Salvia officinalis L.: Antitrypanosomal Activity and Active Constituents against Trypanosoma brucei rhodesiense
Abstract
:1. Introduction
2. Results and Discussion
2.1. Fractionation of Sage Tincture and Antitrypanosomal Activity of the Resulting Fractions
2.2. Partial Least Squares (PLS) Regression Model to Predict Constituents with Main Impact on Bioactivity
2.3. Identification of the Compounds Selected by the PLS Model
2.4. Antitrypanosomal Activity of the Isolated Compounds
3. Materials and Methods
3.1. Investigated Materials
3.2. General Methods
3.3. Extraction and Isolation
3.4. UHPLC/+ESI QTOF MS and MSMS Analysis
3.5. Data Treatment and PLS Modeling
3.6. Biological Testing
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Sample Availability
References
- World Health Organization. Trypanosomiasis, Human African (Sleeping-Sickness). Available online: https://www.who.int/news-room/fact-sheets/detail/trypanosomiasis-human-african-(sleeping-sickness) (accessed on 27 May 2021).
- Chapuis, F. Oral fexinidazole for human African trypanosomiasis. Lancet 2018, 391, 100–102. [Google Scholar] [CrossRef]
- Llurba Montesino, N.; Kaiser, M.; Brun, R.; Schmidt, T.J. Search for antiprotozoal activity in herbal medicinal preparations; new natural leads against neglected tropical diseases. Molecules 2015, 20, 14118–14138. [Google Scholar] [CrossRef] [Green Version]
- Llurba Montesino, N.; Schmidt, T.J. Salvia species as sources of natural products with antiprotozoal activity. Int. J. Mol. Sci. 2018, 19, 264. [Google Scholar] [CrossRef] [Green Version]
- Tasdemir, D.; Kaiser, M.; Brun, R.; Yardley, V.; Schmidt, T.J.; Tosun, F.; Rüedi, P. Antitrypanosomal and Antileishmanial Activities of Flavonoids and Their Analogues: In Vitro, Structure-Activity Relationship, and Quantitative Structure-Activity Relationship Studies. Antimicr. Agents Chemother. 2006, 50, 1352–1364. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marrero, J.G.; Andrés, L.S.; Luis, J.G. Semisynthesis of Rosmanol and its derivatives. Easy access to abietatriene diterpenes isolated from the genus Salvia with biological activities. J. Nat. Prod. 2002, 65, 986–989. [Google Scholar] [CrossRef]
- Marrero, J.G.; Moujir, L.; Andrés, L.S.; Montaño, N.P.; Araujo, L.J.G.; Luis, J.G. Semisynthesis and biological evaluation of abietane-type diterpenes. Revision of the structure of rosmaquinone. J. Nat. Prod. 2009, 72, 1385–1389. [Google Scholar] [CrossRef] [PubMed]
- Cuvelier, M.E.; Berset, C.; Richard, H. Antioxidant constituents in sage (Salvia officinalis). J. Agric. Food Chem. 1994, 42, 665–669. [Google Scholar] [CrossRef]
- Liu, X.; Du, J.; Ou, Y.; Xu, H.; Chen, X.; Zhou, A.; He, L.; Cao, Y. Degradation pathway of carnosic acid in methanol solution through isolation and structural identification of its degradation products. Eur. Food Res. Technol. 2013, 237, 617–626. [Google Scholar] [CrossRef]
- Djarmati, Z.; Jankov, R.M.; Schwirtlich, E.; Djulinac, B.; Djordjevic, A. High antioxidant activity of extracts obtained from sage by supercritical co2 extraction. J. Am. Oil Chem. Soc. 1991, 68, 731–734. [Google Scholar] [CrossRef]
- Álvarez, F.; Tello, E.; Bauer, K.; Diaz, L.; Rodriguez, J.; Jimenez, C. Cytotoxic and Antimicrobial Diterpenes Isolated from Hyptis Dilatata. Curr. Bioact. Compd. 2015, 11, 189–197. [Google Scholar] [CrossRef]
- Wu, Y.B.; Ni, Z.-Y.; Shi, Q.-W.; Dong, M.; Kiyota, H.; Gu, Y.-C.; Cong, B. Constituents from Salvia species and their biological activities. Chem. Rev. 2012, 112, 5967–6026. [Google Scholar] [CrossRef] [PubMed]
- Mokoka, T.A.; Peter, X.K.; Fouche, G.; Moodley, N.; Adams, M.; Hamburger, M.; Kaiser, M.; Brun, R.; Maharaj, V.; Koorbanally, N. Antileishmanial activity of 12-methoxycarnosic acid from Salvia repens Burch. ex Benth. (Lamiaceae). S. Afr. J. Bot. 2014, 90, 93–95. [Google Scholar] [CrossRef] [Green Version]
- Ślusarczyk, S.; Zimmermann, S.; Kaiser, M.; Matkowski, A.; Hamburger, M.; Adams, M. Antiplasmodial and antitrypanosomal activity of tanshinone-type diterpenoids from Salvia miltiorrhiza. Planta Med. 2011, 77, 1594–1596. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bastard, J.; Duc, D.K.; Fetizon, M.; Francis, M.J.; Grant, P.K.; Weavers, R.T.; Kaneko, C.; Baddeley, G.V.; Bernassau, J.-M.; Burfitt, I.R.; et al. CMR Spectroscopy of Labdanic Diterpenes and Related substances. J. Nat. Prod. 1984, 47, 592–599. [Google Scholar] [CrossRef]
- Ulubelen, A.; Topcu, G.; Sömmez, M.; Kurucu, S.; Bozok-Johansson, C. Terpenoids from Salvia sclarea. Phytochemistry 1994, 36, 971–974. [Google Scholar] [CrossRef]
- Ben Farhat, M.; Jordán, M.J.; Chaouech-Hamada, R.; Landoulsi, A.; Sotomayor, J.A. Variations in essential oil, phenolic compounds, and antioxidant activity of tunisian cultivated Salvia officinalis L. J. Agric. Food Chem. 2009, 57, 10349–10356. [Google Scholar] [CrossRef] [PubMed]
- Bernal, F.A.; Kaiser, M.; Wünsch, B.; Schmidt, T.J. Structure–Activity Relationships of Cinnamate Ester Analogs as Potent Antiprotozoal Agents. Chem. Med. Chem. 2020, 15, 68–78. [Google Scholar] [CrossRef] [PubMed] [Green Version]
% GI | ||
---|---|---|
Fraction ID | 10 µg/mL | 2 µg/mL |
FR3 | 10.2 | 11.2 |
FR5 | 28.6 | 15.2 |
FR8 | 18.4 | 20.9 |
FR10 | 15.7 | 14.2 |
FR12 | 24.3 | 19.5 |
FR13 | 59.3 | 20.5 |
FR14 | 71.0 | 19.3 |
FR15 | 70.1 | 25.7 |
FR18 | 79.3 | 11.1 |
FR19 | 100.0 | 18.9 |
FR20 | 100.0 | 28.6 |
FR22 | 75.6 | 51.0 |
FR24 | 84.6 | 26.6 |
FR27 | 65.3 | 37.9 |
FR29 | 58.8 | 30.8 |
FR32 | 30.7 | 21.2 |
FR36 | 24.4 | 18.9 |
Peak | Compound# | tR (min) | m/z | Mol. Formula | |
---|---|---|---|---|---|
[M+H]+ | [M+Na]+ | ||||
A | - | 2.4 | 293.0273 | 315.0065 | n.d. 1 |
B | 1 | 5.5 | 315.0864 | 337.0682 | C17H14O6 |
C | 2 | 5.9 | 347.1858 | n.dt. 2 | C20H26O5 |
D | 5 | 7.0 | 361.2020 | n.dt. 2 | C21H28O5 |
E | 6 | 7.5 | 375.2183 | 397.1982 | C22H30O5 |
F | 8 | 8.4 | 347.2205 | n.dt. 2 | C21H30O4 |
G | n.i. 4 | 8.7 | 283.1702 | 305.1518 | C19H22O2 |
H | 9 | 10.1 | 273.2578 3 | n.dt. 2 | C20H34O |
IC50 Tbr (STIB 900) | IC50 Cytotox L6 | SI | |||
---|---|---|---|---|---|
Compound | µg/mL | µM | µg/mL | µM | |
Cirsimaritin (1) | 1.7 ± 0.5 | 5.4 | 4.6 ± 0.37 | 15 | 2.8 |
Epirosmanol (2) | 3.2 ± 0.3 | 9.3 | 5.0 ± 0.9 | 15 | 1.6 |
Rosmanol (3) + Rosmaquinone (4) (4:1) | 1.1 ± 0.3 | ≈3.1 | 5.2 ± 0.0 | 15 | ≈4.9 |
7-O-Methylrosmanol (5) | 8.3 ± 0.5 | 23 | 6.6 ± 0.8 | 18 | 0.8 |
7-O-Ethylrosmanol (6) + 7-O-Ethyl- rosmaquinone (7) + unidentified compound (6:4:1) | 1.0 ± 0.43 | ≈ 2.7 | 17 ± 0.9 | ≈ 45 | 17 |
12-O-Methylcarnosic acid (8) | 15 ± 2.3 | 44 | 20 ± 0 | 56 | 1.3 |
Manool (9) | 2.6 ± 0.7 | 9.1 | 5.6 ± 0.5 | 19 | 2.1 |
Melarsoprol | 0.0025 ± 0.005 | 0.0063 | |||
Podophyllotoxin | 0.009 ± 0.001 | 0.022 |
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Llurba Montesino, N.; Kaiser, M.; Mäser, P.; Schmidt, T.J. Salvia officinalis L.: Antitrypanosomal Activity and Active Constituents against Trypanosoma brucei rhodesiense. Molecules 2021, 26, 3226. https://doi.org/10.3390/molecules26113226
Llurba Montesino N, Kaiser M, Mäser P, Schmidt TJ. Salvia officinalis L.: Antitrypanosomal Activity and Active Constituents against Trypanosoma brucei rhodesiense. Molecules. 2021; 26(11):3226. https://doi.org/10.3390/molecules26113226
Chicago/Turabian StyleLlurba Montesino, Núria, Marcel Kaiser, Pascal Mäser, and Thomas J. Schmidt. 2021. "Salvia officinalis L.: Antitrypanosomal Activity and Active Constituents against Trypanosoma brucei rhodesiense" Molecules 26, no. 11: 3226. https://doi.org/10.3390/molecules26113226