Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Drugs and Reagents
2.2. Plant Material and Extraction
2.3. Chemical Analyses by LC-DAD-MS
2.4. Ethnopharmacological Studies
2.4.1. Animals
2.4.2. Acute Toxicity
2.4.3. Hypertension Induction (Goldblatt Model; Two Kidneys, One Clip; 2K1C)
2.4.4. Experimental Design
2.4.5. Renal Function
2.4.6. Electrocardiography
2.4.7. Blood Pressure (BP) Assessment
2.4.8. Biochemical Parameters
2.4.9. Mesenteric Vascular Beds (MVBs) Reactivity
2.4.10. Relative Weight and Histopathological Analysis of the Heart and Left Ventricle Morphometry
2.4.11. Cardiac and Vascular Redox Status
2.4.12. Cyclic Guanosine Monophosphate (cGMP) Determination
2.5. Statistical Analyses
3. Results
3.1. Chemical Constituents from AERV
3.2. Toxicological Evaluations
3.3. Effects on Urinary Volume and Renal Electrolyte Excretion
3.4. Effects on Electrical Cardiac Activity
3.5. Effects on Blood Pressure and Heart Rate
3.6. Effects on Serum Parameters
3.7. Effects on MVBs Reactivity
3.8. Effects on Cardiac Morphology
3.9. Effects on Cardiac and Vascular Redox Status
3.10. Effects on Intracellular cGMP Levels
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Peak | RT (min) | UV(nm) | MF | Positive Ion Mode (m/z) | Negative Ion Mode (m/z) | Compound | Metabolite Class | % | |
---|---|---|---|---|---|---|---|---|---|
MS [M+H]+ | MS [M-H]− | MS/MS | |||||||
1 | 1.1 | - | C7H12O6 | 193.0696 | 191.0534 | 191 (bp), 173 | Quinic acid | Carboxylic acid | 18.34 |
2 | 1.1 | - | C12H22O11 | - | 341.1095 | 191(bp) | di-O-hexoside | Primary metabolite | 4.36 |
3 | 1.5 | - | C6H8O7 | 193.0367 | 191.0209 | - | Citric acid | Carboxylic acid | 1.31 |
4 | 2.7 | - | C16H20O10 | 373.1113 | 371.0991 | 191, 173 (bp) | Glycosylated iridoid | Iridoid | 0.31 |
5 | 5.9 | 295 sh, 325 | C16H18O9 | 355.1006 | 353.0873 | 191 (bp), 179 | 3-O-E-caffeoylquinic acid st | Chlorogenic acid | 3.66 |
6 | 9.9 | - | C18H24O12 | - | 431.1195 | 251, 165 (bp) | Asperulosidic acid | Iridoid | 4.67 |
7 | 10.5 | 295 sh, 325 | C16H18O9 | 355.1021 | 353.0873 | 191 (bp), 179 | 5-O-E-caffeoylquinic acid st | Chlorogenic acid | 2.48 |
8 | 11.3 | - | C18H22O11 | 415.1223 | 413.1084 | 191, 147 (bp) | Asperuloside | Iridoid | 11.98 |
9 | 18.7 | 265, 355 | C27H30O16 | 611.1595 | 609.1472 | 300 (bp), 301, 271, 255, 243 | O-hexosyl-deoxyhexosyl quercetin | Flavonol | 3.87 |
10 | 20.0 | - | C24H42O11 | 507.2822 | 505.2655 | 191 (bp) | Unknown | - | 1.81 |
11 | 20.8 | 265, 346 | C27H30O15 | 595.1644 | 593.1521 | 327, 285 (bp), 284, 255, 277, 162 | O-hexosyl-deoxyhexosyl kaempferol | Flavonol | 9.26 |
12 | 25.0 | - | C36H58O12 | 683.3967 | 681.3823 | 519 (bp), 501, 407, 207 | Trachelosperoside B-1 or E-1 | Glycosylated triterpene | 14.40 |
13 | 25.1 | - | C36H58O12 | 683.3981 | 681.3832 | 519 (bp), 501, 489, 457, 407, 207 | Trachelosperoside B-1 or E-1 | Glycosylated triterpene | 12.84 |
14 | 26.6 | - | C36H58O12 | 667.4027 | 665.3757 | 503 (bp), 441, 409 | Glycosylated triterpene (Arjunoglucoside I) | Glycosylated triterpene | 2.25 |
15 | 32.1 | - | C53H84O23 | 1089.5298 | 1087.5303 | 925 (bp), 793, 631, 613, 569, 469, 455, 353, 161 | O-glucoronyl-hexosyl-pentosyl O-hexosyl triterpene | Triperpenoid saponin | 2.09 |
16 | 32.2 | - | C48H76O19 | 957.5026 | 955.4914 | 793 (bp), 749, 731, 631, 613, 569, 551, 455, 337, 179 | O-glucoronyl-hexosyl O-hexosyl triterpene | Triperpenoid saponin | 6.37 |
Group | Urinary Volume (mL/100 g/8 h) | ElNa+ (µEq/min/100 g) | Elk+ (µEq/min/100 g) | ElCa2+ (µEq/min/100 g) | ElCl− (µEq/min/100 g) | pH | Density |
---|---|---|---|---|---|---|---|
Sham | 3.771 ± 0.188 | 1.694 ± 0.108 | 0.571 ± 0.029 | 0.021 ± 0.001 | 1.902 ± 0.113 | 8.5 ± 0.04 | 1015 ± 0.84 |
C- | 4.517 ± 0.219 | 0.826 ± 0.006 b | 0.546 ± 0.010 | 0.012 ± 0.002 b | 0.981± 0.016 b | 8.3 ± 0.02 | 1010 ± 0.28 b |
AERV 30 (mg/kg) | 3.665 ± 0.021 | 0.887 ± 0.087 b | 0.615 ± 0.032 | 0.007 ± 0.001 b | 1.021 ± 0.029 b | 8.7 ± 0.13 | 1015 ± 0.42 |
AERV (100 mg/kg) | 3.831 ± 0.445 | 0.878 ± 0.057 b | 0.614 ± 0.045 | 0.012 ± 0.001 b | 1.026 ± 0.074 b | 8.7 ± 0.15 | 1015 ± 0.42 |
AERV (300 mg/kg) | 3.279 ± 0.129 | 1.473 ± 0.054 a | 0.554 ±0.018 | 0.029 ± 0.001 a | 1.653 ± 0.025 a | 8.6 ± 0.05 | 1016 ± 1.52 |
MPL (25 mg/kg) | 4.378 ± 0.223 | 1.651 ± 0.082 a | 0.520 ± 0.069 | 0.022 ± 0.003 a | 1.791 ± 0.038 a | 8.1 ± 0.17 | 1014 ± 1.15 |
Group | Urinary Volume (mL/100 g/8 h) | ElNa+ (µEq/min/100 g) | Elk+ (µEq/min/100 g) | ElCa2+ (µEq/min/100 g) | ElCl− (µEq/min/100 g) | pH | Density |
---|---|---|---|---|---|---|---|
Sham | 5.272 ± 0.224 | 1.207 ± 0.087 | 0.591 ± 0.031 | 0.011 ± 0.001 | 1.348 ± 0.194 | 7.8 ± 0.06 | 1007 ± 0.42 |
C- | 3.862 ± 0.613 b | 1.261 ± 0.124 | 0.597 ± 0.034 | 0.013 ± 0.003 | 1.344 ± 0.127 | 7.7 ± 0.05 | 1013 ± 0.57 b |
AERV 30 (mg/kg) | 3.661 ± 0.208 b | 1.178 ± 0.026 | 0.570 ± 0.011 | 0.009 ± 0.001 | 1.319 ± 0.122 | 7.8 ± 0.07 | 1017 ± 1.11 b |
AERV (100 mg/kg) | 2.939 ± 0.396 b | 0.906 ± 0.096 | 0.438 ± 0.022 | 0.009 ± 0.001 | 0.971 ± 0.106 | 7.8 ± 0.11 | 1017 ± 1.83 b |
AERV (300 mg/kg) | 3.513 ± 0.334 b | 0.702 ± 0.268 | 0.396 ± 0.099 | 0.008 ± 0.004 | 0.803 ± 0.314 | 7.6 ± 0.14 | 1006 ± 2.30 a |
MPL (25 mg/kg) | 4.043 ± 0.333 | 1.181 ± 0.140 | 0.540 ± 0.078 | 0.009 ± 0.006 | 1.295 ± 0.182 | 7.7 ± 0.02 | 1008 ± 0.57 a |
Group | Urinary Volume (mL/100 g/8 h) | ElNa+ (µEq/min/100 g) | Elk+ (µEq/min/100 g) | ElCa2+ (µEq/min/100 g) | ElCl− (µEq/min/100 g) | pH | Density |
---|---|---|---|---|---|---|---|
Sham | 4.319 ± 0.399 | 1.363 ± 0.101 | 0.635 ± 0.057 | 0.034 ± 0.002 | 1.853 ± 0.124 | 7.8 ± 0.02 | 1016 ± 0.96 |
C- | 3.389 ± 0.032 b | 0.846 ± 0.049 b | 0.809 ± 0.101 | 0.017 ± 0.003 b | 1.376 ± 0.096 b | 7.8 ± 0.14 | 1018 ± 0.80 |
AERV 30 (mg/kg) | 3.139 ± 0.186 b | 0.893 ± 0.028 b | 0.641 ± 0.049 | 0.018 ± 0.002 b | 1.340 ± 0.016 b | 7.7 ± 0.20 | 1018 ± 1.23 |
AERV (100 mg/kg) | 2.794 ± 0.407 b | 1.193 ± 0.141 | 0.658 ± 0.076 | 0.012 ± 0.002 b | 1.003 ± 0.153 b | 7.6 ± 0.16 | 1015 ± 0.73 |
AERV (300 mg/kg) | 4.350 ± 0.164 a | 1.319 ± 0.023 a | 0.796 ± 0.129 | 0.040 ± 0.009 a | 1.807 ± 0.082 a | 7.7 ± 0.02 | 1016 ± 0.28 |
MPL (25 mg/kg) | 3.975 ± 0.050 a | 1.169 ± 0.118 | 0.652 ± 0.009 | 0.009 ± 0.002 b | 1.190 ± 0.134 b | 7.6 ± 0.08 | 1017 ± 1.15 |
Group | Urinary Volume (mL/100 g/8 h) | ElNa+ (µEq/min/100 g) | Elk+ (µEq/min/100 g) | ElCa2+ (µEq/min/100g) | ElCl− (µEq/min/100 g) | pH | Density |
---|---|---|---|---|---|---|---|
Sham | 5.111 ± 0.117 | 1.319 ± 0.144 | 0.667 ± 0.030 | 0.020 ± 0.001 | 1.486 ± 0.041 | 7.2 ± 0.12 | 1012 ± 0.55 |
C- | 3.209 ± 0.422 b | 1.157 ± 0.182 | 0.419 ± 0.069 b | 0.007 ± 0.004 b | 1.279 ± 0.196 | 7.3 ± 0.12 | 1018 ± 1.15 b |
AERV 30 (mg/kg) | 3.143 ± 0.040 b | 1.192 ± 0.011 | 0.523 ± 0.015 | 0.027 ± 0.001 a | 1.422 ± 0.015 | 7.6 ± 0.17 | 1022 ± 0.73 b |
AERV (100 mg/kg) | 3.712 ± 0.099 b | 1.295 ± 0.028 | 0.565 ± 0.013 | 0.018 ± 0.002 a | 1.417 ± 0.052 | 7.6 ± 0.19 | 1017 ± 1.11 b |
AERV (300 mg/kg) | 4.387 ± 0.264 a | 0.899 ± 0.169 | 0.781 ± 0.013 a | 0.041 ± 0.002 a | 1.344 ± 0.060 | 7.3 ± 0.11 | 1012 ± 1.73 a |
MPL (25 mg/kg) | 3.062 ± 0.022 b | 0.880 ± 0.182 | 0.495 ± 0.099 | 0.009 ± 0.003 b | 0.892 ± 0.213 b | 7.3 ± 0.34 | 1019 ± 0.28 b |
Group | Urinary Volume (mL/100 g/8 h) | ElNa+ (µEq/min/100 g) | Elk+ (µEq/min/100 g) | ElCa2+ (µEq/min/100 g) | ElCl− (µEq/min/100 g) | pH | Density |
---|---|---|---|---|---|---|---|
Sham | 4.196 ± 0.098 | 1.348 ± 0.086 | 0.639 ± 0.026 | 0.063 ± 0.005 | 1.532 ± 0.081 | 7.4 ± 0.17 | 1015 ± 0.91 |
C- | 3.350 ± 0.064 b | 0.860 ± 0.022 b | 0.680 ± 0.010 | 0.020 ± 0.001 b | 1.039 ± 0.027 b | 7.6 ± 0.18 | 1019 ± 0.57 b |
AERV 30 (mg/kg) | 3.504 ± 0.142 b | 1.311 ± 0.102 | 0.681 ± 0.045 | 0.022 ± 0.003 b | 1.527 ± 0.085 a | 7.7 ± 0.17 | 1018 ± 0.42 b |
AERV (100 mg/kg) | 3.449 ± 0.125 b | 1.296 ± 0.071 | 0.608 ± 0.001 | 0.015 ± 0.001 b | 1.413 ± 0.077 a | 7.6 ± 0.14 | 1014 ± 0.55 a |
AERV (300 mg/kg) | 3.927 ± 0.192 a | 1.289 ± 0.079 | 0.667 ± 0.026 | 0.037 ± 0.016 | 1.465 ± 0.098 a | 7.5 ± 0.12 a | 1015 ± 0.57 a |
MPL (25 mg/kg) | 3.433 ± 0.215 b | 1.274 ± 0.159 | 0.678 ± 0.106 | 0.016 ± 0.003 b | 1.165 ± 0.171 | 7.3 ± 0.11 | 1017 ± 2.30 |
Group | Na+ (mmol/L) | K+ (mmol/L) | Urea (mg/dL) | Creatinine (mg/dL) | ACE Activity (mmol/min/mL) |
---|---|---|---|---|---|
Sham | 126.5 ± 1.21 | 5.81 ± 0.22 | 57.32 ± 0.93 | 0.32 ± 0.02 | 85 ± 10.10 |
C- | 130.2 ± 1.86 | 6.15 ± 0.35 | 85.80 ± 2.75 b | 0.67 ± 0.03 b | 155 ± 13.22 b |
AERV (30 mg/kg) | 131.7 ± 1.99 | 6.22 ± 0.12 | 77.08 ± 1.56 b | 0.59 ± 0.02 b | 121 ± 9.11 b |
AERV (100 mg/kg) | 129.9 ± 1.23 | 6.13 ± 0.51 | 56.63 ± 1.17 | 0.33 ± 0.01 | 98 ± 10.24 a |
AERV (300 mg/kg) | 126.0 ± 2.03 | 5.77 ± 0.22 | 57.36 ± 1.23 | 0.35 ± 0.03 | 90 ± 12.11 a |
MPL (25 mg/kg) | 129.1 ± 1.92 | 5.41 ± 0.21 | 58.22 ± 3.21 | 0.37 ± 0.05 | 100 ± 11.08 a |
Parameter | Sham | C- | AERV (30 mg/kg) | AERV (100 mg/kg) | AERV (300 mg/kg) | MPL (25 mg/kg) |
---|---|---|---|---|---|---|
Heart | ||||||
SOD | 40.57 ± 1.61 | 30.54 ± 0.61 b | 34.89 ± 1.49 b | 38.03 ± 1.23 a | 40.46 ± 1.40 a | 34.84 ± 1.84 b |
Cat | 45.10 ± 4.33 | 25 ± 5.15 b | 52 ± 6.68 a | 45 ± 3.61 a | 55 ± 9.21 a | 28 ± 75.35 b |
LPO | 16.48 ± 0.97 | 25.17 ± 0.35 b | 18.10 ± 0.65 | 17.99 ± 0.73 | 17.42 ± 0.59 a | 17.93 ± 0.37 |
Aorta | ||||||
SOD | 71.73 ± 5.00 | 62.37 ± 2.55 | 67.48 ± 1.36 | 68.61 ± 1.37 | 69.64 ± 1.73 | 62.83 ± 1.53 |
Cat | 61 ± 3.79 | 41 ± 4.58 b | 52 ± 5.79 | 58 ± 4.38 a | 77 ± 4.25 a | 49 ± 4.31 b |
LPO | 6.90 ± 0.53 | 8.54 ± 0.38 b | 7.61 ± 0.41 | 7.29 ± 0.41 | 6.91 ± 0.47 a | 7.22 ± 0.33 |
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Paulin, F.V.; Palozi, R.A.C.; Lorençone, B.R.; Macedo, A.L.; Guarnier, L.P.; Tirloni, C.A.S.; Romão, P.V.M.; Gasparotto Junior, A.; Silva, D.B. Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation. Pharmaceutics 2021, 13, 1579. https://doi.org/10.3390/pharmaceutics13101579
Paulin FV, Palozi RAC, Lorençone BR, Macedo AL, Guarnier LP, Tirloni CAS, Romão PVM, Gasparotto Junior A, Silva DB. Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation. Pharmaceutics. 2021; 13(10):1579. https://doi.org/10.3390/pharmaceutics13101579
Chicago/Turabian StylePaulin, Fernanda Viana, Rhanany Alan Calloi Palozi, Bethânia Rosa Lorençone, Arthur Ladeira Macedo, Lucas Pires Guarnier, Cleide Adriane Signor Tirloni, Paulo Vitor Moreira Romão, Arquimedes Gasparotto Junior, and Denise Brentan Silva. 2021. "Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation" Pharmaceutics 13, no. 10: 1579. https://doi.org/10.3390/pharmaceutics13101579
APA StylePaulin, F. V., Palozi, R. A. C., Lorençone, B. R., Macedo, A. L., Guarnier, L. P., Tirloni, C. A. S., Romão, P. V. M., Gasparotto Junior, A., & Silva, D. B. (2021). Prolonged Administration of Rudgea viburnoides (Cham.) Benth. Prevents Impairment of Redox Status, Renal Dysfunction, and Cardiovascular Damage in 2K1C-Hypertensive Rats by Inhibiting ACE Activity and NO-GMPC Pathway Activation. Pharmaceutics, 13(10), 1579. https://doi.org/10.3390/pharmaceutics13101579