The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Chemicals and Drugs
2.3. STZ-Induced T1DM
2.4. Experimental Design
2.5. Regimen and Dose Selections
2.6. Collection of Plasma and Biochemical Measurement
2.7. Measurement of Cardiac Function
2.8. LV Collection and Processing
2.9. Serum and LV Lipid Measurement
2.10. Analyses in LV Tissue
2.11. Measurement of the Mitochondria Permeability Transition Pore Potential (mtPTP) Opening
2.12. Real-Time PCR
2.13. Histopathological Evaluation
2.14. Statistical Analysis
3. Results
3.1. AKBA Activated AMPK, Improved Mitochondrial Function, and Increased ATP in the LVs of STZ-Diabetic Hearts
3.2. AKBA Stimulated Glycolysis and FA Oxidation in the LVs of STZ-Diabetic Rats by Stimulating AMPK
3.3. AKBA Attenuated Weight Loss, Hyperglycemia, Hyperlipidemia, and Lipid Accumulation in the Heart and Liver of STZ Rats by Activating AMPK
3.4. The Protective Effect of AKBA on Cardiac Structure and Function Required the Activation of AMPK
3.5. AKBA Stimulated the Nrf2/Antioxidant Axis in the LV of the Control and STZ-Diabetic Rats in an AMPK-Dependent Manner
3.6. AKBA Suppressed NF-κB p65 and Cytokines Levels in the LVs of the Control and STZ-Diabetic Rats in an AMPK-Dependent Manner
3.7. AKBA Inhibited Intrinsic Cell Death in the LV of STZ-Diabetic Rats in an AMPK-Dependent Manner
4. Discussion
Conclusions, Study Limitations, and Future Studies
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Control | ABKA | STZ | STZ + ABKA | STZ + ABKA + CC | ||
---|---|---|---|---|---|---|
Final body weight | 411.5 ± 36.7 | 421.5 ± 31.2 | 301 ± 25.7 ab | 398 ± 31.3 abc | 318 ± 29.2 abd | |
Plasma | Glucose (mg/dl) | 106.3 ± 9.3 | 102.1 ± 8.2 | 341 ± 33.2 ab | 143 ± 12.5 abc | 328 ± 27.8 abd |
Insulin (ng/mL) | 4.7 ± 0.7 | 4.4 ± 0.5 | 2.1 ± 0.3 ab | 3.25 ± 0.4 abc | 2.18 ± 0.3 abd | |
Serum | TGs (mg/dl) | 66.4 ± 4.3 | 52.5 ± 45 a | 137 ± 11.2 ab | 79.4 ± 6.8 abc | 129 ± 11.4 abd |
CHOL (mg/dl) | 78.4 ± 7.9 | 59.7 ± 6.6 a | 168 ± 15.6 ab | 86.8 ± 6.1 abc | 183 ± 4.5 abd | |
LDL-c (mg/dl) | 44.1 ± 5.8 | 31.2 ± 3.7 a | 97.6 ± 8.4 ab | 51.8 ± 5.9 abc | 104 ± 9.3 abd | |
FFAs (μmol/mg) | 398 ± 43.2 | 376.1± 29.8 | 893.2 ± 77.3 ab | 484.2 ± 36.8 abc | 991 ± 86.5 abcd | |
Liver | TGs (mg/g) | 5.8 ± 0.7 | 4.1 ± 0.5 a | 11.3 ± 1.6 ab | 7.1 ± 0.9 abc | 12.4 ± 2.7 abd |
CHOL (mg/dl) | 4.9 ± 0.39 | 3.1 ± 0.4 a | 8.8 ± 0.6 ab | 5.1 ± 0.4 abc | 9.3 ± 0.9 abd | |
FFAs (μmol/mg) | 97.5 ± 8.4 | 76.2 ± 6.4 a | 388.1 ± 29.6 ab | 129 ± 11.3 abc | 369.2 ± 26.8 abd | |
Heart | TGs (μg/g) | 50.4 ± 5.1 | 36.7 ± 3.5 a | 111.4 ± 9.7 ab | 61.3 ± 5.7 abc | 119.4 ± 10.1 abd |
FFAs (nmol/mg) | 123.2 ± 11.3 | 88.2 ± 7.3 a | 365.3 ± 22.5 ab | 162.2 ± 13.8 abc | 389.9 ± 33.5 abd |
Control | ABKA | STZ | STZ + ABKA | STZ + ABKA + CC | ||
---|---|---|---|---|---|---|
Heart weight (g) | 1.2 ± 0.2 | 1.15 ± 0.18 | 1.46 ± 0.31 ab | 1.14 ± 0.27 abc | 1.52 ± 0.5 abd | |
Serum | Troponin-I (pg/mL) | 76.3 ± 6.5 | 71.7 ± 7.5 | 583 ± 42.5 ab | 112.5 ± 11.9 abc | 612 ± 58.3 abd |
CK-MB (pg/mL) | 212.1 ± 18.7 | 209.5 ± 20.4 | 633.4 ± 54.9 ab | 298.6 ± 25.4 abc | 618 ± 52.2 abd | |
LV function | dp/dtmax (mmHg) | 5994 ± 439 | 5778 ± 593 | 2934 ± 209 ab | 4938 ± 398 abc | 2609 ± 211 abd |
dp/dtmin (mmHg) | 4983 ± 375 | 4819 ± 478 | 2022 ± 199 ab | 3772 ± 289 abc | 2231 ± 245 abd | |
LVSP (mmHg) | 122.4 ± 11.3 | 125.1± 12.7 | 75.3 ± 6.9 ab | 108.5 ± 9.9 abc | 69.6 ± 5.8 abd | |
LVEDP (mmHg) | 2.9 ± 0.3 | 3.1 ± 0.3 | 11.5 ± 1.6 ab | 3.7 ± 0.4 abc | 13.1 ± 2.7 abd |
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AlTamimi, J.Z.; AlFaris, N.A.; Alshammari, G.M.; Alagal, R.I.; Aljabryn, D.H.; Yahya, M.A. The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK. Nutrients 2023, 15, 1660. https://doi.org/10.3390/nu15071660
AlTamimi JZ, AlFaris NA, Alshammari GM, Alagal RI, Aljabryn DH, Yahya MA. The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK. Nutrients. 2023; 15(7):1660. https://doi.org/10.3390/nu15071660
Chicago/Turabian StyleAlTamimi, Jozaa Z., Nora A. AlFaris, Ghedeir M. Alshammari, Reham I. Alagal, Dalal H. Aljabryn, and Mohammed Abdo Yahya. 2023. "The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK" Nutrients 15, no. 7: 1660. https://doi.org/10.3390/nu15071660