Abstract
Oxytropis falcata Bunge is a plant used in traditional Tibetan medicine, with reported anti-inflammatory and antioxidants effects and alleviation of myocardial ischemia reperfusion injury (MIRI). However, the underlying mechanism against MIRI and the phytochemical composition of O. falcata are vague. One fraction named OFF1 with anti-MIRI activity was obtained from O. falcata, and the chemical constituents were identified by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS). The potential targets and signaling pathways involved in the action of O. falcata against MIRI were predicted by network pharmacology analysis, and its molecular mechanism on MIRI was determined by in vitro assays. The results revealed that flavonoids are the dominant constituents of OFF1. A total of 92 flavonoids reported in O. falcata targeted 213 potential MIRI-associated factors, including tumor necrosis factor (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2), and the NF-κB signaling pathway. The in vitro assay on H9c2 cardiomyocytes subjected to hypoxia/reoxygenation injury confirmed that the flavonoids in OFF1 reduced myocardial marker levels, apoptotic rate, and the inflammatory response triggered by oxidative stress. Moreover, OFF1 attenuated MIRI by downregulating the ROS-mediated JNK/p38MAPK/NF-κB pathway. Collectively, these findings provide novel insights into the molecular mechanism of O. falcata in alleviating MIRI, being a potential therapeutic candidate.
Highlights
Ischemic heart disease is a highly prevalent threat worldwide, with a mortality rate of16% [1]
H9c2 myoblasts, a cell model used as an alternative for cardiomyocytes, were treated with fractions from the O. falcata extract eluted with different ratios of petroleum ether and ethyl acetate from a silica gel column and subjected to H/R to explore the fraction with anti-myocardial ischemia reperfusion injury (MIRI) activity (Figure S1)
H9c2 myoblasts, a cell model used as an alternative for cardiomyocytes, were treated with fractions from the O. falcata extract eluted with different ratios of petroleum 3etohf e20r and ethyl acetate from a silica gel column and subjected to H/R to explore the fraction with anti-MIRI activity (Figure S1)
Summary
Ischemic heart disease is a highly prevalent threat worldwide, with a mortality rate of16% [1]. Ischemic heart disease is a highly prevalent threat worldwide, with a mortality rate of. The timely restoration of myocardial blood flow can reduce the size of the ischemic myocardium, revascularization may aggravate the functional and structural impairment of the myocardium, thereby resulting in myocardial ischemia reperfusion injury (MIRI) [2,3]. Traditional Chinese medicine (TCM) has been widely used in China for thousands of years, and it has better therapeutic effects on various complicated disorders with few side effects [10]. Numerous clinical and experimental studies have demonstrated that Chinese medical prescriptions and herbal medicine extracts may play a therapeutic role in MIRI by exerting an anti-inflammatory and anti-apoptotic effect, maintaining calcium homeostasis, providing the clearance of oxygen free radicals, and avoiding platelet aggregation [11–14]. TCM extracts or mixtures possess more effective pharmacological activities than purified compounds due to their multiple components and targets [15]. The cardioprotective effects of TCM may provide a therapeutic alternative for MIRI
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