Moxibustion Improves Mitochondrial Energy Metabolism in Rats with Chronic Heart Failure via AMPK/PGC-1α Pathway Activation

Abstract

Background

Impaired energy metabolism is central to chronic heart failure (CHF). While preclinical and clinical studies suggest moxibustion exerts protective effects in CHF, its mechanistic basis—particularly regarding mitochondrial energy regulation—remains poorly understood. Existing work has yet to define whether and how moxibustion modulates key metabolic pathways, such as adenosine 5′-monophosphate-activated protein kinase (AMPK)/PGC-1α signaling, to restore cardiac bioenergetics in CHF. This study tested the hypothesis that moxibustion improves mitochondrial function via AMPK/ PGC-1α activation.

Methods

A doxorubicin-induced CHF rat model was established. HE and Masson's trichrome staining were used to observe myocardial morphology and evaluate myocardial fibrosis, respectively. Colorimetry measured myocardial lactate, pyruvate, and ATPase (Na⁺K⁺-ATPase, Mg²⁺-ATPase, Ca²⁺-ATPase, Ca²⁺Mg²⁺-ATPase) activity. Expression levels of the mitochondrial fusion protein mitofusin 2 (MFN2) and the mitochondrial biogenesis proteins mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1) in cardiomyocytes were detected by Western blotting. AMPK and PGC-1α mRNA expression levels in myocardial tissue were determined by RT-PCR.

Results

Moxibustion at the Feishu (BL13) and Xinshu (BL15) acupoints significantly attenuated CHF-related myocardial damage and reduced myocardial fibrosis. Moxibustion also markedly restored ATPase activity and upregulated the expression of the MFN2, NRF1, and TFAM proteins, as well as mRNA levels of AMPK and PGC-1α, in cardiomyocytes from CHF rats. These effects were partially abrogated by administering compound C—a specific AMPK inhibitor. Moreover, a potentially direct interaction between pyruvate and AMPK was predicted through molecular docking analyses.

Conclusion

Moxibustion ameliorates CHF by stimulating the AMPK/PGC-1α signaling pathway to improve mitochondrial energy metabolism.