Unveiling the cardiopreventive effect of the parasitic weed Orobanche crenata Forsk. extract against isoproterenol-induced myocardial infarction in rats

Abstract

This study explored the preventive effects of Orobanche crenata extract (OCE) against myocardial infarction. LC-MS/MS profiling revealed the presence of 27 metabolites, including phenolic acids, flavonoids and phenylethanoid glycosides. In vitro, OCE exhibited significant antioxidant activity via DPPH and ABTS assays, attributed to its noteworthy TPC = 48.02 mg GAE/g and TFC = 20.83 mg QE/g. In vivo, rats were subjected to isoproterenol injections (29th and 30th days), following pretreatments with OCE (20 and 60 mg/kg) or Pidogrel (Pid 2 mg/kg). Most of the changes were dose-dependent, with a pronounced impact at 60 mg/kg compared to 20 mg/kg. Compared to ISO-treated group, the pretreatment with OCE at (60 mg/kg bw) reduced CK-MB, LDH, AST and cTn-I by 45 %, 43.5 %, 48.3 % and 67 %, respectively (p < 0.0001) and normalized the lipid profile, by alleviating LDL-C levels by 59 % and enhancing HDL-C levels by 67 % (p < 0.01). OCE promoted antioxidant enzymes (CAT, SOD and GPX) by 53 %, 168 % and 209 %, respectively, reducing lipid peroxidation by 65 % (p < 0.0001). Additionally, the findings revealed the inhibitory activity of the extract against ACE and the reduction of plasmatic fibrinogen level, indicating an anti-remodeling activity. Moreover, Molecular docking revealed strong binding affinities (−7 and −9.8 kcal/mol) of orobanchoside, isorhamnetin rhamnosyl glucoside, crenatoside, quercetin coumaroyl glucoside and apigenin with cardiotoxicity related proteins: ACE, TGF-β1, PDI, MAPK14 and CaMK II. Overall, OCE represents a potential source of cardioprotective agents, supported by its richness in phenolic compounds, capable of reducing cardiac damage by countering oxidative stress, inflammation, fibrosis, calcium overload, cardiac remodeling.