Moxibustion alleviates chronic heart failure by regulating mitochondrial dynamics and inhibiting autophagy

Abstract

Moxibustion (MOX) is a traditional Chinese medicine preparation, which has been clinically used to treat cardiac diseases in recent years. The present study aimed to examine the protective effects and possible mechanisms of MOX on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats. The animals were divided into five groups, including the Control (normal saline), DOX (doxorubicin 15 mg/kg), MOX (doxorubicin 15 mg/kg + moxibustion), BEN (doxorubicin 15 mg/kg + benazepril 0.86 mg/kg) and MOX + BEN (doxorubicin 15 mg/kg + moxibustion + benazepril 0.86 mg/kg) groups. After three weeks, echocardiography was performed to assess cardiac function and structure, including left ventricular internal diameter in systole, ejection fraction and fractional shortening (FS). Serum brain natriuretic peptide levels and adenosine triphosphate (ATP) levels were measured by enzyme-linked immunosorbent assay and ATP assay. Cardiac pathology was assessed by hematoxylin and eosin and Masson's trichrome staining. Cardiac ultrastructure and the number of autophagosomes formed were visualized by transmission electron microscopy. Western blotting was performed to assess mitochondrial dynamics, autophagy proteins and mitochondrial autophagy-related pathway proteins. The expression levels of these genes were assessed by reverse transcription-quantitative PCR. The results indicated MOX could improve cardiac function, increased cardiac ATP levels and reduced myocardial fibrosis. Western blotting indicated that MOX treatment elevated the expression of optic atrophy 1 protein (OPA1), while decreasing the expression of dynamin-related protein 1 and mitochondrial fission 1 protein. In addition, MOX inhibited autophagy, as evidenced by decreased number of autophagosomes, reduced LC3II/LC3I ratio and increased p62 expression. Furthermore, MOX downregulated DOX-induced FUNDC1 signaling pathway. In summary, MOX has protective effects on DOX-induced CHF in rats, promoting mitochondrial fusion while inhibiting mitochondrial fission and mitophagy. The underlying mechanisms may be related to the inhibition of the FUNDC1 signaling pathway.

Excessive autophagy of myocardial cells promotes ferroptosis and exacerbates heart failure in the state of myocardial infarction

“…Autophagy is a tightly regulated lysosomal degradation mechanism that plays a crucial role in cell survival, homeostasis, and function [36]. Our team's research, along with studies conducted by others, has shown that autophagy plays a significant role in regulating cardiac homeostasis and function and is closely linked to the development of HF [21][22][23]37]. Impaired or overactivated autophagy in cardiac myocytes is detrimental to the maintenance of cellular homeostasis and contributes to the progression of heart failure.…”

“…Our previous study demonstrated the importance of autophagy in HF pathogenesis. In cardiomyocytes, normal autophagy favors survival whereas excessive autophagy promotes necrosis [21][22][23]. However, the mechanisms by which autophagy influences ferritinophagy, ferroptosis, and post-MI HF development remain unclear.…”

Grain-sized moxibustion at Zusanli (ST36) promotes hepatic autophagy in rats with hyperlipidemia by regulating the ULK1 and TFEB expression through the AMPK/mTOR signaling pathway

“…Moxibustion can activate AMPK by affecting ATP in mice and rats [ 48 , 49 ]. Moxibustion can effectively improve the ATP level, change the energy in local and diseased areas of moxibustion in a chronic disease state, activate the AMPK expression, and stimulate a series of reactions downstream of the pathway [ 46 , 50 ].…”

Role of mitochondria in doxorubicin-mediated cardiotoxicity: from molecular mechanisms to therapeutic strategies

“…Similarly, a recent study in a rat model of doxorubicin-induced chronic heart failure demonstrated that application of moxibustion, a therapy used in traditional Chinese medicine (TCM), to certain acupressure points had cardioprotective effects related to mitophagy inhibition. The latter was evidenced by decreased LC3II/LC3I ratio, attenuated Fundc1 expression, and increased p62 levels in heart tissue [49]. However, as reviewed by Wallace et al [50], some studies suggested that doxorubicin actually halts autophagic fluxes in cardiac cells, pointing to inhibition of lysosome acidification and subsequent accumulation of autophagosomes and autolysosomes as important determinants of DOX-induced cardiotoxicity.…”