Lycorine ameliorates isoproterenol-induced cardiac dysfunction mainly via inhibiting inflammation, fibrosis, oxidative stress and apoptosis

被引:29
作者
Wu, Ji [1 ]
Fu, Yang [1 ]
Wu, Ying-xing [1 ]
Wu, Zu-xiang [1 ]
Wang, Zhen-hua [1 ]
Li, Ping [1 ]
机构
[1] Nanchang Univ, Dept Cardiovasc Med, Affiliated Hosp 2, 1 Minde Rd, Nanchang 330006, Jiangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
Heart failure; cardiac dysfunction; isoproterenol; lycorine; alkaloid; INDUCED HEART-FAILURE; CELL-PROLIFERATION; CANCER; AKT; MIGRATION; INVASION; PATHWAY; GROWTH;
D O I
10.1080/21655979.2021.1967019
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Alleviating cardiac dysfunction improves the prognosis of heart failure patients. Lycorine is an alkaloid with several beneficial biological properties. Here, we used mice to evaluate the effect of lycorine on cardiac dysfunction elicited by isoproterenol. Mice were divided into four groups: control, lycorine, isoproterenol, and isoproterenol + lycorine. Mice in the combined group were treated daily with 10 mg/kg isoproterenol intraperitoneally for 2 weeks and 5 mg/kg lycorine was given simultaneously intraperitoneally for 4 weeks. Cardiac structure and function were assessed by echocardiography, hematoxylin and eosin staining, and Masson's trichrome staining. Isoproterenol-induced cardiac dysfunction and histopathological injury that was significantly improved by treatment with lycorine. Western blotting and the quantitative real-time polymerase chain reaction were used to explore the molecular mechanisms of these effects. Levels of the inflammatory cytokines, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha, were increased by treatment with isoproterenol; these increases were significantly reduced by lycorine, with involvement of the NF-kappa B signaling pathway. The fibrotic factors, collagen I and collagen III, were increased by isoproterenol and decreased by treatment with lycorine through inhibiting activation of the Smad signaling pathway. In addition, lycorine alleviated oxidative stress as evidenced by a reduction in total reactive oxygen species in the isoproterenol + lycorine group compared to the isoproterenol group. Lycorine exerted an anti-apoptotic effect as evidenced by upregulating Bcl-2 and downregulating Bax. Overall, our findings demonstrate that lycorine protects against cardiac dysfunction induced by isoproterenol by inhibiting inflammation, fibrosis, oxidative stress, and apoptosis.
引用
收藏
页码:5583 / 5594
页数:12
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