A.; Aiba, S.; Yamasaki, K. Inhibition of Human Kallikrein 5 Protease by Triterpenoids from Natural Sources. Molecules 2017, 22, 1829. https://doi.org/10.3390/molecules22111829
Matsubara Y, Matsumoto T, Koseki J, Kaneko A, Aiba S, Yamasaki K. Inhibition of Human Kallikrein 5 Protease by Triterpenoids from Natural Sources. Molecules. 2017; 22(11):1829. https://doi.org/10.3390/molecules22111829
Chicago/Turabian StyleMatsubara, Yosuke, Takashi Matsumoto, Junichi Koseki, Atsushi Kaneko, Setsuya Aiba, and Kenshi Yamasaki. 2017. "Inhibition of Human Kallikrein 5 Protease by Triterpenoids from Natural Sources" Molecules 22, no. 11: 1829. https://doi.org/10.3390/molecules22111829