An In Vitro and In Silico Characterization of Salvia sclarea L. Methanolic Extracts as Spasmolytic Agents
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plant Material and Extraction
2.2. HPLC Characterization of the Extracts
2.3. Effects of the Extracts on Ileum and Trachea Contractions
2.3.1. Experimental Animals
2.3.2. Isolation and Placement of Ileum and Trachea
2.3.3. Experimental Design with Ileum
2.3.4. Experimental Design with Rat Trachea
2.4. Molecular Docking Analysis
2.5. Evaluation of Antimicrobial Activity of the Extracts
2.6. Statistical Analysis
3. Results
3.1. Chemical Characterization of the Extracts
3.2. Spasmolytic Effects of the Extracts on Spontaneous Ileum Contractions
3.3. Spasmolytic Effects of the Extracts on KCl-Induced Ileum Contractions
3.4. Spasmolytic Effects of the Extracts on Acetylcholine-Induced Ileum Contractions
3.5. Spasmolytic Effects of the Extracts on KCl-Induced Tracheal Contractions
3.6. Spasmolytic Effects of the Extracts on Carbachol-Induced Tracheal Contractions
3.7. Molecular Docking Analysis
3.8. Antimicrobial Activity of the Extracts
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compounds | RT (min) | MM | MU | M80M | M80U |
---|---|---|---|---|---|
µg/mg | |||||
caffeic acid | 20.5 | 0.79 ± 0.02 a | 0.63 ± 0.04 b | 0.97 ± 0.07 b | 0.81 ± 0.01 a |
luteolin-7-O-glucoside | 29.0 | 5.18 ± 0.21 a | 5.65 ± 0.34 a | 8.84 ± 0.54 b | 5.61 ± 0.31 a |
apigenin-7-O-glucoside | 32.5 | 5.63 ± 0.21 a | 4.56 ± 0.02 b | 7.00 ± 0.55 c | 4.45 ± 0.18 d |
rosmarinic acid | 33.5 | 175.66 ± 2.02 a | 177.77 ± 1.89 a | 197.48 ± 2.00 b | 171.99 ± 1.88 c |
luteolin | 39.3 | 1.45 ± 0.01 a | 1.13 ± 0.01 b | 0.96 ± 0.02 c | 0.80 ± 0.02 d |
apigenin | 42.7 | 0.78 ± 0.01 a | 0.78 ± 0.00 a | 0.72 ± 0.00 b | 0.53 ± 0.00 c |
salvigenin | 53.0 | 3.72 ± 0.09 a | 4.05 ± 0.02 b | 2.54 ± 0.04 c | 2.27 ± 0.01 d |
EC50 | ||
---|---|---|
Spontaneous Contractions | KCl-Induced Contractions | |
mg/mL | ||
MM | 2.62 ± 0.24 a | 3.69 ± 0.30 a |
MU | 2.69 ± 0.22 a | 4.90 ± 0.33 b |
M80M | 2.44 ± 0.10 a | 5.76 ± 0.34 c |
M80U | 4.59 ± 0.33 b | 4.63 ± 0.26 b |
papaverine | 1.2 × 10−4 ± 0.1 × 10−4 c | / |
verapamil | / | 6.3 × 10−4 ± 0.5 × 10−4 d |
MM | MU | M80M | M80U | Atropine | |
---|---|---|---|---|---|
EC50 of Acetylcholine (nM) | |||||
control | 0.29 ± 0.01 a | 0.03 ± 0.00 a | 0.01 ± 0.00 a | 0.17 ± 0.00 a | 0.10 ± 0.00 a |
0.5 mg/mL | 0.40 ± 0.01 b | 0.12 ± 0.00 b | 0.15 ± 0.00 b | 0.36 ± 0.00 b | / |
1.5 mg/mL | 18.21 ± 0.65 c | 0.47 ± 0.01 c | 7.25 ± 0.22 c | 62.15 ± 3.22 c | / |
140 nM | / | / | / | / | 18,261.96 ± 958.32 b |
EC50 | ||
---|---|---|
KCl-Induced Contractions | Carbachol-Induced Contractions | |
mg/mL | ||
MM | 6.27 ± 0.16 a | 6.92 ± 0.04 a |
MU | 15.38 ± 1.02 b | 3.26 ± 0.02 b |
M80M | 6.03 ± 0.33 a | 1.36 ± 0.01 c |
M80U | 9.02 ± 0.11 c | 4.26 ± 0.04 d |
verapamil | 1.53 × 10−2 ± 8.00 × 10−5 d | / |
atropine | / | 9.78 × 10−3 ± 0.00 f |
Compounds | Binding Affinity (kcal/mol) | Hydrogen Bonds | Electrostatic/Hydrophobic Bonds |
---|---|---|---|
V | −6.6 | Conventional hydrogen bond: Arg65 (2.36) | π-Cation: Arg227 (4.23) Alkyl: Lys110 (4.12), Ala409 (4.50), Lys90 (4.13), Pro336 (4.38) π-Alkyl: Ala409 (5.06), Tyr402 (4.64), Tyr406 (5.00) |
A | −6.7 | Conventional hydrogen bond: Asp91 (2.05), Glu111 (2.86), Ala405 (2.30) | π-Cation, π-donor hydrogen bond: Lys110 (2.92) π-Anion: Asp91 (4.07) π-Alkyl: Ala409 (5.37), Ala405 (5.31), Ala409 (4.06), Leu108 (5.34), Lys110 (4.22) |
AG | −8.6 | Conventional hydrogen bond: Val109 (2.09), Glu381 (2.33), Arg65 (2.21) Carbon hydrogen bond: Ser382 (3.65), Ser330 (3.49) | π-Cation: Arg227 (4.24), Arg227 (4.26) π-Anion: Asp384 (3.85), Asp384 (3.84) π-π T-shaped: Phe92 (4.83) |
L | −6.8 | Conventional hydrogen bond: Phe383 (2.49), Asp384 (2.55), Pro326 (2.47), Arg65 (2.65) | π-Alkyl: Pro336 (4.98) |
LG | −8.6 | Conventional hydrogen bond: Pro326 (2.61), Val109 (1.82), Gln380 (2.45), Arg65 (2.52) Carbon hydrogen bond: Ser382 (3.56), Ala335 (3.64), Pro336 (3.67) | π-Cation: Arg227 (4.17), Arg227 (4.00) π-Anion: Asp384 (3.40), Asp384 (3.96) π-π T-shaped: Phe92 (4.82) |
S | −6.9 | Conventional hydrogen Bbond: Pro336 (2.49), Arg65 (2.70), Arg65 (2.14) Carbon Hydrogen Bond: Ala335 (3.51) | Alkyl: Pro378 (4.61), Lys90 (3.85) π-Alkyl: Ala327 (5.26) |
RA | −6.6 | Conventional hydrogen bond: Pro336 (2.72), Arg227 (2.74), Arg227 (2.95) | π-Alkyl: Pro336 (5.05), Ile338 (5.35), Lys90 (4.60) |
CA | −5.8 | Conventional hydrogen bond: Pro336 (2.11) | π-Alkyl: Pro336 (4.89) |
Extracts | MM | MU | M80M | M80U | S | |
---|---|---|---|---|---|---|
Bacterial Strain | MIC/MBC (mg/mL) | MIC/MBC (mg/mL) | MIC/MBC (mg/mL) | MIC/MBC (mg/mL) | MIC/MBC (μg/mL) | |
Gram (+) | ATCC | Chlor. | ||||
Staphylococcus aureus | 6538 | 12.5/>100 | 6.25/>100 | 12.5/100 | 25/>100 | 7.81/15.61 |
Streptococcus pneumoniae | 6301 | 100/>100 | 100/>100 | 50/>100 | 100/100 | 0.06/0.12 |
Streptococcus pyogenes | 19615 | >100/>100 | >100/>100 | 100/>100 | 100/>100 | 0.25/0.49 |
Enterococcus faecalis | 9433 | >100/>100 | >100/>100 | 100/>100 | 100/>100 | 3.91/7.81 |
Bacillus cereus | 11778 | 25.0/>100 | 12.5/>100 | 12.5/>100 | 50/>100 | 7.81/15.61 |
Listeria monocytogenes | 15313 | 25.0/>100 | 25/>100 | 50/>100 | 50/>100 | 0.25/0.49 |
Gram (−) | ATCC | Str. | ||||
Pseudomonas aeruginosa | 9027 | 100/>100 | 50/>100 | 50/50 | 100/100 | 0.60/0.60 |
Proteus mirabilis | 12453 | >100/>100 | >100/>100 | 100/100 | 100/>100 | 0.30/0.30 |
Salmonella enteritidis | 13076 | 100/>100 | >100/>100 | 100/100 | 100/>100 | 0.30/0.30 |
Escherichia coli | 8739 | 100/>100 | >100/>100 | 100/>100 | 100/>100 | 0.16/0.16 |
Enterobacter aerogenes | 13048 | 100/>100 | 50/>100 | 100/>100 | 100/>100 | 0.60/0.60 |
Klebsiella pneumoniae | 10031 | 100/>100 | 100/>100 | 100/>100 | 100/>100 | 0.30/0.30 |
fungal strain | MIC/MFC (mg/mL) | MIC/MFC (mg/mL) | MIC/MFC (mg/mL) | MIC/MFC (mg/mL) | MIC/MFC (μg/mL) | |
yeast | ATCC | Nys. | ||||
Candida albicans | 24433 | 100/>100 | 100/>100 | 100/>100 | >100/>100 | 3.91/7.81 |
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Randjelović, M.; Branković, S.; Jovanović, M.; Kitić, N.; Živanović, S.; Mihajilov-Krstev, T.; Miladinović, B.; Milutinović, M.; Kitić, D. An In Vitro and In Silico Characterization of Salvia sclarea L. Methanolic Extracts as Spasmolytic Agents. Pharmaceutics 2023, 15, 1376. https://doi.org/10.3390/pharmaceutics15051376
Randjelović M, Branković S, Jovanović M, Kitić N, Živanović S, Mihajilov-Krstev T, Miladinović B, Milutinović M, Kitić D. An In Vitro and In Silico Characterization of Salvia sclarea L. Methanolic Extracts as Spasmolytic Agents. Pharmaceutics. 2023; 15(5):1376. https://doi.org/10.3390/pharmaceutics15051376
Chicago/Turabian StyleRandjelović, Milica, Suzana Branković, Miloš Jovanović, Nemanja Kitić, Slavoljub Živanović, Tatjana Mihajilov-Krstev, Bojana Miladinović, Milica Milutinović, and Dušanka Kitić. 2023. "An In Vitro and In Silico Characterization of Salvia sclarea L. Methanolic Extracts as Spasmolytic Agents" Pharmaceutics 15, no. 5: 1376. https://doi.org/10.3390/pharmaceutics15051376
APA StyleRandjelović, M., Branković, S., Jovanović, M., Kitić, N., Živanović, S., Mihajilov-Krstev, T., Miladinović, B., Milutinović, M., & Kitić, D. (2023). An In Vitro and In Silico Characterization of Salvia sclarea L. Methanolic Extracts as Spasmolytic Agents. Pharmaceutics, 15(5), 1376. https://doi.org/10.3390/pharmaceutics15051376