Anti-Proliferative Effects of Iridoids from Valeriana fauriei on Cancer Stem Cells
Abstract
:1. Introduction
2. Results and Discussion
2.1. Isolating Constituents
2.2. Determining the Structures of Valerianairidoids I–VII (1–3, 6, 7, 9, and 12)
2.3. Evaluating Anti-Proliferative Activities against Non-CSCs and CSCs
3. Materials and Methods
3.1. General Experimental Procedures
3.2. Plant Material
3.3. Extracting and Isolating Compounds
3.4. Valerianairidoid I (1)
3.5. Valerianairidoid II (2)
3.6. Valerianairidoid III (3)
3.7. Valerianairidoid IV (6)
3.8. Valerianairidoid V (7)
3.9. Valerianairidoid VI (9)
3.10. Valerianairidoid VII (12)
3.11. Enzymatic Hydrolysis of Valerianairidoids I, II, IV, V, and VI (1, 2, 6, 7, and 9)
3.12. Aglycone of Valerianairidoid I (1a)
3.13. Aglycone of Valerianairidoid IV (6a)
3.14. Aglycone of Valerianairidoid VI (9a)
3.15. Calculating the Theoretical ECD Spectra of 1a, 6a, and 9a
3.16. Acid Hydrolyses of 1–3, 6, 7, 9, and 12
3.17. Cells
3.18. Cell Viability Assay for non-CSCs
3.19. Cell Viability Assay for CSCs
3.20. Statistics
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Wang, P.C.; Ran, X.H.; Luo, H.R.; Hu, J.M.; Chen, R.; Ma, Q.Y.; Dai, H.F.; Liu, Y.Q.; Xie, M.J.; Zhou, J.; et al. Volvalerelactones A and B, Two New Sesquiterpenoid Lactones with an Unprecedented Skeleton from Valeriana officinalis var. latifolia. Org. Lett. 2011, 13, 3036–3039. [Google Scholar] [CrossRef]
- Guo, Y.; Xu, J.; Li, Y.; Watanabe, R.; Oshima, Y.; Yamakuni, T.; Ohizumi, Y. Iridoids and Sesquiterpenoids with NGF-Potentiating Activity from the Rhizomes and Roots of Valeriana fauriei. Chem. Pharm. Bull. 2006, 54, 123–125. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oshima, Y.; Matsuoka, S.; Ohizumi, Y. Antidepressant Principles of Valeriana fauriei Roots. Chem. Pharm. Bull. 1995, 43, 169–170. [Google Scholar] [CrossRef] [Green Version]
- Matsumoto, T.; Kitagawa, T.; Imahori, D.; Matsuzaki, A.; Saito, Y.; Ohta, T.; Yoshida, T.; Nakayama, Y.; Ashihara, E.; Watanabe, T. Linderapyrone: A Wnt Signal Inhibitor Isolated from Lindera umbellate. Bioorg. Med. Chem. Lett. 2021, 45, 128161. [Google Scholar] [CrossRef]
- Matsumoto, T.; Imahori, D.; Achiwa, K.; Saito, Y.; Ohta, T.; Yoshida, T.; Kojima, N.; Yamashita, M.; Nakayama, Y.; Watanabe, T. Chemical Structures and Cytotoxic Activities of the Constituents Isolated from Hibiscus tiliaceus. Fitoterapia 2020, 142, 104524. [Google Scholar] [CrossRef] [PubMed]
- Imahori, D.; Matsumoto, T.; Saito, Y.; Ohta, T.; Yoshida, T.; Nakayama, Y.; Watanabe, T. Cell Death-Inducing Activities via P-Glycoprotein Inhibition of the Constituents Isolated from Fruits of Nandina domestica. Fitoterapia 2021, 154, 105023. [Google Scholar] [CrossRef] [PubMed]
- Matsumoto, T.; Imahori, D.; Ohnishi, E.; Okayama, M.; Kitagawa, T.; Ohta, T.; Yoshida, T.; Kojima, N.; Yamashita, M.; Watanabe, T. Chemical Structures and Induction of Cell Death via Heat Shock Protein Inhibition of the Prenylated Phloroglucinol Derivatives Isolated from Hypericum erectum. Fitoterapia 2022, 156, 105097. [Google Scholar] [CrossRef] [PubMed]
- Matsumoto, T.; Kitagawa, T.; Imahori, D.; Yoshikawa, H.; Okayama, M.; Kobayashi, M.; Kojima, N.; Yamashita, M.; Watanabe, T. Cell Death-Inducing Activities via Hsp Inhibition of the Sesquiterpenes Isolated from Valeriana fauriei. J. Nat. Med. 2021, 75, 942–948. [Google Scholar] [CrossRef] [PubMed]
- Batlle, E.; Clevers, H. Cancer Stem Cells Revisited. Nat. Med. 2017, 23, 1124–1134. [Google Scholar] [CrossRef] [PubMed]
- Hyun, S.Y.; Le, H.T.; Min, H.-Y.; Pei, H.; Lim, Y.; Song, I.; Nguyen, Y.T.K.; Hong, S.; Han, B.W.; Lee, H.Y. Evodiamine Inhibits Both Stem Cell and Non-Stem-Cell Populations in Human Cancer Cells by Targeting Heat Shock Protein 70. Theranostics 2021, 11, 2932–2952. [Google Scholar] [CrossRef] [PubMed]
- Cebrián-Torrejón, G.; Assad Kahn, S.; Lagarde, N.; Castellano, F.; Leblanc, K.; Rodrigo, J.; Molinier-Frenkel, V.; Rojas de Arias, A.; Ferreira, M.E.; Thirant, C.; et al. Antiproliferative Activity of Trans-Avicennol from Zanthoxylum chiloperone var. angustifolium against Human Cancer Stem Cells. J. Nat. Prod. 2012, 75, 257–261. [Google Scholar] [CrossRef] [PubMed]
- Fujiwara, A.; Nishi, M.; Yoshida, S.; Hasegawa, M.; Yasuma, C.; Ryo, A.; Suzuki, Y. Eucommicin A, a β-Truxinate Lignan from Eucommia ulmoides, Is a Selective Inhibitor of Cancer Stem Cells. Phytochemistry 2016, 122, 139–145. [Google Scholar] [CrossRef] [PubMed]
- Matsumoto, T.; Imahori, D.; Saito, Y.; Zhang, W.; Ohta, T.; Yoshida, T.; Nakayama, Y.; Ashihara, E.; Watanabe, T. Cytotoxic Activities of Sesquiterpenoids from the Aerial Parts of Petasites japonicus against Cancer Stem Cells. J. Nat. Med. 2020, 74, 689–701. [Google Scholar] [CrossRef] [PubMed]
- Nishiya, K.; Kimura, T.; Takeya, K.; Itokawa, H. Sesquiterpenoids and Iridoid Glycosides from Valeriana fauriei. Phytochemistry 1992, 31, 3511–3514. [Google Scholar] [CrossRef]
- Iwagawa, T.; Yaguchi, S.; Hase, T. Iridoid Glucosides from Viburnum suspensum. Phytochemistry 1990, 29, 310–312. [Google Scholar] [CrossRef]
- Gering, B.; Wichtl, M. Phytochemical Investigations on Penstemon hirsutus. J. Nat. Prod. 1987, 50, 1048–1054. [Google Scholar] [CrossRef]
- Tanaka, T.; Nakashima, T.; Ueda, T.; Tomii, K.; Kouno, I. Facile Discrimination of Aldose Enantiomers by Reversed-Phase HPLC. Chem. Pharm. Bull. 2007, 55, 899–901. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, Y.; Fang, Y.; Gong, Z.F.; Duan, X.Y.; Liu, Y.W. Two New Terpenoids from Valeriana officinalis. Chin. J. Nat. Med. 2009, 7, 270–273. [Google Scholar] [CrossRef]
- Wavefunction Inc. Available online: https://www.wavefun.com/ (accessed on 15 November 2022).
- Pescitelli, G.; Bruhn, T. Good Computational Practice in the Assignment of Absolute Configurations by TDDFT Calculations of ECD Spectra. Chirality 2016, 28, 466–474. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Petersson, G.A.; Nakatsuji, H.; et al. Gaussian16, Revision A.03; Gaussian, Incorp.: Wallingford, UK, 2016. [Google Scholar]
- Bruhn, T.; Schaumlöffel, A.; Hemberger, Y.; Bringmann, G. SpecDis: Quantifying the Comparison of Calculated and Experimental Electronic Circular Dichroism Spectra. Chirality 2013, 25, 243–249. [Google Scholar] [CrossRef]
Position | 1 | 2 | 3 | |||
---|---|---|---|---|---|---|
δC | δH (J in Hz) | δC | δH (J in Hz) | δC | δH (J in Hz) | |
1 | 93.6 | 5.89 (d, 5.5) | 93.5 | 5.91 (d, 5.5) | 93.3 | 5.93 (d, 5.5) |
3 | 140.1 | 6.37 (s) | 140.2 | 6.39 (s) | 140.2 | 6.41 (s) |
4 | 116.4 | 116.3 | 116.2 | |||
5 | 34.1 | 3.01 (dd-like, 7.6, 15.8) | 34.1 | 3.01 (m) | 33.9 | 3.03 (dd-like, 8.0, 15.6) |
6 | 40.9 | α 1.82 (m) β 2.06 (m) | 40.9 | α 1.84 (m) β 2.05 (m) | 40.7 | α 1.87 (m) β 2.09 (m) |
7 | 73.3 | 4.33 (m) | 73.3 | 4.32 (m) | 72.4 | 4.26 (m) |
8 | 49.8 | 1.94 (m) | 49.0 (overlapping) | 1.95 (m) | 43.4 | 2.16 (m) |
9 | 42.6 | 2.17 (m) | 42.7 | 2.18 (m) | 46.2 | 2.09 (m) |
10 | 62.2 | a 3.73 (dd, 5.5, 11.0) b 3.80 (m) | 62.3 | a 3.69 (dd, 5.5, 11.0) b 3.81 (dd, 5.5, 11.0) | 69.8 | a 3.79 (d-like, 11.6) b 4.14 (d-like, 11.6) |
11 | 69.8 | a 4.08 (d, 11.0) b 4.23 (d, 11.0) | 69.8 | a 4.06 (d, 11.7) b 4.25 (d, 11.7) | 69.7 | a 4.06 (d, 11.7) b 4.26 (d, 11.7) |
1′ | 103.2 | 4.31 (d, 7.6) | 103.3 | 4.28 (d, 7.6) | 103.3 | 4.29 (d, 8.4) |
2′ | 74.9 | 3.20 (m) | 75.0 | 3.21 (m) | 75.0 | 3.21 (m) |
3′ | 76.4 | 3.52 (t, 7.6) | 77.8 | 3.28 (m) | 77.0 | 3.46 (m) |
4′ | 80.7 | 3.57 (t, 7.6) | 71.6 | 3.30 (m) | 71.5 | 3.31 (m) |
5′ | 78.1 | 3.35 (m) | 77.0 | 3.47 (m) | 77.9 | 3.35 (m) |
6′ | 62.4 | a 3.65 (m) b 3.66 (m) | 70.2 | a 3.73 (dd, 6.9, 11.7) b 4.09 (dd, 2.0, 11.7) | 64.7 | a 4.20 (dd, 7.2, 11.2) b 4.29 (d-like, 11.2) |
1″ | 104.6 | 4.40 (d, 7.6) | 105.0 | 4.39 (d, 7.5) | 104.8 | 4.40 (d, 8.2) |
2″ | 74.8 | 3.20 (m) | 75.1 | 3.21 (m) | 75.0 | 3.21 (m) |
3″ | 77.8 | 3.31 (m) | 78.0 | 3.28 (m) | 77.0 | 3.46 (m) |
4″ | 71.3 | 3.28 (m) | 71.7 | 3.34 (m) | 71.5 | 3.35 (m) |
5″ | 76.4 | 3.38 (m) | 75.4 | 3.46 (m) | 77.9 | 3.28 (m) |
6″ | 61.9 | a 3.73 (m) b 3.81 (m) | 64.5 | a 4.19 (dd, 6.2, 11.7) b 4.42 (dd, 2.0, 11.7) | 62.7 | a 3.68 (dd, 9.0, 11.0) b 3.86 (d-like, 11.0) |
1‴ | 173.3 | 173.3 | 173.2 | |||
2‴ | 44.1 | 2.23 (d, 6.9) | 44.2 | 2.23 (d, 7.6) | 44.2 | 2.25 (d, 7.2) |
3‴ | 26.8 | 2.09 (m) | 26.8 | 2.08 (m) | 26.7 | 2.09 (m) |
4‴ | 22.6 | 0.96 (d, 6.9) | 22.7 | 0.97 (d, 6.8) | 22.6 | 0.95 (d, 6.9) |
5‴ | 22.6 | 0.96 (d, 6.9) | 22.7 | 0.97 (d, 6.8) | 22.6 | 0.95 (d, 6.9) |
1′′′′ | 174.7 | 174.8 | ||||
2′′′′ | 44.2 | 2.14 (d, 6.9) | 44.1 | 2.21 (d, 7.0) | ||
3′′′′ | 26.8 | 1.94 (m) | 26.7 | 2.09 (m) | ||
4′′′′ | 22.7 | 0.87 (d, 6.9) | 22.6 | 0.95 (d, 6.9) | ||
5′′′′ | 22.7 | 0.87 (d, 6.9) | 22.6 | 0.95 (d, 6.9) |
Position | 6 | (CD3OD) | 6a | (CDCl3) | 7 | (CD3OD) |
---|---|---|---|---|---|---|
δC | δH (J in Hz) | δC | δH (J in Hz) | δC | δH (J in Hz) | |
1 | 93.6 | 5.88 (d, 5.5) | 91.6 | 5.85 (d, 5.5) | 93.5 | 5.90 (d, 5.5) |
3 | 140.1 | 6.35 (s) | 138.3 | 6.34 (s) | 140.2 | 6.40 (s) |
4 | 116.4 | 117.2 | 116.3 | |||
5 | 34.1 | 2.99 (dd-like, 7.8, 15.6) | 32.5 | 3.03 (dd, 7.8, 15.1) | 34.1 | 3.01 (dd-like, 7.6, 15.8) |
6 | 40.9 | α 1.79 (m) β 2.04 (ddd, 3.0, 7.8, 13.8) | 40.4 | α 1.87 (m) β 2.07 (ddd, 3.4, 6.9, 13.1) | 40.9 | α 1.86 (m) β 2.07 (ddd, 2.0, 6.8, 13.2) |
7 | 73.3 | 4.30 (m) | 74.1 | 4.48 (dd-like, 5.5, 8.9) | 73.3 | 4.33 (m) |
8 | 49.0 (overlapping) | 1.93 (m) | 46.3 | 2.00 (m) | 49.0 (overlapping) | 1.95 (m) |
9 | 42.2 | 2.14 (m) | 39.9 | 2.42 (m) | 42.6 | 2.18 (m) |
10 | 62.2 | a 3.63 (dd, 5.4, 10.8) b 3.70 (dd, 5.4, 10.8) | 61.8 | a 3.83 (m) b 4.00 (m) | 62.2 | a 3.73 (dd, 5.5, 10.3) b 3.82 (dd, 7.6, 10.3) |
11 | 69.7 | a 4.05 (d, 11.4) b 4.24 (d, 11.4) | 62.5 | a 4.00 (m) b 4.09 (d, 6.8) | 69.8 | a 4.07 (d, 11.7) b 4.25 (d, 11.7) |
1′ | 103.4 | 4.26 (d, 7.2) | 103.3 | 4.29 (d, 8.2) | ||
2′ | 75.1 | 3.17 (dd, 7.2, 9.0) | 75.0 | 3.21 (m) | ||
3′ | 78.0 | 3.24 (m) | 77.9 | 3.37 (m) | ||
4′ | 71.7 | 3.28 (dd, 1.8, 3.6) | 71.5 | 3.31 (m) | ||
5′ | 78.1 | 3.32 (m) | 77.0 | 3.46 (m) | ||
6′ | 62.8 | a 3.81 (m) b 3.83 (m) | 69.9 | a 3.77 (dd, 6.2, 10.3) b 4.14 (d-like, 10.3) | ||
1″ | 104.9 | 4.40 (d, J = 7.6) | ||||
2″ | 75.0 | 3.21 (m) | ||||
3″ | 77.9 | 3.37 (m) | ||||
4″ | 71.5 | 3.31 (m) | ||||
5″ | 77.9 | 3.37 (m) | ||||
6″ | 62.7 | a 3.67 (dd, 5.5, 11.0) b 3.86 (d-like, 11.0) | ||||
1‴ | 173.5 | 172.3 | 173.6 | |||
2‴ | 42.7 | a 2.12 (m) b 2.33 (d, 6.0, 15.0) | 41.4 | 2.17 (dd, 8.3, 15.1) 2.36 (dd, 6.2, 15.1) | 42.2 | 2.18 (m) 2.35 (dd, 6.2, 15.1) |
3‴ | 33.2 | 1.84 (m) | 31.8 | 1.89 (m) | 33.1 | 1.86 (m) |
4‴ | 30.3 | a 1.24 (m) b 1.37 (m) | 29.2 | a 1.25 (m) b 1.38 (m) | 30.2 | a 1.25 (m) b 1.39 (m) |
5‴ | 11.6 | 0.89 (t, 7.6) | 11.2 | 0.90 (t, 7.6) | 11.6 | 0.91 (t, 6.9) |
6‴ | 19.5 | 0.92 (d, 6.8) | 19.2 | 0.95 (d, 6.8) | 19.5 | 0.95 (d, 6.8) |
Position | 9 | 12 | ||
---|---|---|---|---|
δC | δH (J in Hz) | δC | δH (J in Hz) | |
1 | 90.5 | 6.30 (br-s) | 89.9 | 6.38 (d, 5.5) |
3 | 142.8 | 6.35 (s) | 141.4 | 6.35 (s) |
4 | 109.2 | 108.3 | ||
5 | 35.4 | 2.98 (d-like, 8.3) | 34.3 | 2.96 (d-like, 8.3) |
6 | 59.7 | 3.95 (d-like, 2.1) | 58.8 | 3.82 (m) |
7 | 60.2 | 3.26 (m) | 59.7 | 3.36 (d, 2.8) |
8 | 80.1 | 79.4 | ||
9 | 43.4 | 1.93 (m) | 42.7 | 2.00 (m) |
10 | 67.0 | a 3.59 (d, 5.5) b 3.59 (d, 5.5) | 66.5 | a 3.68 (m) b 3.68 (m) |
11 | 69.7 | a 4.12 (d, 11.6) b 4.24 (d, 11.6) | 69.0 | a 4.22 (d, 11.7) b 4.30 (d, 11.7) |
1′ | 102.2 | 4.29 (d, 8.3) | 99.6 | 4.60 (d, 8.4) |
2′ | 75.1 | 3.13 (m) | 74.8 | 4.74 (dd, 8.4, 9.6) |
3′ | 77.9 | 3.27 (m) | 75.6 | 3.53 (dd, 8.9, 9.6) |
4′ | 71.6 | 3.21 (m) | 71.2 | 3.34 (m) |
5′ | 77.0 | 3.38 (m) | 77.5 | 3.33 (m) |
6′ | 70.0 | a 3.64 (dd, 2.0, 11.7) b 4.01 (dd, 6.2, 11.7) | 62.1 | a 3.67 (m) b 3.87 (dd, 2.4, 12.0) |
1″ | 104.9 | 4.30 (d, 7.6) | 172.4 | |
2″ | 75.1 | 3.12 (m) | 20.4 | 2.05 (s) |
3″ | 78.1 | 3.10 (m) | ||
4″ | 71.7 | 3.21 (m) | ||
5″ | 75.4 | 3.36 (m) | ||
6″ | 64.5 | a 4.12 (dd, 2.0, 8.3) b 4.33 (dd, 2.0, 11.6) | ||
1‴ | 173.0 | 171.3 | ||
2‴ | 44.1 | 2.08 (d, 7.6) | 43.5 | 2.17 (dd, 4.1, 6.9) |
3‴ | 26.9 | 1.99 (m) | 26.3 | 2.02 (m) |
4‴ | 22.8 | 0.84 (d, 6.8) | 22.0 | 0.94 (d, 6.9) |
5‴ | 22.8 | 0.84 (d, 6.8) | 22.0 | 0.94 (d, 6.9) |
1′′′′ | 174.7 | |||
2′′′′ | 44.2 | 2.14 (d, 6.9) | ||
3′′′′ | 26.8 | 1.94 (m) | ||
4′′′′ | 22.6 | 0.84 (d, 6.9) | ||
5′′′′ | 22.6 | 0.84 (d, 6.9) |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Yoshikawa, H.; Matsumoto, T.; Kitagawa, T.; Okayama, M.; Ohta, T.; Yoshida, T.; Watanabe, T. Anti-Proliferative Effects of Iridoids from Valeriana fauriei on Cancer Stem Cells. Int. J. Mol. Sci. 2022, 23, 14206. https://doi.org/10.3390/ijms232214206
Yoshikawa H, Matsumoto T, Kitagawa T, Okayama M, Ohta T, Yoshida T, Watanabe T. Anti-Proliferative Effects of Iridoids from Valeriana fauriei on Cancer Stem Cells. International Journal of Molecular Sciences. 2022; 23(22):14206. https://doi.org/10.3390/ijms232214206
Chicago/Turabian StyleYoshikawa, Hayato, Takahiro Matsumoto, Takahiro Kitagawa, Masaya Okayama, Tomoe Ohta, Tatsusada Yoshida, and Tetsushi Watanabe. 2022. "Anti-Proliferative Effects of Iridoids from Valeriana fauriei on Cancer Stem Cells" International Journal of Molecular Sciences 23, no. 22: 14206. https://doi.org/10.3390/ijms232214206