Glycyrrhizic acid inhibits myeloid differentiation of hematopoietic stem cells by binding S100 calcium binding protein A8 to improve cognition in aged mice

Xue Gong; Haitao Shen; Liuling Guo; Ce Huang; Tingting Su; Hao Wang; Shengyu Feng; Shanshan Yang; Fenjiao Huo; Haifeng Liu; Jianbo Zhu; Jian-Kang Zhu; Hongbin Li; Hailiang Liu

doi:10.1186/s12979-023-00337-9

Glycyrrhizic acid inhibits myeloid differentiation of hematopoietic stem cells by binding S100 calcium binding protein A8 to improve cognition in aged mice

Immun Ageing. 2023 Mar 11;20(1):12. doi: 10.1186/s12979-023-00337-9.

Authors

Xue Gong^#¹, Haitao Shen^#¹, Liuling Guo², Ce Huang², Tingting Su¹, Hao Wang², Shengyu Feng², Shanshan Yang², Fenjiao Huo², Haifeng Liu³, Jianbo Zhu¹, Jian-Kang Zhu⁴, Hongbin Li⁵, Hailiang Liu^{6

7

8}

Affiliations

¹ Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, Shihezi, 832003, China.
² Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China.
³ China Colored-Cotton (Group) Company, Ltd, Urumqi, 830000, Xinjiang, China.
⁴ Institute of Advanced Biotechnology, Southern University of Science and Technology, Shenzhen, 518055, China.
⁵ Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, Shihezi, 832003, China. lihb@shzu.edu.cn.
⁶ Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, Shihezi, 832003, China. hailiang_1111@tongji.edu.cn.
⁷ Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China. hailiang_1111@tongji.edu.cn.
⁸ Institute of Advanced Biotechnology, Southern University of Science and Technology, Shenzhen, 518055, China. hailiang_1111@tongji.edu.cn.

^# Contributed equally.

Abstract

Background: Glycyrrhizic acid (GA), a saponin compound often used as a flavoring agent, can elicit anti-inflammatory and anti-tumor effects, and alleviate aging. However, the specific mechanism by which GA alters immune cell populations to produce these beneficial effects is currently unclear.

Results: In this study, we systematically analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice. Our in vivo results show that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin^-CD117⁺ hematopoietic stem cells toward lymphoid lineages, especially CD8⁺ T cells. Moreover, GA inhibited differentiation of CD4⁺ T cells and myeloid (CD11b⁺) cells by binding to S100 calcium-binding protein 8 (S100A8) protein. Overexpression of S100A8 in Lin^- CD117⁺ hematopoietic stem cells enhanced cognition in aged mice and the immune reconstitution of severely immunodeficient B-NDG (NOD.CB17-Prkdcscid/l2rgtm1/Bcgen) mice.

Conclusions: Collectively, GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice.

Keywords: Cognitive level; Glycyrrhizic acid (PubChem CID:14,982); Hematopoietic stem cells; Myeloid lineage; S100A8.

Abstract

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