Sanguinarine promotes healthspan and innate immunity through a conserved mechanism of ROS-mediated PMK-1/SKN-1 activation

Fang Liu; Haijuan Wang; Xinting Zhu; Nian Jiang; Feng Pan; Changwei Song; Chunbo Yu; Changyan Yu; Ying Qin; Jing Hui; Sanhua Li; Yi Xiao; Yun Liu

doi:10.1016/j.isci.2022.103874

Sanguinarine promotes healthspan and innate immunity through a conserved mechanism of ROS-mediated PMK-1/SKN-1 activation

iScience. 2022 Feb 4;25(3):103874. doi: 10.1016/j.isci.2022.103874. eCollection 2022 Mar 18.

Authors

Fang Liu^{1

2}, Haijuan Wang^{1

3}, Xinting Zhu^{1

2}, Nian Jiang^{1

3}, Feng Pan^{1

3}, Changwei Song^{1

3}, Chunbo Yu², Changyan Yu^{1

3}, Ying Qin^{1

3}, Jing Hui^{1

3}, Sanhua Li^{1

3}, Yi Xiao^{1

3}, Yun Liu^{1

2

3}

Affiliations

¹ Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, GZ 563000, China.
² College of Basic Medicine, Zunyi Medical University, Zunyi, GZ 563000, China.
³ Institute of Life Sciences, Zunyi Medical University, Zunyi, GZ 563000, China.

Abstract

The longevity of an organism is influenced by both genetic and environmental factors. With respect to genetic factors, a significant effort is being made to identify pharmacological agents that extend lifespan by targeting pathways with a defined role in the aging process. Sanguinarine (San) is a benzophenanthridine alkaloid that exerts a broad spectrum of properties. In this study, we utilized Caenorhabditis elegans to examine the mechanisms by which sanguinarine influences aging and innate immunity. We find that 0.2 μM sanguinarine extends healthspan in C. elegans. We further show that sanguinarine generates reactive oxygen species (ROS), which is followed by the activation of PMK-1/SKN-1pathway to extend healthspan. Intriguingly, sanguinarine increases resistance to pathogens by reducing the bacterial burden in the intestine. In addition, we also find that sanguinarine enhances innate immunity through PMK-1/SKN-1 pathway. Our data suggest that sanguinarine may be a viable candidate for the treatment of age-related disorders.

Keywords: Biological sciences; Immunology; Molecular biology.