Recent global temperature increases have led to climate changes associated with a rising number of heat-related illness [1, 2] As the largest developing country in the world, China has suffered increasing temperatures annually in recent years [3].
Notably, this year, exacerbated by the El Niño phenomenon, China witnessed an unprecedented peak in high-temperature weather events. Consequently, the incidence and mortality of heat-related injuries and illnesses, particularly heat stress (HS), has significantly affected human health and survival [2]. Exposure to high temperatures imposes stress on biological and behavioral functions, potentially leading to physiological disorders. Prolonged exposure to high temperatures increases the risk of heat-related illnesses [4]. In severe cases, it can lead to multiple organ dysfunction syndromes (MODS) or even death [5, 6]. Extremely high-temperature conditions pose substantial risks to cardiovascular health, especially in individuals with preexisting heart conditions [7].
In heat-related reactions, HS serves as an environmental factor that can trigger the production of reactive oxygen species (ROS) [8, 9]. HS can directly induce cellular toxicity and some studies have suggested that HS-induced cytotoxicity may be partially attributable to oxidative stress. Oxidative stress is a pivotal contributor to HS-induced apoptosis [10, 11]. Previous studies have underscored the critical role of oxidative stress in HS-induced apoptosis [12].
When the expression of intracellular ROS becomes imbalanced, disrupting the equilibrium between production and elimination, cells experience oxidative stress. Although a moderate oxidative stress level does not harm normal bodily functions, excessive ROS generation overwhelms the cellular antioxidant defense system, leading to DNA damage and lipid degradation. Consequently, normal cellular functions are compromised [13]. Accumulation of ROS and oxidative stress are closely associated with HS-induced apoptosis [14, 15]. Numerous studies have indicated the pivotal roles of oxidative stress and ROS generation in the pathogenesis of myocardial ischemic injury [12, 16, 17], with recent findings linking ROS overproduction to cardiomyocyte apoptosis [18]. Furthermore, emerging evidence indicates that HS causes excessive ROS production and disruption of the antioxidant system, particularly in the heart, which is essential for maintaining physiological homeostasis [19, 20]. Studies have shown that HS can adversely affect the structure and function of cardiomyocytes, resulting in damage to myocardial contractility and systemic blood circulation [17, 21]. Furthermore, investigations have shown that HS significantly elevates intracellular ROS levels and triggering apoptosis [22]. Several studies have reported mitochondrial cristae disruption, apoptosis, and necrosis in cardiomyocytes following exposure to HS [4, 23]. Previous studies have demonstrated that heat injury disrupts the balance between oxidative and antioxidant systems in cardiomyocytes [4]. Nevertheless, comprehensive understanding of the defense mechanisms involved in HS-mediated cardiac protection remains incomplete, with limited exploration of strategies for mitigating HS-induced heart injury [16]. Consequently, addressing the challenges posed by thermal injuries in high-temperature environments remains a pressing public health concern.
Paeoniflorin (PF), a major monoterpene glycoside, was Isolated from Paeonia lactiflora Palls, a traditional Chinese medicine [24]. PF has beneficial effects on the cardiovascular system, including hypertension, atherosclerosis, and bleeding [25]. PF possesses various pharmacological properties including anti-inflammatory, immunomodulatory, and antioxidant effects. PF effectively diminishes oxidative stress pathways by reducing the levels of lipid peroxidation products malondialdehyde (MDA) and ROS, while concurrently increasing glutathione (GSH) content [25–27]. Recent studies have shown that PF ameliorates oxidative stress injury through a redox homeostasis mechanism that is likely associated with increased activity of antioxidant enzymes such as superoxide dismutase (SOD) [28]. Previous studies have indicated that PF may mitigate oxidative stress injury by enhancing the in vivo activity of SOD and other antioxidant enzymes, thus protecting against the harmful effects of free oxygen radicals [29]. However, the effects of PF on HS-mediated oxidative stress and apoptosis in cardiomyocytes remain unexplored.