The accumulation of the antineoplastic drug Dox causes irreversible impairment of the heart, which limits its use [26]. The clinical cardiotoxic effects of Dox are manifested by the deterioration of cardiac functions, including reduced left ventricular ejection fraction, ROS accumulation, fibrosis, calcium overload, and apoptosis. The mechanism is mainly attributed to nuclear and mitochondrial dysfunction, resulting in apoptosis, necrosis, fibrosis, and autophagy [27]. Zebrafish are highly similar to humans in terms of cardiovascular functions and morphology and are a well-established in vivo model for studying ventricular dysfunction and congestive heart diseases. The hearts of zebrafish embryos can be directly observed using a simple bright-field microscope, which facilitates the study of morphological changes in the heart induced by Dox cardiotoxicity. Thus, zebrafish embryos were used to establish a model of Dox-induced heart injury.
Lipids perform various important biological functions, including energy conversion, material transport, cell development and differentiation, information recognition and transmission, and apoptosis. Furthermore, polyunsaturated lipids possess diverse biological activities, such as cardiovascular protective activity, pro-angiogenic activity, anti-inflammatory activity [28], and hepatoprotective activity [29]. FAs, the key components of the cell membrane and complex lipids, exert cardioprotective effects, and studies performed at the National Heart, Lung, and Blood Institute have shown that alpha-linolenic acid and linoleic acid can reduce the risk of heart disease by 40% and 70%, respectively [30], and endogenous n-3 PUFAs prevents dilated cardiomyopathy via orchestrating gene expression, protein phosphorylation, and lipid metabolism [31].
Lipids have been extensively studied, however, the function of lipids in Chinese herbs has been understudied, and fewer studies have been performed. The lipid component of forsythia has been reported as a basis for active plant growth, development, and metabolism. Lipids in natural products are mainly concentrated in pregnenolone and polyethylene glycol [32]. Lipids in egg yolk contain platelet-activating factor inhibitors, which increase their nutritional value in the prevention of cardiovascular diseases and have anti-atherosclerotic properties [33]. Soybean lipids can effectively inhibit platelet aggregation in the vascular endothelium and improve hemodynamic levels, reduce blood viscosity, lower the levels of inflammatory factors in the body, and improve the activity of regulatory factors, thereby improving blood irrigation in infarcted lesions [34]. Therefore, PQ, SOYA, and YOLK lipids were extracted in the present study. Based on the traditional efficacy and modern pharmacological characteristics of PQ, FA (18:4) standards, PQL, SOL, and YOL were systematically evaluated and compared for anti-Dox cardiotoxicity, and the results showed that the lipid extracts of PQ exerted positive effects, whereas the SOL and YOL did not produce marked effects. Furthermore, differences among the PQL, SOL and YOL were investigated. According to the lipidomics results, the differential metabolites between these three lipid groups showed similar PA and DG contents, with PA accounting for 3%, 1%, and 0% in the PQL, SOL, and YOL, respectively, whereas DG accounted for 9%, 4%, and 1% in the PQL, SOL, and YOL, respectively. FA content varied greatly, accounting for 28%, 0%, and 5% in the PQL, SOL, and YOL, respectively. The screening result indicated that 216 differential metabolites with VIP > 1 were obtained. The VIP value of the FA (18:4) was the highest among the differential metabolites, which accounted for 27.265% in the PQL and 0.005% and 0.002% of the SOL and YOL, respectively.
In addition to ginsenosides and polysaccharides, FAs in PQ may play an essential role in the overall beneficial effects. The FA (18:4) has been previously identified in algae [35] and the leaves of Tabebuia aurea (Silva Manso) [36]. However, a few studies have explored its activity. Based on the lipidomics analysis and the results of this activity assay, it is evident that the highest PUFA content was found in the PQL, which exerted an anti-Dox cardiotoxic effect. The contents of SOL and YOL were low in PUFAs and had no significant anti-Dox cardiotoxic effects. Thus, it is evident that PQ PUFAs have great potential in drug development. The anti-Dox cardiotoxic activity of the differential metabolite FA (18:4) was validated and found to have significant anti-Dox cardiotoxic effects, which reduced cardiac ROS production caused by Dox cardiotoxicity.
The high content of PUFAs in the PQL has unique advantages in terms of physiological functions and biological activities, and these PUFAs have been confirmed to have cardioprotective effects. However, their production is still rare. Their exploitation is promising and has rich research value. However, their activity was not studied in detail in the present study, and their mechanism of action needs in-depth exploration.