Zerumbone ameliorates the induced atherosclerosis-initiated inflammatory conditions through suppression of proinflammatory mediators and inflammatory cytokines

Hemn Hassan Othman; Heshu Sulaiman Rahman; Sherwan Hamasalih Omer; Syam Mohan; Mohammed Abdulabbas Hasan; Kawa Amin; Nagi A AL.Haj; Hareth Yahya Ahmed; Noordin Mohamed Mustapha

Articles

Abstract

Pharmacognosy Magazine,2021,17,75,419-427.

DOI:10.4103/pm.pm_549_20

Published:November 2021

Type:Original Article

Authors:

Author(s) affiliations:

Hemn Hassan Othman¹, Heshu Sulaiman Rahman², Sherwan Hamasalih Omer³, Syam Mohan⁴, Mohammed Abdulabbas Hasan⁵, Kawa Amin⁶, Nagi A AL.Haj⁷, Hareth Yahya Ahmed⁸, Noordin Mohamed Mustapha⁹
¹ Department of Microbiology and Pathology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Department of Pharmacology and Toxicology, College of Pharmacy, Sulaimaniyah, Republic of Iraq
² Department of Physiology, College of Medicine, University of Sulaimani, 46001 Sulaimaniyah; Department of Medical Laboratory Sciences, College of Health Sciences, Komar University of Science and Technology, Sarchinar District, Sulaimaniyah, Republic of Iraq
³ Department of Physiology, College of Medicine, University of Sulaimani, 46001 Sulaimaniyah, Republic of Iraq
⁴ Substance Abuse and Toxicology Research Center, Jazan University, Jazan, Saudi Arabia
⁵ Biology Science Department, College of Education for Women, Thi-Qar University, Thi-Qar, Republic of Iraq
⁶ Department of Microbiology, College of Medicine, University of Sulaimani, 46001 Sulaymaniyah, Republic of Iraq
⁷ Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen
⁸ Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
⁹ Department of Microbiology and Pathology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

Abstract:

Background: Zerumbone (ZER) is a naturally occurring monosesquiterpine and dietary compound from Zingiber zerumbet Smith, an edible ginger. It has been shown to possess anti-inflammatory activities. Inflammation plays an important role in all stages of atherosclerosis. However, little is known about ZER's anti-inflammatory role in atherosclerosis. 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.