Xiaoyaosan (Tiaogan-Liqi therapy) protects peritoneal macrophages from corticosterone-induced stress by regulating the interaction between glucocorticoid receptor and ABCA1

Mingtai Chen; Ruolan Huang; Wenjun Fu; Lijun Ou; Ling Men; Zhong Zhang; Shudong Yang; Qiang Liu; Jienan Luan

doi:10.21037/atm-20-6505

Xiaoyaosan (Tiaogan-Liqi therapy) protects peritoneal macrophages from corticosterone-induced stress by regulating the interaction between glucocorticoid receptor and ABCA1

Ann Transl Med. 2020 Nov;8(22):1506. doi: 10.21037/atm-20-6505.

Authors

Mingtai Chen¹, Ruolan Huang², Wenjun Fu³, Lijun Ou¹, Ling Men⁴, Zhong Zhang¹, Shudong Yang⁴, Qiang Liu¹, Jienan Luan¹

Affiliations

¹ Department of Cardiovascular Disease, Shenzhen Traditional Chinese Medicine Hospital, the 4 Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.
² Department of Neurology, Shenzhen University Clinical Research Center for Neurological Diseases, Shenzhen University General Hospital, Shenzhen, China.
³ Centre for Integrative Medicine, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
⁴ Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, the 4 Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.

Abstract

Background: Previous studies have reported that Xiaoyaosan (XYS), Tiaogan-Liqi therapy, has a protective function in depressive disorder, and can regulate body weight and corticosterone (CORT) level. However, little is known about the effect of XYS in treating atherosclerosis. This study aimed to explore the influence XYS on macrophage foam cell formation and related mechanism.

Methods: Rat peritoneal macrophages (PMs) were separated and stimulated with CORT and oxidized low density lipoprotein (ox-LDL). The serum was obtained from rats treated with different doses of XYS and was added into the medium for macrophages. Then, the cell activity and lipid content of PMs were measured through Cell Counting Kit-8 (CCK-8) assay and oil red staining, respectively. The expressions of glucocorticoid receptor (GR), ATP binding cassette subfamily A member 1 (ABCA1), and heat shock protein 90 (HSP90) were detected. In addition, overexpression of GR and ABCA1 was performed and the effect on XYS treatment was subsequently assessed.

Results: The CCK-8 assay showed the serum increased cell activity of CORT-induced stress PMs in a XYS dose-dependent manner. Oil red staining and enzyme-linked immunosorbent assay (ELISA) showed that the serum decreased lipids of PMs. In the XYS treated groups, HSP90 protein was decreased and protein levels of ABCA1 and GR were increased in cytoplasm, while GR protein in nucleus was decreased. Co-immunoprecipitation (Co-IP) assay indicated GR might interact with HSP90 and be involved with the function of XYS. Furthermore, overexpression of GR attenuated the protective function of XYS on CORT-induced stress in PMs, while overexpression of ABCA1 enhanced that.

Conclusions: This study denoted that XYS could protect PMs from CORT-induced stress by regulating the interaction of GR and ABCA1, which might contribute to the treatment of atherosclerosis.

Keywords: Traditional Chinese medicine; Xiaoyaosan; atherosclerosis; corticosterone; macrophages.