Moxibustion significantly attenuated myocardial damage, reduced fibrosis, and restored ATPase activity in a doxorubicin-induced chronic heart failure rat model via AMPK/PGC-1α activation.
Does moxibustion improve mitochondrial energy metabolism via AMPK/PGC-1α activation in a doxorubicin-induced chronic heart failure rat model?
Moxibustion protects against doxorubicin-induced chronic heart failure in rats by improving mitochondrial energy metabolism through activation of the AMPK/PGC-1α pathway.
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.
Li et al. (Wed,) conducted a other in Chronic Heart Failure. Moxibustion at Feishu (BL13) and Xinshu (BL15) acupoints vs. Compound C (AMPK inhibitor) / Untreated control was evaluated on Myocardial damage, fibrosis, ATPase activity, and AMPK/PGC-1α pathway expression. Moxibustion significantly attenuated myocardial damage, reduced fibrosis, and restored ATPase activity in a doxorubicin-induced chronic heart failure rat model via AMPK/PGC-1α activation.