Nerolidol improves cardiac function in spontaneously hypertensive rats by inhibiting cardiac inflammation and remodelling associated TLR4/ NF-κB signalling cascade

• Published in: Food and chemical toxicology 2021-01, Vol.147, p.111837-111837, Article 111837
• Main Authors: Lin, Yueh-Min, Badrealam, Khan Farheen, Kuo, Wei-Wen, Lai, Pei Fang, Shao-Tsu Chen, William, Hsuan Day, Cecilia, Ho, Tsung-Jung, Viswanadha, Vijaya Padma, Shibu, Marthandam Asokan, Huang, Chih-Yang
• Format: Article
• Language: English
• Subjects: Angiotensin II - pharmacology; Animals; Cell Line; Dose-Response Relationship, Drug; Female; Fibrosis; Gene Expression Regulation - drug effects; Heart Diseases - metabolism; Heart Diseases - prevention & control; Hypertension; Inflammation; Inflammation - prevention & control; Male; Models, Molecular; Molecular Structure; Nerolidol; NF-kappa B - genetics; NF-kappa B - metabolism; Oxidative stress; Protein Conformation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sesquiterpenes - pharmacology; Toll-Like Receptor 4 - chemistry; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2020.111837

Toll-like receptor 4 (TLR4) is an important mediator of hypertension and AngII induced cardiac inflammation and remodelling. In this study, the potential of nerolidol to ameliorate hypertension induced cardiac injuries and the underlying mechanism of action was explored by using in vitro and in vivo models. The in vitro analysis was performed on AngII challenged H9c2 cells and their ability to overcome cardiac inflammation and cardiac remodelling effects was determined by evaluating TLR4/NF-κB signalling cascade using Western blot analysis and immunofluorescence. The results were further ascertained using in vivo experiments. Eighteen week old male rats were randomly allocated into different groups i.e. Wistar Kyoto (WKY) rats, hypertensive SHRs, SHRs treated with a low-dose (75 mg/kg b.w) and high-dose of nerolidol (150 mg/kg b.w) and SHRs treated with captopril (50 mg/kg b.w) through oral gauge and finally analysed through echocardiography, histopathological techniques and molecular analysis. The results show that nerilodol target TLR4/NF-κB signalling and thereby attenuate hypertension associated inflammation and oxidative stress thereby provides effective cardioprotection. Echocardiography analysis showed that nerolidol improved cardiac functional characteristics including Ejection Fraction and Fractional Shortening in the SHRs. Collectively, the data of the study demonstrates nerolidol as a cardio-protective agent against hypertension induced cardiac remodelling. [Display omitted]