Phellinus linteus Mycelium Alleviates Myocardial Ischemia-Reperfusion Injury through Autophagic Regulation

Abstract

The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjected to myocardial IR injury. The left main coronary artery of rats was ligated for 1 h and reperfused for 3 h. The arrhythmia levels were monitored during the entire process and the infarct size was evaluated after myocardial IR injury. Furthermore, the expression levels of proteins in apoptotic and autophagic pathways were observed. Pretreatment with PL mycelium (PLM) significantly reduced ventricular arrhythmia and mortality due to myocardial IR injury. PLM also significantly decreased myocardial infarct size and plasma lactate dehydrogenase level after myocardial IR injury. Moreover, PLM administration resulted in decreased caspase 3 and caspase 9 activation and increased Bcl-2/Bax ratio. Phosphorylation level of AMPK was elevated while mTOR level was reduced. Becline-1 and p62 levels decreased. These findings suggest that PLM is effective in protecting the myocardium against IR injury. The mechanism involves mediation through suppressed pro-apoptotic signaling and regulation of autophagic signaling, including stimulation of AMPK-dependent pathway and inhibition of beclin-1-dependent pathway, resulting in enhancement of protective autophagy and inhibition of excessive autophagy.

Protective Effects of Phellinus linteus Mycelium on the Development of Osteoarthritis after Monosodium Iodoacetate Injection

“…Phellinus linteus mycelium (PLM), a well-known medicinal mushroom, has been used in Asian countries for many centuries to prevent or treat diseases such as gastroenteric dysfunction, hemorrhage, diarrhea, rheumatoid arthritis, and cancers [ 48 ]. Our findings revealed that PLM inhibited inflammatory responses in MIA-induced osteoarthritis rats.…”

An Intervention Target for Myocardial Fibrosis: Autophagy

“…There was a study that reported that the left main coronary artery of rats was ligated for 1 h and then reperfused for 3 h. Administrating of phellinus linteus mycelium could alleviate myocardial damage through autophagic regulation, which the accompanying evidence was that caspase-3 and caspase-9 activation decreased, Bcl-2/Bax ratio increased, AMPK phosphorylation elevated, and Beclin-1 and p62 levels decreased. This study emphasized the enhancement of protective autophagy and inhibition of excessive autophagy to achieve autophagy balance [ 35 ]. The articles of this section are summarized in Table 1 .…”

Coherent apoptotic and autophagic activities involved in regression of chicken postovulatory follicles

“…Beclin1 and microtubule-associated proteins 1A/1B light chain 3B (LC3β) are key proteins regulating both autophagy and cell death. Moreover, sequestosome-1 (SQSTM1/p62) is a protein targeting the specific cargo of autophagy [ 17 ]. Beclin1 can also interact with the anti-apoptotic protein BCL2, where its binding state plays a key part in coordinating the cellular decision to undergo autophagy [ 18 ].…”