Inonotus obliquus (Ach. ex Pers.) Pilát aqueous extract alleviates acute cold exposure/rewarming-induced myocardial injury by regulating mitochondrial dynamics via liver kinase B1/adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator-1 alpha signaling pathway activation.

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Citation abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Acute cold exposure affects the cardiovascular system substantially. Inonotus obliquus (Ach. ex Pers.) Pilát (IO), commonly referred to as "Chaga" in Russian traditional medicine, is a fungus that primarily parasitizes birch trees in cold climate regions. IO is extensively employed in Russian folk medicine for the treatment of cardiovascular diseases, including hypertension, hyperlipidemia, atherosclerosis, and symptoms of coronary heart disease. It is purported to holistically modulate cardiovascular function. However, despite the widespread use of I. obliquus aqueous extract (IOE), its cardioprotective effects against acute cold exposure/rewarming (ACE/R)-induced myocardial injury are yet to be elucidated.

AIM OF THE STUDY: To assess the cardioprotective efficacy of IOE against ACE/R-induced myocardial injury in rats and to elucidate its underlying mechanism of action.

MATERIALS AND METHODS: An ACE/R injury model was established by exposing rats to a temperature of -15 °C for 6 h, and then rewarming them to a temperature of 24 °C for 12 h. The rats were administered IOE (300 and 600 mg/kg) or 0.5% CMC-Na (vehicle control) via the intragastric route for 7 consecutive days prior to acute cold exposure. The ACE/R model was established 1 h after the final administration. Cardiac function, hemorheological parameters, myocardial histopathology, and serum levels of myocardial injury markers were assessed to evaluate the cardioprotective efficacy of IOE against ACE/R. Subsequently, in vivo transcriptomic analyses were performed to elucidate the underlying mechanism of IOE. To assess the expression levels of proteins and genes related to mitochondrial dynamics, mitochondrial function, energy metabolism, and the LKB1/AMPK/PGC-1α signaling pathway, western blotting and qRT-PCR were performed.

RESULTS: IOE significantly attenuated ACE/R-induced hemorheological abnormalities, cardiac dysfunction, and myocardial injury. Transcriptomic sequencing analyses revealed the cardioprotective effects of IOE to be potentially mediated via regulation of mitochondrial dynamics and function. Western blotting and qRT-PCR analyses further confirmed that IOE significantly upregulated the expression of proteins and genes associated with cellular energy metabolism, mitochondrial dynamics, and the LKB1/AMPK/PGC-1α signaling pathway in myocardial tissues.

CONCLUSION: These findings demonstrate that IOE alleviates ACE/R-induced myocardial injury in rats by activating the LKB1/AMPK/PGC-1α signaling pathway, thereby modulating mitochondrial dynamics in cardiomyocytes. However, the present study exclusively assessed the prophylactic effects of IOE via pretreatment prior to ACE/R exposure, while the therapeutic potential of post-injury IOE administration remains to be determined. Furthermore, given the inherent variability of the constituents of natural products, further studies need to be carried out using multiple batches of extracts to validate these findings.