Zerumbone Ameliorates the Induced Atherosclerosis‑Initiated Inflammatory Conditions through Suppression of

Objectives: This study investigated the anti‑inflammatory effect of ZER in mitigating the formation and development of early atherosclerotic lesions in rabbits fed with high‑cholesterol diet. Materials and Methods: A total of 72 New Zealand White rabbits were used in two experimental studies carried out at different times. The first experiment was carried out to investigate the prophylactic effects of ZER in preventing premature atheromas plaque formation. In contrast, the second experiment was carried out to assess the therapeutic efficacy of ZER in reducing atheromas lesion progression and dissemination. Results: ZER significantly (P < 0.05) reduced the inflammatory response through suppression of proinflammatory mediators (nuclear factor kappa‑light‑chain‑enhancer of activated B‑cells, inducible nitric oxide synthase, and cyclooxygenase‑2), which leads to decrease in the secretion of inflammatory cytokines (tumor necrosis factor alpha, interleukin [IL]‑6, IL‑1, and IFN‑γ) evaluated by western blotting and enzyme immunoassay techniques, respectively. Conversely, suppression and reduction of inflammatory mediators then contribute to minimizing macrophages recruitment, which is evident by immunohistochemistry and immunofluorescent assays of regulation of ACE2 and morphogenesis 11 (RAM‑11). In addition, ZER significantly (P < 0.05) reduces the expression of RAM‑11 in the intimal plaque in all supplemented and treated groups in a dose‑dependent manner, which is much profound in the prophylactic trial. Conclusion: The results of the study clearly concluded that ZER is an anti‑inflammatory agent alone as a prophylactic measure or in combination with simvastatin as a remedy. In effect, dietary consumption of ZER can be viewed as beneficial in preventing and attenuating early atherosclerosis.