Nerolidol attenuates cardiac hypertrophy and fibrosis in mice: Modulation of collagen type I, apoptotic and endothelial gene expression
نویسندگان
1 Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
2 Department of Experimental and Clinical Pharmacology, University of Minnesota, College of Pharmacy, 3-120 Weaver Densford Hall, 308 Harvard St SE, Minneapolis, MN 55455, United States
3 Department of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan
4 Faculty of Pharmacy, The University of Lahore, Lahore, Pakistan
5 Division of Endocrinology, Diabetes and Metabolism, New York University, Grossmann School of Medicine, New York, USA
6 Department of Experimental and Clinical Pharmacology, University of Minnesota, College of Pharmacy, 3-120 Weaver Densford Hall, 308 Harvard St SE, Minneapolis, MN 55455, United States
doi
10.22038/ijbms.2026.92642.20001چکیده
Objective(s): Cardiac hypertrophy is a major pathological feature of cardiovascular disease worldwide. The beneficial effects of terpenes on cardiovascular diseases are well known. In the current study, the cardioprotective effects of nerolidol (NRD), a sesquiterpene alcohol, were evaluated using an isoproterenol (ISO) induced cardiac hypertrophy mice model. Materials and Methods: This study was performed by using the chronic subcutaneous infusion model of ISO. Male mice were administered NRD (100 mg/kg) orally for 7 days. On the 8th day with the continuation of NRD dosing, mice received subcutaneous (SC) with ISO (10 mg/kg) for the next 14 days. Cardiac functions, including ejection fraction, cardiac output, and fractional shortening were evaluated by trans-thoracic echocardiography, one day after the final treatment. Then, animals were euthanized and hearts were isolated. The mRNA and protein expressions of cardiac hypertrophy, apoptosis, and fibrosis markers in mice hearts were determined. Results: Results showed an increased heart-to-body weight ratio. NRD reduced cardiac hypertrophy by down-regulating the hypertrophic (ANP), apoptotic (Bax/Bcl-2), and fibrotic (Col1a1) markers and prevented cardiac remodeling by up-regulating expression of endothelial nitric oxide synthase (eNOS) and anti-apoptotic (Bcl-xL) protein compared to ISO-treated mice. Combining PCR and western blotting data results demonstrated that NRD reverted the ISO-induced cardiac hypertrophy. Conclusion: These findings suggest that NRD prevents ISO-induced cardiac hypertrophy possibly by elevating the levels of eNOS and Bcl-xL and reducing expression of hypertrophic, apoptotic, and fibrotic markers. Thus, NRD may be used to treat ISO-induced cardiac hypertrophy.
