Cardioprotective Potential of
                    <i>Fagonia arabica</i>
                    Phytochemicals Against Adrenaline-Induced Myocardial Infarction: Insights From Computational and Experimental Studies

doi:10.1177/11772719261502039

DOI: 10.1177/11772719261502039 ISSN: 1177-2719

Cardioprotective Potential of Fagonia arabica Phytochemicals Against Adrenaline-Induced Myocardial Infarction: Insights From Computational and Experimental Studies

Muhammad Imran Ali Khan, Imran Ahmad Khan, Asma Malik, Mahnoor Malik, Vajiha Khan, Abdul Rehman, Ahsan Anjum, Maliha Khalid Khan, Qasim Ali Ghauri, Muhammad Junaid, Qurat Ul Ain, Hafiza Hamed

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Background

Myocardial infarction (MI) remains a primary cause of cardiovascular death around the world; single-target conventional treatments remain inadequate and have adverse effects.

Objectives

To predict the cardioprotective potential of Fagonia arabica L. (Zygophyllaceae) against adrenaline-induced stress-related MI.

Design and Methods

A combined computational and experimental workflow was used. Independent validation was performed through transcriptomic analysis of the prioritized hub genes using clinical Gene Expression Omnibus (GEO) datasets and in vivo data from a rabbit model of adrenaline-induced cardiac injury. Male albino rabbits were orally administered a hydroethanolic F. arabica extract at doses of 100, 200, or 300 mg/kg/day for 14 days. The animals were challenged with adrenaline at 2 mg/kg subcutaneously on the 14th and 15th days. Serum cardiac markers, including CK-MB, LDH, and cardiac troponin T, were measured on the 16th day.

Results

A total of 147 overlapping targets were identified, including major hub nodes such as AKT1 and TNF, and the predictions indicated favorable interactions with seven lead phytochemicals. In-depth analysis of independent clinical GEO datasets (GSE66360 and GSE48060) using transcriptomic data showed that 20 hub genes among the prioritized genes were significantly differentially expressed in patients with myocardial infarction compared with controls. A 90% concordance in gene regulation was observed across the two cohorts. There was a significant increase in CK-MB, LDH, and troponin T levels following adrenaline injection compared with the control group.

Conclusion

The results of this in vivo study lend preliminary support to the cardioprotective potential of F. arabica extract. Along with the computational results and independent transcriptomic validation of predicted hub genes in clinical GEO datasets, these findings support the multitarget hypothesis involving i) myocardial injury, ii) inflammatory signaling, iii) oxidative stress, and iv) cardiomyocyte survival. However, these findings must be substantiated by further investigations, including direct target engagement and histopathological evidence of protection.