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Crocin attenuates isoprenaline-induced myocardial fibrosis by targeting TLR4/NF-κB signaling: connecting oxidative stress, inflammation, and apoptosis

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Abstract

Crocin is isolated from saffron and has multiple activities. There are many reports on its beneficial effects for cardiovascular disease, but crocin’s effects on anti-myocardial fibrosis have not yet been reported. This study investigated crocin’s effects and potential mechanisms on isoproterenol (ISO)-induced myocardial fibrosis (MF) in mice. Mice were infused intraperitoneally with crocin with concurrent ISO subcutaneous injections over 2 weeks. Electrocardiography, cardiac weight index (CWI), hydroxyproline content, and heart morphology changes were observed. Administration of crocin markedly decreased heart rate, J-point elevation, QRS interval, CWI, and hydroxyproline content in the myocardial tissues, and improved heart pathologic morphology. Versus the control group, the ISO group showed an increase in lactate dehydrogenase and creatine kinase activities and malondialdehyde content. Meanwhile, superoxide dismutase, catalase, and glutathione contents decreased in the ISO group; crocin caused a significant reduction in oxidative stress levels in ISO-induced MF. ISO led to a significant increase in interleukin-1 and -6 and tumor necrosis factor-α in addition to nuclear factor kappa B (NF-κB) (p65) and toll-like receptor (TLR) 4 expressions. Crocin treatment suppressed these inflammatory cytokine expressions. Moreover, crocin treatment caused a significant decrease in connective tissue growth factor and transforming growth factor-β1 mRNA levels in addition to a decrease in B cell lymphoma-2, Bcl-2-associated X protein, caspase-3, and cleaved caspase-3 expressions. Crocin has a protective effect on ISO-induced MF, which may be associated with the TLR4/NF-κB (p65) signal transduction pathway.

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Funding

This work was supported by the Research Foundation of Administration of Traditional Chinese Medicine of Hebei Province, China (No. 2015030 and 2019081), Natural Science Fund of Education Department of Hebei Province (ZD 2018038 and ZD 2016091).

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Authors and Affiliations

  1. School of Basic Medicine, Hebei University of Chinese Medicine, 6 Xingyuan Road, Shijiazhuang, 050200, Hebei, People’s Republic of China

    Weiyue Jin, Yurun Xue, Xuan Zhang, Zhihong Ma, Shengjiang Guan & Ziliang Li

  2. School of Pharmacy, Hebei University of Chinese Medicine, 6 Xingyuan Road, Shijiazhuang, 050200, Hebei, People’s Republic of China

    Yuanyuan Zhang, Xue Han & Li Chu

  3. Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, 050011, Hebei, China

    Shijiang Sun, Jie Cheng & Shengjiang Guan

  4. Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, 050011, Hebei, China

    Xi Chu

  5. Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, 050200, Hebei, China

    Li Chu

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  1. Weiyue Jin
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Contributions

WJ conducted the study design, collected the data, and drafted the manuscript. YZ and YX carried some experimental procedures and acquired the data. XH and XZ provided data analysis and corrected the manuscript. ZM and SS participated in the design and coordinated of the experiments. XC and JC helped design the study and drafted the manuscript. SG, ZL, and LC carried out the study design, analyzed, and interpreted the data. All authors read and approved the manuscript.

Corresponding authors

Correspondence to Shengjiang Guan, Ziliang Li or Li Chu.

Ethics declarations

All of the mouse experiments were approved by the Institutional Animal Experimental Ethics Committee of Hebei University of Chinese Medicine (Shi jiazhuang, China). All of the experimental procedures were performed in compliance with the protocols and ethical regulations approved by the Institutional Animal Experimental Ethics Committee of Hebei University of Chinese Medicine (Shi jiazhuang, China).

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The authors declare that they have no conflict of interest.

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Jin, W., Zhang, Y., Xue, Y. et al. Crocin attenuates isoprenaline-induced myocardial fibrosis by targeting TLR4/NF-κB signaling: connecting oxidative stress, inflammation, and apoptosis. Naunyn-Schmiedeberg's Arch Pharmacol 393, 13–23 (2020). https://doi.org/10.1007/s00210-019-01704-4

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