Improved Myocardial Mitochondrial Energy Metabolism in Rats with Chronic Heart Failure by Modifying Fatty Acid Oxidation Using an Extract of Sand-Fired Aconite (Jianchang Gang Processing)

Hongtao Zhang¹Xingmei Lu¹Songhong Yang¹Feipeng Gong²Bincheng Gu²Qin Xie¹Yanrong Ye¹Lingyun Zhong^1*Yi Huang^1*

• ¹School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
• ²Jiangxi Provincial People's Hospital, Nanchang, Jiangxi Province, China

Introduction: Sand-fired aconite slices (SFAS) demonstrate anti-heart failure effects, but the mechanism remains unclear. This study investigated myocardial mitochondrial energy metabolism as a therapeutic mechanism of SFAS in doxorubicin-induced chronic heart failure (CHF) rats. Methods: The CHF rat model was established via the intraperitoneal injection of doxorubicin (DOX). Following successful model production, rats were randomly assigned to nine groups. After drug administration, their cardiac function was assessed, and their cardiac tissue morphology and myocardial mitochondria were examined. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine (NE), malondialdehyde (MDA), superoxide dismutase (SOD), free fatty acid (FFA), sodium-potassium-ATPase (Na+-k+-ATPase), calcium-magnesium-ATPase (Ca2+-Mg2+-ATPase), and adenosine triphosphate (ATP) levels were quantified using enzyme-linked immunosorbent assays (ELISAs). Fatty acid translocase (CD36), carnitine palmitoyl transferase 1 (CPT1), adenosine 5′-monophosphate-activated protein kinase (AMPK), phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α), and Sirtuin 3 (SIRT3) protein expression levels were assessed by Western blot. Results: SFAS significantly improved cardiac function in CHF rats. It increased the left ventricular ejection fraction (LVEF) (from 34.22%±2.03% to 83.68%±2.34%; P < 0.001) and left ventricular shortening fraction (LVFS) (from 17.06%±1.08% to 53.86%±2.82%; P < 0.001) and decreased ANP (from 551.29±14.63 pg/mL to 291.96±11.28 pg/mL; P < 0.05), BNP (from 743.15±18.03 pg/mL to 478.75±10.57 pg/mL; P < 0.001), and NE levels (from 1105.36±21.79 pg/mL to 672.67±6.70pg/mL; P<0.001). Additionally, it decreased MDA production (from 8.89±0.36 nmol/mL to 5.11±0.35nmol /mL; P<0.05) and increased SOD activity (from 264.82±4.26 pg/mL to 529.64±10.27pg/mL; P<0.001), Na+-K+-ATPase levels (from 7.19±0.65 μmol/mL to 14.08±0.28 μmol/mL;P<0.001), Ca2+-Mg2+-ATPase levels (from 0.86±0.03 μmol/mL to 1.40±0.02 μmol/mL; P<0.05), CD36 levels (P<0.05), and CPT1 levels (P<0.01). Moreover, it improved mitochondrial structural damage and reduced the level of oxidative stress in cardiomyocytes. Furthermore, SFAS promoted FFA oxidation (from 1477.49±7.60 μmol/mL to 768.87±82.53 μmol/mL; P < 0.05) and ATP production (from 2869.85±298.26 nmol/mL to 5483.17±120.03 nmol/mL; P<0.001) and increased p-AMPK, PGC-1α, and SIRT3 levels (P<0.05 and P<0.01). Conclusion: By activating the AMPK/PGC-1α/SIRT3 signaling pathway, SFAS ameliorated the impaired fatty acid oxidation pathway and enhanced mitochondrial function and antioxidant capacity in cardiomyocytes, ultimately reducing myocardial damage and restoring cardiac function in CHF rats.