Liquid-Liquid Chromatography Separation of Guaiane-Type Sesquiterpene Lactones from Ferula penninervis Regel & Schmalh. and Evaluation of Their In Vitro Cytotoxic and Melanin Inhibitory Potential
Abstract
:1. Introduction
2. Results and Discussion
2.1. Liquid-Liquid Chromatography Separation of Sesquiterpene Lactones from Ferula penninervis Methanolic Root Extract
2.2. Structure Elucidation of the New Guaiane-Type Sesquiterpene Lactones
2.3. Effects on Gastrointestinal, Prostate and Skin Cancer and Non-Cancer Cell Viability
2.3.1. Cytotoxic Activity of Ferula penninervis Methanolic Root Extract
2.3.2. Cytotoxic Activity of Guaiane-Type Sesquiterpene Lactones
2.4. Influence on Melanin Synthesis and Release in αMSH-Stimulated Melanoma B16F10 Cells
3. Materials and Methods
3.1. Apparatus
3.2. Chemicals
3.3. Plant Material and Extraction
3.4. Isolation Procedures
3.4.1. Liquid-Liquid Chromatographic Experiments
3.4.2. Semi-Preparative HPLC Separations
3.4.3. Analytical HPLC Separations
3.5. Structure Elucidation
3.6. Cell Viability Assay
3.6.1. Cell Lines and Cell Cultures
3.6.2. Neutral Red Uptake Assay
3.7. Melanin Release/Content Assay
3.8. Statistical Analysis
4. 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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No. | HEMWat | P1 | P2 | P3 | P4 | P5 | P6 | P7 |
---|---|---|---|---|---|---|---|---|
1 | 5/6/5/6 | 5.20 | 5.28 | 8.18 | 10.13 | 14.20 | 15.30 | 21.77 |
2 | 1/1/1/1 | 1.91 | 2.04 | 3.03 | 4.69 | 5.34 | 5.48 | 7.95 |
3 | 6/5/6/5 | 0.95 | 1.04 | 1.66 | 2.43 | 2.89 | 2.98 | 4.49 |
4 | 3/2/3/2 | 0.44 | 0.48 | 0.70 | 1.02 | 1.27 | 1.32 | 1.89 |
α | − | 1.1 | 1.5 | 1.5 | 1.3 | 1.0 | 1.4 |
Position | Ferupennin P (2) | Ferupennin Q (6) | ||
---|---|---|---|---|
δH (Multiplicity, J, nH) | δC | δH (Multiplicity, J, nH) | δC | |
Sesq. | ||||
1 | 130.6 | 130.6 | ||
2 | 197.6 | 197.7 | ||
3 | 6.19 (s, 1H) | 136.3 | 6.20 (p, 1.1 Hz, 1H) | 136.3 |
4 | 173.1 | 173.1 | ||
5 | 3.94 (d, 11.4 Hz, 1H) | 48.8 | 3.94 (d, 11.5 Hz, 1H) | 48.9 |
6 | 4.69 (t, 11.4, 9.7 Hz, 1H) | 80.2 | 4.70 (dd, 11.5, 9.7 Hz, 1H) | 80.2 |
7 | 3.63 (dd, 10.9, 9.7 Hz, 1H) | 48.5 | 3.55 (dd, 11.1, 9.7 Hz, 1H) | 48.8 |
8 | 5.60 (td, 10.9, 3.3 Hz, 1H) | 68.7 | 5.60 (td, 11.1, 3.3 Hz, 1H) | 68.8 |
9 | 2.79 (dd, 19.1, 3.3 Hz, 1H) 2.65 (dd, 19.1, 10.9 Hz, 1H) | 44.4 | 2.80 (dd, 19.1, 3.3 Hz, 1H) 2.64 (dd, 19.1, 10.8 Hz, 1H) | 44.4 |
10 | 147.7 | 147.7 | ||
11 | 79.4 | 79.3 | ||
12 | 175.6 | 175.6 | ||
13 | 1.61 (s, 3H) | 20.7 | 1.61 (s, 3H) | 20.5 |
14 | 2.25 (s, 3H) | 20.3 | 2.25 (s, 3H) | 20.3 |
15 | 2.25 (s, 3H) | 20.2 | 2.26 (t, 1.1 Hz, 3H) | 20.2 |
Acyl-8 | ||||
8a | 177.3 | 177.3 | ||
8b | 2.61 (hept, 7.0 Hz, 1H) | 35.4 | 2.60 (hept, 6.9 Hz, 1H) | 35.4 |
8c | 1.24 (d, 7.0 Hz, 3H) | 19.3 | 1.23 (d, 6.9 Hz, 3H) | 19.3 |
8d | 1.21 (d, 7.0 Hz, 3H) | 19.0 | 1.20 (d, 6.9 Hz, 3H) | 19.1 |
Acyl-11 | ||||
11a | 171.3 | 177.3 | ||
11b | 2.10 (s, 3H) | 20.7 | 2.60 (hept, 6.9 Hz, 1H) | 34.9 |
11c | 1.20 (d, 6.9 Hz, 3H) | 19.0 | ||
11d | 1.19 (d, 6.9 Hz, 3H) | 18.9 |
Cell Line-Type | Cell Line | IC50 (μg/mL) |
---|---|---|
Gastrointestinal cancer cells | N87 | 154.54 ± 4.13 |
Caco-2 | 145.08 ± 6.82 | |
HT-29 | 190.53 ± 9.90 | |
Prostate cancer cells | LNCaP | 112.12 ± 3.82 |
DU145 | >200 | |
PC3 | 112.28 ± 3.98 | |
Skin cancer cells | SCC-15 | 77.84 ± 2.55 |
A375 | 138.48 ± 9.45 | |
B16F10 | 110.04 ± 1.34 | |
Non-cancer cells | PNT2 | >200 |
HaCaT | 159.28 ± 5.70 | |
BJ | >200 |
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Luca, S.V.; Gaweł-Bęben, K.; Strzępek-Gomółka, M.; Jumabayeva, A.; Sakipova, Z.; Xiao, J.; Marcourt, L.; Wolfender, J.-L.; Skalicka-Woźniak, K. Liquid-Liquid Chromatography Separation of Guaiane-Type Sesquiterpene Lactones from Ferula penninervis Regel & Schmalh. and Evaluation of Their In Vitro Cytotoxic and Melanin Inhibitory Potential. Int. J. Mol. Sci. 2021, 22, 10717. https://doi.org/10.3390/ijms221910717
Luca SV, Gaweł-Bęben K, Strzępek-Gomółka M, Jumabayeva A, Sakipova Z, Xiao J, Marcourt L, Wolfender J-L, Skalicka-Woźniak K. Liquid-Liquid Chromatography Separation of Guaiane-Type Sesquiterpene Lactones from Ferula penninervis Regel & Schmalh. and Evaluation of Their In Vitro Cytotoxic and Melanin Inhibitory Potential. International Journal of Molecular Sciences. 2021; 22(19):10717. https://doi.org/10.3390/ijms221910717
Chicago/Turabian StyleLuca, Simon Vlad, Katarzyna Gaweł-Bęben, Marcelina Strzępek-Gomółka, Ainur Jumabayeva, Zuriyadda Sakipova, Jianbo Xiao, Laurence Marcourt, Jean-Luc Wolfender, and Krystyna Skalicka-Woźniak. 2021. "Liquid-Liquid Chromatography Separation of Guaiane-Type Sesquiterpene Lactones from Ferula penninervis Regel & Schmalh. and Evaluation of Their In Vitro Cytotoxic and Melanin Inhibitory Potential" International Journal of Molecular Sciences 22, no. 19: 10717. https://doi.org/10.3390/ijms221910717