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Diet and lifestyle play a crucial role in the progress of some cardiovascular disorders (CVDs). Rising interest in natural products and their pharmacological investigations witnessed therapeutic potential against CVDs. Caffeic acid (CA) is an organic composite hydroxycinnamic acid derivative classified among phenolics. It is a secondary metabolite biosynthesized in all plant species in the form of ester conjugates. The reported pharmacological activities of CA are neuroprotective, cardioprotective, hypoglycemic, antioxidant, and immunomodulatory properties. This work is aimed to examine the outcome of CA in atherogenic diet- (Ath-) induced rat model on lipid profile changes and endothelium function. The method involves a study duration of 35 days utilizing (n = 6) male Wistar rats (180–200 g) that were fed either normal chow or Ath. Study groups are given (i) normal chow diet, (ii) Ath, (iii) Ath + CA (25 or 50 mg/kg, p.o.), (iv) normal chow diet + CA (50 mg/kg, p.o.), and (v) Ath + Atorvastatin (ATORVA) (5 mg/kg, p.o.). Blood samples were collected at the end of the study to measure serum lipid profile, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and tissue oxidative stress level. Hemodynamic parameters and aorta staining were performed. CA treatment ameliorated lipid profile and significantly reduced the oxidative stress level. Aorta staining examination revealed a marked reduction of the atherosclerotic lesions. These findings suggested that CA is an effective treatment approach for preventing atherosclerotic lesion progression attributed to protection against oxidative stress and various enzymatic activities in the Ath model.

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