Spasmolytic, Antimicrobial, and Antioxidant Activities of Spray-Dried Extracts of Gentiana asclepiadea L. with In Silico Pharmacokinetic Analysis
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemical Composition
2.2. Spasmolytic Activity
2.2.1. Spasmolytic Activity on Spontaneous Contractions
2.2.2. Mechanism of Action Involved in the Spasmolytic Effect
2.3. Antimicrobial Activity
2.4. Antioxidant Activity
2.5. In Silico ADME and Drug-Likeness Study
3. Materials and Methods
3.1. Plant Material and Extract Preparation
3.2. Extract Encapsulation
3.3. Phytochemical Characterization
3.3.1. HPLC Analysis
3.3.2. Total Polyphenol Content
3.4. Spasmolytic Activity Assay
3.4.1. Experimental Animals and Housing
3.4.2. Preparation of Rat Ileum
3.4.3. Experimental Design
3.5. Antioxidant Activity Assay
3.5.1. DPPH Radical Scavenging Assay
3.5.2. Linoleic Acid/β-Carotene Bleaching Assay
3.6. Antimicrobial Activity Assay
3.7. In Silico ADME Profiling
3.8. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Class of Phytocompounds | Phytocompound | Extract | |
---|---|---|---|
Without Carrier | Encapsulated with Whey Protein | ||
Secoiridoids | Swertiamarin | 7.84 ± 0.21 | 7.01 ± 0.19 |
Gentiopicroside | 145.27 ± 7.33 | 114.59 ± 6.89 | |
Sweroside | traces | traces | |
Flavones | Isoorientin | 4.12 ± 0.25 | 4.32 ± 0.24 |
Isovitexin | 12.24 ± 0.84 | 10.53 ± 0.78 | |
Xanthones | Isogentisine | 1.43 ± 0.11 | 1.15 ± 0.09 |
Mangiferin | non detect | non detect | |
Total polyphenols content * | 34.56 ± 0.26 | 30.27 ± 0.28 |
Pathogen | ATCC | E | EWP | WP | Positive Control |
---|---|---|---|---|---|
MIC/MMC (mg/mL) | MIC/MMC (µg/mL) | ||||
Gram (+) bacterial strains | |||||
Staphylococcus aureus | 6538 | 12.5/25.0 | 25.0/50.0 | >200.0 | 7.81/15.61 |
Bacillus cereus | 11778 | 12.5/25.0 | 25.0/50.0 | >200.0 | 0.90/15.61 |
Enterococcus faecalis | 19433 | 3.13/3.13 | 3.13/3.13 | >200.0 | 0.90/1.90 |
Gram (−) bacterial strains | |||||
Salmonella enteritidis | 13076 | 12.5/50.0 | 12.5/25.0 | >200.0 | 0.90/1.90 |
Escherichia coli | 25922 | 12.5/25.0 | 6.25/12.5 | >200.0 | 15.61/15.61 |
Enterobacter aerogenes | 13048 | 25.0/50.0 | 50.0/>200.0 | >200.0 | 7.81/15.61 |
Pseudomonas aeruginosa | 9027 | 3.13/12.5 | 6.25/25.0 | >200.0 | 15.61/15.61 |
Yeast strain | |||||
Candida albicans | 24433 | 12.5/>200.0 | 50.0/>200.0 | >200.0 | 3.91/7.81 |
IC50 (µg/mL) | |||||||
---|---|---|---|---|---|---|---|
E | EWP | WP | BHA | BHT | α-Tocopherol | Ascorbic Acid | |
DPPH assay | 2569.58 ± 111.15 b | 4270.15 ± 198.37 a | / | 2.44 ± 0.09 c | 22.82 ± 2.07 c | 10.40 ± 1.73 c | 4.74 ± 0.34 c |
β-carotene bleaching assay | 29.5 ± 1.59 a | 31.41 ± 1.73 a | / | 0.04 ± 0.01 c | 0.03 ± 0.00 c | 0.15 ± 0.00 c | 22.95 ± 1.52 b |
Constituent (PubChem CID) | Swertiamarin (442435) | Gentiopicroside (88708) | Isoorientin (114776) | Isovitexin (162350) | Isogentisine (5281640) |
---|---|---|---|---|---|
Physicochemical Properties | |||||
Molecular weight | 374.34 g/mol | 356.32 g/mol | 448.38 g/mol | 432.38 g/mol | 258.23 g/mol |
Num. rotatable bonds | 4 | 4 | 3 | 3 | 1 |
Num. H-bond acceptors | 10 | 9 | 11 | 10 | 5 |
Num. H-bond donors | 5 | 4 | 8 | 7 | 2 |
TPSA | 155.14 Å2 | 134.91 Å2 | 201.28 Å2 | 181.05 Å2 | 79.90 Å2 |
Log Po/w (WLOGP) | −2.48 | −1.67 | −0.53 | −0.23 | 2.37 |
Consensus Log Po/w | −1.35 | −0.80 | −0.24 | 0.05 | 2.09 |
Pharmacokinetics | |||||
GI absorption | Low | Low | Low | Low | High |
BBB permeant | No | No | No | No | No |
P-gp substrate | No | Yes | No | No | No |
CYP1A2 inhibitor | No | No | No | No | Yes |
CYP2C19 inhibitor | No | No | No | No | No |
CYP2C9 inhibitor | No | No | No | No | No |
CYP2D6 inhibitor | No | No | No | No | Yes |
CYP3A4 inhibitor | No | No | No | No | Yes |
Log Kp (skin permeation) | −10.00 cm/s | −9.35 cm/s | −9.14 cm/s | −8.79 cm/s | −5.91 cm/s |
Drug-likeness | |||||
Lipinski | Yes; 0 violation | Yes; 0 violation | No; 2 violations: NorO > 10, NHorOH > 5 | Yes; 1 violation: NHorOH > 5 | Yes; 0 violation |
Ghose | No; 1 violation: WLOGP < −0.4 | No; 1 violation: WLOGP < −0.4 | No; 1 violation: WLOGP < −0.4 | Yes | Yes |
Veber | No; 1 violation: TPSA > 140 | Yes | No; 1 violation: TPSA > 140 | No; 1 violation: TPSA > 140 | Yes |
Egan | No; 1 violation: TPSA > 131.6 | No; 1 violation: TPSA > 131.6 | No; 1 violation: TPSA > 131.6 | No; 1 violation: TPSA > 131.6 | Yes |
Muegge | No; 1 violation: TPSA > 150 | Yes | No; 3 violations: TPSA > 150, H-acc > 10, H-don > 5 | No; 2 violations: TPSA > 150, H-don > 5 | Yes |
Bioavailability Score | 0.11 | 0.56 | 0.17 | 0.55 | 0.55 |
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Jovanović, M.S.; Milutinović, M.; Branković, S.; Mihajilov-Krstev, T.; Randjelović, M.; Miladinović, B.; Ćujić Nikolić, N.; Šavikin, K.; Kitić, D. Spasmolytic, Antimicrobial, and Antioxidant Activities of Spray-Dried Extracts of Gentiana asclepiadea L. with In Silico Pharmacokinetic Analysis. Plants 2024, 13, 1445. https://doi.org/10.3390/plants13111445
Jovanović MS, Milutinović M, Branković S, Mihajilov-Krstev T, Randjelović M, Miladinović B, Ćujić Nikolić N, Šavikin K, Kitić D. Spasmolytic, Antimicrobial, and Antioxidant Activities of Spray-Dried Extracts of Gentiana asclepiadea L. with In Silico Pharmacokinetic Analysis. Plants. 2024; 13(11):1445. https://doi.org/10.3390/plants13111445
Chicago/Turabian StyleJovanović, Miloš S., Milica Milutinović, Suzana Branković, Tatjana Mihajilov-Krstev, Milica Randjelović, Bojana Miladinović, Nada Ćujić Nikolić, Katarina Šavikin, and Dušanka Kitić. 2024. "Spasmolytic, Antimicrobial, and Antioxidant Activities of Spray-Dried Extracts of Gentiana asclepiadea L. with In Silico Pharmacokinetic Analysis" Plants 13, no. 11: 1445. https://doi.org/10.3390/plants13111445