Protective effects and mechanisms of the Erzhi formula on glucocorticoid induced primary cortical neuron injury

Rui Han; Guoying Han; Yiqi Yan; Lifeng Han; Lin Li; Han Zhang

doi:10.3389/fphar.2023.1038492

Protective effects and mechanisms of the Erzhi formula on glucocorticoid induced primary cortical neuron injury

Front Pharmacol. 2023 Feb 27:14:1038492. doi: 10.3389/fphar.2023.1038492. eCollection 2023.

Authors

Rui Han^{1

2

3}, Guoying Han^{1

2

3}, Yiqi Yan^{1

2

3}, Lifeng Han^{1

3}, Lin Li^{1

2

3}, Han Zhang^{1

2

3}

Affiliations

¹ Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
² Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Ministry of Education, Tianjin, China.
³ State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Abstract

High concentrations of glucocorticoids (GC) can cross the blood-brain barrier into the brain parenchyma, triggering a stress state that can lead to a range of physiological changes. This study investigated whether Erzhi formula has neuroprotective effects against glucocorticoid damage by establishing a dexamethasone-induced primary cortical neuron injury model in vitro. The results showed that Erzhi formula could reduce dexamethasone-induced apoptosis in primary cultured cortical neurons and improve synaptic damage. Further, network pharmacological analysis revealed that Erzhi formula may exert antidepressant effects by multi-component, multi-target, and multi-pathway characteristics, in which Salidroside, Biochanin-A and other ingredients are key components, HSD11B1, NR3C1, and other proteins are key targets, and steroid metabolism may be a key process in its action. Moreover, our study found that the neuroprotective effect of Erzhi formula might be related to the 11β-HSD1-GC/glucocorticoid receptor (GR) signaling pathway. The Erzhi formula could significantly inhibit the activity of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in vitro using homogeneous time-resolved fluorescence. In addition to providing evidence for the pharmacological effects of the Erzhi formula, the present study lays down the foundation for subsequent experiments.

Keywords: apoptosis; depression; glucocorticoids; network analysis; primary cortical neuron; stress; synaptic plasticity; the erzhi formula.

Grants and funding

This work was supported by National Natural Science Foundation of China (81973792). This work is supported by Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No: ZYYCXTD-C-202009).