Key result
Huoxue Huatan Decoction significantly reduced LDL-C levels by up to 47%, decreased myocardial infarct size, and improved cardiac function in hyperlipidemic rats with ischemia/reperfusion injury.
Why the study?
The preventive and therapeutic effects and underlying mechanisms of Huoxue Huatan Decoction on myocardial ischemia/reperfusion injury in hyperlipidemia were not elucidated.
Does Huoxue Huatan Decoction ameliorate myocardial ischemia/reperfusion injury in hyperlipidemic rats?
Does Huoxue Huatan Decoction ameliorate myocardial ischemia/reperfusion injury in hyperlipidemic rats?
Effect estimate: decreased by 47% (high dose)
p-value: p=<0.01
Huoxue Huatan Decoction reduces myocardial ischemia/reperfusion injury in hyperlipidemic rats by lowering blood lipids and enhancing mitochondrial function pathways.
Should not change practice; leaves open whether this TCM formula translates to human hyperlipidemia or I/R injury.
The aim of this study was to elucidate the preventive and therapeutic effects and the underlying mechanisms of Huoxue Huatan Decoction (HXHT) on myocardial ischemia/reperfusion (I/R) injury in hyperlipidemic rats. An I/R model was established in hyperlipidemic Wistar rats. After 4–8 weeks of HXHT treatment, the effects of HXHT on the physical signs of rats were observed. Lipid metabolism, myocardial enzyme spectrum, cardiac function, myocardial histomorphology, and mitochondrial biosynthesis were investigated by a biochemical method, ultrasonography, electron microscopy, pathological examination, real-time PCR, and Western blot. HXHT can affect the lipid metabolism at different time points, and significantly reduce the levels of cholesterol (CHO), triglyceride (TG), high-density lipid-cholesterol (HDL-C), and low-density lipid-cholesterol (LDL-C) in hyperlipidemic rats (P < 0.05 or P < 0.01); it can significantly reduce the levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), reduce the myocardial infarct size and myocardial ischemic area, and improve cardiac function. The results of myocardial histomorphology showed that HXHT could protect myocardial cells, relieve swelling, reduce the number of cardiac lipid droplets, and improve myocardial mitochondrial function. HXHT could significantly increase the levels of total superoxide dismutase (T-SOD) and succinate dehydrogenase (SDH) (P < 0.05 or P < 0.01), increase CuZn-superoxide dismutase (CuZn-SOD) and glutathione-peroxidase (GSH-Px) levels, and decrease the levels of malondialdehyde (MDA) (P < 0.05); it could increase the mRNA and protein expression levels of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (mtTFA) (P < 0.05 or P < 0.01), and increase the synthesis of mitochondrial DNA (mtDNA) (P < 0.01). HXHT can reduce myocardial I/R injury in hyperlipidemic rats. The protective mechanisms may involve a reduction in blood lipids, enhancement of PGC-1α–PPARα pathway activity, and, subsequently, an increase in fatty acid β-oxidation, which may provide the required input for mitochondrial energy metabolism. HXHT can additionally enhance PGC-1α–NRF1–mtTFA pathway activity and, subsequently, reduce antioxidative stress, promote mitochondrial mtDNA synthesis, and reduce mitochondrial damage. The two pathways use PGC-1α as the intersection point to protect mitochondrial structure and function, reduce I/R-induced injury, and improve cardiac function.
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Lin et al. (2020) studied Hyperlipidemia and myocardial ischemia/reperfusion injury (n=168). Huoxue Huatan Decoction vs. Placebo (0.5% sodium carboxymethyl cellulose), Atorvastatin, or Danlou tablets was evaluated on Low-density lipoprotein cholesterol (LDL-C) levels at 8 weeks (decreased by 47% (high dose), p=<0.01). Huoxue Huatan Decoction significantly reduced LDL-C levels by up to 47%, decreased myocardial infarct size, and improved cardiac function in hyperlipidemic rats with ischemia/reperfusion injury.
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