Thymus algeriensis and Thymus fontanesii: Chemical Composition, In Vivo Antiinflammatory, Pain Killing and Antipyretic Activities: A Comprehensive Comparison
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plant Material and Extraction
2.2. HPLC-PDA-ESI-MS/MS
2.3. In Vitro Studies
2.3.1. Cyclooxygenase (COX) Inhibition Assay
2.3.2. Lipoxygenase (LOX) Inhibition Assay
2.3.3. Total Antioxidant Capacity (TAC) Assay
2.4. Animals
2.4.1. The Anti-Inflammatory Activity in Carrageenan-Induced Hind-Paw Edema Model
2.4.2. Leukocytes Recruitment into Peritoneal Cavity in Mice
2.4.3. Acetic Acid-Induced Vascular Permeability
2.4.4. Assay of Anti-Nociceptive Activity by Hot Plate Test
2.4.5. Assay of Anti-Nociceptive Activity by Acetic Acid-Induced Abdominal Writhing
2.4.6. Anti-Pyretic Activity in Brewer’s Yeast Induced Pyrexia in Mice
2.5. Molecular Modeling
2.6. Statistical Analysis
3. Results and Discussion
3.1. In Vitro Activities
3.1.1. Inhibition of Cyclooxygenase (COX-1/2), Lipoxygenase (5-LOX), and Total Antioxidant Capacity (TAC) Assay
3.1.2. Effects of T. algeriensis and T. fontanesii Extracts on Carrageenan-Induced Paw Edema in Rats
3.1.3. Effects on Carrageenan-Induced Leukocyte Migration into the Peritoneal Cavity in Mice
3.1.4. Effects on Acetic Acid-Induced Vascular Permeability in Mice
3.1.5. Effects on Acetic Acid-Induced Writhing and Hot Plate Test in Mice
3.1.6. Effect of Extracts on Brewer’s Yeast Induced Pyrexia in Mice
3.2. Molecular Docking
3.2.1. Cycloxygenase-1
3.2.2. Cycloxygenase-2 Protein
3.2.3. -Lipoxygenase Protein
3.2.4. 5 Lipoxygenase Activating Protein (FLAP)
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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No. | Rt | M-H | MS/MS | Relative Abundance | Proposed Compounds | |
---|---|---|---|---|---|---|
T. algeriensis | T. fontanesii | |||||
1 | 1.46 | 191 | + | - | Quinic acid a | |
2 | 1.60 | 133 | 115 | + | - | Malic acid |
3 | 1.87 | 341 | 179 | + | + | Caffeic acid glucoside a,b |
4 | 2.66 | 305 | 97, 225 | + | + | Gallocatechin a |
5 | 8.58 | 387 | 163, 179, 369 | + | + | 12-Hydroxyjasmonic acid 12-O-hexoside |
6 | 9.47 | 165 | 99, 149, 165 | + | + | Phloretic acid |
7 | 10.55 | 493 | 161, 179, 359 | + | + | Salvianolic Acid A |
8 | 11.68 | 555 | 161, 359, 493 | +++ | + | Salvianolic acid K c |
9 | 12.85 | 521 | 161, 359 | +++ | + | Rosmarinic acid glucoside c |
10 | 14.37 | 359 | 161, 179, 197 | + | + | Rosmarinic acid a,c |
11 | 16.90 | 385 | 153, 161, 223 | - | + | Sinapic acid glucoside |
12 | 17.58 | 623 | 179,315, 447 | + | - | Isorhamnetin pentosyl-glucuronide |
13 | 17.76 | 471 | 165, 309, 369 | + | - | Phloretic acid caffeoyl 3-hydroxy-3-methylglutaroyl |
14 | 18.17 | 327 | 161, 165 | - | + | Caffeoyl-phloretic acid |
15 | 20.12 | 461 | 175, 285 | +++ | + | Luteolin glucuronide c |
16 | 21.55 | 593 | 269, 353, 413, 473 | + | + | Apigenin 6,8-di-C-hexosides c |
17 | 25.79 | 449 | 151, 287 | + | - | Eriodictyol glucoside c |
18 | 26.91 | 551 | 161, 359, 519 | ++ | + | Schizotenuin F |
19 | 29.13 | 549 | 161, 387, 531 | + | + | Caffeoyl ethylrosmarinate |
20 | 32.33 | 303 | 125, 177, 285 | + | + | Dihydroquercetin |
21 | 34.26 | 563 | 193, 387, 531 | + | + | Feruloyl ethylrosmarinate |
22 | 35.53 | 637 | 285, 461 | ++ | - | Luteolin feruloyl glucuronide |
23 | 35.78 | 609 | 301, 447 | - | + | Querectin rhamnosyl-glucoside c |
24 | 38.52 | 579 | 285, 417, 447 | + | - | Luteolin pentosyl-glucoside |
25 | 38.85 | 433 | 301 | - | + | Quercetin pentoside |
26 | 40.79 | 447 | 161, 285 | ++ | + | Luteolin glucoside |
27 | 43.97 | 329 | 125, 229, 329 | - | + | Thymusin |
28 | 44.75 | 417 | 161, 285, 417 | + | - | Luteolin pentoside |
29 | 51.34 | 287 | 151, 269 | + | + | Eriodictyol d |
30 | 59.52 | 271 | 151, 177 | + | + | Naringenin a,e |
31 | 64.01 | 269 | 149, 225, 269 | - | + | Apigenin a |
32 | 74.31 | 329 | 270, 286, 329 | + | ++++ | Carnosol a,b |
33 | 76.29 | 283 | 179, 266, 283 | + | + | Genkwanin |
34 | 77.36 | 343 | 179, 300, 325 | + | + | Xanthomicrol |
35 | 79.16 | 327 | 285, 299, 327 | - | ++++ | Salvigenin |
Treatment | COX-1 | COX-2 | SI | 5-LOX | TAC |
---|---|---|---|---|---|
IC50 (µM) | IC50 (µM) | U/L | |||
T. algeriensis Extract | 12.4 ± 0.49 | 0.05 ± 0.01 * | 248 | 2.70 ± 0.23 | 39.27± 3.47 |
T. fontanesii Extract | 12.88 ± 0.94 | 0.04 ± 0.002 * | 322 | 2.5 ± 0.4 | 44.33 ± 4.6 @ |
Celecoxib | 15.97 ± 1.03 | 0.06 ± 0.01 * | 266.2 | - | - |
Diclofenac | 4.06 ± 0.22 | 0.76 ± 0.06 | 5.34 | 2.60 ± 0.21 | - |
Indomethacin | 0.1 ± 0.01 | 0.72 ± 0.06 | 0.14 | - | - |
Zileuton | - | - | - | 3.20 ± 0.15 | - |
Ascorbic Acid | - | - | - | - | 27.6 ± 1.40 |
Extract | Dose (mg/kg) | Rectal Temperature # | Rectal Temperature Recorded Following Different Treatments | ||||
---|---|---|---|---|---|---|---|
30 min | 1 h | 2 h | 3 h | 24 h | |||
Control | - | 38.36 ±0.27 | 38.68 ± 0.15 | 38.66 ± 0.19 | 38.80 ± 0.20 | 38.84 ± 0.30 | 38.26 ± 0.18 |
T. algeriensis | 200 | 38.78 ± 0.12 | 38.56 ± 0.31 | 38.80 ± 0.40 | 39.00 ± 0.23 | 38.46 ± 0.20 | 37.88 ± 0.53 |
400 | 38.06 ± 0.52 | 38.14 ± 0.34 | 38.54 ± 0.29 | 38.54 ± 0.19 | 38.24 ± 0.16 | 37.52 ± 0.26 | |
600 | 39.18 ± 0.34 | 38.58 ± 0.29 | 37.85 ± 0.30 | 37.8 ± 0.25 | 38.10 ± 0.15 | 37.73 ± 0.18 | |
T. fontanesii | 200 | 38.42 ± 0.29 | 37.90 ± 0.48 | 38.44 ± 0.42 | 38.52 ± 0.15 | 38.30 ± 0.13 | 37.28 ± 0.16 * |
400 | 38.52 ± 0.37 | 38.14 ± 0.28 | 38.44 ± 0.37 | 38.02 ± 0.09 | 37.82 ± 0.11 * | 37.24 ± 0.22 * | |
600 | 38.48 ± 0.24 | 38.15 ± 0.14 | 37.58 ± 0.15 * | 37.35 ± 0.16 * | 37.6 ± 0.12 * | 37.10 ± 0.23 * | |
Paracetamol | 150 | 38.66 ± 0.18 | 38.18 ± 0.20 | 37.56 ± 0.30 | 37.06 ± 0.29 * | 36.94 ± 0.25 * | 36.54 ± 0.23 * |
Compound Name | Docking Score (kcal/mol) | |||
---|---|---|---|---|
COX-1 | COX-2 | 5-LOX | FLAP | |
Quinic acid | −9.29 | −11.98 | −13.78 | −9.20 |
Malic acid | −9.54 | −9.89 | −8.85 | −7.48 |
Caffeic acid glucoside | −15.79 | −18.14 | −12.90 | −16.35 |
Phloretic acid | −9.39 | −10.55 | −9.40 | −12.37 |
Salvianolic Acid A | −21.08 | −23.32 | −20.87 | −17.37 |
Salvianolic acid K | −19.21 | −24.15 | −19.25 | −13.77 |
Rosmarinic acid glucoside | −17.00 | −25.93 | −10.60 | −14.82 |
Rosmarinic acid | −16.20 | −19.46 | −12.72 | −15.09 |
Sinapic acid glucoside | −16.87 | −20.64 | −18.27 | −16.00 |
Phloretic acid caffeoyl 3-hydroxy-3-methylglutaroyl | −16.88 | −22.27 | −1.06 | −10.56 |
Caffeoyl-phloretic acid | −16.63 | −18.03 | −19.66 | −14.35 |
Apigenin 6,8-di-C-hexosides | −20.48 | −25.36 | −22.19 | −14.06 |
Schizotenuin F | −15.91 | −25.75 | −19.45 | −14.92 |
Caffeoylethylrosmarinate | −18.63 | −23.83 | −19.27 | −15.37 |
Feruloyl ethylrosmarinate | −15.63 | −22.04 | −14.17 | −14.62 |
Quercetin pentoside | −17.20 | −18.85 | −19.57 | −16.79 |
Luteolin glucoside | −17.89 | −24.48 | −18.46 | −14.39 |
Naringenin | −13.96 | −14.61 | −11.34 | −12.80 |
Carnosol | −12.78 | −13.47 | −12.88 | −13.23 |
Genkwanin | −13.68 | −14.47 | −10.61 | −11.22 |
Xanthomicrol | −15.16 | −16.07 | −14.87 | −14.71 |
Salvigenin | −17.62 | −17.23 | −14.15 | −12.42 |
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Sobeh, M.; Rezq, S.; Cheurfa, M.; Abdelfattah, M.A.O.; Rashied, R.M.H.; El-Shazly, A.M.; Yasri, A.; Wink, M.; Mahmoud, M.F. Thymus algeriensis and Thymus fontanesii: Chemical Composition, In Vivo Antiinflammatory, Pain Killing and Antipyretic Activities: A Comprehensive Comparison. Biomolecules 2020, 10, 599. https://doi.org/10.3390/biom10040599
Sobeh M, Rezq S, Cheurfa M, Abdelfattah MAO, Rashied RMH, El-Shazly AM, Yasri A, Wink M, Mahmoud MF. Thymus algeriensis and Thymus fontanesii: Chemical Composition, In Vivo Antiinflammatory, Pain Killing and Antipyretic Activities: A Comprehensive Comparison. Biomolecules. 2020; 10(4):599. https://doi.org/10.3390/biom10040599
Chicago/Turabian StyleSobeh, Mansour, Samar Rezq, Mohammed Cheurfa, Mohamed A.O. Abdelfattah, Rasha M.H. Rashied, Assem M. El-Shazly, Abdelaziz Yasri, Michael Wink, and Mona F. Mahmoud. 2020. "Thymus algeriensis and Thymus fontanesii: Chemical Composition, In Vivo Antiinflammatory, Pain Killing and Antipyretic Activities: A Comprehensive Comparison" Biomolecules 10, no. 4: 599. https://doi.org/10.3390/biom10040599