J Appl Biomed 19:142-148, 2021 | DOI: 10.32725/jab.2021.014

Protective effect of sinomenine on isoproterenol-induced cardiac hypertrophy in mice

Le Li1, *, Pu Fang2, Jiekun Chen1, Cailing Zhang3, Houquan Tao4
1 Zhejiang University of Technology, School of Pharmacy, Hangzhou, 310014, PR China
2 Janssen Pharmaceuticals, Spring House, PA 19477, USA
3 Hangzhou Zhijiang College, Hangzhou, 310023, PR China
4 Lab center of Zhejiang Province People's Hospital, Hangzhou, 310014, PR China

To study the effect of sinomenine (Sin) on isoproterenol (Iso, β-agonist)-induced cardiac hypertrophy (CH), we set up four mouse groups: control, Iso model, Iso+metoprolol (Met, β blocker) 60 mg/kg and Iso+Sin 120 mg/kg. CH was induced by Iso (s.c. for 28 days) in mice, and Sin or Met were orally administered by gavage for 28 days in total. Left ventricular diastolic anterior wall thickness (LVAWd), left ventricular diastolic posterior wall thickness (LVPWd), left ventricular ejection fraction (LVEF), and short axis shortening (FS) were measured by echocardiography. Malondialdehyde (MDA) and total superoxide dismutase (T-SOD) were measured by commercial kits. Lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were measured by ELISA kits. Histological changes were observed using hematoxylin-eosin (HE) and Masson staining. Protein level of nuclear transcription factor-kappa B (NF-κB) was detected by immunohistochemistry. Compared with the control group, LVAWd, Left ventricular weight index (LVWI) and myocardial fibrosis of the Iso model group significantly increased, as well as NF-κB, LDH, MDA, TNF-α, and IL-1β levels. However, the activity of T-SOD decreased. Compared with the Iso model group, LVWI of Iso model+Sin or Iso model+Met group was improved, LVAWd, LVPWd and myocardial fibrosis decreased, and NF-κB, LDH, MDA, TNF-α and IL-1β levels decreased. T-SOD activity also increased. This study reveals that Sin inhibits the activation of NF-κB, lowers the levels of TNF-α and IL-1β, has anti-oxidative stress effect and inhibits myocardial inflammation in mouse heart, thereby demonstrating its efficacy in preventing Iso induced CH.

Keywords: Cardiac hypertrophy; Echocardiography; Isoproterenol; Sinomenine; TNF-α; IL-1β
Grants and funding:

This work was supported by project grants from the Natural Science Foundation of Zhejiang province in China (LY13H310005) and in part by project grants from the Key Natural Science Foundation of Zhejiang University of Technology in China (X1168117).

Conflicts of interest:

All authors declare that they have no conflict of interests.

Received: January 20, 2019; Revised: April 21, 2021; Accepted: May 12, 2021; Prepublished online: May 27, 2021; Published: September 17, 2021  Show citation

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Li L, Fang P, Chen J, Zhang C, Tao H. Protective effect of sinomenine on isoproterenol-induced cardiac hypertrophy in mice. J Appl Biomed. 2021;19(3):142-148. doi: 10.32725/jab.2021.014. PubMed PMID: 34907757.
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