Anti-Inflammatory and Antioxidant Activities of Terpene- and Polyphenol-Rich Premna odorata Leaves on Alcohol-Inflamed Female Wistar Albino Rat Liver
Abstract
:1. Introduction
2. Results
2.1. Metabolomic Analysis
2.2. In Silico ADMET Properties for the Crude Extract of Different Premna odorata Metabolites
2.3. In Vitro Measurement of Total Reactive Oxygen Species (ROS)
2.4. Acute Toxicity
2.5. Potential Effects of Premna odorata Extracts in Liver Function Tests
2.6. Potential Effects of Premna odorata Extracts on Oxidative Stress Markers, and Antioxidant
2.7. Potential Effects of Premna odorata Extracts on Inflammatory Markers and Adhesion Molecules
2.8. Histopathological Investigation of Liver
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Plant Material and Extraction
4.3. Metabolomic Analysis Procedure
4.4. In Silico ADMET Properties for the Crude Extract of Different Premna odorata Metabolites
4.5. In Vitro Measurement of Total Reactive Oxygen Species (ROS)
4.5.1. Cell Lines, Culture Conditions
4.5.2. Intracellular ROS Levels Quantification
4.6. Animal Treatment
4.7. Animal Ethical Statement
4.8. Acute Toxicity Test
4.9. Induction of Alcohol Liver Inflammation and Experimental Design
4.9.1. Blood Sampling
4.9.2. Biochemical Analysis
4.10. Statistical Analysis
4.11. Histopathological Examination
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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No. | Identified | Source | MF | tR(min.) | m/z | Adduct | CE | H | DCM | EtOAC | B |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | Vitexin | Premna odorata | C21H20O10 | 9.71 | 433.1361 | [M + H]+ | + | + | |||
2 | Premnoside A | Premna odorata | C39H44O20 | 11.37 | 833.2746 | [M + H]+ | + | + | + | ||
3 | 6- O-α- L-(2’’-O-trans-caffoyl) rhamnopyranosyl catalpol | Premna odorata | C30H38O17 | 11.98 | 671.1910 | [M + H]+ | + | + | + | ||
4 | Daucosterol | Premna japonica | C35H60O6 | 12.33 | 577.1969 | [M + H]+ | + | + | |||
5 | Premnoside D | Premna odorata | C39H44O19 | 12.61 | 817.2282 | [M + H]+ | + | + | + | ||
6 | Premnoside H | Premna odorata | C39H44O18 | 13.00 | 801.2404 | [M + H]+ | + | + | + | ||
7 | Premnoside C | Premna odorata | C40H46O19 | 13.09 | 831.2411 | [M + H]+ | + | + | + | ||
8 | 6- O-α- L-(2’’-O-trans-p-methoxycinnamoyl) rhamnopyranosyl catalpol | Premna japonica | C31H40O16 | 13.20 | 669.1634 | [M + H]+ | + | + | + | ||
9 | Stigmasterol | Premna odorata | C29H48O | 13.33 | 413.2619 | [M + H]+ | + | + | |||
10 | Acacetin | Premna odorata | C16H12O5 | 13.60 | 285.1126 | [M + H]+ | + | + | |||
11 | Premnoside G | Premna odorata | C39H44O18 | 13.72 | 801.2404 | [M + H]+ | + | + | + | ||
12 | 6- O-α- L-(4’’-O-trans-feruloyl) rhamnopyranosyl catalpol | Premna japonica | C31H40O17 | 13.78 | 685.2780 | [M + H]+ | + | + | + | ||
13 | β-sitosterol | Premna odorata | C29H50O | 14.19 | 414.1849 | [M + H]+ | + | + | |||
14 | Verbascoside | Premna odorata | C29H36O15 | 14.47 | 625.1396 | [M + H]+ | + | + | + | ||
15 | Premnoside F | Premna odorata | C41H48O18 | 14.54 | 829.2011 | [M + H]+ | + | + | + | ||
16 | Premnoside E | Premna odorata | C41H48O18 | 14.73 | 829.2011 | [M + H]+ | + | + | + | ||
17 | Linolenic acid | Premna microphylla | C18H30O2 | 14.81 | 277.1807 | [M - H]+ | + | + | |||
18 | Diosmetin | Premna odorata | C16H12O6 | 15.09 | 301.2947 | [M + H]+ | + | + | + | ||
19 | Premnaodoroside A | Premna odorata | C42H66O20 | 15.94 | 891.3561 | [M + H]+ | + | + | |||
20 | Premnaodoroside B | Premna odorata | C42H66O19 | 16.06 | 875.2437 | [M + H]+ | + | + | |||
21 | Premnaodoroside C | Premna odorata | C42H64O19 | 16.12 | 873.3192 | [M + H]+ | + | + | |||
22 | Premnoside D | Premna odorata | C40H46O20 | 16.21 | 847.2782 | [M + H]+ | + | + | + | ||
23 | Premnaodoroside D | Premna subscandens | C42H64O20 | 17.74 | 889.2297 | [M + H]+ | + | + | |||
24 | Β-amyrin | Premna odorata | C30H50O | 18.28 | 465.2018 | [M + K]+ | + | + | |||
25 | Luteolin | Premna odorata | C15H10O6 | 18.66 | 309.2349 | [M + Na]+ | + | + | + | ||
26 | Apigenin | Premna odorata | C15H10O5 | 20.82 | 293.2147 | [M + Na]+ | + | + | |||
27 | Premcoryoside | Premna corymbosa | C45H58O24 | 21.52 | 983.4891 | [M + H]+ | + | + | |||
28 | Arjunolic acid | Premna microphylla | C30H48O5 | 21.64 | 489.2793 | [M + H}+ | + | + |
No. | PPB% | BBB (Cbrain/Cblood) | SP (cm/hour) | HIA% | MDCK (nm/sec) | Caco-2 (nm/sec) | Pgp Inhibition | CYP-2C19 Inhibition | CYP-2C9 Inhibition | CYP-3A4 Inhibition | CYP-3A4 Substrate |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 61.323656 | 0.0385273 | −4.61128 | 31.374153 | 0.5424090 | 5.48785 | No | Inhibitor | Inhibitor | Inhibitor | Weak |
2 | 54.348583 | 0.0287162 | −3.02912 | 3.7348170 | 0.0447556 | 13.6259 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
3 | 33.285061 | 0.0298880 | −4.70662 | 3.3153240 | 0.1538230 | 11.0644 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
4 | 100.000000 | 5.3038700 | −2.20420 | 90.027561 | 0.1220710 | 25.2333 | Inhibitor | No | Inhibitor | Inhibitor | Substrate |
5 | 54.577268 | 0.0305549 | −2.97228 | 8.4947690 | 0.0455697 | 14.1947 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
6 | 56.739888 | 0.0342009 | −2.91786 | 19.057599 | 0.0454732 | 14.7567 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Substrate |
7 | 48.364678 | 0.0424033 | −2.96634 | 16.156072 | 0.0454091 | 14.0366 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
8 | 33.832287 | 0.06277950 | −4.6442 | 13.170559 | 0.1289870 | 12.3956 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
9 | 100.000000 | 19.8938000 | −0.717667 | 100.00000 | 3.783450 | 52.3376 | Inhibitor | No | Inhibitor | Inhibitor | Substrate |
10 | 90.917451 | 0.15030900 | −3.36001 | 93.042708 | 20.230800 | 12.7923 | No | Inhibitor | Inhibitor | Inhibitor | No |
11 | 53.912360 | 0.1319930 | −2.9222 | 52.345314 | 0.0449026 | 15.3124 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
12 | 32.612262 | 0.0411953 | −4.70477 | 5.9983830 | 0.1105100 | 9.11617 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
13 | 100.000000 | 19.8883000 | −0.593439 | 100.00000 | 8.8571900 | 52.3734 | Inhibitor | No | Inhibitor | Inhibitor | Substrate |
14 | 64.288492 | 0.03167600 | −3.5116 | 7.6711810 | 0.0450549 | 11.1087 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
15 | 54.629780 | 0.1252660 | −2.92245 | 52.345571 | 0.0451432 | 15.4511 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
16 | 53.912360 | 0.1319930 | −2.9222 | 52.345314 | 0.0449026 | 15.3124 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
17 | 100.000000 | 6.16921000 | −0.538273 | 98.273607 | 74.789700 | 27.9738 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | No |
18 | 90.160128 | 0.20108600 | −4.13473 | 88.188263 | 23.853100 | 7.02526 | No | Inhibitor | Inhibitor | Inhibitor | No |
19 | 34.413157 | 0.0284513 | −3.29001 | 1.9433930 | 0.2328650 | 16.3835 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Substrate |
20 | 40.461576 | 0.0298628 | −3.70182 | 4.3580790 | 0.0841395 | 17.2768 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Substrate |
21 | 41.088270 | 0.0302347 | −3.26196 | 5.1422870 | 0.1599090 | 15.3574 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Substrate |
22 | 45.368220 | 0.0328157 | −3.02594 | 7.1270550 | 0.0447377 | 12.7477 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Weak |
23 | 34.183542 | 0.0283962 | −3.80436 | 2.2958830 | 0.291627 | 17.4161 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Substrate |
24 | 100.000000 | 21.2500000 | −2.22251 | 100.00000 | 0.1749200 | 46.7500 | Inhibitor | No | Inhibitor | Inhibitor | Substrate |
25 | 99.717233 | 0.36758200 | −4.28017 | 79.427233 | 36.520500 | 4.53973 | No | Inhibitor | Inhibitor | Inhibitor | No |
26 | 97.253409 | 0.56511300 | −4.14570 | 88.122839 | 44.302000 | 10.5468 | No | Inhibitor | Inhibitor | Inhibitor | No |
27 | 37.405289 | 0.0273879 | −2.50822 | 0.3453560 | 0.0434853 | 11.7965 | Inhibitor | Inhibitor | Inhibitor | Inhibitor | Substrate |
28 | 97.049829 | 0.58860800 | −3.57106 | 91.233319 | 0.0434480 | 20.9815 | Inhibitor | No | Inhibitor | Inhibitor | Substrate |
No. | Ames Test | TA100-10RLI | TA100-NA | TA1535-10RLI | TA1535-NA | Carcinogenic for Mice | Carcinogenic for Rats | HERG Inhibition |
---|---|---|---|---|---|---|---|---|
1 | Non-mutagenic | − | − | − | − | + | − | High risk |
2 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
3 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
4 | Non-mutagenic | − | − | − | − | + | − | Low risk |
5 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
6 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
7 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
8 | Non-mutagenic | − | − | − | − | + | − | High risk |
9 | Non-mutagenic | − | − | − | − | + | + | Low risk |
10 | Mutagenic | + | + | − | − | + | + | Moderate risk |
11 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
12 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
13 | Non-mutagenic | − | − | − | − | + | − | Low risk |
14 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
15 | Non-mutagenic | − | − | − | − | + | − | High risk |
16 | Non-mutagenic | − | − | − | − | + | − | High risk |
17 | Mutagenic | − | − | − | + | + | + | Moderate risk |
18 | Mutagenic | − | + | − | − | + | + | Moderate risk |
19 | Mutagenic | − | + | − | − | + | − | Ambiguous |
20 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
21 | Mutagenic | − | + | − | − | + | − | Ambiguous |
22 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
23 | Mutagenic | − | + | − | − | + | − | Ambiguous |
24 | Non-mutagenic | − | − | − | − | + | + | Low risk |
25 | Mutagenic | − | + | − | − | + | + | Moderate risk |
26 | Mutagenic | + | + | − | − | + | + | Moderate risk |
27 | Non-mutagenic | − | − | − | − | + | − | Ambiguous |
28 | Non-mutagenic | − | − | − | − | + | + | Low risk |
Groups | |||||||
---|---|---|---|---|---|---|---|
Parameters | 1 | 2 | 3 | 4 | 5 | 6 | |
Bilirubin (mg/dl) | Mean ± SD | 0.85 ± 0.05 b | 1.41 ± 0.18 a | 0.916 ± 0.07 b | 0.95 ± 0.05 b | 0.916 ± 0.076 b | 0.8 ± 0.05 b |
% change | 65.88 | 7.76 | 11.76 | 7.76 | 5.88 | ||
% improvement | 58.11 | 54.11 | 58.11 | 71.76 | |||
AST (U/I) | Mean ± SD | 39.00 ± 7.81 b | 81.33 ± 21.45 a | 25.47 ± 4.50 d | 28.33 ± 1.53 cd | 32.33 ± 2.08 bc | 31.47 ± 3.51 bcd |
% change | 108.53 | 34.20 | 27.30 | 17.10 | 19.31 | ||
% improvement | 143.23 | 133.23 | 125.64 | 127.84 | |||
ALT (U/I) | Mean ± SD | 108.47 ± 18.85 b | 144.33 ± 25.1 a | 77.33 ± 4.42 bc | 72.00 ± 2.00 bc | 92.47 ± 16.28 b | 93.33 ± 5.77 b |
% change | 33.05 | 28.71 | 33.62 | 14.75 | 13.96 | ||
% improvement | 61.76 | 66.68 | 47.81 | 47.02 | |||
ALP (IU/L) | Mean ± SD | 173.33 ± 29.29 bc | 232.33 ± 2.51 a | 148.33 ± 10.40 bc | 181.47 ± 7.44 b | 185 ± 18.02 b | 141.47 ± 2.51 c |
% change | 34.04 | 14.42 | 4.69 | 6.73 | 18.27 | ||
% improvement | 48.47 | 29.32 | 27.29 | 52.42 | |||
MDA (mmol/l) | Mean ± SD | 2818.85 ± 200.5 c | 4,029.85 ± 200.5 a | 2,026.33 ± 52.50 d | 2,121.47 ± 91.76 d | 2,248.00 ± 141.24 d | 3,250.47 ± 416.41 b |
% change | 42.97 | 28.11 | 24.73 | 20.22 | 15.33 | ||
% improvement | 71.07 | 67.21 | 63.20 | 27.60 | |||
GSH (mg/g tissue used) | Mean ± SD | 412.86 ± 56.94 bc | 299.16 ± 54.98 d | 491.91 ± 27.56 c | 506.88 ± 86.32 b | 495.46 ± 28.99 ab | 411.29 ± 77.11 bc |
% change | 27.42 | 19.15 | 22.77 | 20.26 | 0.24 | ||
% improvement | 46.60 | 50.32 | 47.57 | 27.18 | |||
TAC (mmol/l) | Mean ± SD | 0.26 ± 0.02 a | 0.16 ± 0.02 b | 0.26 ± 0.02 a | 0.26 ± 0.02 a | 0.27 ± 0.03 a | 0.29 ± 0.02 a |
% change | 38.46 | 0 | 0 | 3.84 | 11.53 | ||
% improvement | 38.46 | 38.46 | 42.30 | 50.00 | |||
CRP (ng/mL) | Mean ± SD | 29.30 ± 2.01 b | 54.58 ± 2.18 a | 32.47 ± 2.51 b | 33.33 ± 1.52 b | 29.03 ± 2.74 b | 31.20 ± 1.38 b |
% change | 86.96 | 10.34 | 13.79 | 1.02 | 6.48 | ||
% improvement | 75.86 | 72.40 | 86.20 | 80.34 | |||
TNF-α (pg/mL) | Mean ± SD | 39.33 ± 2.47 bc | 73.03 ± 2.45 a | 43.47 ± 2.76 bc | 33.47 ± 1.53 c | 41.47 ± 2.39 bc | 52.41 ± 1.45 b |
% change | 98.49 | 10.25 | 15.38 | 5.12 | 33.74 | ||
% improvement | 76.92 | 102.56 | 82.76 | 53.84 | |||
ICAM-1 (μg/mL) | Mean ± SD | 5.53 ± 0.47 c | 11.81 ± 1.22 a | 7.46 ± 1.41 b | 6.83 ± 0.77 bc | 6.49 ± 0.41 bc | 6.43 ± 0.56 bc |
% change | 114.54 | 36.36 | 23.50 | 18.18 | 16.30 | ||
% improvement | 78.18 | 90.05 | 96.20 | 98.18 | |||
VCAM-1 (μg/mL) | Mean ± SD | 2.92 ± 0.12 b | 4.46 ± 1.30 a | 3.40 ± 0.20 b | 3.29 ± 0.23 b | 3.22 ± 0.58 b | 2.96 ± 0.11 b |
% change | 51.72 | 17.24 | 13.79 | 13.79 | 3.45 | ||
% improvement | 37.93 | 41.37 | 41.37 | 51.72 |
Experiment | Kit Reagents |
---|---|
ROS | 2’,7’-dichlorodihydrofluorescein diacetate (H2DCF–DA), Roswell Park Memorial Institute (RPMI) 1640 medium, fetal calf serum, penicillin, and streptomycin |
Bilirubin | sulfanilic acid, hydrochloric acid, dimethyl sulfoxide |
AST | phosphate buffer pH 7.5 (100 mmol/L), aspartate (10 0mmol/L), α-ketoglutarate (2 mmol/L) |
ALT | alanine 200 mmol/L, 2,4-dinitrophenyl hydrazine (1 mmol/L) |
ALP | standard phenol (1.59 mmol/L), buffer pH 10 (50 mmol/L), phenyl phosphate (5 mmol/L), EDTA (100 mmol/L), 4-aminophenazone (50 mmol/L), potassium ferricyanide (200 mmol/L) |
MDA | standard MDA (10 mmol/mL), thiobarbituric acid (25 mmol/L), detergent (3 mmol/L), stabilizer (15 mmol/L) |
GSH | DTNB (1 mmol/L) |
TAC | sulfuric acid, sodium phosphate, ammonium molybdate |
CRP | capture antibody-coated microplate: one plate of 96 wells coated with a rabbit anti-rat CRP antibody detection antibody/enzyme conjugates (100 x): concentrated horseradish peroxidase (HRP) conjugated to a rabbit anti-rat CRP antibody containing stabilizers and preservative standard (10 x): rat serum with elevated levels of CRP, wash buffer: powdered phosphate-buffered saline (PBS) with 0.05% Tween-20, TMB substrate: solution containing 3, 3’, 5, 5’-tetramethylbenzidine (TMB) stop solution: diluted phosphoric acid |
TNF-α | Rat TNF-α microplates – 96-well polystyrene microplates (12 strips of 8 wells) coated with a monoclonal antibody specific to rat TNF-α Rat TNF-α conjugate – 23 mL/vial of a polyclonal antibody against the rat TNF-α conjugated to horseradish peroxidase with preservatives Rat TNF-α standard – 1.5 ng/vial of the recombinant rat TNF-α in a buffered protein base with preservatives, lyophilized Rat TNF-α control – the recombinant rat TNF-α in a buffered protein base with preservatives. lyophilized The concentration range of the rat TNF-α after reconstitution. The assay value of the control should be within the range specified on the label, assay diluent RD1-41 – 12.5 mL/vial of the buffered protein base with preservatives, calibrator diluent RDS-17 – 21 mL/vial of the buffered protein base with preservatives, wash buffer concentrate – 50 mL/vial of a 25-fold concentrated solution of a buffered surfactant with preservatives, color reagent A – 12.5 mL/vial of the stabilized hydrogen peroxidase, color reagent B – 12.5 mL/vial of the stabilized chromogen (tetramethylbenzidine) Stop solution – 23 mL/vial of a diluted hydrochloric acid solution, plate covers – adhesive strips |
VCAM-1 | Pre-coated, ready-to-use 96-well strip plate, plate sealer for 96 wells, standard diluent, assay diluent A, assay diluent B, stop solution, standard, detection reagent A, detection reagent B, TMB substrate, wash buffer (30 x concentrate); |
ICAM-1 | Pre-coated 96-well strip microplate, wash buffer, stop solution, assay diluent(s), lyophilized standard, biotinylated detection antibody, streptavidin-conjugated HRP, TMB One-Step Substrate |
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Elmaidomy, A.H.; Alhadrami, H.A.; Amin, E.; Aly, H.F.; Othman, A.M.; Rateb, M.E.; Hetta, M.H.; Abdelmohsen, U.R.; M. Hassan, H. Anti-Inflammatory and Antioxidant Activities of Terpene- and Polyphenol-Rich Premna odorata Leaves on Alcohol-Inflamed Female Wistar Albino Rat Liver. Molecules 2020, 25, 3116. https://doi.org/10.3390/molecules25143116
Elmaidomy AH, Alhadrami HA, Amin E, Aly HF, Othman AM, Rateb ME, Hetta MH, Abdelmohsen UR, M. Hassan H. Anti-Inflammatory and Antioxidant Activities of Terpene- and Polyphenol-Rich Premna odorata Leaves on Alcohol-Inflamed Female Wistar Albino Rat Liver. Molecules. 2020; 25(14):3116. https://doi.org/10.3390/molecules25143116
Chicago/Turabian StyleElmaidomy, Abeer H., Hani A. Alhadrami, Elham Amin, Hanan F. Aly, Asmaa M. Othman, Mostafa E. Rateb, Mona H. Hetta, Usama Ramadan Abdelmohsen, and Hossam M. Hassan. 2020. "Anti-Inflammatory and Antioxidant Activities of Terpene- and Polyphenol-Rich Premna odorata Leaves on Alcohol-Inflamed Female Wistar Albino Rat Liver" Molecules 25, no. 14: 3116. https://doi.org/10.3390/molecules25143116